摘要:ObjectiveTo explore the mechanism of Shangerhuang Wan (SEHW) and its subdivisions in alleviating loperamide-induced functional constipation (FC) in rats by regulating bile acid metabolism.MethodsSixty rats were randomly assigned into six groups (n=10): normal control, model, positive control (domperidone, 8 mg·kg-1), Cimicifugae Rhizoma-Bupleuri Radix (SC, 1.33 g·kg-1), Scutellariae Radix-Coptidis Rhizoma (QL, 1.20 g·kg-1), and SEHW (3.33 g·kg-1). The remaining groups except the normal control group were subjected to subcutaneous injection with loperamide at 3 mg·kg-1 twice daily (total dose of 6 mg·kg-1·d-1) for 7 days to induce a model of FC. Drug administration was initiated on day 3 of modeling, which continued throughout the modeling period. The small intestinal propulsion rate of each group was measured via the ink propulsion method. LC-MS/MS was employed to measure the fecal bile acid content in each group, and the serum bile acid level was measured by a microplate. The 5-hydroxytryptamine (5-HT) and cyclic adenosine monophosphate (cAMP) levels in the colon tissue of each group were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to determine the protein levels of apical sodium-dependent bile acid transporter (ASBT) in the ileum terminus and Takeda G protein-coupled receptor 5 (TGR5) in the colon.ResultsCompared with the normal control group, the model group exhibited decreases in the small intestinal propulsion rate and total fecal bile acid content (P<0.01), an elevation in the serum total bile acid level, lowered 5-HT and cAMP levels (P<0.01), up-regulation in the protein level of ASBT (P<0.01), and down-regulation in the protein level of TGR5 (P<0.05). Compared with the model group, the positive control, SEHW, and QL groups showed increases in the small intestinal propulsion rate (P<0.05, P<0.01) and total fecal bile acid content (P<0.01) and a decline in the serum bile acid level. Compared with the SEHW group, the SC group had decreased total fecal bile acid content (P<0.01) and an elevated serum bile acid level, while the QL group showed increased total fecal bile acid content (P<0.01) and a lowered serum bile acid level. Compared with the model group, the positive control, SEHW, and QL groups demonstrated down-regulation in the protein level of ASBT (P<0.05, P<0.01) and up-regulation in the protein level of TGR5 (P<0.05, P<0.01). The SC group showed no significant change in the protein level of ASBT and up-regulation in the protein level of TGR5 compared with the model group (P<0.05). Additionally, compared with the model group, the positive control, SEHW, and QL groups showed elevated 5-HT and cAMP levels (P<0.05, P<0.01). The SC group showed no significant difference in the 5-HT level but a rise in the cAMP level (P<0.01).ConclusionSEHW, through the compatibility of QL and SC, demonstrates a dual regulatory effect on bile acid metabolism, embodying the principle of descending turbidity and ascending lucidity, which highlights the compatibility and scientific rationale of this formula. SEHW inhibits ASBT expression in the ileum to reduce ileal bile acid reabsorption, increase colonic bile acid content, and bind to colonic TGR5 to release 5-HT, thereby enhancing intestinal motility and promoting intestinal contraction.
摘要:ObjectiveTo investigate the effects of Dihuang Yinzi on the cognitive function in the mouse model of learning and memory impairments induced by scopolamine (SCOP) and explore the treatment mechanism.MethodsA mouse model of learning and memory impairment was induced by intraperitoneal injection of SCOP. Sixty male C57BL/6J mice were randomized into six groups: control (0.9% NaCl, n=10), model (SCOP 1 mg·kg-1·d-1, n=10), low-, medium-, and high-dose Dihuang Yinzi (SCOP 1 mg·kg-1·d-1 + Dihuang Yinzi 5.5, 11.0, and 22.0 g·kg-1·d-1, n=10), and donepezil (SCOP 1 mg·kg-1·d-1 + donepezil 0.84 mg·kg-1·d-1, n=10). Mice were administrated with corresponding drugs for 6 weeks. Modeling started in the 4th week, and mice in other groups except the control group were injected with SCOP intraperitoneally 40 min after daily gavage. Behavioral testing began in the 5th week, 30 min after modeling each day. The Morris water maze and novel object recognition tests were carried out to evaluate the spatial learning and memory function of mice. Nissl staining was employed to observe the survival of neurons and Nissl bodies in the hippocampal CA1 region. Western blot was employed to determine the protein levels of silent information regulator 2 (SIRT2), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor 1 (GluA1), protein kinase A (PKA), cAMP response element-binding protein (CREB), phosphorylated-CREB (p-CREB), postsynaptic density protein 95 (PSD95), growth-associated protein-43 (GAP-43), and synaptophysin (SYN) in the hippocampus. Immunofluorescence was used to detect the expression of doublecortin (DCX) in the hippocampal dentate gyrus (DG) region.ResultsCompared with the control group, the model group showed impaired learning and memory (P<0.01), obvious neuronal damage in the hippocampal CA1 region, a reduction in neuron survival (P<0.01), a decrease in DCX expression in the hippocampal DG region (P<0.01), down-regulated proteins levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 in the hippocampal tissue (P<0.05, P<0.01), and an up-regulated protein level of SIRT2 (P<0.01). Compared with the model group, the medium- and high-dose Dihuang Yinzi groups and the donepezil group showed improvements in learning and memory (P<0.05, P<0.01), while the low-, medium-, and high-dose Dihuang Yinzi groups and the donepezil group had increased neuron survival (P<0.05, P<0.01). The medium-dose Dihuang Yinzi group and the donepezil group showed increased DCX expression (P<0.05, P<0.01). The medium- and high-dose Dihuang Yinzi groups and the donepezil group showed up-regulation in the protein levels of GluA1, PKA, p-CREB/CREB, PSD95, SYN, and GAP-43 (P<0.05, P<0.01) and down-regulation in the protein level of SIRT2 (P<0.01).ConclusionDihuang Yinzi can improve the cognitive function in the mouse model of learning and memory impairments induced by SCOP by inhibiting the upregulation of SIRT2, activating the PKA/CREB signaling pathway, improving synaptic plasticity, and reducing hippocampal neuronal damage.
关键词:Dihuang Yinzi;learning and memory impairments;protein kinase A/cAMP response element-binding protein (PKA/CREB) signaling pathway;silent information regulator 2 (SIRT2);synaptic plasticity
摘要:ObjectiveTo investigate the effects of Xixintang (XXT)-medicated serum on the amyloid β-protein (Aβ)25-35-induced polarization of BV-2 microglial cells by a cell experiment and uncover the potential mechanisms of this formula in the prevention and treatment of Alzheimer's disease (AD), thus providing scientific evidence for the clinical application of XXT.MethodsBV-2 microglial cells were subcultured. The optimal concentrations of XXT-medicated serum and Aβ25-35 were determined via the cell-counting kit-8 (CCK-8) assay. The cell experiment was carried out with the following groups: blank control, model (Aβ25-35 at 40 μmol·L-1), XXT-medicated serum (Aβ25-35 at 40 μmol·L-1 + 10% XXT-medicated serum), and blank serum (Aβ25-35 at 40 μmol·L-1 + 10% blank serum). After 24 hours of cell incubation, immunofluorescence was used to detect the expression of ionized calcium-binding adaptor molecule 1 (IBA1), CD16/32, and CD206. Real-time PCR was performed to measure the mRNA levels of CD206, CD163, inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1). Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of nerve growth factor (NGF), iNOS, and Arg-1. The nitric oxide (NO) concentration was determined via the nitrate reductase method.ResultsCompared with the blank control group, the model group showed increased expression of IBA1 and CD16/32 (P<0.01), decreased expression of CD206 (P<0.05), upregulation in the mRNA level (P<0.01) and content (P<0.05) of iNOS, downregulation in the mRNA levels of CD206, CD163, and Arg-1 (P<0.05, P<0.01), lowered levels of Arg-1 and NGF (P<0.05), and an elevation in the NO level (P<0.05). Compared with the model group, the XXT-medicated serum group exhibited reduced expression of IBA1 and CD16/32 (P<0.05, P<0.01) and increased expression of CD206 (P<0.01). Both the content and mRNA level of iNOS were downregulated (P<0.05, P<0.01), while the mRNA levels of CD206, CD163, and Arg-1 were upregulated (P<0.01) in the XXT-medicated serum group. In addition, the XXT-medicated serum group showed elevated levels of Arg-1 and NGF (P<0.05) and a lowered level of NO (P<0.05). The blank serum group showed no statistically significant differences in the measured parameters compared with the model group.ConclusionThe XXT-medicated serum can inhibit the polarization toward the M1 phenotype and promote the polarization toward the M2 phenotype, exerting anti-inflammatory and neurotrophic effects.
摘要:ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 (ACSL4) signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang.MethodsSPF male SD rats were randomly divided into normal group, sham-operation group, model group, trimetazidine group (5.4 mg·kg-1), low-, medium-, and high-dose group (3.51, 7.02,14.04 g·kg-1) of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome, and continuous treatment for 7 d was conducted, while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed, and indicators such as electrocardiogram, echocardiography, and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin (HE) staining, and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe2+, lipid peroxidation (LPO), glutathione (GSH), and T-GSH/glutathione disulfide (GSSG) in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species (ROS). Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), ACSL4, and ly-sophosphatidylcholine acyltransferase3 (LPCAT3) in myocardial tissue.ResultsCompared with those in the normal group, the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage, bow-back elevation of the ST segments, elevated T waves, J-point elevation, and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01). Blood rheology showed that the viscosity of the whole blood (low, medium, and high rate of shear) was significantly increased (P<0.01). HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken, and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles, and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased (P<0.01). The content of Fe2+, LPO, and ROS in myocardial tissue was significantly increased (P<0.01). The content of GSH was significantly decreased (P<0.01), and T-GSH/GSSG was decreased (P<0.01). The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased (P<0.05, P<0.01), while those of ACSL4 and LPCAT3 increased significantly (P<0.01). Compared with the model group, the general macroscopic symptoms and electrocardiogram results of rats in low-, medium- and high-dose groups of Xuefu Zhuyutang were alleviated, and the differences in LVEF/LVFS ratios were all significantly increased (P<0.05, P<0.01). The differences in whole-blood viscosity (low, medium, and high rate of shear) were all significantly decreased (P<0.01). The results of HE staining and transmission electron microscopy showed that the morphology, structure, and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01). The content of Fe2+, LPO, and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and the content of GSH and T-GSH/GSSG was significantly increased (P<0.05, P<0.01). The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01), and ACSL4 and LPCAT3 were decreased to different degrees in the low-, medium-, and high-dose groups of Xuefu Zhuyutang (P<0.05, P<0.01).ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway, thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.
摘要:ObjectiveTo investigate the potential mechanism of Renshen Yangrongtang in alleviating myelosuppression by regulating the expression of reactive oxygen species (ROS), myeloperoxidase (MPO), and neutrophil extracellular traps (NETs).MethodsK562 cells were divided into blank group, etoposide group (40 μmol·L-1), and etoposide+Renshen Yangrongtang freeze-dried powder groups with low-, medium-, and high-dose (2, 4, 8 g·L-1). Liquid chromatography-mass spectrometry (LC-MS) was used to determine the freeze-dried powder of Renshen Yangrongtang. Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect ROS, MPO, and NETs expression in each group. Western blot analysis was performed to assess intracellular MPO and NE expressions. Twenty 8-week-old male mice were randomly divided into blank group, etoposide group (100 mg·kg-1), and etoposide + Renshen Yangrongtang groups with low-, medium-, and high-dose (0.1, 0.5, 2.0 g·kg-1). Except for the blank group that received PBS via gavage at room temperature, and the etoposide group that received an intraperitoneal injection for 3 days, the remaining groups received gavage of Renshen Yangrongtang for 14 consecutive days after 3 days of etoposide administration. The peripheral blood related indicators were detected through an automated hematology analyzer; Western blot analysis was performed to assess MPO and neutrophil elastase (NE) expression changes in the marrow cells of mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect ROS, MPO, and NETs changes in the marrow cells of mice. MPO and NE on femur bones were stained through immunohistochemistry. Scanning electron microscopy was used to analyze the structural changes of NETs in the marrow cells of mice after drug administration.ResultsLC-MS results showed that the freeze-dried powder of Renshen Yangrongtang contained complete technical materials such as Chinese angelica, Astragalus mongholicus, and ginseng. In K562 cells, compared with the etoposide group, ELISA results indicated that the concentrations of MPO, ROS, and NETs in the etoposide + Renshen Yangrongtang medium and high-dose groups were decreased (P<0.05, P<0.01), and Western blot data showed that the etoposide high-dose group significantly reduced the expression of MPO and NE protein in K562 cells (P<0.05, P<0.01). In vivo, compared with the etoposide group, the number of RBC, WBC, and PLT in the etoposide+Renshen Yangrongtang high-dose group increased significantly (P<0.05). ELISA results suggested that in the etoposide+Renshen Yangrongtang low-, medium-, and high-dose groups, the concentration of mice ROS, MPO, and NETs significantly decreased (P<0.05, P<0.01). Western blot results revealed that compared with the etoposide group, the expressions of MPO and NE in the marrow cells of mice in the etoposide + Renshen Yangrongtang low-, medium- and high-dose groups were significantly decreased (P<0.05, P<0.01). Scanning electron microscopy observations revealed that Renshen Yangrongtang reduced the NETs structure generation in the marrow cells of mice after the influence of etoposide.ConclusionRenshen Yangrongtang can alleviate etoposide-induced myelosuppression by inhibiting ROS/MPO and reducing the formation of intracellular NETs.
关键词:Renshen Yangrongtang;myeloperoxidase (MPO);reactive oxygen species (ROS);neutrophil extracellular traps (NETs);myelosuppression
摘要:Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine, and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation, and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines, Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome (hereinafter referred to as the Guidelines) were compiled by our research group, in cooperation with the renowned experts in research fields including traditional Chinese medicine, clinical medicine, zoology and evidence-based medicine, which provide a meaningful reference for scientific research, teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place, consensus plays an auxiliary role, and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology, behavioral phenotypic consistency, and drug treatment predictability compared between animal models and human diseases, by the nominal group method, "recommendations" were formed for recommendations supported by evidence, and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types, arthritis modeling methods, external stimulation conditions, and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis, investigation of therapeutic mechanisms, and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.
摘要:The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome (hereinafter referred to as the Guidelines) (No. T/CACM1567-2024) was published by Chinese Association of Chinese Medicine on January 11, 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately, and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models, this paper made a declaration of the workflow, technological links, development references, promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".
摘要:ObjectiveTo investigate the efficacy of Xingpi capsules (XPC) in treating diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen deficiency and elucidate its potential molecular mechanisms.MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free (SPF)-grade healthy rats were used as the normal control group. After successful modeling, SPF-grade rats were randomly divided into a model group, a pinaverium bromide group (1.5 mg·kg-1), and low- and high-dose XPC groups (0.135 and 0.54 g·kg-1), with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage, while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day, and the Bristol score was recorded. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 5-hydroxytryptamine (5-HT) in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier, intestinal motility, and expression of related pathway proteins were evaluated by hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot.ResultsCompared with those in the normal control group, rats in the model group showed a significantly decreased body weight and increased diarrhea rate, diarrhea grade, and Bristol score (P<0.01). HE staining revealed incomplete colonic mucosa in the model group, with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier, shedding and disappearance of microvilli, and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated (P<0.01), and the levels of 5-HT in serum and colon tissue were elevated (P<0.01). The small intestine propulsion rate significantly increased (P<0.01), and the expression of contractile proteins Ras homolog family member A (RhoA) and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) in colon and phosphorylation of myosin light chain (MLC20) were upregulated (P<0.01). Compared with the model group, the treatment groups showed alleviated diarrhea, diarrhea-associated symptoms, and pathological manifestations of colon tissue to varying degrees. Specifically, high-dose XPC exhibited effectively relieved diarrhea, promoted recovery of colonic mucosal structure, significantly reduced congestion and edema, upregulated expression of Occludin and Claudin-5 (P<0.01), decreased levels of 5-HT in serum and colon tissue (P<0.05,P<0.01), significantly slowed small intestine propulsion rate (P<0.01), and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC20 (P<0.05,P<0.01).ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction, and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.
关键词:diarrhea-predominant irritable bowel syndrome;Xingpi capsules;5-hydroxytryptamine (5-HT)-Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) pathway
摘要:ObjectiveTo explore the effects of Qingxin Jieyu granules on ventricular remodeling of mice after myocardial infarction, and their regulatory role in mitophagy.MethodsSixty male C57BL/6 mice were randomly assigned to six groups: sham-operated group, model group, Qingxin Jieyu granules low-, medium-, and high-dose groups (1.3, 2.6, 5.2 g·kg-1), and sacubitril valsartan sodium group (0.03 g·kg-1), with 10 mice per group. Except for the sham-operated group, all other groups utilized left anterior descending coronary artery ligation to build a myocardial infarction model. Ultrasound was used to measure left ventricular parameters, including end-diastolic and end-systolic diameters (LVIDd, LVIDs), diastolic and systolic posterior wall thickness (LVPWd, LVPWs), end-diastolic and end-systolic volumes (LV Vold, LV Vols), left ventricular ejection fraction (LVEF), and fractional shortening (LVFS). Additionally, the heart mass index and heart weight/tibia length ratio of mice were calculated. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify brain natriuretic peptide (BNP), creatine kinase isoenzyme (CK-MB), angiotensinⅡ (AngⅡ), and lactate dehydrogenase (LDH) levels in the serum of mice. Histological analysis using hematoxylin-eosin (HE) and Masson staining was conducted to examine morphological changes in myocardial tissue. Immunohistochemistry assessed the expression of vascular growth factors, including basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Transmission electron microscopy was used to scrutinize mitochondrial morphology in the myocardial tissue of mice. Western blot was performed to analyze the expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK) and phosphorylated mammalian target of rapamycin (p-mTOR) proteins in myocardial tissue from each experimental group.ResultsCompared to the sham-operated group, the model group mice exhibited significantly elevated levels of LV Vold, LV Vols, LVIDd, LVIDs, cardiac mass index, heart weight/tibia length ratio, BNP, LDH, and p-mTOR protein expression (P<0.05), along with decreased levels of LVPWd, LVPWs, LVEF, LVFS, and p-AMPK protein expression (P<0.05). The model group also displayed substantial inflammatory cell infiltration, collagen deposition in myocardial cells, reduced expression of bFGF and VEGF, mitochondrial swelling, and cristae fragmentation. Compared to the model group, the sacubitril/valsartan group and mid-dose Qingxin Jieyu granules group showed significant reductions in LVIDs, LV Vold, LV Vols, BNP, CK-MB, LDH, and p-mTOR protein expression (P<0.05), coupled with increases in LVEF, LVFS, and p-AMPK expression (P<0.05). Improvements were observed across all treatment groups, including reduced inflammatory cell infiltration and collagen deposition, increased bFGF and VEGF expression, alleviated mitochondrial swelling, and the presence of autophagosomes and lysosomes.ConclusionThe results show that Qingxin Jieyu granules can regulate mitochondrial autophagy in myocardial tissue and inhibit ventricular remodeling to improve cardiac performance, by up-regulating the p-AMPK expression in the myocardial tissue of mice with ventricular remodeling after myocardial infarction, and down-regulating the p-mTOR expression.
XU Yanru, TAO Lihuiping, QIAN Jingyang, SHEN Weixing, TAN Jiani, YU Chengtao, FAN Minmin, XU Changliang, LAI Yueyang, LI Liu, SUN Dongdong, CHENG Haibo
摘要:ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer (CRC) and investigate the related mechanisms.MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit, followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group, low-dose Xianlian Jiedu prescription (XLJDP-L) group (6.45 g·kg-1·d-1), medium-dose Xianlian Jiedu prescription (XLJDP-M) group (12.9 g·kg-1·d-1), high-dose Xianlian Jiedu prescription (XLJDP-H) group (25.8 g·kg-1·d-1), and 5-fluorouracil (5-FU) group (1×10-3 g·kg-1·d-1). The mice were euthanized after 14 days of continuous intervention, and recurrent tumor tissue was harvested. Hematoxylin and eosin (HE) staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry (IHC) was employed to assess the expression of proliferating cell nuclear antigen (Ki67), vascular endothelial growth factor (VEGF), and platelet-endothelial cell adhesion molecule (CD31) in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 (ANG-2), VEGF, phosphorylated-protein kinase B (p-Akt), protein kinase B (Akt), phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), and phosphatidylinositol 3-kinase (PI3K) in recurrent tumor tissue.ResultsBefore treatment, there were no statistical differences in tumor volume, tumor weight, and body mass among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group, indicating model stability. After treatment, compared with those in the model group, the tumor volume and tumor weight in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01), showing dose dependency. Meanwhile, there were no significant differences in body weight among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group, tumor tissue in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group had loosely arranged cells, increased intercellular spaces, small and shriveled nuclei, light staining, fewer mitotic figures and atypical nuclei, and increased necrotic areas. IHC showed that compared with those of the model group, the positive rates of Ki67, VEGF, and CD31 in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01) in a dose-dependent manner. Western blot results showed that compared with those of the model group, the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly downregulated (P<0.05, P<0.01), and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner (P<0.05, P<0.01).ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2, VEGF, and CD31.
摘要:ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula (MQEF) in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS),network pharmacology, and cell experiments.MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B (UVB). The safe doses of bakuchiol (BAK) and salvianolic acid B (SAB) for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 (CCK-8) method.The reactive oxygen species (ROS) fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress,inflammation,collagen metabolism,and circadian rhythm clock were measured by Real-time PCR.ResultsA total of 24 transdermally absorbed components of MQEF were identified,which acted on 367 potential targets,and 417 targets related to skin photoaging were screened out,among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB,which acted on core proteins such as serine/threonine kinase 1 (Akt1) and mitogen-activated protein kinase 3 (MAPK3) and intervened in core pathways such as the tumor necrosis factor (TNF) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways.Compared with the model group,the administration of BAK and SAB increased the survival rate of HaCaT cells (P<0.01),down-regulated the mRNA levels of cyclooxygenase-2 (COX-2),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),matrix metalloproteinase-1 (MMP-1),and matrix metalloproteinase-9 (MMP-9) (P<0.01),and up-regulated the mRNA levels of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO-1) (P<0.05,P<0.01) in photoaged HaCaT cells.In addition,it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) associated with circadian clock (P<0.05,P<0.01).ConclusionMQEF delays skin photoaging through the coordinated effects of various components,multiple targets,and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties,which involve inhibiting oxidative stress,preventing collagen degradation,mitigating inflammation,and maintaining normal skin circadian rhythms by regulating clock gene expression.
关键词:modified Qing'e formula (MQEF);skin photoaging;circadian rhythm;ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS);network pharmacology
摘要:ObjectiveTo investigate the suppressive effect of 23-hydroxybetulinic acid (23-HBA), a key constituent of Pulsatillae Radix, on the pulmonary inflammation-related carcinogenesis induced by the combined exposure of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and lipopolysaccharide (LPS) in mice, alongside exploring its influence on immune cells and delving into the underlying mechanisms.MethodsA murine model of pulmonary inflammation-related carcinogenesis induced by NNK combined with LPS was established. Mice were randomly assigned into blank control, model, aspirin (10 mg·kg-1), and low-, medium-, and high-dose (3.75, 7.5, 15 mg·kg-1, respectively) 23-HBA groups. The treatment lasted for 26 weeks, after which the spleen, lung, and peripheral blood samples were collected. Lung and spleen indices were calculated. Histopathological changes in the lung tissue were observed by hematoxylin-eosin staining. Immunohistochemistry was employed to assess the expression levels of thyroid transcription factor-1 (TTF-1), neuron-specific enolase (NSE), and proliferating cell nuclear antigen (Ki-67) in the lung tissue. High-throughput protein microarray was employed to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the mouse serum. Flow cytometry was employed to evaluate the expression of macrophages, myeloid-derived suppressor cells (MDSCs), and exhausted T lymphocytes in the lung and spleen tissue. Molecular docking was performed to predict the binding affinity of 23-HBA to Janus kinase 2 (JAK2), Src homology 2 domain-containing phosphatase 2 (SHP2), and suppressor of cytokine signaling 3 (SOCS3). Western blot was performed to assess the protein levels of phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), p53, and SHP2 in the M1-activated macrophages and A549 lung adenocarcinoma cells treated with 23-HBA.ResultsCompared with the normal group, the lung and spleen indexes of the model group were increased to varying degrees (P<0.05, P<0.01), the expression of TTF-1, NSE and Ki-67 protein was significantly increased (P<0.05, P<0.01), and the serum levels of TNF-α, IL-1β and IL-6 were significantly increased (P<0.01). The number of macrophages in the model group was significantly decreased (P<0.01), and the number of exhausted T cells and MDSCs was significantly increased (P<0.05, P<0.01). Compared with the model group, the spleen and thymus index of mice in each dose group of 23-HBA decreased significantly (P<0.05), and the lung index of mice in the middle dose group of 23-HBA decreased significantly (P<0.05). The high and middle dose groups of 23-HBA could improve the occurrence of inflammatory infiltration and malignant lesions in the lungs of mice induced by NNK combined with LPS in the model group. The expression of TTF-1 in the middle and high dose groups of 23-HBA was significantly lower than that in the model group (P<0.05, P<0.01). The expression of NSE and Ki-67 protein in each dose group of 23-HBA was significantly lower than that in the model group (P<0.05, P<0.01). The contents of IL-1β in the low and high dose groups of 23-HBA were significantly decreased (P<0.05), and the contents of IL-6 and TNF-α in each dose of 23-HBA were significantly decreased (P<0.05, P<0.01). The number of macrophages in the lung of the middle dose group of 23-HBA was significantly increased (P<0.05), and the number of exhausted T cells and MDSCs expressing PD-1 in the lung was significantly decreased (P<0.05, P<0.01). In addition, 23-HBA had strong molecular docking ability to SHP2, SOCS3 and JAK2 (≥7 kcal·mol-1), and significantly down-regulated the protein levels of p-STAT3, SHP2 and p53 in M1 macrophages and A549 lung adenocarcinoma (P<0.01).Conclusion23-HBA holds promise as a potential therapeutic agent for mitigating pulmonary inflammation and inhibiting malignant transformation induced by the combination of LPS and NNK. It may exert effects by regulating immune cell responses, improving the tumor immune microenvironment, and regulating key signaling pathways.
关键词:23-hydroxybetulinic acid;4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) combined with lipopolysaccharide (LPS);lung tissue;inflammation-related carcinogenesis;immune cells
摘要:ObjectiveTo investigate the effects of jujuboside A (JuA) on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment (VCI) and explore the potential mechanisms by which JuA treats VCI.MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group (n=10), a blank control group (n=10), and a modeling group (n=30). The rats in the modeling group underwent bilateral carotid artery ligation (2-VO) for the modeling of VCI. After stabilization, the VCI rats were randomized into model, JuA (20 mg·kg-¹), and donepezil (0.45 mg·kg-¹) groups. After 4 weeks of gavage, the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β (GSK-3β), cAMP response element-binding protein (CREB), B cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β, p-GSK-3β, p-CREB, Bcl-2, PI3K, p-PI3K, Akt, and p-Akt in the hippocampal tissue.ResultCompared with the sham operation group, the model group exhibited declines in the learning and memory abilities (P<0.01), neuronal damage and decreased neurons in the hippocampal CA1 region (P<0.01), up-regulation in the mRNA level of GSK-3β (P<0.01), and down-regulation in the mRNA levels of PI3K, Akt, CREB, and Bcl-2, as well as the protein levels of p-PI3K, p-Akt, p-GSK-3β, p-CREB, and Bcl-2 (P<0.01). In comparison to the model group, both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities (P<0.05, P<0.01), with reduced neuronal damage and increased neurons (P<0.05, P<0.01). In addition, the two groups showed down-regulation in the mRNA level of GSK-3β (P<0.01) and up-regulation in the mRNA levels of PI3K, Akt, CREB, and Bcl-2 and the protein levels of p-PI3K, p-Akt, p-GSK-3β, p-CREB, and Bcl-2 (P<0.05, P<0.01). There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities, neuron count, and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors.ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway, reducing the apoptosis of hippocampal neurons, and alleviating the hippocampal neuronal damage.
摘要:ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop (TTFL) of biorhythm in the rat model of non-alcoholic fatty liver disease (NAFLD) and its mechanism for prevention and treatment of NAFLD.MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank (n=20), model (n=15), and low-, medium-, and high-dose (2.68, 5.36, and 10.72 g·kg-1·d-1, respectively) modified Ditan tang (n=10) groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage, and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid (NEFA) assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining, and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 (BMAL1/ARNTL) in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1, circadian locomotor output cycles kaput (CLOCK), period circadian clock 2 (PER2), and cryptochrome1 (Cry1) in the hypothalamus and liver were determined by Real-time PCR and Western blot, respectively.ResultsCompared with the blank group, the model group showed elevated levels of TG, TC, LDL-C, AST, and ALT (P<0.01) and a lowered level of HDL-C (P<0.05) in the serum, elevated levels of TG and NEFA in the liver (P<0.01), pyknosis and deep staining of hypothalamic neuron cells, and a large number of vacuoles in the brain area. In addition, the model group showed lipid deposition in the liver, up-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.01), and down-regulated mRNA and protein levels of Cry1 and PER2 (P<0.01) in the hypothalamus and liver. Compared with the model group, all the three modified Ditan tang groups showed lowered levels of TG, TC, LDL-C, ALT, and AST (P<0.05, P<0.01) and an elevated level of HDL-C (P<0.05) in the serum, and lowered levels of TG and NEFA (P<0.05, P<0.01) in the liver. Furthermore, the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells, reduced lipid deposition in the liver, down-regulated mRNA and protein levels of CLOCK and BMAL1 (P<0.05, P<0.01), and up-regulated mRNA and protein levels of Cry1 and PER2 (P<0.05, P<0.01) in the hypothalamus and liver.ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK, BMAL1, Cry1, and PER2 in the TTFL of NAFLD rats.
关键词:non-alcoholic fatty liver disease;modified Ditan tang;biorhythm;Hypothalamus;spleen governing four seasons
摘要:ObjectiveTo observe the inhibitory effect of the Weiliuan mixture (WLAHJ) on the subcutaneous xenograft tumor of MKN-74 gastric cancer cells, and explore the potential anti-gastric cancer mechanism of WLAHJ by using transcriptomic sequencing technology to reveal related genes and pathways.Methods30 Balb/c nude mice were randomly divided into model, low-, medium-, and high-dose(15,30,45 g·kg-1) WLAHJ and 5-FU (0.025 g·kg-1) groups to build a subcutaneous xenograft tumor model with MKN-74 human gastric cancer cells. After modeling,each group was continuously treated with the corresponding drugs for 28 days. During the treatment period, the body weight and tumor size of the mice were observed and recorded every 2 days. At the end of the treatment, the mice were sacrificed, and required samples were collected to calculate the tumor inhibition rate of WLAHJ on the subcutaneous xenograft tumor. High-throughput transcriptomic sequencing (RNA-seq) technology was used to analyze the differentially expressed genes in the subcutaneous tumor tissues of the model group and the medium-dose WLAHJ group, thus exploring the potential mechanism of WLAHJ in gastric cancer intervention. Immunofluorescence experiments were conducted to detect the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein-1 (TFR-1), and acyl-CoA synthetase long-chain family member 4 (ACSL4) in subcutaneous xenograft tumors of each group. Cell counting kit-8(CCK-8) and colony formation assays were used to detect the viability and anti-proliferative ability of human gastric cancer AGS and MKN-74 cells at different concentrations of WLAHJ. Kits were used to detect the levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in cells. Western blot was used to detect the expression levels of GPX4, SLC7A11, TRF-1, ACSL4, spermidine/spermine N1-acetyltransferase 1 (SAT1), arachidonic acid 15-lipoxygenase (ALOX15), and key proteins in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.ResultsThe mechanism of WLAHJ in gastric cancer intervention may be related to ferroptosis and the PI3K/Akt /mTOR signaling pathway. The growth of subcutaneous xenograft tumors in nude mice of the WLAHJ and 5-FU groups(P<0.05,P<0.01), GPX4, and SLC7A11 dropped significantly(P<0.01), while TFR-1, ACSL4, SAT1, and ALOX15(P<0.05,P<0.01)increased significantly compared with those in the model group. The levels of ROS, Fe2+, and MDA increased in the WLAHJ and 5-FU groups and the proliferation of gastric cancer cells, SOD activity, the ratios of phosphorybation (p)-mTOR/mTOR, p-PI3K/PI3K, and p-Akt/Akt protein expressions(P<0.05,P<0.01)decreased compared with those in the blank group.ConclusionThe mechanism of WLAHJ in treating gastric cancer may be related to the regulation of the PI3K/ Akt /mTOR signaling pathway to intervene in ferroptosis.
关键词:Weiliuan mixture;gastric cancer;ferroptosis;phosphatidylinositol 3-kinase /protein kinase B /mammalian target of rapamycin (PI3K/ Akt /mTOR);transcriptomics
摘要:ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3)/cysteinyl aspartate-specific proteinase (Caspase)-1/gasdermin D (GSDMD) signaling pathway.MethodsForty db/db mice were randomly assigned into model, positive control (0.001 3 g·kg·d-1 dapagliflozin suspension), and high-, medium-, and low-dose Gelian Tiaotang pills (3.12, 1.56, and 0.78 g·kg·d-1 suspension of Gelian Tiaotang pills, respectively) groups, with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water, while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose (FBG) and body mass were measured every 4 weeks. Kidneys were weighed after sampling, and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride (TG), total cholesterol (TC), serum creatinine (SCr), and blood urea nitrogen (BUN). The pathological changes, extracellular matrix deposition, and renal fibrosis degree were examined by hematoxylin-eosin, periodic acid-schiff (PAS), and Masson staining, respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin (IL)-1β and IL-18 in the renal tissue. Immunohistochemistry (IHC) was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, and GSDMD-N in the renal tissue.ResultsCompared with the normal group, the model group generally had poor general states and increases in the body mass, kidney weight, kidney index, and levels of FBG, TG, TC, SCr, and BUN (P<0.01). In addition, glomerular pyknosis, increased matrix, vacuolar degeneration of renal tubular epithelial cells, and interstitial infiltration of inflammatory cells were observed in the model group (P<0.01), together with rises in the levels of IL-1β and IL-18 in the renal tissue (P<0.01) and up-regulated protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, GSDMD-N, fibronectin, and collagen Ⅰ in the renal tissue (P<0.01). Compared with the model group, 12 weeks of drug interventions reduced the body mass, kidney weight, and kidney index and lowered the levels of FBG, TG, TC, SCr, and BUN in the serum and IL-1β and IL-18 in the renal tissue (P<0.05, P<0.01). Furthermore, drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, GSDMD-N, fibronectin, and collagen Ⅰ in the renal tissue (P<0.05, P<0.01). The high-dose group of Gelian Tiaotang pills had the best effects.ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway, thus delaying the process of renal fibrosis in diabetes.
摘要:ObjectiveTo observe the clinical efficacy and safety of Guben Quyu Jiedu prescription in treating nocturnal hypoxemia of chronic obstructive pulmonary disease (COPD) combined with Obstructive sleep apnea hypopnea syndrome ( OSAHS ) (deficiency of lung, spleen and kidney with blood stasis and toxicity).MethodsThe paper used a forward-looking, random double-blind, placebo-controlled design method to select 96 patients with COPD combined with OSAHS, and their traditional Chinese medicines (TCM) syndrome differentiation was deficiency of lung, spleen and kidney with blood stasis and toxicity. These patients were randomly divided into the observation group and the control group, with 48 cases in each group. Based on conventional Western medicine treatment, the observation group was treated with Guben Quyu Jiedu prescription and the control group was treated with traditional Chinese medicine placebo. Both courses of treatment were 90 days. Then the paper compared the changes in minimum pulse oxygen saturation (SpO2) during the night, apnea index (AHI), OSAHS efficacy evaluation, TCM syndrome efficacy evaluation, and TCM symptom score before and after treatment between the two groups.ResultsThere were 5 withdrawals in the observation group and 8 withdrawals in the control group, so 43 cases in the observation group and 40 cases in the control group completed the trial. Compared with the condition before treatment, the minimum SpO2 during the night and AHI in the observation group were significantly improved at night (P<0.01) and were better than those in the control group (P<0.01). OSAHS efficacy in the observation group was better than in the control group (χ2=7.085, P<0.05). In terms of TCM syndrome efficacy, the total effective rate was 81.40% (35/43) in the observation group, significantly higher than that in the control group, which was 15.00% (6/40) (χ2=36.78, P<0.01). The TCM symptom scores of the two groups were improved compared with the condition before treatment, and the effect of the two groups was similar in the four main symptoms of snoring, choking, lethargy, and cough. However, the observation group was better than the control group in 10 details such as dizziness, headache, chest tightness, chest pain, wheezing, dry mouth, and thirst (P<0.05).ConclusionUsing Guben Quyu Jiedu prescription combined with conventional Western medicine can treat COPD combined with OSAHS hypoxemia at night (deficiency of lung, spleen and kidney with blood stasis and toxicity). In this way, the minimum pulse oxygen saturation (SpO2) of patients, the level of disease control, and the quality of life of patients can be improved, and the clinical symptoms can be relieved.
摘要:ObjectiveTo construct and validate a clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure (CHF),aiming to assist clinical diagnosis and provide tools and methods for individualized treatment of CHF.MethodsThe clinical data of patients with chronic heart failure treated at Dongzhimen Hospital of Beijing University of Chinese Medicine from January 2022 to January 2024 were retrospectively collected. The patients were randomly divided into a training group and a validation group with a ratio of 7∶3. First, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to preliminarily screen the predictive factors affecting the diagnosis of Qi deficiency and blood stasis syndrome in CHF. Subsequently, the Logistic regression method was applied to conduct a more in-depth and detailed analysis of these factors. Variables with P<0.05 in the results of the multi-factor Logistic regression were carefully selected and included. Based on the regression coefficients obtained from this analysis, a model was constructed, and a nomogram was accurately drawn. Using R software,the receiver operating characteristic (ROC) curve,calibration curve,and decision curve analysis (DCA) were precisely drawn. These analyses were used to comprehensively evaluate the model from three crucial aspects: discrimination,calibration,and clinical applicability. Additionally, the accuracy,specificity,sensitivity,positive predictive value,and negative predictive value of the model were meticulously calculated to conduct a more all-round and comprehensive assessment.ResultsIn total, 168 cases were successfully obtained in the training group, and 71 cases were included in the validation group. After a thorough comparison, it was found that there were no statistically significant differences in the baseline data between the two groups. After being rigorously screened by the LASSO-multivariate logistic regression method, dark red tongue,smoking history,cardiac troponin I,and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were identified as the influencing factors for diagnosing patients with the Qi deficiency and blood stasis syndrome in CHF. The constructed model demonstrated an area under the curve (AUC) of 0.812 in the training group and 0.719 in the validation group. The calibration curve showed that the predicted curve of the model was close to the actual observed curve. DCA indicated that the model could provide substantial clinical benefits for patients at the decision thresholds ranging from 0.2 to 0.9.ConclusionThe clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure constructed in this study shows good performance. It has certain application value in clinical practice, which may contribute to the improvement of the diagnosis and treatment of CHF patients with this syndrome.
关键词:chronic heart failure;Qi deficiency and blood stasis syndrome;nomogram;clinical prediction model
摘要:ObjectiveTo observe the clinical efficacy of renal failure enema for retention enema as an adjuvant therapy in patients with chronic kidney disease stages 3-4 and its effect on serum uremic toxins including indoxyl sulfate (IS),p-cresol sulfate (PCS),and trimethylamine oxide (TMAO).MethodsA total of 60 patients with stage 3-4 chronic kidney disease in the Department of Nephrology,Affiliated Hospital of Tianjin Institute of Traditional Chinese Medicine from June 2023 to November 2023,were divided into a control group and an observation group. Each group consisted of 30 patients,and the random number table method was used for the division. Both groups received routine symptomatic treatment of traditional Chinese medicine (TCM) and Western medicine in the department. The observation group,based on the treatment of the control group,was additionally given 100-200 mL of the hospital-made renal failure enema capsules once every other day. The total treatment course was 4 weeks. The changes in serum creatinine (SCr),blood urea nitrogen (BUN),uric acid (UA),24-hour urine total protein quantification (24 h UTP),and serum uremic toxins such as IS,PCS,and TMAO were compared between the two groups before and after treatment. The total clinical effective rate of TCM and Western medicine was calculated and the adverse reactions were recorded.ResultsBefore treatment,the baseline levels of the two groups were comparable. After treatment,the total effective rate of the observation group (80.0%,24/30) was superior to that of the control group (53.3%,16/30),and the difference was statistically significant (Z=2.267,P=0.023). After treatment,the TCM pattern scores of the two groups were lower than before,and the constipation symptoms in the observation group were improved(P<0.01). Compared with the control group after treatment,the observation group showed decreased TCM syndrome scores,and the difference before and after treatment was larger (P<0.05). Compared with before treatment,the SCr in both groups decreased after treatment (P<0.05). BUN levels decreased in the observation group(P<0.05),and IS and PCS levels decreased in the observation group(P<0.05,P<0.01). Compared with the control group after treatment,the IS level of the observation group decreased (P<0.05). During the trial,no adverse reactions occurred in either group.ConclusionRenal failure enema can be used as an adjuvant therapy for patients with CKD stages 3-4. It can not only slow down the progression of renal function but also effectively down-regulate the levels of uremic toxins. In addition,it can significantly improve the TCM syndrome of kidney disease patients,which makes it worthy of clinical application and promotion.
关键词:renal failure enema;chronic kidney disease;observation of therapeutic effect;uremic toxin
摘要:ObjectiveTo observe the effectiveness and safety of Jiuzihuichun decoction combined with spleen- strengthening moxibustion in patients with asthenospermia infertility with spleen-kidney deficiency pattern.MethodsA total of 82 patients with asthenospermia of spleen-kidney deficiency pattern in Shanghai Seventh People's Hospital were included. The patients were randomly divided into an observation group and a control group, with 41 patients in each group. The control group received oral administration of WuziYanzong pills combined with spleen-strengthening moxibustion. The dosage of Wuzi Yanzong pills was 1 bag each time, and it was taken twice a day. The spleen-strengthening moxibustion was carried out once a week. The observation group, on the other hand, took Jiuzi Huichun decoction orally combined with spleen-strengthening moxibustion. The Jiuzi Huichun Decoction was taken 200 mL each time, twice a day, with one dose in the morning and one in the evening. The spleen-strengthening moxibustion for the observation group was also performed once a week. The treatment course for both groups was 12 weeks, and they were followed up for an additional 12 weeks. During the treatment process,12 cases were either lost to follow-up or excluded. Eventually, 70 cases were available for evaluation,with 35 cases in the control group and 35 cases in the observation group. The pregnancy status of the patients' spouse within 6 months was recorded. The traditional Chinese medicine (TCM) syndrome scores of spleen-kidney deficiency pattern before and after treatment were evaluated. The semen volume,semen routine parameters,normal sperm morphology,sperm DNA fragmentation index,seminal plasma fructose,seminal plasma acid phosphatase, and seminal plasma α-glucosidase levels of the two groups were detected before and after treatment. In addition, the safety indicators related to liver and kidney functions of the two groups were detected before and after treatment.ResultsDuring the 6-month observation period, when compared with the situation before treatment in their respective groups,the semen volume of the observation group and the control group increased. In contrast, the sperm concentration,sperm motility,proportion of a+b-grade sperm,normal sperm morphology,seminal plasma fructose,seminal plasma acid phosphatase,seminal plasma α-Glucosidase,the proportion of a-grade sperm,linear sperm motility,linear sperm concentration, and linear sperm count all increased significantly(P<0.05). At the same time, the sperm DNA fragmentation index and the TCM syndrome scores of the spleen-kidney deficiency pattern decreased significantly(P<0.05). When the observation group was compared with the control group after treatment, the clinical efficacy of the observation group was better(Z=-2.276,P<0.05). The pregnancy rate of the observation group's spouses was 14.3%,which was higher than the 2.9% of the control group. The sperm motility, the proportion of a+b-grade sperm,seminal plasma fructose,the proportion of a-grade sperm,normal sperm morphology,α-glucosidase, and linear sperm motility in the observation group were higher than those in the control group (P<0.05). Moreover, the sperm DNA fragmentation index and the TCM syndrome scores of spleen-kidney deficiency pattern in the observation group were lower than those in the control group (P<0.01). No serious adverse reactions occurred in the two groups,and no abnormalities were found in the safety indicators after treatment.ConclusionJiuzi Huichun decoction combined with spleen-strengthening moxibustion can enhance sperm viability and sperm concentration. It can also improve the TCM-related symptoms of asthenospermia of spleen-kidney deficiency pattern and sperm morphology. Additionally, it can reduce the sperm DNA fragmentation index and regulate the level of seminal plasma bioenzyme in patients with male asthenospermia infertility of spleen-kidney deficiency pattern. Therefore, it is worthy of further promotion and application in clinical practice.
关键词:male infertility;asthenospermia;spleen-kidney deficiency pattern;Jiuzi Huichun decoction;strengthening spleen and kidney
摘要:Shegan Mahuangtang was a famous classical formula for treating asthma and is included in the the Catalogue of Ancient Famous Classical Formulas(The Second Batch). By means of bibliometrics, this study conducts a textual research and analysis on the key information of its formula origin, composition, drug origins, processing, dosage, decocting methods, efficacy, and clinical application. According to research, Shegan Mahuangtang was first recorded in Synopsis of the Golden Chamber and is the ancestral formula for treating cold asthma, which has been used to this day. Suggestions for the drug origins in Shegan Mahuangtang is as follows:Shegan is selected from the dried rhizomes of Belamcanda chinensis(Iridaceae), Mahuang is selected from the dried herbaceous stems of Ephedra sinica(Ephedraceae), Shengjiang is selected from the fresh rhizomes of Zingiber officinale(Zingiberaceae), Xixin is selected from the dried roots and rhizomes of Asarum heterotropoides var. mandshuricum, A. sieboldii var. seoulense or A. sieboldii(Aristolochiaceae), Ziwan is selected from the dried roots and rhizomes of Aster tataricus(Compositae), Kuandonghua is selected from the dried flower buds of Tussilago farfara(Compositae), Nanwuweizi is selected from the dried mature fruits of Schisandra sphenanthera(Magnoliaceae), Dazao is selected from the dried mature fruit of Ziziphus jujuba(Rhamnaceae), and Banxia, a plant of the Araceae family, is selected as the processed products of dried tubers from Pinellia ternata. The recommended dosage is 41.4 g of Shegan, Xixin, Ziwan and Kuandonghua, 55.2 g of Mahuang and Shengjiang, 37.5 g of Nanwuweizi, 21 g of Dazao, 34.5 g of Banxia. The decoction method is to boil Mahuang first in 2.4 L of water, remove the froth on the top, and add the rest of the herbs and decoct them together, and then boil them to 600 mL, and then take it at warm temperature, 200 mL each time, 3 times a day. In terms of clinical application, Shegan Mahuangtang is most commonly used for respiratory system diseases, especially in the treatment of adult or pediatric bronchial asthma and cough variant asthma. Phlegm sound in the throat is the core symptom of Shegan Mahuangtang in clinical practice, and the core pathogenesis is "cold fluid stagnated in the lungs". By excavating and sorting out the ancient and modern literature of Shegan Mahuangtang, key information is confirmed, which can provide literature reference for the modern clinical application and new drug development of this famous classical formula.
关键词:famous classical formulas;Shegan Mahuangtang;source of formula;origin;processing;decoction method;efficacy;clinical application
摘要:Xiaoji Yinzi is one of the classic prescriptions for treating urinary diseases, originated from the Yan's Prescriptions to Aid the Living (Yan Shi Ji Sheng Fang) written by YAN Yonghe in the Song dynasty. Xiaoji Yinzi is composed of Rehmanniae Radix, Cirsii Herba, Talcum, Akebiae Caulis, Typhae Pollen, Nelumbinis Rhizomatis Nodus, Lophatheri Herba, Angelicae Sinensis Radix, Gardeniae Fructus, and Glycyrrhizae Radix et Rhizoma and has the effects of cooling blood and stopping bleeding, draining water and relieving stranguria. The medical experts of later generations have inherited the original prescription recorded in the Yan's Prescriptions to Aid the Living, while dispute has emerged during the inheritance of this prescription. In this study, the method of bibliometrics was employed to review and analyze the ancient documents and modern clinical studies involving Xiaoji Yinzi. The results showed that Xiaoji Yinzi has two dosage forms: powder and decoction. According to the measurement system in the Song Dynasty, the modern doses of hers in Xiaoji Yinzi were transformed. In the prepration of Xiaoji Yinzi powder, 149.2 g of Rehmanniae Radix and 20.65 g each of Cirsii Herba, Talcum, Akebiae Caulis, stir-fried Typhae Pollen, Nelumbinis Rhizomatis Nodus, Lophatheri Herba, wine-processed Angelicae Sinensis Radix, stir-fried Gardeniae Fructus, and stir-fried Glycyrrhizae Radix et Rhizoma are grounded into fine powder with the particle size of 4-10 meshes and a decocted with 450 mL water to reach a volume of 240 mL. After removal of the residue, the decoction was taken warm before meals, 3 times a day (i.e., 7.77 g Rehmanniae Radix and 0.97 g each of the other herbs each time). In the preparation of Xiaoji Yinzi decoction, 20.65 g each of the above 10 herbs are used, with stir-fried Typhae Pollen, wine-processed Angelica Sinensis Radix, stir-fired Gardeniae Fructus, stir-fired Glycyrrhizae Radix et Rhizoma, and raw materials of other herbs. Xiaoji Yinzi is specialized in treating hematuresis and blood stranguria due to heat accumulation in lower energizer, which causes injury of the blood collaterals of gallbladder and dysfunction of Qi transformation. In modern clinical practice, Xiaoji Yinzi is specifically used for treating urinary diseases and can be expanded to treat diseases of the cardiovascular system and other systems according to pathogenesis. The comprehensive research on the key information could provide a scientific reference for the future development of Xiaoji Yinzi.
关键词:Xiaoji Yinzi;classic fomular;ancient and modern clinical application;key information
摘要:Chaihu Guizhitang is one of the classical formulas in the Catalogue of Ancient Classical Formulas (the second batch). Through extensive searching and systematic review of ancient medical books on Chaihu Guizhitang, this study summarized the key information of this formula, which encompassed the origin and development, medicinal composition, original plants and processing, dosage, preparation method, usage, compatibility, and indications. A total of 173 valid data entries were obtained, involving a total of 97 ancient books of traditional Chinese medicine. Chaihu Guizhitang is first recorded in ZHANG Zhongjing's Treatise on Cold Damage and consists of nine herbs: Bupleuri Radix, Scutellariae Radix, Cinnamomi Ramulus, Paeoniae Alba Radix, Ginseng Radix et Rhizoma, Pinelliae Rhizoma, Glycyrrhizae Radix et Rhizoma, Rhizoma Zingiberis Recens, and Jujubae Fructus. In ancient medical books, this formula has synonyms such as Chaihu Jia Gui Tang, Chaihu Jia Guizhitang, and Guizhi Chaihu Ge Ban Tang. The medicinal composition of this formula recorded in ancient medical books is basically consistent with that of the original formula, and it is thus recommended that the composition of the original formula should be followed in the current clinical application. The original plants of the herbal medicines in this formula are in accordance with those in the Pharmacopoeia of the People's Republic of China (2020 edition). In terms of processing methods, Pinelliae Rhizoma processed with ginger, and Glycyrrhizae Radix et Rhizoma is stir-fried. Other herbal medicines in this formula are used with the raw materials. According to the record in the Treatise on Cold Damage, Chaihu Guizhitang is mainly used to treat diseases involving Greater Yang and Lesser Yang. Ancient medical books record that this formula can treat sudden pain in the heart and abdomen, cold abdominal colic, delirium, malaria, thermal imbalance of kidney Qi, and motive Qi. Considering modern medication practice, it is recommended that Chaihu Guizhitang is composed of 14.92 g Bupleuri Radix, 5.60 g Scutellariae Radix, 5.60 g Cinnamomi Ramulus, 5.60 g Paeoniae Alba Radix, 5.60 g Ginseng Radix et Rhizoma, 5.60 g Rhizoma Zingiberis Recens, 4.66 g Pinelliae Rhizoma, 3.73 g Glycyrrhizae Radix et Rhizoma, and 4.30 g Jujubae Fructus, which should be decocted with 1 400 mL water to reach a volume of 600 mL. The decoction should be taken warm after meals, 200 mL each time, three times a day.
关键词:classical formulas;Chaihu Guizhitang;Treatise on Cold Damage;textural research;key information
摘要:ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma, and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione(GSH) peroxidase 4(GPX4)/GSH pathway from an antioxidant perspective.MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma, including curcumol, curgerenone, curdione, curzerene, curcumenol, curcumenone, dehydrocurdione, isocurcumenol, furanodienone, furanodiene and zederone, were detected using 1,1-diphenyl-2-picrylhydrazyl(DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt(ABTS) radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress(CUMS), and W1118 wild-type male D. melanogaster were randomly divided into blank group, model group, curcumol group, curgerenone group, curdione group, curzerene group, curcumenol group,curcumenone group, dehydrocurdione group, isocurcumenol group, furanodienone group, furanodiene group, zederone group and fluoxetine group(10 μmol·L-1). The treatment groups received a dose of 0.1 g·L-1 of 11 characteristic components from Curcumae Rhizoma, while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test, climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry(LC-MS) was used to detect the levels of 5-hydroxytryptamine(5-HT) and dopamine(DA) in the brain of D. melanogaster, and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators, resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition, a mouse depression model was established by CUMS, and C57BL/6J mice were randomly divided into blank group, model group, low and high dose groups of curzerene(0.5, 1 mg·kg-1), and fluoxetine group(10 mg·kg-1) to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species(ROS) in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate(ATP), superoxide dismutase(SOD), catalase(CAT) and GSH. Transmission electron microscope(TEM) was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein, and Nrf2 inhibitor(ML385) was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to detect the effect of curzerene on the mRNA expression level of GPX.ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals, and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group, the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center(P<0.01), as well as a significant increase in immobility time in the forced swimming and tail suspension tests(P<0.01), and the ROS content in hippocampus significantly elevated(P<0.01), while the ATP content significantly reduced(P<0.01). In the hippocampal neurons of the model group, mitochondrial cristae were disordered, with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased(P<0.05), and the antioxidant enzymes SOD, CAT and GSH contents were also significantly reduced(P<0.05, P<0.01), and the gene expression levels of GPX1, GPX4 and GPX7 were significantly decreased(P<0.01). Compared with the model group, the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center(P<0.05), as well as a significant decrease in immobility time in the forced swimming and tail suspension tests(P<0.05, P<0.01). The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced(P<0.01), while the ATP content was significantly increased(P<0.05). The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated, and the expression level of Nrf2 protein was significantly increased(P<0.05). The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.01), while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased(P<0.05), while there were no significant differences in other GPX genes.ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.
摘要:ObjectiveTo explore the changes in volatile components, total polysaccharides, enzyme activity, and chromaticity value of Myristicae Semen Koji(MSK) during the fermentation process, and conduct correlation analysis.MethodsBased on gas chromatography-mass spectrometry(GC-MS), the changes of volatile components in MSK at different fermentation times were identified. The phenol sulfuric acid method, dinitrosalicylic acid method(DNS), and carboxymethyl cellulose sodium salt method(CMC-Na) were used to investigate the total polysaccharide content, amylase activity, and cellulase activity during the fermentation process. Visual analysis technology was used to explore the changes in chromaticity values, revealing the fermentation process of MSK and the dynamic changes of various measurement indicators, partial least squares-discriminant analysis(PLS-DA) was used to explore the differential compounds of MSK at different fermentation degrees, and Pearson correlation analysis was used to explore the correlation between volatile components of MSK and total polysaccharides, enzyme activity, and chromaticity values.ResultsA total of 60 volatile compounds were identified from MSK, the relative contents of components such as (+)-α-pinene, β-phellandrene, β-pinene, (+)-limonene, and p-cymene obviously increased, while the relative contents of components such as safrole, methyl isoeugenol, methyleugenol, myristicin, and elemicin significantly decreased. During the fermentation process, the total polysaccharide content showed an upward trend, while the activities of amylase and cellulase showed an initial increase followed by a decrease, and reached their maximum value at 40 h. the overall brightness(L*) and total color difference(ΔE*) gradually increased, while the changes in red-green value(a*) and yellow-blue value(b*) were not obvious. PLS-DA results showed that MSK could be clearly distinguished at different fermentation times, and 13 differential biomarkers were screened out. Pearson correlation analysis results showed that the contents of α-terpinene, β-phellandrene, methyleugenol, β-cubebene and myristic acid had an obvious correlation with chromaticity values.ConclusionAfter fermentation, the volatile components, total polysaccharides, amylase activity, and cellulase activity of MSK undergo significant changes, and there is a clear correlation between them and chromaticity values, which reveals the dynamic changes in the fermentation process and related indicators of MSK, laying a foundation for the quality control.
摘要:ObjectiveTo analyze the metabolomic characteristics of platelets in fibrinogen(FIB) overexpression rats of coronary heart disease with blood stasis syndrome(CHD-BSS), explore potential biomarkers, and investigate the mechanism of FIB overexpression on CHD-BSS.MethodsSD rats were randomly divided into BSS group and BSS+FIB overexpression group(BSS+FIB group), with 10 rats in each group. Both the BSS+FIB group and the BSS group were fed a high-fat diet combined with oral administration of vitamin D3 and subcutaneous injection of isoproterenol, but rats in the BSS+FIB group were overexpressed with FIB during the initial modeling stage by transfection with adeno-associated virus(AAV). The overexpression level of FIB in rat liver and plasma samples was detected by enzyme-linked immunosorbent assay(ELISA) and real-time fluorescence quantitative polymerase chain reaction(Real time PCR), as well as the expression level of liver FIB A(FGA) mRNA. The characteristics of metabolites in rat platelet samples were analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS), and the differential metabolites between groups were screened by principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), and the enriched pathways were analyzed. The accuracy of potential biomarkers in the diagnosis of CHD-BSS was evaluated by receiver operating characteristic(ROC) curve. The expression of autophagy related proteins phosphorylated adenosine monophosphate(AMP) activated protein kinase(p-AMPK)/AMPK, phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR, microtubule-associated protein 1 light chain 3(LC3) Ⅱ/Ⅰ and p62 in platelets were detected by Western blot.ResultsCompared with the BSS group, the expression levels of FIB in liver and plasma samples of the BSS+FIB group were significantly increased(P<0.05, P<0.01), and the expression level of FIB mRNA in the liver was remarkably increased(P<0.01), indicating successful overexpression of FIB. Platelet metabolomics results showed significant differences in metabolic profiles between the BSS+FIB group and the BSS group, and a total of 25 significantly enriched metabolic pathways and 8 metabolites involved in these metabolic pathways, among which uric acid, guanosine and ribose 1-phosphate levels were up-regulated, while adenosine diphosphate(ADP), AMP, guanosine diphosphate(GDP), adenylosuccinate and norepinephrine levels were down-regulated. The diagnostic ability analysis of differential metabolites showed that all 8 differential metabolites had good diagnostic ability, with an area under the curve(AUC)>0.85. Western blot results showed that compared with the BSS group, the expression levels of p-mTOR/mTOR and p62 proteins in platelets of the BSS+FIB group was significantly reduced(P<0.01), while the expression levels of p-AMPK/AMPK and LC3Ⅱ/Ⅰ proteins were increased, but the difference was not statistically significant.ConclusionOverexpression of FIB can change the metabolic characteristics of CHD-BSS rat model, involving multiple aspects such as vascular endothelial injury, platelet activation and myocardial function damage. Among them, overexpression of FIB may enhance the occurrence of platelet autophagy, thereby inducing platelet activation and promoting thrombus formation.
关键词:overexpression of fibrinogen;coronary heart disease with blood stasis syndrome;platelets;metabolomics;biomarkers;autophagy
摘要:Through consulting herbal medicine, medical books, and local chronicles from past dynasties to modern times, this paper systematically researched Spatholobi Caulis from name, origin, producing areas, harvesting, processing, usage, quality evaluation, functions and indications, providing a reference for the development and utilization of famous classical formulas containing Spatholobi Caulis. According to the research, Spatholobi Caulis was first recorded in the Annals of Shunning Prefecture from the Qing dynasty. It was originally a medicinal herb commonly used in Shunning, Yunnan, and was named from the red juice resembling chicken blood that flowed out after the vein was cut off. The mainstream original plants of each dynasty were Kadsura heteroclita and Spatholobus suberectus. Among them, K. heteroclita mainly focused on dispersing blood stasis and unblocking meridians, mainly treating rheumatic pain and injuries caused by falls or blows, and it is mostly used as the raw material of Jixueteng ointments. S. suberectus was commonly used as decoction pieces in decoction, which had the functions of promoting blood circulation and replenishing blood, activating meridians and collaterals, and mainly used for treating anemia, irregular menstruation, and rheumatic bone pain. The production area of Spatholobi Caulis recorded in the Qing dynasty was Yunnan. Currently, the main production area of S. suberectus is Guangxi, while the main production area of K. interior is Yunnan. In the Qing dynasty, the usage of Spatholobi Caulis was an individual prescription with other herbs before making ointments, which was usually composed of the juice of it, safflower, angelica, and glutinous rice. But in modern times, Spatholobi Caulis is mostly sliced and dried for use. The quality of Spatholobi Caulis is often determined by the number of reddish-brown concentric circles on the cut surface, with a higher number indicating better quality. Additionally, the presence of resinous secretions is also considered desirable. Based on the research findings, it is suggested that when developing famous classical formulas containing Spatholobi Caulis, the choice of the primary source should be S. suberectus or K. heteroclita, taking into consideration the therapeutic effects of the formula. It is also recommended that the latest plant classification be referenced in the next edition of Chinese Pharmacopoeia, adjusting the primary source of Kadsurae Caulis to K. heteroclita to avoid confusion caused by inconsistent original names, and the functions adjust to promote Qi circulation and relieve pain, disperse blood stasis and unblock collaterals, treating injuries caused by falls and bruises.
关键词:famous classical formulas;herbal textual research;name;Spatholobi Caulis;Kadsurae Caulis;origin;producing area;functions and indications
摘要:ObjectiveStarting from the etiology, pathogenesis, and treatment strategies of endometriosis and adenomyosis, to integrate and sort out the academic characteristics of contemporary renowned experts and schools in the field of traditional Chinese medicine gynecology.MethodsAccording to the systematic review of text and opinion (SrTO) process developed by the Joanna Briggs Institute (JBI) in Australia, this paper determined literature screening criteria by searching China National Knowledge Infrastructure (CNKI), VIP, Wanfang, and China Biomedical Literature Database. Information was extracted after literature screening, and quality evaluation was conducted using the JBI Narrative, Text, and Opinion Systematic Review Strict Evaluation Checklist. The JBI Narrative, Opinion, Text Evaluation, and Review Tool Summary Table was used for information synthesis, and data analysis and display were conducted in the form of text and charts.ResultsThe 146 articles related to 39 renowned experts and 19 articles related to 10 schools of thought were included. Research has found that contemporary experts and schools in traditional Chinese medicine gynecology consider blood stasis as the core pathogenesis in understanding the etiology and pathogenesis of two diseases and related infertility. Their viewpoints varied from multiple aspects such as clinical symptom characteristics, meridian circulation location, pathological product evolution, disease duration, emotional psychology, lifestyle habits, preference for food and drink, innate endowment, and acquired injury. In terms of treatment, it was advocated to divide the stage, treat according to different types, adapt to the times, integrate nature and humans, and combine multiple methods to treat comprehensively when necessary. It was also recommended to skillfully use insects, make good use of classic formulas and small prescriptions, pay attention to protecting the spleen and stomach and regulating emotions, and make good use of self-formulated empirical formulas for internal or external use. Besides, individualized long-term management of patients was also advocated.ConclusionThis study applies the SrTO process to systematically summarize the academic ideas of contemporary renowned experts and schools in traditional Chinese medicine gynecology regarding the causes, mechanisms, diagnosis, and treatments of endometriosis, providing a scientific and standardized reference for future theoretical exploration.
关键词:famous traditional Chinese medicine expert;traditional Chinese medicine school;endometriosis;adenomyosis;endometriosis disease;academic characteristics
摘要:Tracheobronchial adenoid cystic carcinoma (TACC) is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression,it is characterized by high invasiveness,frequent recurrence,and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However,an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine (TCM) as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly,collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor (pseudo)angiogenesis. This resulted in imbalances in the functions of circulation,perfusion,and reverse injection of the pulmonary collaterals,and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly,the remodeling of the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) in TACC were critical processes in vascular co-option (VCO),representing the micro-level manifestation of the displacement of nutrient and defense. During this process,ECM remodeling made TACC cells more likely to hijack normal blood vessels,creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment,this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi",and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals,repair the functions of abnormal collaterals,and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques,it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment,providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.
关键词:tracheobronchial adenoid cystic carcinoma(TACC);abnormal collateral;vascular recruitment;collateral hyperactivity;displacement of nutrient and defense
摘要:ObjectiveTo explore the listed varieties and prescription characteristics of Chinese patent medicines for stroke in China, explore the medication rules of Chinese medicine for stroke, and provide guidance for further clinical research and development of Chinese patent medicines.MethodsExcel 2021 and the Ancient and Modern Medical Record Cloud Platform (V2.3.5) were used to systematically mine and analyze the varieties and prescriptions of Chinese patent medicines for stroke in China.ResultsA total of 244 Chinese patent medicines (two for different dosage forms of the same prescription), 1 736 approval documents for Chinese patent medicines, 792 manufacturers, and 83 varieties of protected Chinese patent medicines were finally included in the database. The top three dosage forms were capsules (75), pills (53), and tablets (42). There were 28 Chinese patent medicines for stroke in the National Essential Drug Catalogue (2018), 129 in the National Essential Medical Insurance, Industrial Injury Insurance and Maternity Insurance Drug Catalogue (2023), and 4 in the National Non-prescription Drug Catalogue. Among the 138 prescriptions screened out, Chinese patent medicines mainly treated stroke patients with the syndrome of Qi deficiency and blood stasis. The top three most frequent medicinal herbs were Chuanxiong Rhizoma (63), Pheretima (47), and Salviae Miltiorrhizae Radix et Rhizoma (47). The medicinal herbs used were mainly warm, pungent, with the meridian tropism to the liver meridian. The correlation analysis showed that the herb pair with the highest support was Astragali Radix-Chuanxiong Rhizoma, and that with the highest confidence was Carthami Flos-Chuanxiong Rhizoma. Five herb combinations were identified based on the cluster analysis.ConclusionThe Chinese patent medicines for stroke mainly treat patients with the syndrome of Qi deficiency and blood stasis. The medicinal herbs used in the prescriptions mainly have the functions of activating blood and resolving stasis, extinguishing wind and stopping convulsions. Drug compatibility usually focuses on activating blood and resolving stasis, as well as expelling phlegm and opening orifices. This review of the varieties and prescription characteristics of Chinese patent medicines for stroke helps optimize clinical decision-making, guide drug research and development, promote medical research and scientific progress, and provide more effective support and guarantee for the treatment of stroke patients.
关键词:stroke;traditional Chinese patent medicines;drug catalog;correlation analysis;cluster analysis
摘要:Jianghuanglian is one of the representative processed products of Coptidis Rhizoma for treating cold syndrome with drugs of heat nature, and ginger is used to restrict the bitter cold of Coptidis Rhizoma, which can be traced back to Bojifang, and it is suitable for stagnation of damp-heat in middle-jiao, cold-heat mutual knots and other symptoms. Jianghuanglian retains the alkaloids, phenylpropanoids and flavonoids of Coptidis Rhizoma, and also introduces gingerol components such as 6-gingerol in ginger, which has pharmacological activities such as anti-inflammatory, antibacterial, anti-tumor, and improving gastrointestinal function. The 2020 edition of Chinese Pharmacopoeia and many local processing specifications have included the traditional processing process and quality standards of Jianghuanglian, but the specific process parameters and quality standards are incomplete, which limits the production and clinical application of this processed product. By summarizing the processing history, process research, quality evaluation, pharmacodynamic and medicinal property changes and application of Jianghuanglian in the past 20 years, there are differences in the processing methods and standards in various provinces and cities, which are mainly reflected in the preparation method, dosage, processing process and quantitative standards of ginger juice. In addition, there are also certain differences in the changes of the main components of Jianghuanglian prepared from ginger or dried ginger, as well as their efficacy and medicinal properties. The research on the processing process of Jianghuanglian plays an important role in improving its quality standards, and this review can provide a reference for improving the quality evaluation system of Jianghuanglian.
关键词:Jianghuanglian;treating cold syndrome with drugs of heat nature;processing technology;chemical composition;quality evaluation;efficacy and properties;pharmacological effects
摘要:Recurrent spontaneous abortion (RSA) is a common gynecological disease during pregnancy, clinically characterized by repeated spontaneous abortions, yet its pathological mechanism remains incompletely understood. Traditional Chinese medicine attributes the pathogenesis of RSA to the deficiency of Chong Ren and the lack of fetal solidity. It has amassed experience in treating RSA, with Shoutaiwan being widely utilized for addressing miscarriage symptoms such as habitual abortion due to kidney deficiency, bleeding during pregnancy, and fetal movement. In recent years, there has been a gradual increase in experimental studies on the application of Shoutaiwan in treating RSA and on related experiments. These studies have demonstrated that Shoutaiwan preserves the fetus mainly by modulating hormone balance, alleviating immune inflammation, and enhancing blood coagulation equilibrium during pregnancy. Besides, through the modulation of key signaling pathways such as nuclear factor, erythroid 2 like 2 (Nrf2)/heme oxygenase-1 (HO-1) and Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT), as well as mitogen-activated protein kinase (MAPK), Shoutaiwan has improved cellular antioxidant capacity, adjusted the phenotype of trophoblast and metaphase cells, and inhibited immune rejection, thus improving the pregnancy success rate. These findings not only elucidate the diverse biological foundations underlying Shoutaiwan's efficacy in treating RSA but also offer a scientific rationale for its clinical application and further mechanism research. Nonetheless, there remains a dearth of systematic reviews on RSA treatment with Shoutaiwan. Therefore, this review summarizes and synthesizes existing research findings to systematically analyze existing literature and studies, delving deeply into the principal pharmacological effects and associated signaling pathways of Shoutaiwan in regulating RSA. It aims to establish crucial reference points for its clinical application in RSA treatment and future experiments and research.
摘要:Acute lung injury (ALI) is one of the most common and critical diseases in clinical practice, with extremely high morbidity and mortality, seriously threatening human life and health. The pathogenesis of ALI is complex, in which the inflammatory response is a key factor. Studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasomes are involved in ALI through mechanisms such as inflammation induction, increased microvascular permeability, recruitment of neutrophils, oxidative stress, and pyroptosis, playing a key role in the occurrence and progression of ALI. Therefore, regulating NLRP3 inflammasomes and inhibiting the release of inflammatory factors can alleviate the damage in ALI. At present, ALI is mainly treated by mechanical ventilation and oxygen therapy, which have problems such as high costs and poor prognosis. In recent years, studies have shown that traditional Chinese medicine (TCM) can reduce the inflammatory response and the occurrence of oxidative stress and pyroptosis by regulating the NLRP3 inflammasome, thus alleviating the damage and decreasing the mortality of ALI. Based on the relevant literature in recent years, this article reviews the research progress in TCM treatment of ALI by regulating NLRP3 inflammasomes, discusses how NLRP3 inflammasomes participate in ALI, and summarizes the active ingredients, extracts, and compound prescriptions of TCM that regulate NLRP3 inflammasomes, aiming to provide new ideas for the clinical treatment of ALI and the development of relevant drugs.
关键词:acute lung injury;NOD-like receptor protein 3 (NLRP3) inflammasome;traditional Chinese medicine;review
摘要:Thyroid diseases are common clinical endocrine disorders, and their pathogenesis is generally considered to be closely related to genetic predisposition factors, immune system disorders, hormone levels, etc. Xiaoyaosan is widely used in the treatment of various thyroid diseases with excellent effects. This study summarized the relevant literature on the treatment of thyroid diseases with modified Xiaoyaosan prescriptions and their active ingredients from aspects such as theoretical analysis, clinical research, and mechanism research. Theoretical analysis revealed that Xiaoyaosan could not only disperse stagnated liver qi but also replenish deficient spleen Qi, which was consistent with the etiology and pathogenesis of thyroid diseases. Clinical studies found that Xiaoyaosan and its modified prescriptions could be widely used in the treatment of multiple thyroid diseases, such as hyperthyroidism, Hashimoto's thyroiditis, and thyroid nodules. Both the use of modified Xiaoyaosan alone and in combination with medications such as methimazole, propylthiouracil, and euthyrox could effectively improve patients' clinical symptoms. In the mechanism research, this study discovered that the whole formula of Xiaoyaosan and its modified prescriptions could inhibit inflammatory reactions, regulate immune balance, and delay liver damage during the treatment of thyroid diseases. The research on Xiaoyaosan for treating thyroid diseases mainly focused on thyroid cancer, autoimmune thyroiditis, hyperthyroidism, and hypothyroidism. The mechanisms of action mainly involved promoting cell apoptosis, inhibiting cell proliferation and migration, arresting the cell cycle, and regulating thyroid hormone levels. In conclusion, this study systematically combs and summarizes the research status of Xiaoyaosan in treating thyroid diseases through literature retrieval, aiming to provide new perspectives and new ideas for the prevention and treatment of thyroid diseases with traditional Chinese medicine.
关键词:Xiaoyaosan;thyroid diseases;clinical research;mechanism of action
摘要:The occurrence of diabetes mellitus (DM) is closely related to insulin resistance and islet β cell dysfunction. Modern studies have found that macrophages are widely present in the liver,fat,skeletal muscle,islets, and other tissues and organs. Macrophage M1/M2 polarization plays an important role in the occurrence and development of diabetes mellitus and its related complications by intervening in inflammatory response,improving insulin resistance,and promoting tissue repair. Most of the traditional Chinese medicines that regulate the activation and polarization of macrophages are Qi-replenishing and Yin-nourishing,heat-clearing, and detoxicating medicinal,which are consistent with the etiology and pathogenesis of diabetes and its related complications. Therefore,by summarizing the mechanisms between macrophage activation,polarization, and insulin resistance in various tissues,this paper reviewed traditional Chinese medicine and its effective components and compounds in improving diabetes mellitus and its related complications through multi-channel regulation of macrophage polarization and regulation of M1/M2 ratio,providing references for the future treatment of DM and its related complications with traditional Chinese medicine.
关键词:macrophages;diabetes mellitus;traditional Chinese medicine;insulin resistance
摘要:The pathological changes of myocardial infarction (MI) are mainly characterized by progressive myocardial ischemic necrosis, decline in cardiac diastolic function, thinning of the ventricular wall, and enlargement of the ventricles. The clinical manifestations include myocardial ischemia, heart failure, arrhythmia, shock, and even sudden cardiac death, rendering MI one of the most perilous cardiovascular diseases. Currently, the clinical treatment for MI primarily involves interventional procedures and drug therapy. However, due to their significant side effects and high complication rates associated with these treatments, they fail to ensure a satisfactory quality of life and long-term prognosis for patients. On the other hand, traditional Chinese medicine has demonstrated remarkable potential in improving patient prognosis while reducing side effects. Research has elucidated that various signaling pathways such as nuclear transcription factor-κB (NF-κB), adenosine 5̒-monophosphate-activated protein kinase (AMPK), transforming growth factor-β (TGF-β)/Smads, mitogen-activated protein kinase (MAPK), Wnt/β-catenin (β-catenin), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt) play crucial roles in regulating the occurrence and development of MI. Effectively modulating these signaling pathways through its therapeutic interventions, traditional Chinese medicine can enhance MI management by inhibiting apoptosis, providing anti-inflammatory properties, alleviating oxidative stress levels, and resisting myocardial ischemia. Due to its notable efficacy and favorable safety, it has become an area of focus in clinical practice.
关键词:signal pathway;traditional Chinese medicine;myocardial infarction;review