摘要:ObjectiveTo investigate the effects of Anmeidan (AMD) on cognitive function, cytochrome C (Cyt C) signaling pathway protein expression, and apoptosis in a geriatric sleep deprivation model.MethodSixty aged C57 mice were randomly divided into a blank group, a model group, AMD high, medium, and low dose (26.26, 13.13, 6.565 g·kg-1·d-1) groups, and a melatonin group (1.3 mg·kg-1·d-1), with 10 mice in each group. Continuous sleep deprivation was performed for 4 weeks using a homemade sleep deprivation box. Cognitive function was assessed using the Morris water maze, and morphological changes in pyramidal cells in the CA1 area of the hippocampus were observed by hematoxylin-eosin (HE) staining and Nissl staining. Transmission electron microscopy was used to observe the mitochondrial morphology and structure of hippocampal neurons. Western blot was used to detect Cyt C, cysteine-aspartate protease-3 (Caspase-3), cysteine-aspartate protease-9 (Caspase-9), brain-derived neurotrophic factor (BDNF), mitochondrial transcription factor A (TFAM), and voltage-dependent anion channel 1 (VDAC1) protein expression. Immunohistochemistry was used to detect protein expression levels of Cyt C, Caspase-3, and Caspase-9, and immunofluorescence was used to detect the protein expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax).ResultCompared with the blank group, the model group showed prolonged platform latency (P<0.01), reduced number of platform crossings, and reduced time and distance in the target quadrant (P<0.01). The mitochondrial structure was damaged, with disappearance or breakage of cristae, and increased swelling and deformation. The protein expression levels of Cyt C, Caspase-3, Caspase-9, Bax, and VDAC1 were significantly increased (P<0.01), while BDNF, TFAM, and Bcl-2 protein expression levels were decreased (P<0.01). Compared with the model group, the AMD high, medium, and low dose groups improved spatial exploration and navigation abilities in geriatric sleep-deprived mice (P<0.05, P<0.01), alleviated mitochondrial damage, and increased the number of Nissl bodies. Additionally, the expression levels of Cyt C, Caspase-3, Caspase-9, Bax, and VDAC1 proteins were significantly reduced (P<0.05, P<0.01), while the expression levels of BDNF, TFAM, and Bcl-2 proteins were significantly increased (P<0.05, P<0.01).ConclusionAMD improved the cognitive function of geriatric sleep-deprived mice, and its effect may be related to the reduction of apoptosis mediated by the Cyt C signaling pathway.
关键词:Anmeidan;geriatric sleep deprivation;apoptosis;mitochondria;cytochrome C (Cyt C) signaling pathway
摘要:ObjectiveTo investigate the effect and mechanism of modified Guizhi Fulingwan in preventing colorectal adenoma (CRA) in mice by regulating mitochondrial apoptosis pathway through the regulation of the phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway.MethodSixty SPF-grade male C57BL/6 mice were randomly divided into six groups: Normal group, model group, low, medium, and high dose groups of modified Guizhi Fulingwan (13, 26, 52 g·kg-1·d-1), and positive control aspirin group (0.015 g·kg-1·d-1). A mouse model of CRA was chemically induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). During the modeling process, mice received modified Guizhi Fulingwan or aspirin. Body weight of mice was measured weekly during the treatment. After 9 weeks, the number of adenomas formed was observed. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the histopathologic changes in adenoma tissues. The expression of Cyclin D1 and proliferative nuclear antigen (Ki67) was detected by immunohistochemistry (IHC). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to assess the apoptosis in adenoma tissues. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to observe the mRNA and protein expression levels of PTEN, PI3K, Akt, phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome C (Cyt C), Caspase-9, and caspase-3.ResultCompared with the normal group, the model group showed no significant change in body weight from week 1 to week 2, but a significant decrease from week 3 to week 9 (P<0.05,P<0.01). The colorectal length was significantly shortened, and the colorectal weight increased with visible varying sized tumor-like protrusions on the mucosal surface (P<0.01). Serum levels of TNF-α, IL-6, and IL-1β were elevated (P<0.01). Histopathology showed disordered epithelial gland structure, elongated nuclei with pathological mitosis, and numerous lymphocytic infiltrations in the lamina propria. The positive expression rates of Cyclin D1 and Ki67 were significantly increased (P<0.01), while the apoptosis rate of adenoma cells was significantly decreased (P<0.01). Expression levels of PI3K, Akt, Bcl-2 mRNA and proteins, as well as p-PI3K and p-Akt proteins, were significantly increased (P<0.01), whereas PTEN, Bax, Cyt C, Caspase-9, and Caspase-3 mRNA and protein levels were significantly decreased (P<0.05, P<0.01). Compared with the model group, all drug treatment groups showed an increase in body weight (P<0.01), decreased intestinal weight, increased colorectal length, reduced number of adenomas significantly (P<0.05, P<0.01), and significantly lowered serum levels of TNF-α, IL-6, and IL-1β (P<0.01). Histopathology indicated improved glandular structure and reduced neutrophil infiltration in the mucosal lamina propria. The positive expression rates of Cyclin D1 and Ki67 significantly decreased (P<0.01), while the apoptosis rate of adenoma cells significantly increased (P<0.05, P<0.01). Expression levels of PI3K, Akt, Bcl-2 mRNA and proteins, and p-PI3K and p-Akt proteins were significantly reduced (P<0.05, P<0.01), while PTEN, Bax, Cyt C, Caspase-9, and Caspase-3 mRNA and protein levels significantly increased (P<0.05, P<0.01). The high-dose modified Guizhi Fulingwan group exhibited the most significant intervention effects.ConclusionModified Guizhi Fulingwan may prevent CRA in mice by regulating the PTEN/PI3K/Akt signaling pathway and inducing the mitochondrial apoptosis pathway.
关键词:modified Guizhi Fulingwan;colorectal adenoma;phosphatase and tension homolog/phosphatidylinositol 3-kinase /protein kinase B (PTEN/PI3K/Akt);mitochondrial pathway;apoptosis
摘要:ObjectiveTo explore the mechanism of modified Shuyuwan in treating vascular dementia (VaD) complicated with depression in mice.MethodThe VaD model was established by bilateral carotid artery stenosis (BCAS) in seven 3-month-old male C57/BL6 mice. The regional cerebral blood flow (rCBF) of mice was measured by laser speckle imaging before and after BCAS surgery. Then, the BCAS method was combined with chronic unpredictable mild stress (CUMS) to establish a mouse model of VaD complicated with depression. BCAS/CUMS mice were assigned into BCAS/CUMS, fluoxetine (0.01 g·kg-1), and high-, medium-, and low-dose (20, 10, 5 g·kg-1, respectively) modified Shuyuwan groups. The shame group underwent sham operation without CUMS (n=10). The tail suspension test and sucrose preference test were carried out to examine the depressive behaviors of mice. The distribution and expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neurofilament heavy polypeptide (NF200), and anti-non-phosphorylated neurofilament epitope antibody (SMI32) in the corpus callosum (CC) were detected by the immunofluorescence assay. Western blot was employed to determine the protein levels of monocarboxylate transporter 1 (MCT1), MBP, MAG, oligodendrocyte glycoprotein (MOG), amyloid precursor protein (APP), NF200, contactin-associated protein (Caspr), and voltage-gated sodium channel (Nav1.6) in the corpus callosum. The level of lactic acid in the serum was measured by the lactic acid assay kit, and the ultrastructure of myelin was observed by ultraprojective electron microscope.ResultLaser speckle imaging showed that rCBF decreased immediately 10 min after BCAS surgery (P<0.01), and the rCBF was still cerebral hypoperfusion and did not return to the preoperative level 2 weeks after surgery. Behavioral test results showed that compared with the sham group, the BCAS/CUMS group presented decreased percentage of sucrose preference (P<0.01) and prolonged immobile time in the tail suspension test (P<0.01). Compared with the BCAS/CUMS group, fluoxetine and modified Shuyuwan increased the percentage of sucrose preference (P<0.01) and shortened the immobile time in the tail suspension test (P<0.01). The level of lactic acid was the highest in the BCAS/CUMS mice (P<0.01), and modified Shuyuwan lowered the lactic acid level (P<0.01). Immunofluorescence results showed that compared with the sham group, the BCAS/CUMS group presented decreased fluorescence intensity of MAG, MBP and NF200 and increased fluorescence intensity of SMI32 in the corpus callosum, and such changes were reversed by modified Shuyuwan at different doses and fluoxetine. Western blot results showed that compared with the sham group, the BCAS/CUMS modeling down-regulated the protein levels of MCT1, MBP, MOG, MAG, NF20, and Caspr (P<0.05, P<0.01) and up-regulated the protein levels of APP and Nav1.6 in the corpus callosum, and the above trends were reversed by modified Shuyuwan (P<0.05, P<0.01). Compared with the sham group, BCAS/CUMS modeling led to myelin ultrastructure damage and axon atrophy, which were alleviated by modified Shuyuwan.ConclusionModified Shuyuwan can ameliorate the transport disorder of lactic acid between myelin sheath and axon by upregulating the expressin of MCT1, promote the regeneration of myelin sheath in the corpus callosum, and improve the integrity of myelin sheath structure, thereby alleviating depression in VaD mice.
摘要:ObjectiveTo investigate the effects of modified Chunzetang on urinary retention in rats with spinal cord injury (SCI) and the c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathway.MethodBefore modeling, 10 of the 70 female SD rats were randomly selected to assign to the blank group, and 10 to the sham group. The remaining 50 rats were used to prepare a SCI-induced urinary retention model using the spinal cord transection method. The model rats were randomly divided into model group, low-dose modified Chunzetang group, high-dose modified Chunzetang group, and inhibitor group. After modeling, the blank group, sham group, and inhibitor group were given 2 mL of saline by gavage. The high-dose and low-dose groups of modified Chunzetang were given modified Chunzetang at 28.8 g·kg-1 and 14.4 g·kg-1 by gavage, respectively. The inhibitor group was injected intraperitoneally with the JNK inhibitor SP600125 twice a week at a dose of 15 mg·kg-1. All rats were gavaged for a total of 28 days. Urodynamic and bladder muscle tension tests were conducted to evaluate bladder function. Hematoxylin-eosin (HE) staining was performed to observe the morphology of bladder smooth muscle tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of JNK, phosphorylated (p)-p38 MAPK, B cell lymphoma-2 (Bcl-2), and cysteinyl aspartate-specific proteinase-3 (Caspase-3). Western blot was used to detect the expression levels of p-JNK, p-p38 MAPK, ETS-like protein-1 (ELK-1), and activator protein-1 (AP1) in the detrusor muscle. Immunofluorescence was used to detect the expression levels of p-JNK, p-p38 MAPK, and AP1. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was conducted to measure cell apoptosis.ResultCompared with blank group and sham group, the model group showed a significant increase in maximum bladder capacity and bladder compliance, and a significant decrease in leak point pressure. The minimum contraction force was increased, and the contraction frequency was significantly decreased (P<0.01). The structure of bladder smooth muscle was disordered, with a large number of vacuolar cells, tissue edema, mononuclear cell infiltration, obvious hemorrhage, and a trend towards fibrosis in connective tissue. TUNEL positive cells increased significantly. The protein expression levels of p-JNK, p-p38 MAPK, AP1, and ELK-1 were significantly increased (P<0.01). Compared with model group, all intervention groups showed significant improvement in urodynamic and bladder muscle contraction tests. In the low-dose modified Chunzetang group, the levels of p-p38 MAPK and Caspase-3 was decreased (P<0.05,P<0.01). The levels of JNK, p-p38 MAPK and Caspase-3 in the high-dose group were significantly decreased (P<0.01), and the level of Bcl-2 was significantly increased (P<0.01). The expression levels of p-JNK, p-p38 MAPK, and AP1 proteins were significantly reduced (P<0.01), and ELK-1 protein expression was decreased (P<0.05). The positive rate of p-JNK and AP1 receptors was significantly decreased (P<0.01). The positive cell rate was significantly decreased (P<0.01). The high-dose modified Chunzetang group was positioned between the low-dose group and the inhibitor group, with no significant difference compared to the inhibitor group.ConclusionModified Chunzetang can improve urinary retention in SCI and enhance the contraction force of bladder smooth muscle. This effect is related to the inhibition of the JNK/p38 MAPK signaling pathway activation, thereby reducing apoptosis of bladder smooth muscle cells.
关键词:modified Chunzetang;spinal cord injury-induced urinary retention;c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathway;apoptosis of cells
摘要:ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang (XXMT) combined with electroacupuncture (EA) collaboratively in alleviating cerebral ischemia/reperfusion (I/R) injury.MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling, rats in the XXMT+EA groups were administered XXMT at low (15 g·kg-1), medium (30 g·kg-1), and high (60 g·kg-1) doses, alongside daily 20-min EA treatment (stimulating acupoints GV14 and GV20). Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score, TTC staining, and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 (NLRP3), Gasdermin D (GSDMD), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the ischemic area of the cerebral cortex.ResultCompared with the sham group, the I/R group showed a significant increase in neurological deficit scores and infarct volume (P<0.01), along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05). In contrast, the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume (P<0.01), and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3, GSDMD, Caspase-1, IL-1β, and IL-18 (P<0.05). The improvement showed a dose-dependent relationship with XXMT.ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway, thereby reducing neurological deficits, minimizing brain infarct size, and improving cortical neuronal damage.
关键词:electroacupuncture;ischemia-reperfusion;NOD-like receptor hot protein domain related protein 3 (NLRP3);Xiao Xumingtang
摘要:ObjectiveTo explore the biological foundation of colorectal adenoma in damp-heat accumulation syndrome and the possible anti-tumor mechanism of Shenbai Jiedu prescription.MethodEight patients with colorectal adenoma in damp-heat accumulation syndrome, 11 patients with non-damp-heat accumulation syndrome, and 10 patients with colorectal cancer recruited by Jiangsu Provincial Hospital of Traditional Chinese Medicine from February 2019 to December 2020 meeting the inclusion criteria were clinically obtained, and the tissue of the three groups of patients was subjected to transcriptome sequencing to screen for the differentially expressed genes between the syndrome and the diseases. The intersection of the differentially expressed genes between the syndrome and the disease was taken for further screening of the differentially expressed genes sequentially increasing or sequentially decreasing in patients with non-damp-heat accumulation syndrome, damp-heat accumulation syndrome, and colorectal cancer, and functional enrichment analysis and signaling pathway enrichment analysis were carried out. Real-time polymerase chain reaction (Real-time PCR) was used to detect the effect of Shenbai Jiedu prescription on the expression of the above key differential genes.ResultBy comparing the damp-heat accumulation syndrome and non-damp-heat accumulation syndrome, a total of 384 differentially expressed genes were screened, of which 203 were up-regulated genes, and 181 were down-regulated genes. By comparing the colorectal adenoma of colorectal cancer and damp-heat accumulation syndrome, a total of 2 965 differentially expressed genes were screened, of which 2 460 were up-regulated genes, and 505 were down-regulated genes. The intersection of differentially expressed genes of the two groups was taken, and a total of 58 differentially expressed genes with the same changes were screened. The gene ontology functions were mainly enriched in UDP-galactose: β-N-acetylglucosamine beta-1,3-galactosyltransferase activity, N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity, and poly-N-acetyllactosamine biosynthetic process. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were mainly enriched in glycosphingolipid biosynthesis-globo and isoglobo series, glycosphingolipid biosynthesis-lacto and neolacto series, and IL-17 signaling pathway. Shenbai Jiedu prescription significantly inhibited the expression of key genes involved in the enrichment, such as FOSB and B3GALT5, in a dose-dependent manner (P<0.05).ConclusionGlycolipid metabolism may be the biological foundation of colorectal adenoma in damp-heat accumulation syndrome, and Shenbai Jiedu prescription may inhibit colorectal adenoma carcinogenesis by down-regulating the expression of FOSB and B3GALT5.
关键词:Shenbai Jiedu prescription;colorectal adenoma carcinogenesis;damp-heat accumulation syndrome;transcriptome sequencing;biological foundation of syndrome
摘要:ObjectiveTo observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets.MethodA total of 21 patients diagnosed with colorectal adenoma were enrolled in this study. Following a four-week administration of Shenbai Jiedu prescription, their clinical symptoms were observed, and fecal samples of patients before and after treatment were collected. Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry (LC-MS) were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients.ResultThe total scores of traditional Chinese medicine (TCM) syndromes of patients after drug administration decreased significantly (P<0.01). The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration, and a total of 106 differential metabolites were screened out (P<0.05). The Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed that arginine-proline metabolism, ferroptosis, glycine, and serine and threonine metabolism were significantly enriched metabolic pathways (P<0.05). Notably, L-4-hydroxyglutamate semialdehyde, glutathione, isopentenyl pyrophosphate, creatinine, 4-acetamido-2-aminobutanoic acid, and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways. Furthermore, the association between these metabolites and different intestinal flora was analyzed, and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium, Eggerthella, and Dialister (P<0.05).ConclusionShenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria, reducing the abundance of harmful bacteria, and regulating metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma. This study may provide some research ideas and directions for Shenbai Jiedu prescription to interfere with colorectal adenoma recurrence and carcinogenesis.
摘要:Colorectal adenoma is a benign tumor originating from the mucosal glandular epithelium of the colorectum and belongs to the category of intraepithelial neoplasia. Its etiology and pathogenesis are not completely clear, and some patients have genetic factors. In recent years, with the improvement in living standards, the incidence of colorectal adenoma has gradually increased due to high-fat diets, intestinal flora disorder, and emotional disturbance. As one of the precancerous lesions of colorectal cancer, colorectal adenoma is increasingly threatening human health. Surgical resection is the most direct and effective method for the treatment of colorectal adenoma, but some patients with colorectal adenoma have the possibility of recurrence after resection. At present, there is still a lack of effective prevention and treatment measures for the recurrence of colorectal adenoma. Traditional Chinese medicine (TCM) plays a unique advantage in improving the clinical symptoms of patients with colorectal adenoma and preventing postoperative recurrence and carcinogenesis. Therefore, this review summarized the clinical research and mechanism of TCM compounds in the prevention and treatment of colorectal adenoma in recent years. The clinical study on the prevention and treatment of colorectal adenoma by TCM compounds can be divided into internal treatment, external treatment, and internal and external combined treatment. The internal treatment mainly focuses on strengthening the spleen, and the external treatment includes retention enema, acupoint application, and other methods. The internal and external combined treatment is mainly based on the internal administration of TCM compounds combined with acupuncture, retention enema, and acupoint stimulation. The study on the mechanism of TCM compounds in preventing and treating colorectal adenoma was mainly explored from the aspects of regulating intestinal flora, regulating cell proliferation immune function, and achieving anti-inflammation. This review summarized the research progress of TCM compounds in the prevention and treatment of colorectal adenoma in recent years and provided a reference for future treatment with TCM.
关键词:colorectal adenoma;traditional Chinese medicine (TCM) compounds;clinical research;mechanism research
摘要:ObjectiveTo explore the effect of Tongluo Jiedu Xiezhuo prescription (TLJDXZ) on alleviating inflammatory response in rats with gouty arthritis (GA) by regulating the formation and release of neutrophil extracellular traps (NETs).MethodOxonic acid potassium salt solution combined with uric acid sodium solution was used to establish the GA rat model by injection. Seventy-two SD rats were randomly divided into control model, model group, and low-, medium-, and high-dose (1.58, 3.15, and 6.30 g∙kg-1) TLJDXZ groups, and colchicine group (0.30 mg∙kg-1). Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to characterize the chemical components of TLJDXZ. HE staining was used to observe the ankle joint tissue structure of rats. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of inflammatory factors interleukin (IL)-1β, IL-6,IL-8, blood uric acid (BUA) tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and myeloperoxidase (MPO) in serum and tissue. PicoGreen staining method was used to measure ds-DNA concentration in plasma. Western blot was used to detect the expression of citrullinated histone H3 (Cit-H3) and MPO proteins. Immunofluorescence was used to detect the expression of neutrophil elastase (NE) and MPO. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect peptidylarginine deiminase 4 (PAD4) mRNA expression.ResultCompared with control group, the model group had severe joint swelling, with shed cell debris, synovial and connective tissue proliferation, and inflammatory cell punctate infiltration visible in the joint cavity. Blood circulation, oxidative damage, and inflammation in joint tissues significantly worsened (P<0.05). The expression of NETs-related proteins Cit-H3, MPO, NE, and PAD4 was significantly upregulated (P<0.05). Compared with the results in model group, joint damage in the TLJDXZ groups was significantly reduced, and the swelling was alleviated. The inflammatory infiltration in the joint cavity, cartilage and synovial morphology, and joint structure were significantly relieved. TLJDXZ significantly reduced oxidative damage and inflammation in peripheral blood circulation and joint tissues (P<0.05). The expression of NETs-related proteins Cit-H3, MPO, NE, and PAD4 was significantly downregulated (P<0.05).ConclusionTLJDXZ can effectively alleviate joint inflammatory response in GA rats, and its mechanism of action may be related to the regulation of the formation and release of NETs.
摘要:ObjectiveTo observe the neuroprotective effects of ginsenoside Rb1 on lipopolysaccharide (LPS)-induced neuroinflammation in mice and to preliminarily investigate its mechanism of action.MethodSeventy ICR mice were randomly divided into blank group, model group, dexamethasone sodium phosphate injection group, and low-dose, high-dose ginsenoside Rb1 groups, with 14 mice in each group. A mouse brain neuroinflammation model was prepared using the LPS dose escalation method, starting with a dose of 1 mg·kg-1 and administered via intraperitoneal injection every 48 h (every other morning). Each subsequent dose increased by 2 mg·kg-1, for a total of 7 injections, culminating in a final dose of 13 mg·kg-1. The dexamethasone sodium phosphate injection group received an intraperitoneal injection at 5 mg·kg-1·d-1. The low-dose and high-dose ginsenoside Rb1 groups were given intraperitoneal injections at 10 mg·kg-1·d-1 and 20 mg·kg-1·d-1, respectively, while the blank and model groups received the same volume of normal saline for 14 days. The behavioral activity of LPS mice was observed, anxiety-like behavior was assessed using the Y-maze and elevated plus maze, and brain levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). Neuronal damage of microglia, and the activation status of microglia and astrocytes in the brain were assessed using immunofluorescence staining. The protein expression of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and nuclear factor-κB (NF-κB) in mouse brain were detected by Western blot.ResultCompared with the blank group, the model group showed significantly increased anxiety-like behavior in the Y-maze and elevated plus maze (P<0.05, P<0.01), significantly elevated levels of MCP-1, TNF-α, and IL-1β in the brain (P<0.01), a significant decrease in the number of neuronal positive cells in the somatosensory cortex and hippocampus CA1 region (P<0.01), significant activation of microglia and astrocytes (P<0.01), and a significant increase in the expression of phosphorylated PI3K, Akt, and NF-κB proteins (P<0.01). Compared with the model group, the ginsenoside Rb1 low-dose and high-dose groups showed significantly reduced anxiety-like behavior in the Y-maze and elevated plus maze (P<0.05, P<0.01), significantly decreased levels of MCP-1, TNF-α, and IL-1β in the brain (P<0.01), a significant increase in the number of neuronal positive cells in the somatosensory cortex and hippocampus CA1 region (P<0.01), significant inhibition of microglia and astrocyte activation (P<0.05, P<0.01), and a significant decrease in the expression of phosphorylated PI3K, Akt, and NF-κB proteins (P<0.05, P<0.01).ConclusionGinsenoside Rb1 has neuroprotective effects on LPS-induced inflammation in mice, which may involve the regulation of the PI3K/Akt signaling pathway.
摘要:ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription (ZJYP) in Goto-Kakizaki (GK) rats with early-stage diabetic kidney disease (DKD).MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding, with fasting blood glucose (FBG) ≥ 11.1 mmol·L-1 and urinary albumin/creatinine ratio (ACR) ≥ 30 mg·g-1 used as model criteria. After successful modeling, DKD rats were randomly divided into five groups (n=10 in each group): the model group, the western medicine group treated with dapagliflozin (1.0 mg·kg-1·d-1), low-, medium-, and high-dose ZJYP groups (4.9, 9.9, 19.9 g·kg-1·d-1 by gavage). Ten Wistar rats served as normal controls, with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR, FBG, body weight, and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect miRNA-27a, Wnt, and β-catenin mRNA and protein expression levels in renal tissues.ResultCompared with the results in the normal group, the FBG levels in DKD rats of the model group increased significantly at 0, 2, 4, 6, and 8 weeks of drug intervention (P<0.05), and urinary ACR increased significantly at 0, 4, 8 weeks (P<0.05). Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix, slight thickening of the basement membrane, and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a, Wnt, and β-catenin were significantly higher in the model group than in the normal group (P<0.05). Renal Wnt and β-catenin protein levels were also significantly higher in the model group (P<0.05). After drug intervention, the FBG levels in the low-, medium-, and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks (P<0.05). The urinary ACR also showed a dose-dependent decrease in the low-, medium-, and high-dose ZJYP groups, but the differences were not statistically significant. There were no significant differences in liver function, renal function, renal index, or routine blood lipid test results among the low-, medium-, and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group, with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a, Wnt, and β-catenin were significantly lower in the high-dose ZJYP group (P<0.05), and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group (P<0.05). The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group, but the differences were not statistically significant.ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats, thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.
摘要:ObjectiveTo investigate the effect and mechanism of Yiqi Wenyang Huwei decoction (YWHD) on airway inflammation in bronchial asthma (BA) rats based on transforming growth factor-β1 (TGF-β1)/SMAD family member 3 (Smad3) signaling pathway.MethodSixty male SD rats were randomly divided into a normal group, a model group, a dexamethasone (DEX) group, and low-, medium-, and high-dose YWHD groups, with 10 rats in each group. The BA model was induced by intraperitoneal injection of 1 mL of ovalbumin (OVA)-aluminum hydroxide suspension for sensitization, followed by nebulization with 2% OVA. One hour before daily OVA nebulization, the control group was treated with saline, the DEX group with DEX solution at 0.2 g·L-1, and the low-, medium-, and high-dose YWHD groups with YWHD at 1, 2, 4 g·mL-1, respectively. General conditions and lung function were observed. Bronchoalveolar lavage fluid (BALF) and serum were collected to count inflammatory cells in BALF and measure immunoglobulin E (IgE) levels in serum and inflammatory cytokines in BALF using enzyme-linked immunosorbent assay (ELISA). Pathological changes in lung tissues, collagen deposition, and airway mucus secretion were observed by hematoxylin-eosin (HE), Masson, and periodic acid-Schiff (PAS) staining. TGF-β1/Smad3-related mRNA and protein levels in lung tissues were determined by Real-time fluorescent quantitative polymerase chain translation (Real-time PCR) and Western blot analysis.ResultCompared with the normal group, the model group showed increased total airway resistance (RL) and decreased dynamic compliance (Cdyn) (P<0.05, P<0.01), elevated serum IgE levels, increased inflammatory cell counts, and higher inflammatory cytokine levels in BALF (P<0.01). Additionally, there was significant inflammatory cell infiltration, collagen deposition, and mucus secretion in lung tissues. The levels of TGF-β1, α-smooth muscle actin (α-SMA), and Smad3 phosphorylation in lung tissues were significantly increased (P<0.01). Compared with the model group, the DEX group and high-dose YWHD group exhibited significantly reduced RL (P<0.01), improved lung dynamic compliance (P<0.05), and lower serum IgE levels, inflammatory cell counts, and inflammatory cytokine levels in BALF (P<0.05). Moreover, these treatments alleviated pathological damage in lung tissues and reduced the levels of TGF-β1, α-SMA, and Smad3 phosphorylation (P<0.01).ConclusionYWHD reduces airway inflammation, improves pathological damage, and mitigates airway remodeling in bronchial asthma rats, possibly by downregulating TGF-β1, α-SMA protein levels, and Smad3 phosphorylation.
摘要:ObjectiveThis study aims to explore the molecular mechanism of endometrial cell senescence during the window of implantation (WOI) in unexplained recurrent spontaneous abortion (URSA) and the intervention effect of Bushen Huoxue method through the integrated research strategy of bioinformatics, machine learning, and animal experiments.MethodThe microarray gene sets of the endometrium of healthy women of childbearing age and patients with URSA during WOI were retrieved through the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) of URSA were screened by using the limma package of R language. Weighted gene co-expression network analysis (WGCNA) was used to obtain the most relevant module genes of URSA, and the gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed. Gene sets related to cell senescence were obtained by the Human Gene Database (GeneCards) and Online Mendelian Inheritance in Man (OMIM). The Venn online mapping software was used to screen the intersection genes of DEGs of URSA, the most relevant module genes, and the genes related to cell senescence. Then, the search tool for the retrieval of interacting genes/proteins (STRING) was used to analyze the protein-protein interaction (PPI) network of the interacting genes, and the hub genes were screened through Cytohubba. In addition, the least absolute selection and shrinkage operator (LASSO) and random forest algorithm were used to screen diagnostic genes related to cell senescence of URSA. Finally, mouse models with URSA were established and randomly divided into the model group, Bushen Huoxue group, and aspirin group, with six mice in each group, and six normal pregnant mice were selected as a blank group. The Bushen Huoxue group was given Shoutai pill combined with Danggui powder formula granular liquid (12.35 g·kg-1) by gavage, and the aspirin group was gavaged with aspirin at a dose of 0.011 mL·g-1. The blank group and model group were given the same volume of distilled water by gavage. Drug administration began on the first day after the discovery of vaginal thrombus (recorded as the first day of gestation, i.e. GD1), and the mice were sacrificed 12 hours after administration at GD5. The endometrium samples were collected. Quantitative real-time polymerase chain reaction (Real-time PCR) and immunofluorescence were used to detect the expression of cell senescence-related diagnostic genes in the endometrium tissue of URSA mice during WOI and the intervention effect of the Bushen Huoxue method.ResultThe gene set of the GSE165004 microarray was included for bioinformatics analysis. According to the “limma” package of R language, 585 DEGs of URSA were selected (P<0.05). WGCNA results suggested that the gene in the magenta module was the most closely related to URSA (r=0.32, P<0.05). The results of the KEGG analysis of the magenta module suggested that the genes were mainly enriched in cell senescence, Hippo, and NF-κB signaling pathways (P<0.05). In addition, 2 138 genes related to cell senescence were obtained from Genecards and OMIM websites. The Venn online mapping tool was used to obtain 27 intersecting genes of DEGs of URSA, the magenta module genes, and cell senescence-related genes, namely, cell senescence-related DEGs in endometrium tissue during WOI of URSA. PPI analysis showed that synuclein alpha (SNCA), heme oxygenase 1 (HOMX1), and matrix metallopeptidase 1 (MMP1) were hub genes. Besides, four diagnostic genes were identified by LASSO regression and random forest, including gelsolin (GSN), cyclin2 (CCND2), RB binding protein 8 (RBBP8), and lysophosphatidic acid receptor 1 (LPAR1). Animal experiments confirmed that the mRNA level and fluorescence intensity of GSN were significantly increased (P<0.05), while the mRNA and fluorescence intensity of CCND2, LPAR1, and RBBP8 were significantly decreased (P<0.05) in the model group when compared with the blank group. The expression level of GSN was decreased (P<0.05), while the expression levels of CCND2, LPAR1, and RBBP8 were remarkably increased (P<0.05) in the Bushen Huoxue group when compared with the model group.ConclusionThe senescence of endometrial cells during WOI of URSA is related to multiple genes. Bushen Huoxue method can act on multiple targets that are related to cell senescence, which may be the key mechanism of improving endometrial receptivity in URSA.
关键词:unexplained recurrent spontaneous abortion;window of implantation;cell senescence;Bushen Huoxue method;machine learning
摘要:ObjectiveTo investigate the mechanism of astragaloside-Ⅳ (AS-Ⅳ) in regulating pyroptosis to alleviate intestinal ischemia-reperfusion injury (IRI) by combining network pharmacology and in vivo experiments.MethodFirstly, the corresponding target genes of AS-Ⅳ were obtained from TraditionalChineseMedicineSystemsPharmacology(TCMSP) database and Swiss Target Prediction database, and the target genes related to intestinal IRI and Pyroptosis were obtained from GeneCards database, and the common target genes of the three were obtained by drawing Venn diagrams through unspiralized website. Protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape software to screen common target genes and imported into Cytoscape software to obtain core target genes. Microbiotics platform was used for gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis and prediction of the mechanism of action of AS-Ⅳ in regulating Pyroptosis to alleviate intestinal IRI. Then C57/BL6J mice were randomly divided into 5 groups normal group, model group(IR), drug administration group (IR+AS-Ⅳ), nucleotide-binding oligomerization structural domain-like receptor protein 3 (NLRP3) agonist NSS group (IR+AS-Ⅳ+NSS), and NLRP3 inhibitor MCC950 group (IR+AS-Ⅳ+MCC950) by using a randomized numerical table method. The intestinal IRI model was established by clamping the superior mesenteric artery for 45 min and resuming perfusion for 2 h in the model group, the drug administration group, the NLRP3 agonist NSS group, and the NLRP3 inhibitor MCC950 group, and the normal group was only separated from the vessels without clamping. The administration group, the NLRP3 agonist NSS group, and the NLRP3 inhibitor MCC950 group were gavaged with astragaloside dissolved in 0.1% dimethylsulfoxide (50 mg·kg-1) for 3 consecutive days before modeling, with the last gavage 2 h before modeling, and the remaining two groups were gavaged with equal amounts of saline. The NLRP3 agonist NSS group was injected intraperitoneally with 4 mg·kg-1 of NSS 1 h before modeling, and the NLRP3 inhibitor MCC950 group was injected intraperitoneally with 10 mg·kg-1 of MCC950 1 h before modeling.The mice were put to death by reperfusion for 2 h, and intestinal tissues were obtained. The levels of IL-18 and IL-1β were detected by enzyme linked immunosorbent assay(ELISA), and the protein expression of thioredoxin-binding protein (TXNIP), NLRP3, Caspase-1 and pyrocatechin D (GSDMD) were detected by Western blot, and the pathological changes of intestinal tissues were evaluated by Chiu's score.ResultNetwork pharmacological analysis showed that there were 1599 targets of intestinal IRI, 199 targets of AS-Ⅳ action, 197 targets of pyroptosis, and 20 targets common to all three. There were 10 core targets, including NLRP3, TXNIP, silencing information regulator 1 (SIRT1), high mobility group protein 1 (HMGB1), interleukin-18 (IL-18), GSDMD, and metallo matrix protease-9 (MMP-9),et al. The results of in vivo experiments showed that compared with the normal group, Chiu's score was elevated in the model group, the levels of IL-18,IL-1β inflammatory factors in mouse intestinal tissues were elevated (P<0.05), and the protein expression levels of TXNIP, NLRP3, Caspase-1, and GSDMD were elevated (P<0.05). Compared with the model group,Chiu's score was decreased in the administered group and NLRP3 inhibitor MCC950 group,the level of IL-18,IL-1β inflammatory factors in the intestinal tissue of mice was decreased(P<0.05), and the level of TXNIP,NLRP3,Caspase-1,GSDMD protein expression was decreased(P<0.05). Compared with the administered group, Chiu's score was elevated in the NLRP3 agonist NSS group, the levels of IL-18, IL-1β inflammatory factors in mouse intestinal tissues were elevated (P<0.05), and the protein expression levels of NLRP3, Caspase-1, and GSDMD were elevated (P<0.05). Compared with the NLRP3 inhibitor MCC950 group, the NLRP3 agonist NSS group had elevated Chiu's scores, elevated levels of IL-18,IL-1β inflammatory factors in mouse intestinal tissues (P<0.05), and elevated levels of TXNIP,NLRP3, Caspase-1, and GSDMD protein expression (P<0.05).ConclusionNetwork pharmacological predictions were consistent with the results of in vivo experiments, and astragaloside attenuated intestinal ischemia-reperfusion injury by inhibiting cellular pyroptosis through the TXNIP-NLRP3 signaling pathway.
关键词:astragaloside Ⅳ;intestinal ischemia-reperfusion injury;thioredoxin-binding protein (TXNIP)-nucleotide-binding oligomerization structural domain-like receptor protein 3 (NLRP3) signaling pathway;pyroptosis;network pharmacology
摘要:ObjectiveTo employ the effective components and antiarrhythmic mechanism of Wenxin Granules (WXKL) by cell membrane chromatography (CMC) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), combined with network pharmacology.MethodIn this study, the CMC/UPLC-Q-TOF/MS technique was employed to identify the components in WXKL that could specifically bind to myocardial cell membranes. By utilizing databases such as SwissTarget Prediction and GeneCards, the targets of WXKL's effective components and arrhythmia-related targets were mined. Cytoscape software was used to construct a "component-target-disease" network. Gene ontology(GO) function and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses were carried out, and molecular docking of key components and targets was performed. Finally, further verification was conducted through in vivo experiment of rats.ResultA total of 39 effective components were identified in WXKL. These included 13 components derived from Panax notoginseng, 15 components from Codonopsis pilosula, seven components from Glycyrrhizae Radix et Rhizoma, one component from Succinum, one component from Polygonatum odoratum, one component shared by both P. odoratum and C. pilosula, and one component shared by both Panax notoginseng and C. pilosula. Network pharmacology predicted that WXKL had 16 core antiarrhythmic targets and 79 related pathways, mainly involving adrenergic signaling in cardiomyocytes, cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG), calcium signal, cyclic adenosine monophosphate (cAMP), interleukin (IL)-17, mitogen-activated protein kinase (MAPK), and tumor necrosis factor (TNF) signaling pathways. The results of in vivo experiment of rats showed that WXKL significantly improved the expression of β1-adrenergic receptor (β1-AR), cAMP, TNF-α, and calcium voltage-gated channel subunit alpha 1C (CACNA1C).ConclusionWXKL can exert its antiarrhythmic effects through multiple components, multiple targets, and multiple pathways. This study provides a scientific basis for explaining the potential pharmacodynamic substance foundation and mechanism of action of traditional Chinese medicine in treating arrhythmia.
摘要:ObjectiveTo analyze the influence of Jianpi Yuwei decoction combined with omeprazole on ulcer area, gastrointestinal symptoms, and serum trefoil factor family 2 (TFF2) in patients with gastric ulcer (symptom of deficiency-cold in spleen and stomach).MethodA total of 100 patients with gastric ulcer of symptom of deficiency-cold in spleen and stomach admitted to the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine from May 2020 to April 2022 were regarded as the research subjects. They were randomly grouped into two groups according to the number table method. 50 cases in the control group received omeprazole treatment, while 50 cases in the traditional Chinese medicine (TCM) group received Jianpi Yuwei decoction treatment on the basis of the control group. The clinical efficacy, periodic gastrointestinal symptom score, serum cytokines, gastrin indexes, and ulcer area of the two groups were compared.ResultAfter treatment, the total treatment efficiency of the TCM group was 94.00% (47/50), while the total effective rate of the control group was 76.00% (38/50). The total effective rate of the TCM group was higher than that of the control group (χ2=6.353, P<0.05). After treatment, the scores of periodic upper abdominal pain, bloating, acid reflux, and belching symptoms in both groups decreased (P<0.05). Compared with that in the control group after treatment, the score of periodic upper abdominal pain, bloating, acid reflux, and belching symptoms in the TCM group decreased more significantly (P<0.05). After treatment, the levels of TFF2 increased in both groups (P<0.05), and C-reactive protein (CPR) and tumor necrosis factor (TNF-α) decreased (P<0.05). Compared with the control group after treatment, the TCM group showed a more significant increase in TFF2 levels (P<0.05), and CRP and TNF-α levels decreased more significantly (P<0.05). After treatment, the levels of motilin (MTL), gastrin (GAS), cholecystokinin (CCK)-33, and ulcer area decreased in both groups (P<0.05). Compared with those in the control group after treatment, the levels of MTL, GAS, CCK-33, and ulcer area in the TCM group decreased more significantly (P<0.05).ConclusionJianpi Yuwei decoction combined with omeprazole can reduce the ulcer area, alleviate periodic gastrointestinal symptoms, and increase serum TFF2 level in patients with gastric ulcer of symptom of deficiency-cold in spleen and stomach, with remarkable effects.
关键词:Jianpi Yuwei decoction;omeprazole;gastric ulcer;symptom of deficiency-cold in spleen and stomach;ulcer area;gastrointestinal symptoms;trefoil factor family 2
摘要:ObjectiveTo evaluate the clinical efficacy of Chaigui Zengmian prescription (composed of Bupleuri Radix, Codonopsis Radix, Scutellariae Radix, Cinnamomi Ramulus, Paeoniae Radix Alba, Astragali Radix, Atractylodis Macrocephalae Rhizoma, and Scorpio) in treating recurrent respiratory tract infections in children with syndrome of Qi deficiency in lung and spleen and the influences of this prescription on immune factors.MethodSixty-six children suffering from recurrent respiratory tract infections due to Qi deficiency in lung and spleen were selected and randomized into a control group (33 cases) and an observation group (33 cases). The control group received spleen aminopeptide oral lyophilized powder and the observation group was treated with self-made Chaigui Zengmian prescription granules. Both groups were treated for two months (as two consecutive courses of treatment). The traditional Chinese medicine (TCM) symptom scores and the serum levels of total immunoglobulins (IgA, IgM, and IgG) and T-helper cells (Th1, Th2, and Th1/Th2) were measured in both groups before and after treatment and then compared.Result① After treatment, the TCM symptom scores of both groups declined and the observation group had lower scores than the control group (P<0.05). ② The observation group[87.50%(28/32)] had higher total response rate than the control group[96.88%(31/32)](Z=7.921,P<0.05).Also the observation group[28.13%(9/32)] had more cured children than the control group[6.25(2/32)] (χ2=5.379,P<0.05) ③ After treatment, the serum levels of IgA, IgM, IgG, Th1, and Th1/Th2 elevated while that of Th2 declined (P<0.05), and the changes were more obvious in the observation group than in the control group (P<0.05).ConclusionChaigui Zengmian prescription is effective in treating recurrent respiratory tract infections in children with the syndrome of Qi deficiency in lung and spleen. It can alleviate the symptoms and rectify immune disequilibrium, demonstrating a clinical application value.
关键词:Chaigui Zengmian prescription;children with recurrent respiratory tract infections;syndrome of Qi deficiency in lung and spleen;clinical efficacy;immune factor
摘要:ObjectiveBased on real-world clinical data of traditional Chinese medicine (TCM), a Cox proportional hazards model was built to predict the risk factors of complications in patients with Corona Virus Disease 2019 (COVID-19) or influenza A/B, and the cumulative occurrence function graph was used to present the prediction output.MethodThe medical records of the patients with respiratory infectious diseases, including COVID-19 and influenza A/B, treated in the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from November 2022 to October 2023 were collected. The data from the electronic medical record system were integrated into a data warehouse. The information of the patients with respiratory diseases caused by influenza A and B viruses and SARS-CoV-2 from November 2022 to October 2023 was retrospectively collected. The information involved age, gender, disease course, past medical history, laboratory test results, tongue manifestation, pulse manifestation, TCM syndrome, and main therapeutic drugs. The outcome indicators of whether complications occurred were obtained by telephone follow-up and review of readmission records. The data was divided into a training set and a validation set in a ratio of 70% and 30%, respectively. In the training set, the Cox proportional hazards model was used to identify the key factors affecting patient complications. Then, the combination of variables was optimized by stepwise elimination method, and an efficient complication risk assessment model was constructed, which was visualized in the form of histogram. The C-index, receiver operating characteristic (ROC) curve, calibration error graph, and decision curve analysis were employed to comprehensively measure the prediction performance of the model.ResultThe history of chronic lung diseases [hazard ratio (HR) 4.46, 95% confidence interval (95%CI) 1.79-11.12], Qi deficiency (HR 5.74, 95%CI 2.14-15.39), thready and weak pulse (HR 4.45, 95%CI 1.88-10.50), hormone use history (HR 4.57, 95%CI 2.04-10.23), procalcitonin (PCT>10 μg·L-1) (HR 1.23, 95%CI 0.06-0.86), serum amyloid A (SAA)>100 mg·L-1 (HR 9.80, 95%CI 7.24-59.75), and platelet (PLT)>303×109 /L (HR 5.66, 95%CI 2.01-16.00) were the risk factors for complications. Chinese medicine intervention (HR 0.20, 95%CI 0.06-0.70) was the protective factor for complications. Based on the above risk factors, the prediction model was constructed. In the training set, the C-index was estimated to be 0.765, and the CI was within the range of 0.667 to 0.859. In the validation set, the C-index was 0.804, and the CI varied within the range of 0.773 to 0.855. The temporal variation graph of C-index was then described. The area under the ROC curve (AUC) at 5, 10, 15 months was 0.61, 0.72, and 0.79 in the training set and 0.60, 0.67, and 0.62 in the validation set, respectively. In addition, calibration and decision curves were drawn for 5, 10, 15 months for both training and validation sets, which showed that the model had good calibration performance and was effective in clinical practice.ConclusionThe history of chronic lung diseases, Qi deficiency, thready and weak pulse, hormone use history, PCT>10 μg·L-1, SAA>100 mg·L-1, and PLT>303×109 /L were risk factors for complications in patients with COVID-19 or influenza A/B, while Chinese medicine intervention was a protective factor. The prediction model was established based on the indicators above. The model showcased excellent distinguishing performance, calibration performance, and clinical practicability, providing scientific support for the prevention and control of complications caused by respiratory viral infections.
关键词:complications of respiratory viral infections;risk prediction model;traditional Chinese medicine;nomogram
摘要:ObjectiveTo evaluate the efficacy and safety of modified Qingjin Huatantang combined with Western medicine in the treatment of phlegm-heat and to provide reference for the clinical application of this therapy and development of new drugs.MethodChina Biology Medicine (CBM),Chinan National Knowledge Infrastructure (CNKI),Wanfang Data,VIP,and PubMed were searched for the randomized controlled trials (RCTs) of modified Qingjin Huatantang in the treatment of phlegm-heat that were published from inception to November 1,2023. Two researchers independently screened the RCTs and extracted data according to pre-set inclusion and exclusion criteria. The Cochrane Collaboration's tool for assessing risk of bias was used for quality evaluation. Revman 5.4 was used for the Meta-analysis of outcome indicators.ResultA total of 91 RCTs were included,involving 7 868 patients (3 942 patients in the experimental group and 3 926 patients in the control group). The results of Meta-analysis showed that compared with simple Western medicine treatment,modified Qingjin Huatantang combined with Western medicine improved the clinical response rate [relative risk (RR)=1.16,95% confidence interval (CI)[1.14,1.19],P<0.000 01] and PaO2 [mean difference (MD)=4.65,95%CI [1.88,7.43],P=0.001]. The combined therapy had advantages in decreasing the scores of clinical symptoms including cough [MD=-0.69,95%CI [-1.33,-0.06],P=0.03),expectoration [MD=-1.04,95%CI [-2.02,-0.07],P=0.04),phlegm volume [MD=-0.38,95%CI [-0.69,-0.07],P=0.02],fever [MD=-0.22,95%CI [-0.36,-0.09],P=0.000 8],wheezing [MD=-0.34,95%CI [-0.40,-0.29],P<0.000 01],chest tightness [MD=-0.32,95%CI [-0.39,-0.26],P<0.000 01],and rales [MD=-0.35,95%CI [-0.42,-0.27],P<0.000 01]). Moreover,the combined therapy outperformed Western medicine treatment alone in reducing PaCO2 (MD=-5.42,95%CI [-7.12,-3.72],P<0.000 01], white blood cell count (WBC) [MD=-1.27,95%CI [-1.56,-0.97],P<0.000 01],C-reactive protein (CRP) [standard mean difference (SMD)=-1.52,95%CI [-1.96,-1.07],P<0.000 01], procalcitonin (PCT) [SMD=-1.23,95%CI [-1.87,-0.58],P=0.000 2],and tumor necrosis factor (TNF)-α [SMD=-2.63,95%CI [-3.19,-2.08],P<0.000 01]), shortening hospital stay [MD=-2.45,95%CI [-3.34,-1.57],P<0.000 01], and lowering the incidence of adverse reactions [RR=0.66,95%CI (0.49,0.88),P=0.005].ConclusionModified Qingjin Huatantang combined with Western medicine in the treatment of patients with phlegm-heat syndrome has advantages in improving clinical response rate and PaO2, reducing symptom scores and inflammatory factors, and shortening hospital stay, with high safety.
摘要:ObjectiveTen Chinese patent medicines for stable angina pectoris with qi stagnation and blood stasis were comprehensively evaluated, with the aim of providing reference for optimizing the drug list of medical institutions and promoting rational drug utilization.MethodAccording to the Expert Consensus on the Selection of Chinese Patent Medicines in Medical Institutions 2022, an evaluation framework of "6+1" dimensions was established for comprehensive evaluation of the drugs based on the indicators in three levels.ResultThe evaluation results showed that Compound Danshen dripping pills, Shexiang Baoxin pills, Di'ao Xinxuekang capsules, and Xuefu Zhuyu capsules were strongly recommended for stable angina pectoris with Qi stagnation and blood stasis, with the scores of 78.5, 76, 72, and 70.8, respectively. Suxiao Jiuxin pills, Xinkeshu Tablets, Guanxin Danshen Dripping pills, and Yindan Xinnaotong soft capsules were weakly recommended, with the scores of 68.5, 65.5, 60.5, and 60.5 respectively. Lemai pills and Yangxin Dawayimixike migao were not recommended for the time being due to their low scores (50.5 and 48.8, respectively). There is a lack of research on special populations, pharmacokinetic parameters, post-marketing re-evaluation, and economics of the medicines.ConclusionWith the updating of Chinese patent medicines, real-world research data are needed to enhance the evidence-based support. This evaluation can only reflect the comprehensive situation at a certain stage, and dynamic evaluation remains to be carried out to provide support for decision makers.
关键词:Chinese patent medicine;comprehensive clinical evaluation of drugs;angina pectoris due to coronary heart disease;Qi stagnation and blood stasis;drug selection
摘要:ObjectiveThe pyrolysis temperature range of Scutellariae Radix(SR) and wine-processed SR(WSR) was studied by thermal analysis technique, and the quality difference in the contents of main components and fingerprint of WSR from different producing areas was compared, in order to provide a basis for the production process and quality evaluation of WSR.MethodThermal analysis technology was used to analyze the pyrolysis properties of SR, WSR, extract of SR and main components(baicalin, baicalein, wogonoside and wogonin), so as to determine the optimal processing temperature range of WSR. Then combined analytic hierarchy process(AHP), criteria importance through intercrieria correlation(CRITIC) and weighting evaluation, the optimal processing time was optimized. Based on the optimal conditions, SR from Shanxi, Hebei and Gansu provinces were processed. Ultra performance liquid chromatography(UPLC) was employed to establish the fingerprint of WSR, and the similarity analysis and common peak identification were carried out. At the same time, the contents of seven representative components(baicalin, chrysin-7-O-glucuronide, oroxylin A-7-O-β-D-glucuronide, wogonoside, baicalein, wogonin and oroxylin) were determined, then the quality differences of SR and WSR from different origins were compared. Based on the contents of seven active components, different batches of WSR were classified by hierarchical cluster analysis(HCA), principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the variable importance in the projection(VIP) value>1 was used to screen the differential components of each group.ResultThe optimum processing temperature of WSR was 190-200 ℃, and 190 ℃ for 8 min was selected as the frying process. The similarities between the fingerprints of SR and their control fingerprint were≥0.97, and the similarities between the fingerprints of WSR and their control fingerprint were≥0.98, suggesting that the processing could make the quality of decoction pieces consistent to a certain extent. The content determination results showed that the content of glycosides in SR from Gansu was lower than that from the other 2 producing areas, but the content of aglycones was higher. After being processed with wine, the content of 7 index components in SR from all producing areas decreased slightly, and the content of sample from Gansu province decreased greatly. The results of multivariate statistical analysis and discriminant analysis showed that wogonoside was the key ingredient for distinguishing WSR from different producing areas.ConclusionThis study determined the best processing technology of WSR and screened out the different component of wogonoside to distinguish between different origins of WSR, which can provide reference for the quality evaluation of WSR.
摘要:Xianfang Huomingyin is known as the first prescription of surgery, also known as Shenxian Huomingyin and Zhenren Huomingyin. The earliest one was from Renzhai Zhizhi in the Southern Song dynasty. It was composed of 13 mainstream medicines such as Angelicae Dahuricae Radix, Saposhnikoviae Radix, Paeoniae Radix Rubra, and three modified medicines such as Rhei Radix et Rhizoma, Momordicae Semen and Astragali Radix. It has the effects of clearing heat and detoxifying, detumescence and ulceration, promoting blood circulation and relieving pain, and is mainly used to treat Yang syndrome. In this study, the bibliometrics method was used to systematically study the historical evolution, prescription composition, dosage, indications, decocting methods, administration methods, drug processing and ancient and modern applications of Xianfang Huomingyin. As for the drug origin, pangolin is consistent with the 2015 edition of Chinese Pharmacopoeia, the origins of the remaining drugs are consistent with the 2020 edition of Chinese Pharmacopoeia. According to the ancient and modern dosage conversion, the dosage of each drug is as follows:Angelicae Dahuricae Radix, Paeoniae Radix Rubra, Fritillariae Thunbergii Bulbus, Glycyrrhizae Radix et Rhizoma and Trichosanthis Radix, Olibanum of 4.13 g, Gleditsiae Spina and Myrrha of 2.07 g, Angelicae Sinensis tail(stir-fried with wine) and Citri Reticulatae Pericarpium of 6.2 g, Saposhnikoviae Radix(removing reed) of 2.89 g, pangolin(stir-fried with clam powder) of 4.14 g, Lonicerae Japonicae Flos of 12.39 g, or adding Rhei Radix et Rhizoma of 4.13 g and Momordicae Semen(shelled) of 3.3 g, adding Astragali Radix of 4.13 g for body deficiency. The above medicines were decocted with 450 mL of yellow rice wine to 300 mL, 1 dose for each time, 3 doses for each day, and warmed before or 0.5 h after meals, 1-6 doses, and discontinue medication as soon as get effect. Because this formula is easy to hurt the spleen and stomach, it should not be taken more. In the follow-up, it should be used in conjunction with Tuoli Xiaodusan, and other related symptoms of patients can be further improved through dialectical addition and subtraction. This formula has the efficacy of disinfection and pus discharge, removing blood stasis and relieving pain. All carbuncle gangrene without ulceration at the beginning, and for the empirical and heat syndrome. Modern applications involve more than 200 kinds of diseases with heat syndrome, emergency and excess syndrome as the main syndrome differentiation points in dermatology, peripheral vascular department and other departments. In a word, this paper studies the literature of Xianfang Huomingyin in order to provide a basis for its wider and deeper clinical application and development research.
关键词:Xianfang Huomingyin;Zhenren Huomingyin;Shenxian Huomingyin;ancient books;historical evolution;modern clinical application;textual research
摘要:ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine(TCM) compounds, a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection(SHLI), in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI.MethodAfter one week of adaptive feeding, 72 SPF-grade SD male rats were randomly divided into blank group, SHLI standard group, Lonicerae Japonicae Flos(LJF) group, Scutellariae Radix(SR) group, Forsythiae Fructus(FF) group, and 7 groups of SHLI matching groups(groups 1-7), with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state, high performance liquid chromatography(HPLC) characterization profiles of the testing drugs and plasma components in each group were established, and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay(ELISA) was used to determine the changes of immunoglobulin E(IgE), histamine(HIS), tryptase(TPS), total complement(CH50) and terminal complement complex(C5b-9) in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets, and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values.ResultELISA results showed that, compared with the blank group, groups 1-3 could significantly increase the IgE level, groups 1-2, groups 4-6 and SHLI standard group could significantly increase the HIS level, group 4 could significantly increase the CH50 level, groups 1, 3-4, LJF group and FF group could significantly increase the TPS level, SR group could significantly increase the C5b-9 level, and the differences were all statistically significant(P<0.05). According to the retention time of chromatographic peaks, it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2, indicating that C6 had the greatest effect on the allergic reaction, and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS, indicating that component group C2 had the greatest contribution to the whole network.ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network, this study clarified that component group C6 may be a potential allergen in SHLI, and the component group C2 may be a key node in the mechanism of drug action, which can provide new strategies and methods for the screening of allergens in TCM injections.
关键词:Shuanghuanglian;traditional Chinese medicine(TCM) injection;anaphylactoid reaction;network relevance;quantitative spectroscopy of TCM;topological network analysis;high performance liquid chromatography(HPLC)
摘要:ObjectiveTo compare the quality of two kinds of honey-processed Lilii Bulbus(HPLB) prepared by empirical and pharmacopoeial methods based on chemical analysis and intelligent sensory technology, and to improve and upgrade the quality standard of HPLB on the basis of excavating and inheriting the traditional experience of famous experts in traditional Chinese medicine(TCM).MethodSamples of HPLB were prepared according to the method in the 2020 edition of Chinese Pharmacopoeia(honey was added before frying) and the empirical method of the old pharmacists(honey was added after frying), and the appearance characteristics, thin layer chromatography(TLC) identification, inspection, leachables and other items of the two kinds of samples were detected according to the methods under the Lilii Bulbus in the 2020 edition of Chinese Pharmacopoeia. The fingerprints of HPLB with different honey addition methods were established by high performance liquid chromatography(HPLC), and the contents of regaloside A, regaloside B and 5-hydroxymethylfurfural(5-HMF) were determined, the quality difference between the two HPLB samples was evaluated by multivariate statistical analysis. Meanwhile, electronic nose and electronic tongue were used to measure the sense of smell and taste, and combined with multivariate statistical analysis, the difference sensors were screened with the variable importance in the projection(VIP) value>1 in order to compare the differences between the two kinds of HPLB.ResultCompared with HPLB prepared by the pharmacopoeial method, the sample prepared by the empirical method had lower water content, slightly higher soluble extract content, better appearance and easy storage. HPLC fingerprints of two kinds of HPLB samples were established, and the similarity between them was≥0.999, indicating that the composition of two species was similar. And 29 common peaks were calibrated, among which peaks 8 and 18 were regaloside A and regaloside B. The quantitative analysis of the index components in the two kinds of HPLB samples showed that the difference in the contents of regaloside A and regaloside B was not statistically significant, whereas the content of 5-HMF in empirical HPLB was significantly higher than that of the pharmacopoeial HPLB(P<0.01). The electronic tongue and electronic nose test results showed that the umami, umami richness and saltiness of the empirical HPLB were higher than those of the pharmacopoeial HPLB. The results of electronic nose detection showed that the four sensors W1W, W2S, W5S and W1S were the differential odor sensors of the two samples, among which the response values of W1S and W2S sensors were higher than those of the pharmacopoeial HPLB, which might be related to the content of 5-HMF.ConclusionCompared with the pharmacopoeial HPLB, the empirical sample is of better quality, but the two can be clearly distinguished by electronic nose and electronic tongue, which can provide a reference for excavating and inheriting the traditional experience of famous experts in TCM and further improving the processing methods and quality standards of HPLB.
关键词:honey-processed Lilii Bulbus;processing of traditional Chinese medicine;fingerprint;intelligent sensory;chemical analysis;electronic tongue;electronic nose
摘要:ObjectiveTo mine the medication patterns of Chinese medicines for neurodermatitis based on contemporary medical cases in published articles.MethodThe medical cases of treating neurodermatitis with Chinese medicines were retrieved from the medical case articles published by contemporary famous and old Chinese medicine doctors in the library of Shandong University of Traditional Chinese Medicine, CNKI, VIP, and Wanfang Data. A case library was established, and SPSS Statistics 26.0 and SPSS Modeler 18.0 were employed to analyze the symptoms and syndromes of neurodermatitis and mine the medication patterns.ResultAccording to the inclusion and exclusion criteria, 130 medical case articles were included in this study. Neurodermatitis was prevalent in young adults between 20 and 39 years old (female patients of 30-49 years old and male patients of 20-39 years old), and male patients were more than female patients. The patients mainly presented the clinical manifestations of itchy rashes, thickened skin, and lichenification. Symptoms included skin injury, emotional abnormalities, and Yin damage caused by prolonged illness. Red tongue, thin white or yellow tongue coating, and wiry pulse were common in the patients. The patients with the syndrome of blood deficiency and wind dryness were often treated with Angelicae Sinensis Radix, Rehmanniae Radix, Glycyrrhizae Radix et Rhizoma, Tribuli Fructus, and Chuanxiong Rhizoma. The commonly used herb pairs included Chuanxiong Rhizoma-Paeoniae Radix Alba, Chuanxiong Rhizoma-Glycyrrhizae Radix et Rhizoma, and Rehmanniae Radix Praeparata-Saposhnikoviae Radix, and the commonly used prescriptions were Siwutang and Dangguiyinzi. The patients with the syndrome of muscle and skin dystrophy were mainly treated with Rehmanniae Radix, Sophorae Flavescentis Radix, Paeoniae Radix Alba, Tribuli Fructus, and Dictamni Cortex. The commonly used herb pairs included Polygoni Multiflori Caulis-Sophorae Flavescentis Radix, Polygoni Multiflori Caulis-Dictamni Cortex, and Salviae Miltiorrhizae Radix et Rhizoma-Paeoniae Radix Alba, and the commonly used prescriptions were Jingjie Siwutang and Baixianpiyin. The patients with the syndrome of liver depression transforming into fire were often treated with Rehmanniae Radix, Gentianae Radix et Rhizoma, Gardeniae Fructus, Bupleuri Radix, and Scutellariae Radix. The commonly used herb pairs included Gentianae Radix et Rhizoma-Polygoni Multiflori Caulis, Polygoni Multiflori Caulis-Gardeniae Fructus, and Gentianae Radix et Rhizoma-Saposhnikoviae Radix, and the commonly used prescriptions were Longdan Xiegantang and Danzhi Xiaoyaosan.ConclusionThis study enriches the knowledge about neurodermatitis, clarifies the treatment principles and methods as well as the medication patterns, and provides a theoretical basis for clinical treatment and medication based on syndrome differentiation.
摘要:Viral pneumonia (VP) is an inflammatory disease caused by one or more viruses that infect the upper respiratory tract and spread downward. Causing varying degrees of pulmonary parenchymal damage, VP poses a serious threat to the society and public health. The treatment of VP now faces the dilemma of drug shortage, since Western medicine can only alleviate symptoms and lacks specific treatment methods. In traditional Chinese medicine (TCM), VP is assigned as an epidemic disease, with the etiology attributed to epidemic toxin and six excesses and the pathological factors of dampness, heat, toxin, deficiency, and stasis. The basic pathogenesis of VP is Yin-Yang imbalance, dysfunction of Zang-Fu organs, and healthy Qi deficiency. Accordingly, the treatment should follow the principle of replenishing healthy Qi and expelling pathogen. The treatment method of VP is mainly developed based on syndrome differentiation of six meridians, defense-Qi-nutrient-blood, and triple energizer. Xuanfei Baidu prescription (XFBD) is an effective prescription developed by Academician ZHANG Boli and Professor LIU Qingquan by literature research and selection of multi-component Chinese medicine. It is the product of modern research combined with TCM. XFBD is modified from Maxing Shigantang, Maxing Yigantang, Tingli Dazao Xiefeitang, Qianjin Weijingtang, and Buhuanjin Zhengqisan. It is mainly used to treat epidemic diseases with the syndrome of dampness toxin stagnating in the lung, with the effects of ventilating lung and resolving dampness, clearing heat and expelling pathogen, purging lung, and removing toxin, demonstrating the potential for the prevention and treatment of VP. This paper reviews the research progress of XFBD in combating VP in terms of the prescription composition, compatibility ideas, indications, and clinical new applications, as well as the pharmacological mechanisms of inhibiting virus, reducing inflammation, regulating immune system, ameliorating pulmonary fibrosis, and modulating intestinal flora. In addition, we put forward our thoughts and suggestions on the problems in the research, with a view to informing the clinical use of drugs and the basic research on the treatment of VP including COVID-19.
关键词:Xuanfei Baidu prescription;viral pneumonia;traditional Chinese medicine theory;pharmacological effects;mechanism
摘要:Diabetic cognitive dysfunction (DCD) is one of the complications of diabetes, which is characterized by impaired brain structure and progressively decreased learning and memory ability. With the increasing incidence of diabetes worldwide, DCD has become a serious medical and social problem. However, its pathophysiological mechanisms are not well understood. The occurrence and development of DCD involve multiple pathological links and mechanisms, and the prevention and treatment require multi-link and multi-target therapeutic measures. At present, there is no specific drug to prevent or improve DCD. Hypoglycemic drugs such as metformin and vigagliptin or anti-dementia drug including Donepezil are commonly used in clinical treatment to delay the occurrence and progression of cognitive dysfunction, but these drugs have a single target and obvious side effects. Traditional Chinese medicine has a long history in the prevention and treatment of diabetes and central cognitive diseases, and it has many unique advantages such as multiple components, multiple targets, side effects, and low price. A large number of studies have confirmed that traditional Chinese medicine has a significant prevention and treatment effect on DCD, which can improve insulin resistance, synaptic dysfunction, inflammation, oxidative stress, endoplasmic reticulum stress, and neuronal apoptosis by regulating phosphatidylin-ositol 3-kinase (PI3K)/protein kinase B (Akt), advanced glycation end products (AGEs)/advanced glycation end products receptor (RAGE)/nuclear transcription factor-κB (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, and endoplasmic reticulum stress and nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. This article reviewed the effects and related mechanisms of traditional Chinese medicine on DCD in recent years, so as to provide a reference for the prevention and treatment of DCD by traditional Chinese medicine.
关键词:diabetes;cognitive dysfunction;traditional Chinese medicine;signaling pathway
摘要:Lung cancer is the most common malignant tumor of the respiratory system, and its pathogenesis is still not fully understood. Despite the significant clinical efficacy achieved through treatments such as surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, they still come with many complications and significant adverse reactions. In recent years, numerous basic and clinical studies have confirmed the effectiveness of Chinese medicine in treating lung cancer. Chinese medicine features synergistic regulation through its multiple components, targets, pathways, and approaches. Active monomeric constituents in Chinese medicine are diverse, and their mechanisms of action are intricate, making it challenging to fully understand the mechanisms by which Chinese medicine prevents and treats lung cancer. Therefore, there is an urgent need to approach Chinese medicine intervention in lung cancer from a modern medical perspective, exploring the mechanisms of Chinese medicine intervention in lung cancer at the molecular biology and network pharmacology levels. According to traditional Chinese medicine (TCM), the occurrence of lung cancer is predominantly attributed to factors such as deficiency of healthy Qi, presence of pathogenic factors, internal accumulation of heat-toxins, internal accumulation of phlegm-dampness, and Qi stagnation and blood stasis. Literature analysis reveals that Chinese medicine compound formulas for lung cancer predominantly include tonifying agents and heat-clearing and toxin-removing agents, such as Shashen Maidongtang, Xiaoyan prescription, and Feijinsheng prescription. The single herbs used mainly include heat-clearing, deficiency-tonifying, blood-activating, stasis-resolving, phlegm-resolving, cough-relieving, and asthma-calming categories. The use of Chinese medicine aligns with the TCM understanding of the etiology and pathogenesis of lung cancer. Studies have shown that TCM can regulate the expression of key molecules in lung cancer-related signaling pathways, such as the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), nuclear factor-kappa B (NF-κB), Wnt/β-catenin, mitogen-activated protein kinase (MAPK), and Janus kinase/signal transducer and activator of transcription (JAK/STAT), thereby exerting effects such as reducing lung cancer cell activity, blocking the cell cycle, inhibiting proliferation and invasion of lung cancer cells, inducing apoptosis in lung cancer cells, promoting cell autophagy, and reversing drug resistance, and intervening in the progression of lung cancer. This study systematically summarized recent research progress on how Chinese medicine monomers or formulas regulated the aforementioned signaling pathways and key protein expression to exert anti-lung cancer effects, aiming to elucidate the mechanisms by which Chinese medicine intervenes in the progression of lung cancer and provide insights and theoretical basis for further research and clinical application of Chinese medicine in lung cancer intervention.
关键词:lung cancer;signaling pathway;Chinese medicine;research progress;mechanisms of action
摘要:Knee osteoarthritis (KOA) is a common degenerative joint disease characterized primarily by the degeneration and damage of knee joint cartilage, accompanied by osteophyte formation and inflammation. In recent years, the prevalence of KOA has been increasing globally, significantly impacting the quality of life patients. However, the pathogenesis of KOA remains not fully understood, and current treatment methods are limited. Therefore, finding new therapeutic strategies is a research hotspot. Previous studies have found that the onset of KOA is related to abnormal mitochondrial regulation. Mitochondria, functioning as secondary messengers, play crucial roles in cellular respiration, reactive oxygen species (ROS) generation, and adenosine triphosphate (ATP) production through oxidative phosphorylation. Mitochondrial quality control is a pivotal mechanism for maintaining the morphology, quantity, and quality of mitochondria. The connection between mitochondrial quality control and the pathogenesis of KOA involves several factors, such as mitochondrial oxidative stress, mitophagy, imbalances in mitochondrial biogenesis, abnormal mitochondrial dynamics (fission and fusion), and dysregulation of calcium ions. Metabolic abnormalities in the body lead to mitochondrial structural damage, which in turn contributes to the onset and progression of KOA. Traditional Chinese medicine (TCM) has made some progress in intervening in mitochondrial quality control, employing multi-faceted, multi-pathway, and multi-target strategies to treat KOA. Several studies have shown that mitochondrial quality control may be one of the therapeutic targets of TCM in treating KOA. However, there is currently a lack of comprehensive reviews summarizing the TCM interventions in mitochondrial quality control for treating KOA. This paper systematically reviewed the research progress in TCM treatment of KOA based on five aspects of mitochondrial quality control, aiming to provide a theoretical basis for the clinical prevention and treatment of KOA.
关键词:knee osteoarthritis;mitochondrial quality control;traditional Chinese medicine;multi-faceted;multi-pathway;multi-target;review
摘要:Thyroid diseases are common endocrine disorders with high incidence. The diseases are closely related to genetic factors, immune system disorders, and hormone levels. Although modern medical therapies have achieved certain therapeutic effects, the side effects have affected clinical treatment. In recent years, studies have proven that gut microbiota is a key factor affecting thyroid diseases, and increasing studies have referred to the bidirectional information interaction system between the gut and thyroid as the gut-thyroid axis. This study adopts the meridian-collateral theory and the visceral manifestation theory of traditional Chinese medicine (TCM) to explain the functions, physiological characteristics, and pathological mechanisms of the gut and thyroid. Furthermore, this paper clarifies the mechanism of gut microbiota in modulating thyroid homeostasis by inducing inflammation and altering thyroid hormone metabolism from the perspective of molecular biology, clarifying the rationality of the gut-thyroid axis from the perspectives of TCM and Western medicine. Meanwhile, under the guidance of the gut-thyroid axis, increasing studies have been carried out regarding the application of TCM in regulating gut microbiota in the treatment of thyroid diseases. Both the active component emodin and compound prescription Yiqi Huatan Huoxue prescription of Chinese medicine can treat thyroid diseases by regulating the abundance and diversity of gut microbiota and improving the intestinal mucosal barrier. However, the systematic review of the research on TCM treatment of thyroid diseases by regulating gut microbiota remains to be conducted. This study expounds the gut-thyroid axis from both TCM and Western medicine and reviews the research progress in the TCM treatment of thyroid diseases by regulating gut microbiota, aiming to give new insights into the prevention and treatment of thyroid diseases with TCM.
摘要:Osteoarthritis (OA) is characterized by articular cartilage degeneration, synovial hyperplasia, hyperosteogeny, and narrowing of joint space, which can be caused by trauma, inflammation, and other factors. With the increasing global population aging, the incidence of OA is rising year by year, making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex, including oxidative stress, autophagy, and apoptosis. Recent studies have found that ferroptosis, a new type of cell death, is also an important pathogenic factor in OA, characterized by a series of complex changes such as iron ion accumulation, glutathione (GSH) depletion, and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation, delay extracellular matrix (ECM) degradation, and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement, but there are limitations. Traditional Chinese medicine (TCM) has been widely used in the treatment of various diseases because of its low cost, low drug resistance, and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets, multiple levels, and aspects, but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism, lipid peroxidation, cysteine/glutamate transporter system Xc- (system Xc-)/GSH/glutathione peroxidase 4 (GPX4) pathway, nicotinamide adenine dinucleotide phosphate(NADPH)/ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10) pathway, tumor protein p53 in OA, and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs.
关键词:ferroptosis;traditional Chinese medicine;osteoarthritis;mechanism;research progress
摘要:Saponins are widely found in various Chinese medicines such as Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Bupleuri Radix. They possess multiple biological activities, including anti-inflammatory, antioxidant, antitumor, hepatoprotective, lipid-lowering, and hypoglycemic effects. They play an important role in the prevention and treatment of diseases such as acute lung injury, hyperlipidemia, and diabetic cardiovascular complications, and hold significant research potential and value. Metabolism-related fatty liver disease is a prevalent chronic liver disease characterized by excessive lipid accumulation in hepatocytes. According to the "multiple hit" theory, its occurrence is the result of systemic homeostasis disorder, influenced by abnormal lipid metabolism, oxidative stress, inflammation, insulin resistance, mitochondrial dysfunction, and intestinal microbiota. However, there is currently no effective treatment available in clinical practice. Recent studies have found that Chinese herbal saponins can alleviate metabolism-related fatty liver disease through various pathways, including regulating abnormal lipid metabolism, inhibiting inflammatory responses, alleviating oxidative stress, reducing insulin resistance, improving mitochondrial dysfunction, modulating intestinal flora, inhibiting hepatocyte programmed death, regulating liver autophagy, and correcting immune imbalances. Therefore, this review summarized the pharmacological effects and related mechanisms of Chinese herbal saponins in improving metabolism-related fatty liver disease in recent years, aiming to provide a theoretical reference for the clinical application and experimental research of Chinese herbal saponins in the prevention and treatment of metabolism-related fatty liver disease.
摘要:Sepsis is one of the common severe diseases caused by the dysregulated host response to infection, which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high, and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present, anti-infection, fluid resuscitation, mechanical ventilation and other programs are most used in clinic to treat sepsis, but their poor prognosis and high cost and other issues remain to be resolved. Therefore, it is necessary to explore a new, efficient, safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine (TCM) is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis, maintain the homeostasis of the body, and has fewer adverse reactions. It has achieved good clinical results. In recent years, a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4(TLR4) signaling pathway, thereby reducing the severity and mortality of sepsis patients. However, there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore, this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients, Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response, repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However, due to various limitations, some studies have directly focused on the differential expression and function of TLR4, ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism, relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance, which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.
关键词:sepsis;Toll-like receptor 4(TLR4) signaling pathway;traditional Chinese medicine;review
摘要:Dryness is an important concept in the theory of traditional Chinese medicine, which is closely related to the transformation of the body, etiology and pathogenesis. As one of the medicinal properties of Chinese materia medica, there are various types of Chinese materia medica with dryness. Atractylodis Rhizoma(AR) is a representative medicine with warm and dry properties, which has the function of drying dampness and strengthening the spleen. Due to its strong dryness, it can cause certain adverse reactions. In clinical practice, stir-fried AR with bran is often used as medicine. The dryness of AR is closely related to its efficacy, but the underlying mechanism of the relationship between dryness and efficacy is still unclear. At present, the research on dryness Chinese materia medica has been increasing year by year, but there are still problems such as insufficient systematic research, insufficient in-depth research and lack of research on the mechanism of dryness effect, which limit the breakthrough of the theory of processing for slowing down dryness, and hinder the precise application of dryness Chinese materia medica in clinical practice. Therefore, this article comprehensively reviewed the differences in dryness characterization indicators of different Chinese materia medica by searching domestic and foreign literature, focusing on the relevant research on dryness of AR. A systematic summary and induction were made from the characterization indicators, research techniques of dryness markers, the influence of processing on dryness of AR, and the application mining of dryness of AR. The results showed that the dryness characteristics of AR mainly included the upregulation of macroscopic indicators such as water intake, urine output and whole blood viscosity, as well as energy metabolism indicators, the downregulation of water metabolism indicators, and pathological changes such as submandibular gland acinar atrophy. Based on the changes of dryness and component content of AR after processing, it is determined that the main dryness components of AR may be volatile components such as β-eudesmol and atractylon. Due to its dryness, AR is mainly used to treat diseases such as spleen deficiency, rheumatism and edema. However, the current understanding of the correlation between dryness and efficacy of AR is still insufficient, and there are still many bottlenecks in understanding and explaining its dryness. In the future, systematic evaluation and characterization should be carried out to find the common mechanism of AR exerting dryness and efficacy, providing reference for the rational clinical use.
关键词:Atractylodis Rhizoma;dryness characterization;Chinese medicine processing;quality markers;bran-fried products;β-eudesmol;atractylon