最新刊期

    30 12 2024
    • 最新研究发现,四逆散通过激活Nrf2/HO-1信号通路,显著改善胆汁淤积性肝炎大鼠的肝脏氧化应激损伤,为治疗相关疾病提供了新策略。
      CAO Dan, CHEN Qi, CHEN Xiaolu, CHEN Linzhen, WANG Haiyan, HAO Juhui, ZHANG Wei, MA Zhiqiang
      Vol. 30, Issue 12, Pages: 1-7(2024) DOI: 10.13422/j.cnki.syfjx.20240602
      摘要:ObjectiveBased on the nuclear factor erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway, this paper explores the effect of Sinisan (SNS) on liver oxidative stress injury in cholestatic hepatitis rats and its mechanism.MethodThirty 6-week-old male SD rats were randomly divided into a control group, model group, low and high dose groups of SNS (2.5 and 5 g·kg-1) and ursodeoxycholic acid group (UDCA, 63 mg·kg-1), with six rats in each group. Rats were administrated for seven consecutive days. On the 5th day, the control group was given olive oil of 10 mL·kg-1, and the other groups were given alpha-naphthalene isothiocyanate (ANIT) of 80 mg·kg-1. The serum biochemical indicator levels of cholestasis and the content of antioxidant factors in rat liver were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in liver tissue. The relative mRNA and protein expressions of Nrf2, HO-1, and quinone oxidoreductase 1 (NQO1) in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot.ResultCompared with the control group, the model group showed a significant increase in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue (P<0.01). There were obvious pathological changes in the model group such as the disordered arrangement of hepatocytes, obvious congestion and necrosis in the portal area, infiltration of inflammatory cells, and destruction of the interlobular bile duct. The relative mRNA and protein expressions of Nrf2, HO-1, and NQO1 in liver tissue were significantly down-regulated in the model group (P<0.05, P<0.01). Compared with the model group, the groups of SNS showed a significant decrease in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue (P<0.01), and the pathological liver injury was obviously improved. The necrotic area was reduced, and the infiltration of inflammatory cells was decreased. In addition, there was a small amount of extravasated blood in the interlobular vein. The relative mRNA and protein expressions of Nrf2, HO-1, and NQO1 in liver tissue were significantly up-regulated (P<0.05, P<0.01).ConclusionSNS can significantly improve liver injury in cholestatic hepatitis rats, and its mechanism may be related to the inhibition of oxidative stress response mediated by the Nrf2/HO-1 signaling pathway.  
      关键词:Sinisan;cholestatic hepatitis;oxidative stress;nuclear factor erythroid 2 related factor 2 (Nrf2);heme oxygenase 1 (HO-1)   
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    • 最新研究发现,补中益气汤通过调控NLRP3/Caspase-1/GSDMD信号通路,有效抑制自身免疫性甲状腺炎小鼠细胞焦亡,为治疗自身免疫性甲状腺炎提供新策略。
      WANG Zhimin, YANG Xiao, CHEN Yiran, LIU Ziyu, LIU Qingyang, GAO Chenghan, WANG Chen, GAO Tianshu
      Vol. 30, Issue 12, Pages: 8-15(2024) DOI: 10.13422/j.cnki.syfjx.20240121
      摘要:ObjectiveTo explore the mechanism of Buzhong Yiqitang on pyroptosis in autoimmune thyroiditis (AIT) mice based on the NOD-like receptor hot protein domain related protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1(Caspase-1)/Gasdermin D (GSDMD) pathway.MethodSixty NOD.H-2h4 mice were divided into normal group, model group, low, medium, and high dose groups (4.10, 8.19, 16.38 g·kg-1)of Buzhong Yiqitang, and selenium yeast tablet group (0.26 mg·kg-1), with 10 mice in each group. Except for the normal group, all other groups were given 0.05% NaI by gavage for eight weeks to establish a model and then received the drug treatment for eight weeks. The serum levels of thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TgAb) were detected using enzyme-linked immunosorbent assay (ELISA) method. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in mouse thyroid tissue. The immunohistochemical method was used to detect the protein expression of NLRP3, Caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18. Western blot was used to detect the levels of pyroptosis-related proteins in thyroid tissue.ResultCompared with the normal group, the serum levels of TPO-Ab and TgAb in the model group were significantly increased (P<0.01). Thyroid follicles either increased in a cubic shape or were damaged and atrophied, with a large number of lymphocytes infiltrating around the follicles. Compared with the model group, the levels of TPO-Ab and TgAb in other groups were significantly reduced (P<0.01), and the morphology and structure of follicles were improved. The degree of lymphocyte infiltration was reduced. Among them, the medium dose group of Buzhong Yiqitang had the most significant reduction and improvement effect. Compared with the normal group, the positive products and mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18 proteins in the thyroid tissue of the model group significantly increased (P<0.01), and the protein expression levels of NLRP3, cleaved Caspase-1, IL-1β, IL-18, and GSDMD-N were significantly increased (P<0.05, P<0.01). Compared with the model group, the positive products and mRNA expression of NLRP3, Caspase-1, IL-1β, and IL-18 proteins in other groups were significantly reduced (P<0.05, P<0.01), with the most significant reduction effect in the medium dose group of Buzhong Yiqitang. The protein expression levels of NLRP3, cleaved Caspase-1, IL-1β, IL-18, and GSDMD-N were significantly reduced (P<0.05, P<0.01).ConclusionBuzhong Yiqitang can improve AIT, and its mechanism may be achieved by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to inhibit pyroptosis.  
      关键词:Buzhong Yiqitang;autoimmune thyroiditis;pyroptosis;NOD-like receptor hot protein domain related protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1(Caspase-1)/Gasdermin D (GSDMD) pathway   
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    • CHEN Hongyun, YANG Dongying, LIAO Huiqing, ZENG Yanyan, PAN Linke, BAI Shasha, DENG Di, SHI Yafei, ZHANG Rong, YANG Lei
      Vol. 30, Issue 12, Pages: 16-23(2024) DOI: 10.13422/j.cnki.syfjx.20240606
      摘要:ObjectiveTo investigate the antidepressant effect of Sinisan (SNS) by regulating glycogen aynthase kinase-3β (GSK-3β)/tumor necrosis factor alpha-induced protein 3(A20)/CCAAT enhancer binding protein β(C/EBPβ) to inhibit the activation of microglia.MethodA total of 72 male C57/6J mice were randomly divided into the normal group, model group, fluoxetine group (5.0 mg·kg-1), low-dose Sinisan group (4.9 g·kg-1), medium-dose Sinisan group (9.8 g·kg-1), and high-dose Sinisan group (19.6 g·kg-1), with 12 mice in each group. After one week of adaptive feeding, chronic unpredictable mild stress (CUMS) was performed to establish the depression model. In the fifth week, drug treatment was conducted for four weeks. In the ninth week, behavioral tests were performed, including sucrose preference test (SPT), open field test (OPT), elevated plus maze (EPM) test, and forced swimming test (FST). Western blot was used to detect the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), nitric oxide synthase (iNOS), GSK-3β, A20, and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation 68 (CD68) in microglia was detected by immunofluorescence.ResultAfter eight weeks of CUMS, compared with the normal group, the mice in the model group had a significantly reduced sucrose preference rate (P<0.01), and the activity in the central area of the OPT was significantly reduced (P<0.01). The activity in the open arm area of the EPM test was significantly reduced (P<0.05), and the immobility time of FST was increased (P<0.01). The expression levels of inflammatory proteins IL-1β, IL-6, and iNOS were increased (P<0.01), and the fluorescence co-localization index of Iba1 and CD68 was increased (P<0.05). The protein expression levels of GSK-3β and C/EBPβ were significantly increased (P<0.05, P<0.01). After four weeks of SNS intervention, compared with the model group, the mice in the SNS group had significantly increased sucrose preference rate (P<0.01), significantly increased activities in the central area and the open arm area in the OPT and the EPM test (P<0.05), and significantly reduced immobility time in the FST (P< 0.01). The protein expression levels of IL-1β, IL-6, and iNOS were significantly decreased (P<0.05), and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group (P<0.05). The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased (P<0.01), and that of A20 was significantly increased (P<0.01).ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.  
      关键词:depression;chronic unpredictable mild stress;microglia;Sinisan;neuroinflammation   
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    • 最新研究发现,补中益气汤通过调节Adipor1/AMPK/PGC-1α信号通路,提高骨骼肌对脂肪的利用率,有效延缓运动性疲劳小鼠的发生。
      PENG Juan, WEI Huani, JIANG Ting, LIU Wei, PAN Huashan, CHEN Daorui
      Vol. 30, Issue 12, Pages: 24-30(2024) DOI: 10.13422/j.cnki.syfjx.20240604
      摘要:ObjectiveTo discuss the impact of Buzhong Yiqitang on lipid metabolism in skeletal muscle of exercise-induced fatigue (EIF) mice through adiponectin receptor 1 (Adipor1)/adenosine 5'-monophosphate(AMP)-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α).MethodC57BL6J mice were randomly divided into the control group, model group, low, middle, and high dose groups of Buzhong Yiqitang, and vitamin C group. No intervention was given to the control group, while the other groups were subjected to exhaustive swimming training to establish the EIF model. One hour before exhaustion, 0.2 mL distilled water was given to the control group and the model group, while the mice in the low, middle, and high dose groups of Buzhong Yiqitang were given intragastrically Buzhong Yiqitang of 4.1, 8.2, and 16.4 g·kg-1, respectively, and the vitamin C group was given vitamin C of 0.04 g·kg-1 via gavage for a duration of six weeks. After six weeks of the experiment, the growth rate of body weight, organ index, and exhaustive swimming time were calculated. Enzyme colorimetry was utilized to detect the levels of blood urea nitrogen (BUN), creatine kinase acid (CK), lactate dehydrogenase acid (LDH), and lactic acid (LD). The pathological changes of skeletal muscle were observed using hematoxylin -eosin (HE) staining, while the ultrastructure of skeletal muscle was observed with transmission electron microscope (TEM). The contents of free fatty acids (NEFA) and triglyceride acid (TG) in serum were also examined by microplate method. The protein expressions of Adipor1, p-AMPK/AMPK, PGC-1α, and HK2 in the skeletal muscle were measured by Western blot.ResultCompared with those of the control group, the growth rate of body weight and thymus index of the model group were decreased, and the serum levels of BUN, CK, LD, and LDH were increased (P<0.01). The contents of NEFA and TG were decreased (P<0.01), and the protein expression of Adipor1, p-AMPK/AMPK, PGC-1 α, and HK2 in the skeletal muscle decreased (P<0.05, P<0.01). Compared with those in the model group, the growth rate of body weight, thymus index, and exhaustive swimming time were significantly increased (P<0.01), and the levels of BUN, CK, LD, and LDH dropped in the high dose group of Buzhong Yiqitang (P<0.01). The levels of NEFA and TG were greatly improved (P<0.01). The protein expressions of Adipor1, p-AMPK/AMPK, PGC-1α, and HK2 in the skeletal muscle were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the thymus index and exhaustive swimming time were significantly increased in the vitamin C group, and the levels of BUN, CK, and LD dropped (P<0.05, P<0.01). The levels of NEFA and TG were improved significantly (P<0.01), and the protein expression of Adipor1 in skeletal muscle was increased greatly (P<0.01).ConclusionBuzhong Yiqitang can delay the development of EIF, which may be connected with the regulation of the Adipor1/AMPK/PGC-1α signaling pathway and the improvement of the utilization rate of skeletal muscle to fat.  
      关键词:exercise-induced fatigue;Buzhong Yiqitang;skeletal muscle;lipid metabolism;adiponectin receptor 1 (Adipor1)/adenosine 5'-monophosphate(AMP)-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) signaling pathway   
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    • 最新研究发现,升陷汤能有效改善特发性肺纤维化大鼠肺功能,其机制可能通过调节Wnt3a/β-catenin信号途径抑制细胞衰老和上皮间质转化。
      YAN Yanan, LIANG Yulei, WANG Jiepeng, FANG Chaoyi
      Vol. 30, Issue 12, Pages: 31-38(2024) DOI: 10.13422/j.cnki.syfjx.20240138
      摘要:ObjectiveTo observe the effect of Shengxiantang (SXT) on cell senescence mediated by wingless/integrated (Wnt)3a/β-catenin pathway in rats with idiopathic pulmonary fibrosis (IPF) and reveal the possible mechanism in improving lung function of IPF rats.MethodA total of 32 SPF level SD rats were randomly divided into sham group, model group, pirfenidone group, and SXT group. The IPF rat model was established by intratracheal instillation of bleomycin (0.005 g·kg-1). The following day after surgery, rats in the SXT group were given the aqueous solution of SXT granules (0.78 g·kg-1), and the pirfenidone group was given pirfenidone suspension (0.05 g·kg-1). The other groups were given deionized water (10 mL·kg-1) for 28 consecutive days. Lung tissue was collected after the lung function was measured. The pathological changes of the lung tissue were observed by hematoxylin-eosin (HE) and Masson staining, and then the Szapiel score and Ashcroft score were performed. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect telomere length. Western blot was applied to detect the expressions of epithelial-mesenchymal transformation (EMT) markers [α-smooth muscle actin (α-SMA) and E-cadherin], telomere reverse transcriptase (TRET), aging-related proteins (p53 and p21), senescence-associated secretory phenotype [interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1)], and key proteins of Wnt signaling pathway [Wnt3a, glycogen synthase kinase-3β (GSK-3β), β-catenin, Cyclin D1, and c-Myc].ResultCompared with those in the Sham group, peak expiratory flow (PEF) and minute ventilation volume (MV) in the model group were significantly decreased (P<0.01), and the frequency of respiratory (f) was significantly increased (P<0.01). The Szapiel score, Ashcroft score, and protein expression of α-SMA, p53, p21, IL-6, MMP-1, Wnt3a, GSK3β, β-catenin, Cyclin D1, and c-Myc were increased (P<0.01). The expressions of E-cadherin and TERT, as well as telomere length were significantly decreased (P<0.01). Compared with those in the model group, PEF and MV in the SXT group were significantly increased (P<0.01), while f was significantly decreased (P<0.01). The Szapiel score, Ashcroft score, and protein expression of α-SMA, p53, p21, IL-6, MMP-1, Wnt3a, GSK3β, β-catenin, Cyclin D1, and c-Myc were significantly decreased (P<0.05, P<0.01). Nevertheless, the expression of E-cadherin and TERT, as well as telomere length were significantly increased (P<0.01).ConclusionSXT presents a significant protective effect on lung function in IPF rats, and the prescription may act on the Wnt3a/β-catenin signaling pathway to regulate cell senescence induced by TERT to inhibit EMT.  
      关键词:Shengxiantang;telomere;cell senescence;idiopathic pulmonary fibrosis;wingless/integrated (Wnt)3a signaling pathway;epithelial-mesenchymal transformation;lung function   
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    • 最新研究发现,芍药苷能有效抑制非小细胞肺癌细胞生长并诱导其凋亡,通过改善细胞缺氧状态和抑制Hippo信号通路,为非小细胞肺癌治疗提供新策略。
      LI Yan, PENG Liang, JIANG Lifeng, WANG Sheng, WANG Ge, YU Xiaolin, YAO Yulin
      Vol. 30, Issue 12, Pages: 39-44(2024) DOI: 10.13422/j.cnki.syfjx.20232023
      摘要:ObjectiveTo observe the apoptosis induced by paeoniflorin (PF) in non-small cell lung cancer (NSCLC) cells and explore its mechanism.MethodCell counting kit-8 (CCK-8) was used to detect the inhibition rates of H1299, H292 and A549 cells with different concentrations of PF (2.5, 5, 10, 20, 25 µmol·L-1), and to screen suitable concentrations of PF and experimental cells. The inhibitory effect of PF on lung cancer cells was detected by clone formation assay. The effect of PF on cell apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide (PI) double staining. With the right concentration of drugs, levels of apoptosis-associated protein B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved Caspase-3 and Caspase-3 were detected by Western blot. At the same time, the molecular expressions of hypoxia inducible factor -1α (HIF-1α) and Hippo signaling pathway were determined.ResultCompared with the blank group, PF significantly inhibited the growth of H1299, H292 and A549 cells of human lung cancer (P<0.01). PF significantly induced apoptosis in A549 cells (P<0.01), decreased the Bcl-2/Bax ratio (P<0.01), and significantly increased the cleaved Caspase-3 expression (P<0.01). Compared with those in the blank group, the expression levels of HIF-1α, transcriptional coactivator with PDZ-binding motif (TAZ), large tumor suppressor 1 (LATS1), Mps one binding 1 (MOB1) and Yes-associated protein (YAP) in A549 cells of the PF treatment group were significantly decreased (P<0.01), while the expressions of p-LATS1, p-MOB1 and p-YAP were significantly increased (P<0.01). At the same time, there was no significant effect on the expression levels of phosphorylated mammalian Ste20-like kinase 1 (p-MST1) and MST1, which did not reach a statistical difference.ConclusionAll data demonstrated that PF showed an anti-tumor effect by improving hypoxic conditions and inhibiting the abnormally activated Hippo signaling pathway, thereby inducing and promoting apoptosis in non-small cell lung cancer.  
      关键词:paeoniflorin;Hippo pathway;anoxia;apoptosis   
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    • 最新研究发现,温肺化纤汤通过NAMPT/SIRT1信号通路延缓肺间充质干细胞衰老,为肺纤维化治疗提供新策略。
      HU Junxia, XU Yueqi, WANG Jun, ZHU Guoshaung, KE Shiwen, QIU Mingliang, LIU Liangji, MO Lisha
      Vol. 30, Issue 12, Pages: 45-53(2024) DOI: 10.13422/j.cnki.syfjx.20240601
      摘要:ObjectiveThe lung mesenchymal stem cells (LMSCs) induced by D-galactose (D-gal) were intervened by Wenfei Huaxian decoction-containing serum to explore the mechanism of Wenfei Huaxian decoction in delaying the senescence of LMSCs through the nicotinamide phosphoribosyltransferase/silent information regulator 1 (NAMPT/SIRT1) signaling pathway.MethodWenfei Huaxian decoction-containing serum was prepared. LMSCs were isolated by gradient density centrifugation, and they were cultured and identified in vitro. The senescence model in vitro was established by stimulating cells via D-gal for 24 h. LMSCs cells were modeled after being treated with different volume fractions (5%, 10%, 20%, 40%, and 80%) of Wenfei Huaxian decoction-containing serum for 24 h, and the cell proliferation level was detected by methyl thiazolyl tetrazolium (MTT) method. The cells were randomly divided into blank serum group, model group, and high, medium, and low dose groups of Wenfei Huaxian decoction-containing serum. Senescence-associated β-galactosidase (SA-β-gal) staining was used to detect the senescence of LMSCs in each group. The content of NAD + was detected by colorimetry. The levels of senescence-associated factors (p16 and p53), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the relative expression of senescence-associated proteins and NAMPT/SIRT1 signaling pathway-related proteins.ResultCompared with the blank serum group, the proliferation of LMSCs was significantly inhibited after D-gal stimulation for 24 h (P<0.01). Compared with the model group, the proliferation of LMSCs could be promoted after intervention with the corresponding Wenfei Huaxian decoction-containing serum (P<0.05, P<0.01). Compared with the blank serum group, the SA-β-gal staining of LMSCs in the model group after D-gal stimulation was enhanced, and the content of NAD+ was increased (P<0.01). The expression levels of senescence factors p16 and p53, as well as SASP pro-inflammatory factors IL-6 and TNF-α in the cell culture supernatant, were significantly increased (P<0.01). The expression of senescence-associated proteins p16, p21, and p53 increased (P<0.01), and the protein expression of NAMPT, SIRT1, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), and forkhead box family transcription factor O1 (FoxO1) decreased (P<0.01). Compared with the model group, the SA-β-gal staining of LMSCs in each group of Wenfei Huaxian decoction-containing serum was significantly reduced, and the content of NAD+ was decreased (P<0.01). The senescence factors (p16 and p53) and inflammatory factors (IL-6 and TNF-α) in the cell culture supernatant were significantly decreased (P<0.01). The expression of senescence-associated proteins (P16, P21, and P53) decreased (P<0.05, P<0.01). The protein expressions of NAMPT, SIRT1, PGC-1α, and FoxO1 were significantly up-regulated (P<0.05, P<0.01).ConclusionWenfei Huaxian decoction can alleviate senescence and inflammatory response damage of D-gal-induced LMSCs, and its mechanism may be related to the regulation of the NAMPT/SIRT1 signaling pathway.  
      关键词:Wenfei Huaxian decoction;lung mesenchymal stem cells;senescence;nicotinamide phosphoribosyltransferase/silent information regulator 1 (NAMPT/SIRT1) signaling pathway   
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    • 最新研究发现,血府逐瘀胶囊通过调控Notch1/Jagged1/Hes1信号通路,减少动脉粥样硬化小鼠主动脉斑块面积和脂质沉积,减轻炎症,抑制M1型巨噬细胞、促进M2型巨噬细胞的表达,为抗动脉粥样硬化治疗提供新策略。
      LIU Menghua, CHENG Xu, ZHAO Mengzhu, WEI Qiong, ZHANG Dongmei
      Vol. 30, Issue 12, Pages: 54-61(2024) DOI: 10.13422/j.cnki.syfjx.20240714
      摘要:ObjectiveTo investigate the mechanism of Xuefu Zhuyu capsules against atherosclerosis via regulating polarization of macrophages based on Notch1/jagged canonical Notch ligand 1(Jagged1)/Hes family BHLH transcription factor 1(Hes1) signaling pathway.MethodThe mouse models with atherosclerosis were prepared by feeding the mice with an ApoE-/- high-fat diet for four weeks, and they were randomly divided into the model group, Xuefu Zhuyu capsule group, and atorvastatin group. C57BL/6 mice were fed as a normal group. The Xuefu Zhuyu capsule group was intragastrically given Xuefu Zhuyu capsules (0.728 g·kg-1·d-1), and the atorvastatin group was intragastrically given atorvastatin tablet (6.07 mg·kg-1·d-1). The normal group and the model group were given equal volume of the deionized water by intragastric administration, and the intervention lasted for 12 weeks. Aortic plaque morphology was observed by hematoxylin-eosin (HE) staining, and aortic plaque area and lipid deposition were observed by oil red O staining. The positive expression levels of CD86 and CD206 in aortic tissue were detected by immunohistochemistry, and serum levels of tumor necrosis factor (TNF)-α, interleukin(IL)-1β, transforming growth factor (TGF)-β1, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). The relative mRNA expressions of inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), Notch1, Jagged1, and Hes1 in aortic tissue were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The relative protein expression of iNOS, Arg-1, Notch1, Jagged1, and Hes1 in aortic tissue was detected by Western blot.ResultCompared with the normal group, the model group had significant aortic plaque and lipid deposition, and the expression levels of pro-inflammatory cytokines TNF-α and IL-1β were increased (P<0.01). The expression level of anti-inflammatory cytokine TGF-β1 showed a downward trend, but the difference was not statistically significant. The mRNA and protein expressions of iNOS were increased (P<0.01). The protein expression of Arg-1 was decreased (P<0.01), and the mRNA expression of related pathway molecule Jagged1, as well as the protein expressions of Notch1, Jagged1, and Hes1 were increased in the model group (P<0.05, P<0.01). Compared with those in the model group, the plaque area and lipid deposition had a decreasing trend in the Xuefu Zhuyu capsule group, and the expressions of TNF-α and IL-1β showed a downward trend. The expression of TGF-β1 was increased (P<0.05), and the expression of macrophage marker CD86 was decreased. The mRNA and protein expressions of iNOS were decreased (P<0.01). The mRNA and protein expressions of Arg-1 were increased (P<0.05, P<0.01). Furthermore, the mRNA and protein expressions of Notch1, Jagged1, and Hes1 were decreased (P<0.01).ConclusionXuefu Zhuyu capsules can reduce aortic plaque area and lipid deposition in mice with atherosclerosis, alleviate inflammation, inhibit M1 macrophages, and promote the expression of M2 macrophages, and the mechanism may be related to the regulation of Notch1/Jagged1/Hes1 signaling pathway.  
      关键词:Xuefu Zhuyu capsules;atherosclerosis;macrophage polarization;Notch1 signaling pathway;inflammation   
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    • 最新研究发现,抵当陷胸汤通过激活PI3K/Akt信号通路,抑制足细胞凋亡,有效减缓糖尿病肾病发展。
      ZHANG Kejing, WANG Yueqi, CHU Quangen, CHU Jun
      Vol. 30, Issue 12, Pages: 62-69(2024) DOI: 10.13422/j.cnki.syfjx.20240139
      摘要:ObjectiveTo observe the protective effect of Didang Xianxiong decoction on the kidneys of diabetic rats, its regulation on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, and its influence on podocyte apoptosis and explore the mechanism of Didang Xianxiong decoction in improving diabetic nephropathy.MethodThe diabetic model was established by a single intraperitoneal injection of streptozotocin (STZ) solution of 55 mg·kg-1. The successfully replicated model rats were randomly divided into the model group, Didang Xianxiong decoction group (8.10 g·kg-1), Xiao Xianxiongtang group (4.05 g·kg-1), Didangtang group (4.05 g·kg-1), and alagebrium (ALT-711) group (3 mg·kg-1), with six rats in each group. In addition, six rats were included in the blank group. After continuous administration for eight weeks, hematoxylin-eosin (HE) staining was used to observe the pathological changes in rats' kidney tissue. Masson staining was used to observe the degree of collagen deposition. Periodic acid-Schiff (PAS) staining was used to observe basement membrane lesions, and immunohistochemistry was used to detect the expression of phosphorylation (p)-PI3K and p-Akt proteins in rats' kidney tissue. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to detect podocyte apoptosis. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of PI3K and Akt in rats' kidney tissue. Western blot was used to detect the protein expression of PI3K, p-PI3K, Akt, p-Akt, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), phosphorylation glycogen synthase kinase-3β (p-GSK-3β), and Caspase-3 in the kidney tissue.ResultCompared with the normal group, the model group had compensatory expansion of glomeruli, proliferation of mesangial cells, a large amount of collagen deposition in the mesangial stroma, thickening of the basement membrane, decreased mRNA expression of PI3K and Akt, and inhibition of PI3K and Akt protein phosphorylation (P<0.01). It also underwent enhanced apoptotic signaling, decreased expression of anti-apoptotic protein Bcl-2 (P<0.01), and increased expression of Bax, p-GSK-3β, and Caspase-3 (P<0.01). Compared with the model group, Didang Xianxiong decoction significantly improved kidney tissue pathology, increased mRNA expression of PI3K and Akt (P<0.01), significantly up-regulated phosphorylation levels of PI3K and Akt proteins (P<0.01) and Bcl-2 expression (P<0.01), downregulated the expression of Bax, p-GSK-3β, and Caspase-3 (P<0.01), and weakened podocyte apoptotic signaling.ConclusionDidang Xianxiong decoction may promote the activation of the PI3K/Akt signaling pathway, inhibit podocyte apoptosis, and thus slow down the progression of diabetic nephropathy.  
      关键词:diabetic kidney disease;Didang Xianxiong decoction;co-treatment of phlegm and stasis;phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway;podocyte apoptosis   
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    • 最新研究发现,南蛇藤提取物(COE)通过调节Lgr5/Wnt/β-catenin信号通路,促进胃类器官增殖分化,有望逆转胃癌前病变。
      ZHANG Xiaoze, ZHU Fangyuan, WEN Junsong, LIU Yanqing, ZHU Yaodong
      Vol. 30, Issue 12, Pages: 70-77(2024) DOI: 10.13422/j.cnki.syfjx.20240223
      摘要:ObjectiveThis study aims to investigate the mechanism in which Celastrus orbiculatus extract (COE) affects the proliferation and differentiation of gastric organoids and the expression of Lgr5 and thus reverses the precancerous lesions of gastric cancer (PLGC) by regulating the leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5)/Wingless (Wnt)/β-catenin signaling pathway based on a gastric organoid injury model.MethodGastric organoids were established based on stem cells of the mouse gastric gland. Gastric organoid injury models were constructed by treating gastric organoids with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 0.02 mg·L-1). Gastric organoid injury models were randomly divided into normal group, model group (0.02 mg·L-1 MNNG), low, medium, and high dose (5, 10, 20 mg·L-1) groups of COE, and Wnt inhibitor Dickkopf-related protein 1 (DKK1) (0.5 mg·L-1) group, and they were treated with respective agents for 24 h. The number and volume of gastric organoids under different drug concentrations were observed under a microscope. The viability of the gastric organoid injury models was detected by Methyl thiazolyl tetrazolium (MTT) assay. The morphology and pathology of gastric organoids were observed using Hematoxylin and Eosin (HE) staining. The expression levels of Lgr5, Mucin2 (MUC2), Mucin5AC (MUC5AC), Mucin6 (MUC6), Wnt, and β-catenin in gastric organoids under different drug concentrations were detected by Western blot (WB).ResultCompared with the normal group, the number, volume, and activity of gastric organoids in the model group were decreased (P<0.01), while the expressions of Lgr5, MUC2, Wnt, and β-catenin were significantly increased (P<0.01). The expressions of MUC5AC and MUC6 were significantly decreased (P<0.01). Compared with the model group, the number and volume of gastric organoids in the low, medium, and high dose groups of COE were all improved (P<0.01), and the vitality of gastric organoids was significantly enhanced (P<0.01). The effect was the most significant at a COE concentration of 20 mg·L-1 (P<0.01). The expressions of Lgr5 and MUC2 in the medium and high dose groups of COE were significantly reduced (P<0.01), while the expression of MUC5AC and MUC6 were significantly increased in the low, medium, and high dose groups of COE (P<0.05, P<0.01). Compared with the model group, Wnt inhibitors could promote the expression of MUC5AC and MUC6 in gastric organoids (P<0.05, P<0.01) and reduce the expression of MUC2, Wnt, and β-catenin. In addition, the combined use of COE at high concentrations and Wnt inhibitors could further promote this trend (P<0.01).ConclusionCOE inhibits the Wnt/β-catenin pathway by inhibiting the expression of Lgr5, MUC2, Wnt, and β-catenin and promoting the expression of MUC5AC and MUC6, thus promoting the proliferation and differentiation of gastric organoids and reversing the PLGC process.  
      关键词:Celastrus orbiculatus extract;precancerous lesions of gastric cancer;gastric organoid injury model;leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5)/Wingless (Wnt)/β-catenin signaling pathway   
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    • ZHANG Luning, LIU Lingling, JIANG Shengnan, WU Qifeng, YAN Guiming
      Vol. 30, Issue 12, Pages: 78-86(2024) DOI: 10.13422/j.cnki.syfjx.20240136
      摘要:ObjectiveTo investigate whether paeonol exerts a protective effect on mice with alcoholic liver injury by regulating the takeda G-protein-coupled receptor 5 (TGR5)/protein kinase A (PKA)/cAMP response binding element (CREB) signaling pathway mediated by Eubacterium.MethodC57BL/6 mice were randomly divided into five groups: normal group, model group, paeonol group (480 mg·kg-1), antibiotic group (Abs group), and antibiotic + paeonol group. Lieber-DeCarli liquid was used to feed C57BL/6 mice on the second day of modeling for 10 days. The blood lipids, liver function, inflammatory factors, and oxidative stress levels in mice were measured. Hematoxylin-eosin staining (HE) and oil red O staining were used to observe the morphological changes and fat accumulation in liver tissue. 16S rDNA sequencing was used to detect the diversity of intestinal microbiota in the blank, model, and paeanol groups. Western blot was used to detect the effect of paeonol on the expression levels of protein related to the signaling pathway of atresia band protein 1 (ZO-1), Claudin-1, and TGR5/PKA/CREB in mouse ileal tissue.ResultCompared with those in the blank group, the blood lipids, liver function, oxidative stress levels, and the expression of inflammatory factors in the model group increased (P<0.01), and the liver fat vacuoles were obvious. The ileal mucosa was seriously damaged, and the protein contents of ZO-1, Claudin-1, and TGR5/PKA/CREB in the ileal tissue decreased significantly (P<0.01). The intestinal microbiota changed, and the proteobacteria phylum increased significantly. The ratio of Bacteroidetes to Firmicutes decreased. The relative abundance of Dubosiella newyorkensis, Lactobacillus, Bifidobacterium, and other genera decreased, while the relative abundance of Escherichia-Shigella, Morganella, Providencia, and Proteus increased significantly. Compared with the model group, paeonol significantly reduced the blood lipids, liver function, oxidative stress levels, and expression of inflammatory factors in mice with alcohol diet-induced liver injury (P<0.05), decreased liver fat vacuoles, improved and restored the ileal intestinal barrier, and restored the normal structure of hepatocytes and ileal cells. The intestinal microbiota disorder caused by alcohol was improved, and the relative abundance of beneficial bacteria such as Eubacterium spp. was increased. The protein expression levels of ZO-1, Claudin-1, and TGR5/PKA/CREB in ileal tissue were increased (P<0.05).ConclusionPaeonol has a protective effect on alcoholic liver injury in mice, and the mechanism of action is achieved by regulating the Eubacterium-mediated TGR5/PKA/CREB signaling pathway to ensure anti-inflammatory effect and improve the intestinal barrier.  
      关键词:paeonol;acute alcoholic liver injury;inflammation;takeda G-protein-coupled receptor 5 (TGR5)/protein kinase A (PKA)/cAMP response binding element (CREB) signaling pathway;Eubacterium   
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    • 最新研究发现,加味当归贝母苦参丸能显著抑制H22肝癌小鼠肿瘤生长,并通过调节T细胞免疫活性,为联合免疫检查点抗体治疗肝癌提供实验依据。
      MA Xiaojie, LIU Ben, WANG Lei, LI Hailong, LI Yaling, LI Changtian, SHE Yali
      Vol. 30, Issue 12, Pages: 87-96(2024) DOI: 10.13422/j.cnki.syfjx.20232224
      摘要:ObjectiveTo explore the effects of modified Danggui Beimu Kushen pills on tumor growth and T-cell subsets in H22 hepatocellular carcinoma-bearing mice and to provide an experimental basis for the treatment of hepatocellular carcinoma with modified Danggui Beimu Kushen pills combined with immune checkpoint antibodies.MethodA H22 hepatocellular carcinoma-bearing mouse model was established. The modeled mice were randomized into model, cisplatin, low- (4 g·kg-1·d-1), medium- (8 g·kg-1·d-1), and high-dose (16 g·kg-1·d-1) modified Danggui Beimu Kushen pills groups. After continuous administration for 14 days, the mice were sacrificed on day 15. The tumor volume was measured on days 0, 4, 8, 12, 15 of drug administration. Tumors were weighed and thymus index and spleen index were calculated. Spleen lymphocytes were co-cultured with H22 hepatoma cells, and the tumor cell-killing rate was detected by the cell counting kit-8 (CCK-8). Real-time polymerase chain reaction was carried to determine the mRNA levels of programmed cell death protein-1 (PD-1) and lymphocyte activation gene-3 (LAG-3) in spleen and tumor tissues. The number of CD4+ and CD8+ T cells and the expression of PD-1 and LAG-3 were detected by immunohistochemistry (IHC).ResultOn day 8 of drug administration, tumor volumes in all treatment groups decreased compared with that in the model group. On day 15, both tumor volume and tumor weight were significantly lower in the treatment groups than in the model group (P<0.01), with the cisplatin group showing the most pronounced reduction. Compared with the model and cisplatin groups, medium- and high-dose modified Danggui Beimu Kushen pills increased the thymus index (P<0.01). Compared with the model group, all treatment groups showed increased spleen index (P<0.05, P<0.01), with the cisplatin group showing the most significant increase. Compared with the model and cisplatin groups, all the groups of modified Danggui Beimu Kushen pills demonstrated increased number of CD4+ and CD8+ T cells and tumor cell-killing rate in the spleen and tumor tissues (P<0.01) and down-regulated mRNA and protein levels of LAG-3 (P<0.05, P<0.01). The high-dose group of modified Danggui Beimu Kushen pills had lower mRNA level of PD-1 in the tumor tissue than the model and cisplatin groups (P<0.01).ConclusionModified Danggui Beimu Kushen pills may promote the proliferation and tumor microenvironment infiltration of CD4+ and CD8+ T cells in H22 tumor-bearing mice by down-regulating LAG-3 expression, thereby improving T-cell immune activity and inhibiting tumor growth. This study provides an experimental basis for the combination of modified Danggui Beimu Kushen pills and immune checkpoint antibodies in the treatment of hepatocellular carcinoma.  
      关键词:modified Danggui Beimu Kushen pills;hepatocellular carcinoma;lymphocyte activation gene-3 (LAG-3);programmed cell death protein-1 (PD-1);tumor-infiltrating lymphocyte (TIL)   
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    • 最新研究揭示,益气养血方联合西药治疗再生障碍性贫血,通过分析免疫学指标,可预测血象升高效果,为治疗方案调整提供科学依据。
      ZHANG Yaoyin, ZHANG Chaochang, HE Jiaqi, WANG Wenru, DING Yubin, WANG Jinhuan, XU Ruirong, DI Haixia, WAN Jiangwei, LIU Qifeng, WANG Haixia, SUN Antao, TANG Xudong
      Vol. 30, Issue 12, Pages: 97-104(2024) DOI: 10.13422/j.cnki.syfjx.20241593
      摘要:ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia (AA) and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters, thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen.MethodA retrospective study was conducted, involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters [including hemoglobin (HGB), white blood cell count (WBC), platelet (PLT), and absolute neutrophil count (ANC)] after 6 months of treatment. One group had the elevation <50%, and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups.Result① Compared with the group with HGB elevation<50%, the group with HGB elevation≥50% showed elevated level of CD3+ human leukocyte antigen-DR (HLA-DR)+ and increased proportion of patients with T-helper cell type 2 (Th2)<5%, CD8+≥50%, and CD3+HLA-DR+≥9% before treatment (P<0.05, P<0.01). The multivariate Logistic regression analysis showed that CD8+≥50% before treatment was the independent influencing factor for HGB elevation ≥50% [odds ratio (OR)=12.000, 95% confidence interval (CI) 2.218, 64.928, P<0.01]. ② Compared with the group with WBC elevation<50%, the group with WBC elevation≥50% showed increased proportion of patients with CD3+HLA-DR+<6% and T-box transcription factor (T-bet)≥200% before treatment (P<0.05). The multivariate Logistic regression analysis showed that CD3+HLA-DR+<6% (OR=2.998, 95%CI 1.036, 8.680, P<0.05) and T-bet≥200% (OR=3.634, 95%CI 1.076, 12.273, P<0.05) before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%, the group with PLT elevation≥50% presented lowered Th1 and CD3+HLA-DR+ levels and increased proportion of patients with Th1<12%, CD4+≥6%, and CD3+HLA-DR+<5% before treatment (P<0.05, P<0.01). The multivariate Logistic regression analysis showed that CD3+HLA-DR+<5% before treatment was the independent influencing factor for PLT elevation≥50% (OR=16.190, 95%CI of 3.430 to 76.434, P<0.01). ④ Compared with the group with ANC elevation<50%, the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment.ConclusionAs for the AA patients with rapid elevation in HGB, Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3+HLA-DR+≥9%, especially those with CD8+≥50%. As for the AA patients with rapid elevation in WBC, the therapy was particularly effective in the patients with CD3+HLA-DR+<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT, the therapy was particularly effective in the patients with Th1<12% and CD4+≥6%, especially those with CD3+HLA-DR+<5%.  
      关键词:aplastic anemia;Yiqi Yangxue prescription;blood routine;immunity;prediction   
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    • 江苏省中医院研究显示,中药通脑饮能显著改善急性脑梗死患者脑血流灌注,提高临床疗效,为缺血性脑卒中治疗提供新方案。
      JI Lianhong, LIU Peian, LI Li, LI Yunze, ZHU Qing, TANG Xiaogang, JIANG Hui, LIU Yongkang, YUAN Cuiping, LI Wenlei, ZHU Yuan, WU Minghua
      Vol. 30, Issue 12, Pages: 105-111(2024) DOI: 10.13422/j.cnki.syfjx.20241491
      摘要:ObjectiveTo investigate the changes in cerebral blood perfusion in patients with acute cerebral infarction after taking Tongnaoyin, a traditional Chinese medicine, based on head and neck computed tomography (CT) angiography (CTA) combined with brain CT perfusion imaging (CTP).MethodA total of 240 patients with cerebral infarction of phlegm and blood stasis syndrome treated in Jiangsu Province Hospital of Traditional Chinese Medicine from March 2018 to September 2023 were randomly divided into a control group (99 cases) and a Tongnaoyin group (141 cases). Based on the guidelines, the control group was treated with conventional treatment such as anti-aggregation, anticoagulation, lipid-lowering and plaque stabilization, brain protection, and supportive treatment. The Tongnaoyin group was treated with Tongnaoyin of 200 mL in warm conditions in the morning and evening on the basis of the control group. Both groups underwent CTA combined with CTP within 24 hours after admission, and they were reexamined by CTA and CTP in the sixth month after admission. The degree of intracranial artery stenosis was determined according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. The relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), mean transit time (MTT), and time to peak (TTP) of the lesion area before and after treatment were compared. The adverse outcomes of the two groups within six months after discharge were compared.ResultCompared with the group before treatment, the degree of vascular stenosis in the Tongnaoyin group was significantly reduced, and the difference was statistically significant (Z=105.369,P<0.05). Compared with the control group after treatment, the improvement rate of vascular stenosis in the Tongnaoyin group was higher (χ2=84.179,P<0.01), and the curative effect was better.After treatment, the rCBV and rCBF of patients in the Tongnaoyin group were significantly increased, and the difference was statistically significant (P<0.01). MTT and TTP showed a trend of shortening, but the difference was not statistically significant. There was no statistically significant difference in rCBV, rCBF, MTT, and TTP in the control group. Compared with those in the control group after treatment, the rCBV and rCBF in the Tongnaoyin group were significantly increased, while MTT and TTP were significantly reduced (P<0.01). After six months of discharge, the risk of poor prognosis in the Tongnaoyin group was significantly reduced compared with the control group (P<0.05).ConclusionTongnaoyin has a good effect on improving cerebral blood perfusion in patients with acute cerebral infarction. It can be used as an effective supplement for the conventional treatment of ischemic stroke to improve clinical efficacy.  
      关键词:acute cerebral infarction;Tongnaoyin;computed tomography angiography(CTA);computed tomography perfusion imaging(CTP);hemodynamics   
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    • 最新研究显示,肝豆灵(GDL)能有效改善肝豆状核变性(WD)患者的铜、脂代谢水平,具有较高的临床安全性和应用价值。同时,肝脂肪变性预测模型能准确反映WD患者的脂代谢异常程度。
      LIANG Feng, DONG Ting, TIAN Liwei, ZHAO Chenling, GUO Ruixue, WANG Qiong, ZHANG Yuqi
      Vol. 30, Issue 12, Pages: 121-128(2024) DOI: 10.13422/j.cnki.syfjx.20241592
      摘要:ObjectiveTo investigate the clinical efficacy of Gandouling tablet (GDL) on abnormal lipid metabolism in Wilson's disease (WD) and the correlation between the prediction model of hepatic steatosis and the related indexes of lipid metabolism in WD.MethodA total of 86 patients with abnormal lipid metabolism in WD were selected. The 24-hour urine copper, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum triglyceride (TG), total cholesterol (TC), apolipoprotein B (ApoB), low density lipoprotein cholesterol (LDL-C), bile acid (BA), γ-glutamyl transferase (GGT), prediction model of hepatic steatosis [hepatic steatosis index (HSI) and Zhejiang University index (ZJU index)], ultrasonic attenuation coefficient imaging (ATT), and traditional Chinese medicine (TCM) syndrome score were statistically analyzed before treatment. Pearson correlation test was used to analyze the correlation between TG, TC, LDL-C, ApoB, ALT, AST, ALT/AST, BA, GGT, TCM syndrome score, ATT, and HIS and ZJU. The patients were divided into an observation group and a control group by random number table method, with 43 cases in each group. The observation group was treated with GDL combined with sodium dimercaptopropane sulfonate (DMPS), while the control group was only treated with DMPS as a control. After six courses of treatment, 24-hour urine copper, TC, TG, LDL-C, ApoB, HSI, ZJU, ATT, TCM syndrome score, and clinical efficiency before and after treatment were observed and compared between the two groups. The correlation between HSI and ZJU and serum TC, TG, LDL-C, ApoB, ALT, AST, ALT/AST, BA, GGT, TCM syndrome scores, and ATT was analyzed.ResultPearson correlation analysis showed that serum TC (r = 0.811), TG (r = 0.826), LDL-C (r = 0.802), ApoB (r = 0.820), ALT (r = 0.497), ALT/AST (r = 0.826), TCM syndrome score (r = 0.716), and ATT (r = 0.736) were positively correlated with HSI (P<0.01), while AST, BA, and GGT had no significant correlation with HSI. TC (r = 0.718), TG (r = 0.765), LDL-C (r = 0.667), ApoB (r = 0.699), ALT/AST (r = 0.403), TCM syndrome score (r = 0.666), and ATT (r = 0.684) were positively correlated with ZJU (P<0.01). ALT, AST, BA, and GGT had no significant correlation with ZJU. The total effective rate of the observation group was 86.05 (37/43), and that of the control group was 72.09% (31/43). The total effective rate of the observation group was higher than that of the control group (Z = -2.301, P<0.05). After treatment, the 24-hour urine copper of the two groups increased significantly. The levels of TC, TG, LDL-C, and ApoB were significantly decreased, and the HSI, ZJU, and ATT were significantly decreased (P<0.01). Compared with those in the control group after treatment, the above indexes improved better in the observation group (P<0.05, P<0.01).ConclusionGDL can effectively improve the level of copper and lipid metabolism in patients with WD, with high clinical safety and good clinical application value. The prediction model of hepatic steatosis can effectively reflect the degree of abnormal lipid metabolism in WD.  
      关键词:Wilson's disease;abnormal lipid metabolism;Gandouling Tablet;prediction model;Ultrasound attenuation coefficient imaging   
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    • 最新研究显示,生脉散联合多黏菌素B治疗耐碳青霉烯类革兰阴性杆菌感染脓毒症合并重度急性呼吸窘迫综合征,能显著提高细菌清除率,降低炎症因子水平,调节免疫状态,改善患者短期预后。
      ZHANG Yu, CHEN Qingfeng, YIN Xi, WANG Xiaoyue, DENG Zhaokui, SHI Shan, LU Xiaohui
      Vol. 30, Issue 12, Pages: 129-135(2024) DOI: 10.13422/j.cnki.syfjx.20232226
      摘要:ObjectiveTo observe the clinical efficacy of Shengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome.MethodA total of 90 patients suffering from carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome were randomly divided into a control group and an observation group, with 45 cases in each group. The control group was treated with polymyxin B, and the observation group was treated with Shengmaisan combined with polymyxin B. The treatment course of both groups was seven days. The infection-related indicators [white blood cell (WBC) count, procalcitonin (PCT), neutrophil apolipoprotein (HNL)], inflammatory factors [interleukin-6 (IL-6), serum chemokine ligand 2 (CXCL2)], and T lymphocyte subpopulations (CD3+, CD4+, CD8+, and CD4+/ CD8+ value), acute physiological and chronic health Ⅱ (APACHE Ⅱ) score before and after treatment, as well as bacterial clearance rate and 28-day survival rate after treatment were observed.Result① The experiment was completed, and 81 cases were included, including 41 cases in the observation group and 40 cases in the control group. The general data of the two groups were comparable. ② The bacterial clearance rate of the observation group and the control group was 75.6% (31/41) and 52.5% (21/40), respectively, and the observation group was higher than the control group (χ2=4.7, P<0.05). ③ The WBC count, PCT, HNL, IL-6, CXCL2, and APACHE Ⅱ scores of the observation group and the control group all decreased after treatment (P<0.05). Except for the WBC count, the PCT, HNL, IL-6, CXCL2, and APACHE Ⅱ scores of the observation group were lower than those of the control group (P<0.05). ④ The values of CD3+, CD4+, and CD4+/CD8+ in the observation group were increased after treatment (P<0.05), and CD8+ was decreased (P<0.05). In the control group, only CD3+ value was increased (P<0.05). The values of CD3+, CD4+, and CD4+/CD8+ in the observation group were higher than those in the control group, and the value of CD8+ was lower than that in the control group (P<0.05). ⑤ The 28-day survival rate in the observation group was higher than that in the control group (χ2=4.3, P<0.05).ConclusionShengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome can better clear bacteria, control infection, reduce the level of inflammatory factors, regulate the immune state of the body, and improve the short-term prognosis.  
      关键词:sepsis;severe respiratory distress syndrome;carbapenem-resistant gram-negative bacilli;Shengmaisan;polymyxin B;clinical randomized controlled trial   
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    • Textual Research and Clinical Application of Chaihu Guizhi Ganjiangtang AI导读

      最新研究发现,柴胡桂枝干姜汤作为经典名方,其临床应用广泛,对消化系统、呼吸系统等疑难杂症具有显著疗效。通过对古籍文献的深入挖掘,为该方的临床应用和新药研发提供了科学参考。
      WANG Xuejie, LIANG Lyuyuan, CAO Jialei, LIU Lan, LI Weixiao, WANG Yiping, WEI Bingqi, MA Bingxiang, SHI Wenli
      Vol. 30, Issue 12, Pages: 136-146(2024) DOI: 10.13422/j.cnki.syfjx.20240419
      摘要:Chaihu Guizhi Ganjiangtang with a definite clinical effect has been widely used and recorded since the Han Dynasty. As a classic prescription of Chaihu classic formula praised by doctors ofsuccessive generations, it has been included in the Ancient Classic Prescription Catalogue (Second Batch): Han Medicine published by the National Administration of Traditional Chinese Medicine in August 2023. We carried out a bibliometric study involved 34 ancient books of traditional Chinese medicine, with 37 records including the name and composition of the prescription. This paper summarizes the source name, composition, original medicinal plant, dose, preparation method, usage, ancient and modern indications, and clinical application of Chaihu Guizhi Ganjiangtang. The results of textual research show that Chaihu Guizhi Ganjiangtang is derived from the Treatise on Febrile Diseases (Shanghanlun) written by ZHANG Zhongjing in the Han dynasty, and the original plants of medicines in this prescription are basically the same in ancient and modern times. Most records about the doses in ancient books are consistent with those in the Treatise on Febrile Diseases (Shanghanlun). The efficacy of Chaihu Guizhi Ganjiangtang is to harmonize lesser yang and resolve water retention by warming. This prescription was used to treat a variety of diseases, especially those caused by disturbance of Qi movement in the greater Yang and lesser Yang. It is now mainly used to treat the diseases in the digestive system, respiratory system, dermatology, nervous system, etc., being effective for difficult and complicated diseases. Through the excavation and combing of the ancient records of Chaihu Guizhi Ganjiangtang, this paper clarifies the key information, providing a reference for the clinical application of classical prescriptions and the development of new drugs.  
      关键词:Chaihu Guizhi Ganjiangtang;classical prescription;textual research;ancient and modern application   
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    • 《证治准绳》养胃汤研究取得新进展,系统梳理历史源流,考证方义组成,为现代临床应用提供参考。
      LIANG Lyuyuan, CAO Jialei, WANG Yiping, GENG Mengmeng, ZHU Lujun, WEI Wenxin, WEI Bingqi, SHI Wenli, MA Bingxiang
      Vol. 30, Issue 12, Pages: 147-157(2024) DOI: 10.13422/j.cnki.syfjx.20240418
      摘要:The classical prescription Yangweitang, derived from Zhengzhi Zhunsheng, is specialized in treating syndromes of chill and fever due to exogenous pathogens, inner-cooling, and malaria, and it has been included in the Catalogue of Ancient Classical Formulas (the First Batch) published by the National Administration of Traditional Chinese Medicine (TCM) in 2018. Through bibliographical research, the relevant ancient books and modern documents were systematically sorted out, and it was found that there were many prescriptions related to the Yangweitang from Zhengzhi Zhunsheng. They were interwoven with Yangweitang from Zhengzhi Zhunsheng and widely used in clinical practice. In order to clarify their history and evolution, this paper combed the historical origin of Yangweitang and its related prescriptions and conducted textual analysis on key information such as semantic composition, herb origin, processing method, and efficacy. A total of 896 pieces of data on Yangweitang from Zhengzhi Zhunsheng were collected. 26 pieces of effective data were included after the screening, involving 17 ancient TCM books. Then, a total of 28 pieces of data on prescriptions related to the Yangweitang from Zhengzhi Zhunsheng were included, involving 23 ancient TCM books for reference. The textual analysis showed that Yangweitang originated from the Renshen Yangweitang recorded in Taiping Huimin Heji Jufang in the Song dynasty. Based on the original formula, medical experts from later generations have modified it into many different versions. A comparative analysis showed that Yangweitang from different generations had similar compositions, and the herb origin and processing method were basically clear. The recommended prescriptions are as follows: 37.3 g of Pinelliae Rhizoma Praeparatum Cum Alumine, Magnoliae Officinalis Cortex(fried with ginger juice), and frying with rice water Atractlodis Rhizoma, 27.98 g of Citri Exocarpium Rubrum, 18.65 g of Pogostemon cablin leaf, Tsaoko Fructus, Poria, and Ginseng Radix et Rhizoma, and 9.33 g of Glycyrrhizae Radix et Rhizoma. They could be ground into a coarse powder, with 14.92 g for every dose, and they could be orally taken after being decocted with 450 mL of water, 7 g of fresh ginger, and 2 g of Mume Fructus to 270 mL in warm conditions. Yangweitang from Zhengzhi Zhunsheng has the effect of warming the middle and releasing the external, and it can treat many syndromes including spleen and stomach disharmony caused by chill and fever due to exogenous pathogens and inner-cooling, as well as all kinds of malaria. Modern clinical applications mainly focus on chronic atrophic gastritis and other digestive system diseases.  
      关键词:classic prescription;Yangweitang;textual analysis;Zhengzhi Zhunsheng;key information;Xiangsha Yangweitang;Huoxiang Yangweitang   
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    • 茵陈蒿汤,源自《伤寒论》,是清热利湿退黄的经典名方。通过文献计量学方法,对36部中医古籍的801条数据进行分析,确定了茵陈蒿汤的现代用量及用法。其在肝胆系统、皮肤系统、内分泌系统、消化系统等领域具有广泛应用,尤其在黄疸、黄疸型肝炎、乙型病毒性肝炎治疗中显示出独特优势。本研究挖掘梳理古籍文献,为经典名方的临床应用及新药研发提供了科学参考。
      HE Qing, LIANG Lyuyuan, CAO Jialei, BIAN Yulu, WEI Bingqi, HUANG Chongyi, WAN Hejia, MA Bingxiang, SHI Wenli
      Vol. 30, Issue 12, Pages: 158-165(2024) DOI: 10.13422/j.cnki.syfjx.20240516
      摘要:Yinchenhao Tang has definite clinical efficacy. It has been inherited and documented since the ancestor of Shanghanlun in the Eastern Han dynasty and is a classical formulas for clearing away heat, promoting diuresis, and eliminating jaundice adopted by medical experts of successive generations. It has been included in the Catalogue of Ancient Classical Formulas (the Second Batch of Han Medicine) published by the National Administration of Traditional Chinese Medicine (TCM) in 2023. By means of bibliometrics, 801 pieces of ancient literature data related to Yinchenhao Tang were collected, and 36 pieces of effective data were selected, involving 36 ancient books of TCM. The origin, name, composition, efficacy, formula and meaning analysis, drug origin, dosage, preparation method and usage, indications, and modern clinical application of Yinchenhao Tang were analyzed. It was suggested that the modern dosage and application of Yinchenhao Tang should be as follows: The 82.8 g of Artemisiae Scopariae Herba, 12.6 g of Gardeniae Fructus, and 27.2 g of Rhei Radix et Rhizoma. The formulas was prepared by firstly adding 2 400 mL of water into Artemisiae Scopariae Herba and boiling it to about 1 200 mL, then adding Gardeniae Fructus and Rhei Radix et Rhizoma to boil it for 600 mL, and removing the residue. It could be orally taken for 200 mL each time in warm conditions, three times a day. Yinchenhao Tang has the effect of clearing away heat, promoting diuresis, and eliminating jaundice, and it mainly treats symptoms of hygropyretic jaundice. In the formulas, Yinchenhao Tang is the monarch drug, which is mainly to remove dampness and jaundice. Gardeniae Fructus is the ministerial drug, which is mainly responsible for clearing the triple energizer and facilitating urination. Rhei Radix et Rhizoma is an adjuvant, mainly responsible for clearing away heat and eliminating jaundice. The modern application of this formulas involves the hepatobiliary system, skin system, endocrine system, digestive system, etc., and it has more advantages in treating jaundice, icteric hepatitis, and hepatitis B. In this study, the ancient literature related to Yinchenhao Tang was sorted out to determine its key information, so as to provide a scientific reference for clinical application of classic formulas and new drug development.  
      关键词:Yinchenhao Tang;classic formulas;literature research;ancient and modern application;key information   
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    • 最新研究揭示了天元芷通方入脑成分及其脑内分布特征,为头痛治疗药物成分选择和药效机制研究提供了重要参考。
      CHENG Yi, LAN Qun, WU Bingyu, WANG Jinyu, LIU Dewen, TONG Yan
      Vol. 30, Issue 12, Pages: 166-172(2024) DOI: 10.13422/j.cnki.syfjx.20240661
      摘要:ObjectiveTo investigate the brain absorption components of Tianyuan Zhitong prescription and their distribution based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), desorption electrospray ionization mass spectrometry imaging(DESI-MSI) and hyperspectral imaging techniques.MethodTen BALB/c mice were randomly divided into blank group(n=3) and administration group(n=7), the administration group was gavaged with 0.3 mL of Tianyuan Zhitong prescription liquid at a concentration of about 5 g·mL-1 of the raw material, and the blank group was gavaged with an equal volume of normal saline, and the whole brain of the mice were taken for the preparation of tissue homogenates and frozen sections, respectively. The tissue homogenates were qualitatively analyzed by UPLC-Q-TOF-MS for the brain absorption components in positive and negative ion modes, frozen sections were used for imaging to observe the distribution of these components in the brain. Cytoviva dark-field enhancement microscope was used to perform hyperspectral imaging scanning on the brain sections of mice from each group, and the scattered light data of at least 1 000 pixels in the visible-near-infrared(400-1 000 nm) band in the microscopic field of view were collected and average spectrum were created, which were used to compare the components in the brain tissues of mice from the blank and administration groups.ResultA total of 27 brain absorption components of Tianyuan Zhitong prescription were identified by UPLC-Q-TOF-MS, including 10 organic acids, 5 glycosides, 4 alkaloids, 1 phenol, 4 flavonoids, 2 phthalides and 1 other compound, which were mainly derived from Gastrodiae Rhizoma, Chuanxiong Rhizoma, vinegar-processed Corydalis Rhizoma, Ziziphi Spinosae Semen and processed Morindae Officinalis Radix. A total of 14 components were identified by mass spectrometry imaging, of which ferulic acid, tetrahydropalmatine and N-methyl dehydroberberine were mainly distributed in the cerebral cortex, vitamin B5, vemonoic acid and ricinoleic acid were mainly distributed in the hypothalamus, elemicin, octadecenic acid and octadecanoic acid were mainly distributed in the cortex and hypothalamus, while senkyunolide B, ligustilide, linoleic acid, 9,12-octadecadienoyl ethyl ester and spinosin were distributed in most regions of the brain tissues. Hyperspectral imaging showed that in the visible-near-infrared band range, the average spectrum of the brain tissues of mice in the administration group was significantly red-shifted, indicating that there were differences in the physical properties or contents of the chemical components in the brain between mice in the blank group and those in the administration group, and further verified the results of mass spectrometry imaging.ConclusionThrough the combination of UPLC-Q-TOF-MS and imaging techniques, the pharmacodynamic components of Tianyuan Zhitong prescription in the treatment of headache and the regional characteristics in brain tissue are clarified, which can provide reference for the selection of the index components of the research on the quality standard of this prescription and the research on the mechanism of the pharmacological effect.  
      关键词:Tianyuan Zhitong prescription;brain absorption components;intracerebral distribution;desorption electrospray ionization mass spectrometry imaging(DESI-MSI);hyperspectral imaging;ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)   
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    • 在胶质瘤治疗领域,科研团队成功制备了一种共载榄香烯和卡巴他赛的双靶向阳离子脂质体,通过体外药效学试验,揭示了其增强抗胶质瘤疗效的优势及作用机制,为提高治疗效果、减少不良反应提供了新策略。
      YIN Liyan, WANG Rongrong, LI Jie, XIE Tian
      Vol. 30, Issue 12, Pages: 173-184(2024) DOI: 10.13422/j.cnki.syfjx.20230961
      摘要:ObjectiveTo investigate whether elemene(ELE) enhances the anti-glioma efficacy of cabazitaxel(CTX), and prepare a double-targeted cationic liposome(LIP) co-loaded with ELE/CTX for the treatment of glioma, and to achieve the effect of increasing the efficacy and reducing the adverse reactions. Pharmacodynamic tests in vitro were performed to explore the advantages and mechanism of its preparation.MethodELE/CTX@LIP was prepared by high speed shear combined with probe ultrasound, the particle size and potential were characterized by nano-particle size potentiometer, and high performance liquid chromatography(HPLC) was used to determine the encapsulation efficiency and drug loading capacity of CTX/ELE. The cytotoxicity of ELE/CTX in vitro was detected by cell proliferation and activity assay(CCK8). JMP Pro 16 software was used to optimize the process parameters of ELE/CTX@LIP based on encapsulation efficiency. The optimal cationic material type, content and ratio were screened by in vitro cytotoxicity and in vitro cell uptake, on this basis, the dual-targeted cationic liposome T7/arginine glycine aspartate tripeptide sequence(T7/cRGD)-ELE/CTX@CLIP was prepared, the stability of morphology and particle size were characterized, and the effect of T7/cRGD-ELE/CTX@CLIP on the apoptosis inducing ability and cell cycle regulation ability of glioma cells was analyzed by cell cycle and apoptosis.ResultELE/CTX showed stronger anti-glioma activity on C6 and RG2 cells. The results of in vitro cytotoxicity and in vitro cell uptake showed that the amount of cationic material was 0.10% of the total content. The optimum ratio of T7, cRGD and phospholipids was 1∶1∶50. T7/cRGD-ELE/CTX@CLIP[1,2-dilinoleyloxy-3-dimethylaminopropane(Dlin-MC3-DMA)] and T7/cRGD-ELE/CTX@CLIP[1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000(DMG-PEG2000)] showed multi-level spherical nanostructures with particle sizes of 146.0, 111.3 nm, respectively, and were stable in serum. In vitro cytotoxicity results showed that T7/cRGD-ELE/CTX@CLIP had higher cytotoxicity to glioma cells than single-targeted liposomes or dual-targeted non-cationic liposomes. T7/crGD-ELE/CTX@CLIP affected the apoptosis and cycle of glioma cells, the results showed that ELE/CTX combined with liposomes could more effectively activate the apoptosis channel and inhibit the proliferation of glioma cells, and the use of T7/cRGD short peptide and cation modification enhanced the ability of apoptosis induction. ELE/CTX could effectively block glioma cell cycle at G2/M phase, and the effect was enhanced after T7/cRGD targeted modification.ConclusionELE can enhance the anti-glioma effect of CTX. The preparation parameters of ELE/CTX@LIP are stable and feasible. Combined with the in vitro efficacy test, the anti-glioma mechanism of T7/cRGD-ELE/CTX@CLIP is preliminarily revealed.  
      关键词:dual-targeted;cationic liposomes;glioma;elemene;cabazitaxel;synergism;process optimization   
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    • Effect of Cannabidiol on Pulmonary Fibrosis Analyzed by UPLC-Q-TOF-MS AI导读

      最新研究发现,大麻二酚通过调节亚油酸代谢等途径,对肺纤维化具有显著缓解作用,为肺纤维化治疗提供了新思路。
      SUN Mengdi, ZHANG Feiyu, YANG Huicong, WANG Yu, CHEN Pingping, LU Fang, LIU Shumin
      Vol. 30, Issue 12, Pages: 185-193(2024) DOI: 10.13422/j.cnki.syfjx.20240662
      摘要:ObjectiveTo investigate the mechanism of anti-pulmonary fibrosis of cannabidiol by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS).MethodSD rats were randomly divided into blank group, model group, prednisone group(3.15 mg·kg-1) and cannabidiol low, medium and high dose groups(12, 36, 108 mg·kg-1), with 8 rats in each group. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin(5 mg·kg-1), which was administered continuously for 28 days after successful modeling. The pathological changes of rat lung tissue were observed, and enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of matrix metalloproteinase-7(MMP-7), type Ⅱ alveolar cell surface antigen(KL-6), pulmonary surfactant-associated protein A(SP-A) and SP-D in serum. The expression levels of type Ⅰ collagen(Col-Ⅰ) and fibronectin(FN) in lung tissues were detected by immunohistochemistry, and the expression of mucin 5 subtype AC(MUC5AC) was detected by immunofluorescence. UPLC-Q-TOF-MS was used to search for potential biomarkers and related metabolic pathways of cannabidiol in treating pulmonary fibrosis.ResultCompared with the blank group, there were a large number of inflammatory cell infiltration and continuous fibrosis lesions in the lung tissue of rats in the model group. Compared with the model group, the inflammatory infiltration and blue collagen deposition in the lung tissue of rats in the prednisone and cannabidiol groups were reduced. Compared with the blank group, the expressions of MMP-7, KL-6, SP-A and SP-D in serum of the model group were significantly increased(P<0.01), while the expressions of MMP-7, KL-6, SP-A and SP-D in the prednisone and cannabidiol high dose groups were significantly decreased by comparing with the model group(P<0.05, P<0.01). Compared with the blank group, the expression levels of Col-Ⅰ and FN in the lung tissues of the model group were significantly increased, and the fluorescence intensity of MUC5AC was significantly increased(P<0.01). Compared with the model group, the expression levels of Col-Ⅰ and FN in the lung tissues of the prednisone and cannabidiol high dose groups were significantly decreased(P<0.05, P<0.01), and the expression of MUC5AC was significantly decreased(P<0.01). Compared with the blank group, a total of 18 differential compounds were screened out in the model group, which could be used as potential biomarkers, and cannabidiol could call back 16 of them, mainly involving 4 metabolic pathways(linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, and niacin and niacinamide metabolism). Compared with the blank group, the relative contents of potential biomarkers arachidonic acid and linoleic acid were significantly increased in the model group(P<0.05, P<0.01), while the relative contents of 5,6-EET, L-tyrosine and niacinamide were significantly decreased(P<0.01). Compared with the model group, cannabidiol could significantly reduce the relative contents of arachidonic acid and linoleic acid, and significantly increase the relative contents of 5,6-EET, L-tyrosine and niacinamide(P<0.01).ConclusionCannabidiol has an intervention and remission effect on pulmonary fibrosis, and its mechanism may be related to linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, niacin and niacinamide metabolism.  
      关键词:cannabidiol;pulmonary fibrosis;metabolomics;inflammation;immunity;ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)   
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    • WANG Huanhuan, CHANG Mengli, LI Yu, ZHANG Fengrong, XU He, ZHANG Yi, TANG Shihuan
      Vol. 30, Issue 12, Pages: 194-202(2024) DOI: 10.13422/j.cnki.syfjx.20232441
      摘要:ObjectiveBased on the integrated strategy of "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis", this study aims to explore and analyze the prescriptions and medical cases for treating tremors in traditional Chinese medicine (TCM), predict their efficacy, and obtain the core prescriptions for treating tremors in TCM, providing references for clinical application and new drug development.MethodThe Chinese Medicine Prescription Database and the China National Knowledge Infrastructure (CNKI) were searched for relevant prescriptions and medical cases for treating tremors in TCM to establish a database of prescriptions for tremors. The Traditional Chinese Medicine Inheritance Computer System (V3.0) was used to analyze and explore the medication rules including drug frequency, properties, flavor, meridian tropism, and pharmacological effects, as well as core drugs and formula associations. A multi-target drug efficacy prediction platform based on network robustness was used to evaluate the predicted efficacy of the core prescriptions obtained. Based on the integration of ancient prescriptions, prestigious doctors' medical cases, and network analysis results, the priority level of the developed prescriptions was determined through comprehensive evaluation.ResultA total of 81 ancient prescriptions were screened, involving 246 drugs, and 171 prescriptions were screened from prestigious doctors' medical cases, involving 278 drugs. The frequently used TCM drugs were mostly warm in nature and sweet in flavor, mainly acting on the liver, spleen, and kidney meridians. In terms of efficacy, they were mainly effective in tonifying deficiency, soothing liver and extinguishing wind, activating blood and resolving blood stasis, clearing heat, and resolving exterior. Through association rules and K-means clustering, the core prescriptions were composed of high-frequency drugs such as Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Angelicae Sinensis Radix, Poria, Gastrodiae Rhizoma, and Uncariae Ramulus Cum Uncis. Drug combinations mainly focused on tonifying Qi and nourishing blood, with the additional functions of calming wind and dredging collaterals. Clustering analysis of core prescriptions from ancient prescriptions and prestigious doctors' medical cases, as well as multi-target drug efficacy prediction, showed that Combination 1 had the highest disturbance score on the disease network. Furthermore, comparative analysis revealed consistent results with both the analysis of ancient prescriptions and prestigious doctors' medical cases, indicating its optimal development potential based on theoretical inheritance and empirical practice. In comparison, Combinations 3, 2, and 4 were less utilized in contemporary clinical practice, with lower rankings in network disturbance scores, suggesting that their development value still warranted further exploration.ConclusionTCM clinical treatment of tremors emphasizes the regulation of the liver, spleen, and kidney. In line of syndrome differentiation, drugs potent in soothing liver, extinguishing wind, activating blood, and resolving blood stasis are added based on deficiency-tonifying drugs. The core prescriptions based on Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Astragali Radix, Poria, and Atractylodis Macrocephalae Rhizoma (combination 1) have the highest potential development value. The integrated strategy "empirical prescriptions in ancient books-medical cases by prestigious doctors-computational analysis" can be used for the screening of candidate prescriptions for new TCM drugs.  
      关键词:tremor;empirical prescriptions in ancient books;medical cases by prestigious doctors;computational analysis;medication rule   
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    • 在药材质量提升领域,专家揭示了逆境条件下活性氧对次生代谢的调控作用,为提高药材有效成分含量和质量提供了新途径。
      MENG Xiangcai, MENG Zhaoping, YOU Yafei, ZHANG Wei
      Vol. 30, Issue 12, Pages: 203-208(2024) DOI: 10.13422/j.cnki.syfjx.20240716
      摘要:The quality of Chinese medicinal materials is related to the environment, with an optimal quality under adversity. The origin of Chinese medicinal materials has converted from wild collection to cultivation, and a better cultivation environment leads to a decline in their quality. At present, there are few effective methods to improve the quality of Chinese medicinal materials. Plants are bound to produce a large amount of reactive oxygen species (ROS) under adversity, and the quality improvement of Chinese medicinal materials under adversity may be achieved through ROS. This paper described the relationship between plant adversity-ROS-secondary metabolism: ROS can alter the structure of proteins (including enzymes) and regulate enzyme activities, thus affecting secondary metabolism to improve the adaptive capacity of plants. Therefore, ROS is the essential cause of adversity changing secondary metabolism. The cells of plants are omnipotent, and the medicinal parts of plants can independently complete the whole process of secondary metabolism, so regulation of secondary metabolism during the processing of fresh Chinese medicinal materials can significantly improve the quality of Chinese medicinal materials. Exogenous ROS can be used as inducible factors to stimulate medicinal parts, inducing a physiological state of fresh medicinal parts similar to that under adversity, thus enhancing secondary metabolism, and improving the contents of active ingredients in Chinese medicinal materials. In addition, the content and ratio of each ingredient in Chinese medicinal materials are closer to those of wild Chinese medicinal materials. The mechanism of plant adaptation to adversity is the mechanism of the quality formation of Chinese medicinal materials, and the application of ROS as inducible factors can provide a new pathway for the production of high-quality Chinese medicinal materials.  
      关键词:reactive oxygen species (ROS);cultivated Chinese medicinal materials;physiological ecology;secondary metabolism   
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    • 最新研究揭示,川芎嗪在心血管功能、氧化应激、炎症反应等方面对阿尔茨海默病具有潜在治疗作用,为防治这一社会问题提供了新思路。
      YIN Jianing, ZHAO Xitong, FAN Wenqian, DU Baojian, FANG Fang, GUAN Jun
      Vol. 30, Issue 12, Pages: 209-218(2024) DOI: 10.13422/j.cnki.syfjx.20240509
      摘要:With intensified aging, Alzheimer's disease has become a serious problem in China's health field. In the field of traditional Chinese medicine (TCM), Alzheimer's disease mainly describes cognitive deficits such as dementia and amnesia. After the inheritance and summary by medical experts of successive generations, the theory of "toxin damaging brain collaterals" has become a mature pathogenesis hypothesis of this disease. Blood stasis, as one of the main viral pathogens, is also closely related to the theory of Alzheimer's disease in modern pharmacology. Chuanxiong Rhizoma is used frequently in clinical prescriptions for Alzheimer's disease. As the main component of Chuanxiong Rhizoma, tetramethylpyrazine has a series of pharmacological effects on the cardiovascular system such as vasodilation, anti-platelet aggregation, anti-atherosclerosis, and anti-myocardial ischemia, which reflects the effects of Chuanxiong Rhizoma in activating blood circulation and removing blood stasis. However, few studies have focused on the effect of tetramethylpyrazine on the pathogenesis of Alzheimer's disease. From the perspective of TCM theory and modern pharmacology, this article discussed the effects of tetramethylpyrazine on the pathology and pathogenesis of Alzheimer's disease from the aspects of cardiovascular function, oxidative stress, inflammatory response, mitochondrial function, and cholinergic system and made prospects for the future application of tetramethylpyrazine to prevent and treat Alzheimer's disease.  
      关键词:toxin damaging brain collaterals;blood stasis;tetramethylpyrazine;Alzheimer's disease;pharmacological effects;mechanism   
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    • 恶性肿瘤成全球70岁前主要死因,中医药小柴胡汤在肿瘤治疗中显示潜力。研究总结小柴胡汤阻断癌前病变、控制恶性肿瘤发展等作用,为临床用药提供新思路。
      ZHAO Yue, WANG Wenping, LI Xiaobin, WANG Huawei, CAO Ying
      Vol. 30, Issue 12, Pages: 219-231(2024) DOI: 10.13422/j.cnki.syfjx.20240998
      摘要:Malignant tumors have surpassed stroke and coronary heart disease to become the main cause of death before the age of 70 in the world. The incidence of malignant tumors is increasing year by year, which seriously affects the living standards and social and economic development of Chinese people. Surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy are the main means of Western medicine to intervene in tumors, which are of great significance for prolonging the survival time of patients. However, there are many disadvantages such as adverse reactions and drug resistance. Traditional Chinese medicine has become a research hotspot in recent years because of its definite curative effect and wide application in tumor treatment. Xiao Chaihutang is derived from the Treatise on Febrile and Miscellaneous Diseases. It is composed of Bupleuri Radix, Scutellariae Radix, Ginseng Radix, Pinelliae Rhizoma, Glycyrrhizae Preparata Radix, Ginger, and Jujube. It has the effects of reconciling Shaoyang, reconciling cold and heat Yin and Yang, soothing the liver, and relieving depression. This prescription and the prescriptions based on it are widely used in various stages of tumors. This study summarized the Chinese and foreign research of Xiao Chaihutang in the field of tumors in the past 10 years and explored the role and mechanism of Xiao Chaihutang in blocking precancerous lesions, controlling the development of malignant tumors, reducing the occurrence of adverse reactions after intervention, and alleviating common complications, with a view to expanding the clinical medication ideas.  
      关键词:Xiao Chaihutang;malignant tumor;cancer;whole process management;precancerous lesions   
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    • 最新研究发现,中药有效单体与复方可调节乳腺癌缺氧微环境,抑制癌细胞增殖、侵袭和转移,提高患者生存质量。
      WANG Xinnan, HU Wenxiu, SUN Shuo, ZHANG Wenjie, ZHAO Yi, SUN Youzhi
      Vol. 30, Issue 12, Pages: 232-241(2024) DOI: 10.13422/j.cnki.syfjx.20232428
      摘要:The tumor microenvironment includes blood vessels, lymph, nerves, non-malignant cells, and their metabolites at and near the tumor lesion site, which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption, or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply, forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors, widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer, occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets, the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer, inhibit the proliferation, invasion, and metastasis of breast cancer cells in the hypoxia environment, induce apoptosis, reverse their drug resistance, intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment, and inhibit their angiogenesis, thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation, invasion, metastasis, drug resistance, immune function, metabolic reprogramming, non-coding RNA, iron death, and autophagy of breast cancer cells, which affected the occurrence and development of breast cancer, and it elaborated the mechanism behind it. Then, the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine, so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.  
      关键词:hypoxia microenvironment;breast cancer;effective monomers of traditional Chinese medicine;compound of traditional Chinese medicine;review   
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    • 最新研究发现,中医药通过调节线粒体膜电位,有效干预心血管疾病发展,保护心功能,提高治愈率,降低致死率。
      MA Jingzhuo, TAN Yuqing, CHEN Hengwen
      Vol. 30, Issue 12, Pages: 242-250(2024) DOI: 10.13422/j.cnki.syfjx.20232325
      摘要:Mitochondrial membrane potential (MMP) is one of the most sensitive indicators of cell damage and one of the potential targets of traditional Chinese medicine (TCM) intervention in the cardiac function. Cardiovascular diseases, with complex mechanisms of the occurrence and development, often involve the myocardium and other organs and present slow development and high mortality, seriously affecting the quality of life of patients. The TCM treatment of cardiovascular diseases is praised for small side effects, low drug resistance, and holistic treatment and can effectively relieve symptoms and improve prognosis. In recent years, the research on the occurrence mechanism of cardiovascular diseases from mitochondrial function has gained increasing attention. MMP is closely related to the functioning mechanism of mitochondria. Studies have shown that TCM regulates MMP to treat cardiovascular diseases by modulating energy metabolism, improving mitochondrial structure and function, and inhibiting oxidative stress and apoptosis, thus protecting the heart function, improving the cure rate, and reducing the mortality of patients. This paper systematically reviews the studies about the mechanisms of TCM regulation of MMP in cardiovascular diseases including atherosclerosis, heart failure, myocardial ischemia-reperfusion injury, diabetic cardiomyopathy disease, and pulmonary artery hypertension. Most of Chinese medicine compound prescriptions, Chinese medicinal herbs, effective fraction, and active components can protect mitochondrial function by regulating MMP. However, relevant clinical trials and TCM theoretical studies of MMP remain to be carried out to provide more ideas for TCM treatment of cardiovascular diseases.  
      关键词:mitochondria;membrane potential;traditional Chinese medicine;cardiovascular diseases   
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    • Da Chaihutang Treats Digestive System Tumors: A Review AI导读

      大柴胡汤在消化系统肿瘤治疗领域取得显著进展,通过促进肿瘤细胞凋亡、抑制增殖等机制,为中西医治疗模式构建和药物研发提供参考。
      ZHU Ranpei, SANG Tianqing, XIE Hui, SUN Tingting, QU Haoran, LI Shanshan, ZHENG Yuling
      Vol. 30, Issue 12, Pages: 251-260(2024) DOI: 10.13422/j.cnki.syfjx.20232321
      摘要:Da Chaihutang from the Treatise on Febrile Disease (Shanghanlun) has the function of harmonizing lesser Yang and discharging internal heat. It is formulated by ZHANG Zhongjing for the concurrent diseases of lesser Yang and Yang brightness and has been widely used in the treatment of digestive system diseases, especially malignant tumors. By review of the articles published in the last 20 years, this paper summarizes the application of Da Chaihutang in treating digestive system tumors from syndrome analysis, clinical research, and mechanism research. Da Chaihutang can treat the syndrome involving lesser Yang and Yang brightness in the digestive system, release interior and exterior to expel pathogen, and remove obstruction by conforming to the descending nature of the six fu-organs. In clinical practice, Da Chaihutang can directly treat digestive system malignant tumors such as liver cancer, pancreatic cancer, intestinal cancer, gastric cancer, and gallbladder cancer. In addition, it can relieve common complications of digestive system malignant tumors, such as cancerous fever, malignant obstructive jaundice, and constipation. Moreover, it can alleviate the adverse reactions caused by Western medical treatment, such as post-embolization syndrome, side effects of chemotherapy, and incomplete postoperative obstruction. Da Chaihutang is effective when used alone as it can relieve clinical symptoms, improve prognosis, and prolong survival of advanced patients and is safe and non-toxic, suitable for long-term use by tumor patients. Regarding the mechanism, Da Chaihutang can promote the apoptosis and inhibit the proliferation of tumor cells, reduce inflammation and inflammatory injury, and improve the liver function. The clear effect and mechanism confirms the anti-tumor effect of Da Chaihutang. This paper comprehensively describes the current research status of Da Chaihutang in the treatment of digestive system tumors and puts forward the deficiencies and improvement measures for the current research, aiming to provide reference for the application of this formula in treating digestive system tumors, the establishment of Chinese and Western medicine treatment schemes of tumors, and the research and development of anti-tumor drugs.  
      关键词:Da Chaihutang;digestive system tumors;research progress;traditional Chinese medicine;review   
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    • 在中药多糖口服吸收机制研究领域,专家综述了其吸收途径及标记技术,为全面阐明中药多糖作用机制提供参考。
      ZHU Weifeng, DENG Shuangyan, OUYANG Hui, YANG Wenjing, FU Jianing, WEI Huangqing, LI Qiong
      Vol. 30, Issue 12, Pages: 261-269(2024) DOI: 10.13422/j.cnki.syfjx.20240765
      摘要:Polysaccharides are the important material basis of traditional Chinese medicine(TCM), and have various pharmacological activities such as immunomodulation, antitumor and anti-aging. Due to the large molecular weight of TCM polysaccharides, their structural analysis and oral absorption mechanism are facing technical challenges, and the current research on their structure-activity relationships has made some breakthroughs, while the research on their oral absorption mechanisms is relatively slow. In-depth study of the oral absorption mechanism of TCM polysaccharides is not only crucial for the interpretation of their action pathways and efficacy in vivo, but also helpful for the interpretation of their pharmacological effects, rational clinical applications and the discovery of new targets. In recent years, the application of fluorescent labeling and isotopic labeling methods has provided new technical means for the oral absorption studies of polysaccharides, which has promoted the development of oral absorption studies of TCM polysaccharides. In this paper, we reviewed the oral absorption pathways and labeling techniques of TCM polysaccharides, and concluded that they can be absorbed orally through transmembrane, cellular bypass, and M-cell-mediated transport, of which transmembrane pathway is the main absorption pathway, and summarized the labeling reactions of four fluorescent labeling and isotopic labeling methods with TCM polysaccharides, which can provide references for evaluating the absorption pathways of TCM polysaccharides, screening active TCM polysaccharides, establishing pharmacodynamic models and comprehensively elucidating the mechanism of TCM polysaccharides.  
      关键词:traditional Chinese medicine;polysaccharides;oral absorption;structure-activity relationship;labeling techniques;structural analysis;pharmacodynamic model   
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    • 最新研究揭示,GLUT1靶向型中药活性成分纳米递送系统在肿瘤治疗中具有突破性进展,为恶性肿瘤的靶向治疗提供了新策略,有望在预防和治疗中发挥重要作用。
      ZHU Hua, LUO Huimin, LIN Si, WANG Bingbing, LI Jinwei, XU Liba, ZHANG Miao, XIE Fengfeng, CHEN Long, LI Meilin, LU Lu
      Vol. 30, Issue 12, Pages: 270-280(2024) DOI: 10.13422/j.cnki.syfjx.20240665
      摘要:Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation, namely the Warburg effect. Even under aerobic conditions, tumor cells mainly rely on glycolysis to provide energy. Therefore, glucose transporter protein 1(GLUT1), which is involved in the process of glucose metabolism, plays an important role in tumorigenesis, development and drug resistance, and is considered to be one of the important targets in the treatment of malignant tumors. In recent years, research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism, among which the role of GLUT1 is the most critical. In this paper, the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine(TCM) active ingredient nano-delivery system in tumor therapy, aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention(EPR) effect. In summary, the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.  
      关键词:glucose transporter protein 1(GLUT1);targeting;drug delivery system;Warburg effect;tumor microenvironment;high-permeability long retention effect;traditional Chinese medicine   
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    • 最新研究揭示,活性氧(ROS)在阿尔茨海默病(AD)中扮演关键角色,可能成为疾病进展的新靶点。中医药通过调控ROS防治AD,为防治提供新思路和方法。
      WANG Jiawei, WEI Benjun
      Vol. 30, Issue 12, Pages: 281-288(2024) DOI: 10.13422/j.cnki.syfjx.20241499
      摘要:The pathological mechanism of Alzheimer's disease (AD) is complex, and there are many hypotheses. The mainstream theory is the amyloid-beta protein (Aβ) and Tau protein phosphorylation. Oxidative stress (OS) is a bridge between other hypotheses and mechanisms and plays a key role in many hypotheses. Therefore, the treatment of OS in AD (ADOS) is beneficial in alleviating disease progression. Reactive oxygen species (ROS) is a kind of antioxidant and a kind of oxidation products, with Aβ and Tau protein interactions, activating microglia and astrocytes, triggering inflammation and mitochondrial dysfunction, leading to the deterioration of the environment in the brain, and accelerating the development of disease. ROS, as a signal messenger inducing OS, is widely involved in the progression of AD and may be a new target for the progression of AD. Traditional Chinese medicine (TCM) monomers and compounds play an increasingly important role in the prevention and treatment of AD. Recent studies have found that the effective prevention and treatment of AD by TCM is closely related to the regulation of ROS. There are many studies on the mechanism of TCM in the treatment of AD via regulating ROS, but there is a lack of systematic review. By analyzing and summarizing the literature in China and abroad in recent years, this paper reviewed the generation and physiology of ROS, the mechanism of action of AD, and the prevention of AD by TCM via regulating ROS through relevant ways, so as to provide references for the research on the regulation of ROS by TCM and provide new targets and new methods for the prevention and treatment of AD.  
      关键词:traditional Chinese medicine;Alzheimer's disease (AD);oxidative stress (OS);amyloid-beta protein (Aβ);Tau protein phosphorylation;reactive oxygen species (ROS)   
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    • 最新研究发现,中医药通过调控NF-κB、Nrf2/HO-1、Wnt/β-catenin、SIRT1、AMPK、HIF-1α/VEGF等信号通路,有效防治类风湿关节炎。这些信号通路在炎症控制、氧化应激调节、细胞稳态维护等方面发挥关键作用。中药干预为RA治疗提供了新思路和科学依据。
      LU Zengpeng, YU Haiyang, ZHANG Xiaogang, ZHANG Hulin, GUO Chenglong, ZHAO Yuping
      Vol. 30, Issue 12, Pages: 289-298(2024) DOI: 10.13422/j.cnki.syfjx.20232439
      摘要:Rheumatoid arthritis (RA), as an autoimmune disease, is mainly characterized by persistent synovitis. It often involves multiple joints symmetrically and can lead to joint deformity, joint function loss, and even disability in severe cases. The pathogenesis of RA is complex, and the prevention and treatment are complicated. Therefore, it is difficult to cure the disease completely. Previous studies have validated important targets and mechanisms for the prevention and treatment of RA, including the nuclear factor-κB (NF-κB) signaling pathway that controls the inflammatory process, nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway that regulates oxidative stress, inhibits inflammation, and maintains cell homeostasis, Wnt/β-catenin signaling pathway that plays a key role in cell growth, differentiation, apoptosis, and inflammatory response, anti-inflammatory, anti-oxidation, and silent information regulator 1 (SIRT1) signaling pathway that regulates synovial cells, anti-inflammatory adenylate-activated protein kinase (AMPK) signaling pathway that regulates energy metabolism, and hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway related to angiogenesis in RA. At the same time, many studies have confirmed that traditional Chinese medicine prevents and treats RA by regulating the above signaling pathways and exerting their related effects, indicating the advantages of traditional Chinese medicine such as multiple regulatory pathways, long-term effects, and less adverse reactions. In this paper, by consulting many research reports, the role of the above-mentioned signaling pathways in RA was clarified, and the latest research results of traditional Chinese medicine intervention in the above-mentioned signaling pathways in the prevention and treatment of RA in recent years were summarized in detail. This paper aims to promote the in-depth study of the pathogenesis of RA and its treatment with traditional Chinese medicine, provide a scientific basis for the rational application of traditional Chinese medicine, and offer useful enlightenment for the development of new drugs and clinical practice for the treatment of RA in the future.  
      关键词:rheumatoid arthritis;traditional Chinese medicine;signaling pathway   
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