Four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: a systematic review and network meta-analysis.

OBJECTIVE: To perform an evidence-based evaluation of the clinical efficacy of Taijiquan, Baduanjin, Yijinjing and Wuqinxi in interventions for type 2 diabetes. DESIGN: A systematic review and network meta-analysis. METHODS: The comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpta Medica Database (Embase), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, VIP and China Biomedical Literature Database (CBM). Clinical randomized controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Taijiquan, Baduanjin, Yijinjing and Wuqinxi, were retrieved. The search time was conducted from the establishment of the database to 30 October 2022. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language, Stata and ADDIS statistical software programs were used to conduct statistics and analysis of intervention measures. RESULTS: A total of 33 randomized controlled trials with 2609 patients were identified. All patients were from China. The results of the network meta-analysis showed that Taijiquan ranked the best for improving HbA1c, 2-h postprandial blood glucose (2hPG), low-density lipoprotein cholesterol (LDL-C) and insulin sensitivity index indicator levels; Yijinjing reduced fasting plasma glucose (FPG) and total cholesterol (TC) indicator levels for the best probability ranking; Baduanjin improved the triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) probability ranking the most. When the training period was less than 12 weeks, Baduanjin had better effects in improving 2hPG, TC, TG, HDL-C and LDL-C indicator levels. Taijiquan had better effects in reducing FPG levels. When the training period was 12 weeks, the effect of Yijinjing in improving FPG, HbAlc, TC and HDL-C levels was better than that in other traditional Chinese exercise, and Taijiquan had better effects in improving 2hPG, TG and LDL-C indicator levels. When the training period was longer than 12 weeks, Taijiquan had better effects in improving FPG, HbAlc, 2hPG and LDL-C indicator levels, and Baduanjin had better effects in improving TC, TG and HDL-C indicator levels. CONCLUSION: The four traditional Chinese exercise therapies can improve blood glucose levels, blood lipid levels and insulin-related indicators of type 2 diabetes to varying degrees. Studies have shown that Taijiquan has a better targeted treatment effect on type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: CRD42020214786. PROTOCOL PUBLISHED: We published the protocol article "Network meta-analysis of four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: Protocol for a systematic review" in the BMJ Open magazine 2021, Issue 11, Volume 7.

Exploring the mechanism of ellagic acid against gastric cancer based on bioinformatics analysis and network pharmacology.

Ellagic acid (EA) is a natural polyphenolic compound. Recent studies have shown that EA has potential anticancer properties against gastric cancer (GC). This study aims to reveal the potential targets and mechanisms of EA against GC. This study adopted methods of bioinformatics analysis and network pharmacology, including the weighted gene co-expression network analysis (WGCNA), construction of protein-protein interaction (PPI) network, receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival curve analysis, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics simulations (MDS). A total of 540 EA targets were obtained. Through WGCNA, we obtained a total of 2914 GC clinical module genes, combined with the disease database for screening, a total of 606 GC-related targets and 79 intersection targets of EA and GC were obtained by constructing Venn diagram. PPI network was constructed to identify 14 core candidate targets; TP53, JUN, CASP3, HSP90AA1, VEGFA, HRAS, CDH1, MAPK3, CDKN1A, SRC, CYCS, BCL2L1 and CDK4 were identified as the key targets of EA regulation of GC by ROC and KM curve analysis. The enrichment analysis of GO and KEGG pathways of key targets was performed, and they were mainly enriched in p53 signalling pathway, PI3K-Akt signalling pathway. The results of molecular docking and MDS showed that EA could effectively bind to 13 key targets to form stable protein-ligand complexes. This study revealed the key targets and molecular mechanisms of EA against GC and provided a theoretical basis for further study of the pharmacological mechanism of EA against GC.

Exploring the Potential Mechanism of Action of Ursolic Acid against Gastric Cancer and COVID-19 using Network Pharmacology and Bioinformatics Analysis.

BACKGROUND: Patients with gastric cancer (GC) are more likely to be infected with 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the prognosis is worse. It is urgent to find effective treatment methods. OBJECTIVE: This study aimed to explore the potential targets and mechanism of ursolic acid (UA) on GC and COVID-19 by network pharmacology and bioinformatics analysis. METHODS: The online public database and weighted co-expression gene network analysis (WGCNA) were used to screen the clinical related targets of GC. COVID-19-related targets were retrieved from online public databases. Then, a clinicopathological analysis was performed on GC and COVID-19 intersection genes. Following that, the related targets of UA and the intersection targets of UA and GC/COVID-19 were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome Analysis (KEGG) pathway enrichment analyses were performed on the intersection targets. Core targets were screened using a constructed protein-protein interaction network. Finally, molecular docking and molecular dynamics simulation (MDS) of UA and core targets were performed to verify the accuracy of the prediction results. RESULTS: A total of 347 GC/COVID-19-related genes were obtained. The clinical features of GC/COVID-19 patients were revealed using clinicopathological analysis. Three potential biomarkers (TRIM25, CD59, MAPK14) associated with the clinical prognosis of GC/COVID-19 were identified. A total of 32 intersection targets of UA and GC/COVID-19 were obtained. The intersection targets were primarily enriched in FoxO, PI3K/Akt, and ErbB signaling pathways. HSP90AA1, CTNNB1, MTOR, SIRT1, MAPK1, MAPK14, PARP1, MAP2K1, HSPA8, EZH2, PTPN11, and CDK2 were identified as core targets. Molecular docking revealed that UA strongly binds to its core targets. The MDS results revealed that UA stabilizes the protein-ligand complexes of PARP1, MAPK14, and ACE2. CONCLUSION: This study found that in patients with gastric cancer and COVID-19, UA may bind to ACE2, regulate core targets such as PARP1 and MAPK14, and the PI3K/Akt signaling pathway, and participate in antiinflammatory, anti-oxidation, anti-virus, and immune regulation to exert therapeutic effects.

Study on the Mechanism of Action of Different Acupuncture Regimens on Premature Ovarian Failure Model Rats.

Objective: To study the mechanism of acupuncture on premature ovarian failure (POF) through the apoptosis pathway mediated by Bcl-2/Bax. Methods: POF rats were successfully obtained by cyclophosphamide. They were divided into five groups. After that, acupuncture was performed. The blank group and model group were not treated. The routine acupuncture group was acupuncture at Guanyuan, Sanyinjiao, Zhongji, and Guilai four points. The Neck-seven-acupuncture group was selected from Fengchi, Fengfu, Tianzhu, and Wangu four acupoints; the three-viscera simultaneous treatment group selected Guanyuan, Shenshu, Sanyinjiao, Taichong, and Baihui five points; and the data mining group selected Guanyuan and Sanyinjiao two points for 14 days of treatment. During the treatment, some rats were shed one after another due to the side effects of bone marrow suppression caused by mold-making. After treatment, serum estradiol (E2), follicle forming hormone (FSH), and luteinizing hormone (LH) were detected by radioimmunoassay, Bcl-2 and Bax proteins were analyzed by Western blot method, and Bcl-2 and Bax RNA were analyzed by PCR method. Results: Bcl-2 increased and Bax decreased in rats with premature ovarian failure treated with acupuncture. It shows that acupuncture can affect the secretion of ovarian-related hormones and the expression of apoptosis-related proteins, which is more significant in the conventional acupuncture point group. Conclusion: Acupuncture can inhibit the apoptosis of granulosa cells in ovarian tissue of rats with premature ovarian failure and improve ovarian function. The mechanism of its effect is to promote Bcl-2 gene expression and protein synthesis and inhibit Bax gene expression and protein synthesis. The conventional treatment group works best. This provides an experimental basis for the clinical use of acupuncture to intervene in the treatment of premature ovarian failure.

Potential Material Basis of Yupingfeng Powder for the Prevention and Treatment of 2019 Novel Coronavirus Pneumonia: A Study Involving Molecular Docking and Molecular Dynamic Simulation Technology.

Objective: In this study, we investigated the potential material basis of Yupingfeng powder in the prevention and treatment of 2019 novel coronavirus pneumonia (NCP) by applying molecular docking and molecular dynamic simulation technology. Design: The active ingredients and predictive targets of Yupingfeng powder were sourced using the TCMSP, ETCM, and TCMIP traditional Chinese medicine databases. NCP-related targets were then acquired from the DisGeNET and GeneCards databases, and common disease-drug targets were imported into the STRING database, and Cytoscape software was used to generate a protein-protein interaction network following the use of a network topology algorithm to identify key target genes. Gene Ontology (GO) and KEGG pathway enrichment analysis was then performed using the target genes and GOEAST and DAVID online tools. The mechanism of Yupingfeng powder in the prevention and treatment of NCP was analyzed with reference to the relevant literature. AutoDock software was used for molecular docking, the preliminary analysis of binding status, and to identify the best conformation. Desmond software was used to perform molecular dynamic simulations for protein and compound complexes, perform free energy calculations and hydrogen bond analysis, and to further verify the binding mode. Results: Overall, 38 main active components and 218 predictive targets of Yupingfeng powder were identified and 298 disease targets related to NCP were retrieved from disease databases. Yupingfeng powder was found to act predominantly on the TNF, Toll-like receptor, HIF-1, NOD-like receptor, cytokine-receptor interaction, MAPK, T cell receptor, and VEGF signaling pathways. Molecular docking of the three selected key active components with the 3CL-like protease (3CL-Pro) of SARS-CoV-2 showed that they each had a strong binding force and good affinity. Conclusions: Yupingfeng powder primarily acts on multiple active ingredients and potential targets through multiple action channels and signal pathways. Molecular docking and molecular dynamic simulation technology were used to effectively predict and analyze the potential mechanism by which this Chinese medicine can combat NCP. These results provide a reference for developing new modern Chinese medicine preparations against NCP in the future.

Effects of Fu's subcutaneous needling on mitochondrial structure and function in rats with sciatica.

To observe the effects of Fu's subcutaneous needling (FSN) and acupuncture treatment on the mitochondrial structure and function of the skeletal muscle tissue of rats with sciatica. Forty Sprague-Dawley rats were divided into control, model, acupuncture, and FSN groups (10 each) according to a random number table. The control group was left untreated. Rats in the FSN group were treated with FSN once every 2 days for three times, respectively (days 1, 3, 5, and 7), to cooperate with reperfusion approach. The acupuncture group was treated at the same timeline as that of the FSN group. Changes in the mechanical pain threshold, mitochondrial ultrastructure, mitochondrial citrate synthase (CS) activities, mitochondrial respiratory chain complex II, and mitochondrial COX- I protein expression in the skeletal muscle of rats treated with different treatments were compared with those of the model group. The pain thresholds of the rats were remarkably higher after FSN treatment and acupuncture, and the pain threshold of the FSN group was higher than that of the acupuncture group. Compared with the control group, the mitochondria of the model group had a damaged ultrastructure, were arranged in a disorganized manner, accumulated under the basement membrane, and appeared vacuolated with autophagosomes. The state of mitochondria in the FSN group was close to that in the control group and was remarkably better than that in the acupuncture group. The activities of mitochondrial CS and respiratory chain complex II in the skeletal muscle of the treated rats decreased compared with the control group (p < 0.05), and their levels were better in the FSN group than in the acupuncture group (p < 0.05). FSN treatment for 1 week considerably improved the pain thresholds and improved the skeletal muscle mitochondrial ultrastructure and mitochondrial function in rats with sciatica.

Chinese Herb Injections in the Adjuvant Treatment for Ulcerative Colitis: A Network Meta-Analysis of Randomized Controlled Trials.

Ulcerative colitis refers to an inflammatory disease lasting for a long time, which affects the colon. In China, injections of traditional Chinese herbs have been generally combined with traditional Western medicines such as mesalazine and sulfasalazine to treat ulcerative colitis. Nevertheless, the safety and efficacy exhibited by different CHIs for treating UC remains controversial. Therefore, a network meta-analysis method was employed in this study for the assessment of the effect and safety exhibited by CHI for treating UC. Seven English and Chinese databases were searched for relevant randomized controlled trials (RCTs) from the time of database creation to December 30, 2021. An assessment was conducted for the included RCTs' quality with the use of the Cochrane risk offset assessment device, and this study processed the data with the use of Review Manager 5.3 or Stata16.0 software. On the whole, 42 literature with data on 3668 patients were included. The overall response rate, inflammatory factors, recurrence rate, and adverse reactions were evaluated. In comparison with traditional Western medicines-based treatment, CHI integrated with traditional Western medicines presented an overall response rate (P < 0.05) and could better reduce the TNF-α (P < 0.05), IL-6(P < 0.05), and IL-8 level rate (P < 0.05) while better increasing the IL-10 level rate (P < 0.05). Besides, adverse reactions of CHI integrated with traditional Western medicine had a lower incidence (P < 0.05), and no significant distinction was identified in recurrence rate levels between the two interventions. CHI has some efficacy for treating UC. Xiangdan injection, Shenmai injection, Shengmai injection, and Danshen injection may be the most effective CHI. Nevertheless, more multicenter randomized controlled double-blind trials with great quality and large samples are required for research confirmation. Trial Registration: the registration was made for the protocol of this network meta-analysis in PROSPERO with ID CRD42021251429.

A Network Meta-Analysis of the Clinical Efficacy and Safety of Commonly Used Chinese Patent Medicines in the Auxiliary Treatment of Poststroke Depression.

BACKGROUND: Poststroke depression (PSD) is a serious complication of clinical cerebrovascular disease. Patients not only have depression-related emotional symptoms but also have physical symptoms, such as autonomic dysfunction. At the same time, patients with varying degrees of depression will delay the neurological function of stroke patients. The recovery time of cognitive function and limb function will increase the risk of accidental death and even aggravate the mortality of cerebrovascular disease. Through combining data analysis and related literature, seven types of Chinese patent medicines (CPMs) widely used in the clinical treatment of PSD have been screened out. These herbs exhibit some clinical comparability under the conditions that the syndrome type and dosage form are relatively uniform. Therefore, in this study, the network meta-analysis method was used to evaluate the safety and efficacy of the seven CPMs screened out, and the probability ranking was performed to screen the best clinical auxiliary treatment plan of CPM. METHODS: We searched the Chinese databases, including CNKI, WANFANG, and VIP, as well as the English databases, including the Cochrane Library, EMBASE, and PubMed, from inception to May 31, 2020, to identify randomized controlled trials (RCTs) on seven kinds of CPMs that were the subjects of the clinical research. The bias risk and quality of the included studies were analyzed with the Cochrane Handbook (version 5.1), ADDIS, and R software, and the results were compared in a network meta-analysis (NMA). RESULTS: In terms of clinical effectiveness, the seven kinds of CPMs all improved clinical curative effects, with Jieyu Anshen capsule adjuvant treatment having the most significant effect [odds ratio (OR) = 5.00, 95% CI (1.72-9.48)]. Wuling capsule AT can effectively reduce the score index of scale factors for the HAMD score, NIHSS score, and TESS score [mean difference (MD) = -3.95, 95% CI (-4.88-3.00); OR = -3.25, 95% CI (-5.46)-1.05); OR = 0.22, 95% CI (0.05-0.79), resp.]. CONCLUSION: The mechanisms of seven CPMs in the adjuvant treatment of PSD have advantages. In terms of safety and efficacy, the CPMs had better clinical adjuvant treatment performance. Although this study concluded that the Jieyu Anshen capsule is the preferred drug for clinical treatment, a clear conclusion still needs to be verified in a high-quality randomized controlled study. In clinical practice, accurate selection and application can be carried out according to the specific characteristics of patients.

Analysis of Herbal Mechanisms and Prescriptions for Chronic Cerebral Circulatory Insufficiency Based on Data Mining and Network Pharmacology.

BACKGROUND: Traditional Chinese medicine has accumulated rich resources and experience through clinical research to explore the prevention and treatment of chronic cerebral circulatory insufficiency, but current medicine lacks in-depth research and confirmation on the established protocols and mechanism of prescribed TCMs at the macro and micro levels. OBJECTIVE: To explore the prescription of Chinese medicines for the treatment of Chronic Cerebral Circulation Insufficiency (CCCI) and to explore the mechanism of core drugs. METHODS: 229 Chinese prescriptions for CCCI were collected from CNKI, CBM, VIP and WANFANG databases for this study. The frequency and association rules of drugs were analyzed and the core drugs by TCMISSV2.5 software was extracted. The active ingredients and targets were obtained by TCMSP, and genes of CCCI were collected from the DisGeNET, OMIM, DrugBank disease databases. The intersection targets of herbal medicine and disease were imported into the STRING database for PPI network. The key targets were screened by the network topology algorithm. The Systems Dock website was used to verify the molecular docking. The GOEAST and DAVID tools were used to perform GO and KEGG pathway analysis with the key target genes. RESULTS: 117 drugs involved in 229 prescriptions were identified, 2 core drugs were identified. We identified 8 active ingredients, which were mandenol, myricanone, perlolyrine, senkyunone, wallichilide, sitosterol, beta-sitosterol and stigmasterol. 371 herbal targets predicted and 335 disease targets. The enrichment analysis showed that the core herbal medicines could prevent CCCI by 15 key signaling pathways. CONCLUSION: There are direct or indirect connections in key signaling pathways, which not only participate in energy metabolism, hormone regulation, signal transduction, but also play a role in the comprehensive intervention of nervous system, immune system, circulatory system and other systems, which is consistent with the comprehensive pathogenesis of CCCI induced by multiple factors.

Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus.

Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using online Mendelian inheritance in man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein-protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for gene ontology and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. Molecular dynamics simulation was carried out according to the molecular docking results. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include "AGE-RAGE signaling pathway in diabetic complications," "pathways in cancer," and "MAPK signaling pathway" (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.

[Effect of Banxia Xiexin Decoction on intestinal flora of mice with ulcerative colitis induced by dextran sodium sulfate].

The aim of this paper was to investigate the effect of Banxia Xiexin Decoction(BXD) on inflammatory factors and intestinal flora in a dextran sulfate sodium induced ulcerative colitis(DSS-UC) mouse model, and to explore the mechanism of BXD in treating ulcerative colitis from the perspective of flora disorder. Forty C57 BL/6 J mice were randomly divided into control group, model group and BXD group. A 2.5% DSS-induced ulcerative colitis model was established. On the 8 th day, normal saline, normal saline, and BXD were given daily for 14 days. After 14 days, HE staining was used to observe histopathological changes of the colon. Serum inflammatory factor content was detected by ELISA, and the change of intestinal flora in mice feces was detected by 16 S rRNA sequencing technology. Compared with control group, the colonic tissue of mice in model group was damaged seriously, and the contents of IL-6 and TNF-α in serum were significantly increased(P<0.05). Compared with model group, mice in BXD group had less colonic damage, and the contents of IL-6, TNF-α in serum were decreased significantly(P<0.05). After creation, the richness of Patescibacteria was increased significantly at the phylum level(P<0.05). At the same time, the richness of Faecalibaculum(P<0.01), norank_f_Muribaculaceae(P<0.01) were decreased significantly at the genus level, while the richness of Turicibacter(P<0.01), Romboutsia(P<0.01), Clostridium_sensu_stricto_1(P<0.01) were increased significantly. After the intervention with BXD, the content of Patescibacteria was significantly reduced at the phylum level(P<0.05), and the contents of Lactobacillus(P<0.01), Clostri-dium_sensu_stricto_1(P<0.01), Enterorhabdus(P<0.01), Candidatus_Saccharimonas(P<0.05), Eubacterium_fissicatena_group(P<0.05) were decreased significantly at the genus level, while the contents of Dubosiella, Bacteroides and Allobaculum were increased significantly. Therefore, BXD could significantly improve the symptoms of DSS-UC mice. It not only could reduce the contents of IL-6 and TNF-α, but also could reduce the richness of Patescibacteria at the phylum level, and those of Clostridium_sensu_stricto_1, Candidatus_Saccharimonas, Eubacterium_fissicatena_group at the genus level. Inaddition, BXD could increase the richness of Bacteroides and Bifidobacterium. It suggested that BXD could play a role in the treatment of ulcerative colitis partially through reducing inflammatory factors and regulating the structure of the gut microbiota.

Network meta-analysis of four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: protocol for a systematic review.

INTRODUCTION: Traditional Chinese exercise therapy, as one of the commonly used exercise interventions for the treatment of type 2 diabetes patients in China, has been proven effective by many clinical practices, but there is still a lack of evidence-based research. This study aims to integrate clinical randomised controlled correlations via network meta-analysis evidence. METHODS AND ANALYSIS: The comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpt Medica Database (EMBASE), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database (VIP), China Biomedical Literature Database (CBM). Clinical randomised controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Tai Chi, Ba Duan Jin, Yi Jin Jing and Wu Qin Xi were retrieved. The search time was conducted from the establishment of the database to 30 October 2020. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table, and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language and ADDIS statistical software were used to conduct statistics and analysis of intervention measures. PROSPERO REGISTRATION NUMBER: CRD42020214786.

Network meta-analysis of Chinese patent medicine adjuvant treatment of poststroke depression.

BACKGROUND: Poststroke depression is one of the common complications of clinical cerebrovascular diseases. It is commonly seen in 3 to 6 months after the onset of stroke. The incidence rate is 22% to 75%. The patient not only has depression-related emotional symptoms, but also are accompanied by autonomic nervous disorders and other physical symptoms. It will also delay the recovery time of patients' neurological function, cognitive function, and limb function due to different degrees of depression, and even further aggravate the mortality and risk of accidental death of cerebrovascular disease. In recent years, Chinese patent medicine combined with western medicine has been widely used in the treatment of this disease. Many clinical practices have proved that the adjuvant treatment of pure Chinese herbal medicine can effectively alleviate the poststroke depression state and reduce the neurological deficits. The author has sorted out the relevant literature and data analysis to screen out the seven most representative and commonly used Chinese patent medicine preparations in clinical treatment of poststroke depression, which have certain clinical comparability when the dosage form and syndrome type are relatively unified. The network meta-analysis method is used to select the best clinical treatment plan, so as to provide reference value and evidence-based medicine evidence for the clinical optimization of drug selection. METHODS: Using computer retrieval technology, comprehensive retrieval of CNKI, VIP, CBM, and WANFANG Chinese electronic database and the Cochrane Library, PubMed, Web of Science and EMBASE foreign electronic database. Search the clinical randomized controlled trials of these 7 kinds of Chinese patent medicines for adjuvant treatment of poststroke depression, and set a period of time is from the establishment of the database to May 31, 2020. The 3 authors will screen the literatures that meets the inclusion criteria, extract the data independently according to the predesigned rules, and evaluate the literature quality and bias risk of the included research according to the Cochrane 5.1 manual standard. R and the Aggregate Data Drug Information System software were used for data consolidation and network meta-analysis to evaluate the ranking probability of all interventions. RESULTS: This network meta-analysis and probability ranking will identify the best Chinese patent medicine adjuvant treatment for poststroke depression. CONCLUSION: This study will provide systematic evidence-based medicine evidence for Chinese patent medicine adjuvant treatment for poststroke depression, and help clinicians, patients with poststroke depression and decision-makers to make more effective, safer, and economic optimal treatment plan in the decision-making process. PROSPERO REGISTRATION NUMBER: CRD42020164543.

Analysis of the pharmacological mechanism of Banxia Xiexin decoction in treating depression and ulcerative colitis based on a biological network module.

BACKGROUND: The network pharmacology method was used to predict the active components of Banxia Xiexin decoction, its targets and the key signalling pathways that are activated in the treatment of depression and ulcerative colitis to explore the common mechanism. METHODS: The active components and targets of Banxia Xiexin decoction were obtained by searching the ETCM,TCMSP and TCMIP database. The disease targets of depression and ulcerative colitis were obtained by combining the following the DisGeNET, OMIM,Drugbank,CTD and PharmGKB disease databases. The drug and disease target genes were obtained from the intersection of the herbal medicine targets and the disease targets and were imported into the STRING platform for the analysis of PPI network. The network modules were constructed using Cytoscape software. An analysis of the functional annotations of GO terms and KEGG signalling pathways was performed for each network module. Then, the tissue distribution, sub-cellular distribution and protein attributes of the key targets in the pathway were analysed by the BioGPS, Genecards and DisGeNET databases. RESULTS: The mechanism of Banxia Xiexin Decoction in the treatment of depression and ulcerative colitis is related to drug reaction, steroid metabolism, lipid metabolism, inflammatory response, oxidative stress response, cell response to lipopolysaccharide, insulin secretion regulation, estradiol response and other biological functions, mainly through the regulation of 5-hydroxytryptamine synaptic, arachidonic acid metabolism, HIF-1 signaling pathway and NF-kappa B signaling pathway can achieve the effect of same treatment for different diseases. CONCLUSIONS: The mechanism of Banxia Xiexin Decoction in treating different diseases involves direct or indirect correlation of multiple signal pathways, mainly involved in drug metabolism and lipid metabolism, but also through comprehensive intervention of the body's nervous system, immune system, digestive system and other systems. The effective components of Banxia Xiexin Decoction are mainly act on eight key target proteins (such as ALB, IL6, VEGFA, TNF, PTGS2, MAPK1, STAT3, EGFR) to carry out multi-target effect mechanism, biological mechanism of treating different diseases with the same treatment, and related mechanism of overall treatment, which provide theoretical reference for further research on the material basis and mechanism of Banxiaxiexin decoction on antidepressant and prevention and treatment of ulcerative colitis.

Anti-Apoptotic Effects of Diosgenin in D-Galactose-Induced Aging Brain.

The purpose of this study was to evaluate the effects of diosgenin on the D-galactose-induced cerebral cortical widely dispersed apoptosis. Male 12-week-old Wistar rats were divided into four groups: Control (1mg/kg/day of saline, i.p.), DD0 (150mg/kg/day of D-galactose, i.p.), DD10, and DD50 (D-galactose+10 or 50mg/kg/day of diosgenin orally). After eight weeks, histopathological analysis, positive TUNEL and Western blotting assays were performed on the excised cerebral cortex from all four groups. The TUNEL-positive apoptotic cells, the components of Fas pathway (Fas, FADD, active caspase-8 and active caspase-3), and mitochondria pathway (t-Bid, Bax, cytochrome c, active caspase-9 and active caspase-3) were increased in the DD0 group compared with the control group, whereas they were decreased in the DD50 group. The components of survival pathway (p-Bad, Bcl-2, Bcl-xL, IGF-1, p-PI3K and p-AKT) were increased in the DD50 group compared to the control group, whereas the levels of Bcl-xL, p-PI3K, and p-AKT were also compensatorily increased in the DD0 group compared to the control group. Taken together, diosgenin suppressed D-galactose-induced neuronal Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced the Bcl-2 family associated pro-survival and IGF-1-PI3K-AKT survival pathways, which might provide neuroprotective effects of diosgenin for prevention of the D-galactose-induced aging brain.

Efficacy and safety of oral traditional Chinese patent medicine in treatment of liver stagnation and spleen deficiency of depression: A protocol for systematic review.

BACKGROUND: Depression is a kind of chronic and recurrent mental disorder, the main clinical characteristics of the patients are marked and persistent depression. At the same time, it is often accompanied by chronic physical disease, cognitive impairment, and functional damage, which is one of the common diseases that seriously threaten human health. At present, 3 kinds of oral Chinese patent medicine have clinical comparability in the treatment of depression of liver stagnation and spleen deficiency, but there is no evidence for clinical efficacy and safety. Therefore, this study aims to integrate the clinical related syndromes of direct and indirect comparison by using systematic evaluation and network meta-analysis (NMA). According to the data, the different Chinese patent medicines with the same evidence body for the treatment of the disease are collected, analyzed, and sequenced in a quantitative and comprehensive way, and then the advantages and disadvantages of the efficacy and safety between different Chinese patent medicines are screened out to get the best choice scheme, thus providing reference value and evidence-based theoretical evidence for the clinical optimization of drug selection. METHODS: Comprehensive retrieval of China National Knowledge Infrastructure, Chinese scientific journal database (VIP), China biological feature database (CBM) and WANFANG Data Chinese electronic database and the Cochrane Library, PubMed, Web of Science, and EMBASE foreign database. Search and publish the clinical randomized controlled trials of these 3 Chinese patent medicines combined with fluoxetine compared with fluoxetine. The retrieval time is from the establishment of the database to October 31, 2019. The 2 first authors will screen the literatures that meet the inclusion criteria, extract the data independently according to the predesigned rules, and evaluate the literature quality and bias risk of the included research according to the Cochrane 5.1 manual standard. R and Aggregate Data Drug Information System software were used for data consolidation and NMA to evaluate the ranking probability of all interventions. RESULTS: This result will show that the best oral Chinese patent medicine to assist the treatment of liver stagnation and spleen deficiency depression provides reliable evidence. CONCLUSION: This study will provide systematic evidence-based medicine evidence for TCM assisted treatment of depression of liver stagnation and spleen deficiency type, and help clinicians, patients with depression and decision-makers to make more effective, safer, and economic optimal treatment plan in the decision-making process. PROSPERO REGISTRATION NUMBER: CRD42019115695.

Allocryptopine: A Review of Its Properties and Mechanism of Antiarrhythmic Effect.

Abstract：Throughout the last decade, extensive efforts have been devoted to developing a percutaneous catheter ablation and implantable cardioverter-defibrillator technique for patients suffering from ventricular arrhythmia. Antiarrhythmic drug efficacy for preventing arrhythmias remains disappointing because of adverse cardiovascular effects. Allocryptopine is an isoquinoline alkaloid widely present in medicinal herbs. Studies have indicated that allocryptopine exhibits potential anti-arrhythmic actions in various animal models. The potential therapeutic benefit of allocryptopine in arrhythmia diseases is addressed in this study, focusing on multiple ion channel targets and reduced repolarization dispersion. The limitations of allocryptopine research are clear given a lack of parameters regarding toxicology and pharmacokinetics and clinical efficacy in patients with ventricular arrhythmias. Much remains to be revealed about the properties of allocryptopine.

[Network Meta-analysis of Chinese patent medicines in treatment of liver stagnation and spleen deficiency of depression].

To evaluate the clinical efficacy and safety of Shugan Jieyu Capsules,Jieyu Pills and Xiaoyao Pills in the treatment of liver-stagnation and spleen-deficiency depression by the network Meta-analysis( NMA),so as to provide evidence-based clinical practice. Chinese databases,including CNKI,VIP,Wan Fang Data,CBM as well as English databases including the Cochrane Library,PubMed,EMbase and Web of Science were retrieved from inception to October 30,2018,to collect randomized controlled trials( RCTs) about clinical study of the three kinds of Chinese patent medicines. The quality and bias risk of the included studies were assessed by 5. 1 standard in Cochrane Handbook,ADDIS software was applied in the statistical analysis,and the result were compared by NMA. A total of 37 studies involving 3 105 patients were included. The results of NMA showed that the adjuvant therapy with the three kinds of traditional Chinese patent medicines could improve the clinical efficacy. Jieyu Pills had the most significant effect( OR = 4. 59,95%CI[1. 94,12. 71],P<0. 05). In HAMD,Shugan Jieyu Capsules( MD = 3. 22,95%CI[2. 07,4. 39],P< 0. 05) and Xiaoyao Pills( MD= 2. 23,95%CI[0. 41,4. 03],P<0. 05) can effectively reduce the depression scale indicators. In the incidence of adverse reactions,the three kinds of Chinese patent medicines can reduce the incidence of adverse reactions. The three kinds of Chinese patent medicines can be combined with auxiliary Western medicine to treat liver-stagnation and spleen-deficiency depression,with complementary advantages in action mechanisms. In the clinical efficacy and safety,the Chinese patent medicines had good clinical manifestations. Although this study showed that Jieyu Pills may be the referred medicine for depression,this conclusion is still immature and needs to be further verified by high-quality RCTs studies,and the application shall be selective based on specific characteristics in clinic.

Ultrasensitive and universal fluorescent aptasensor for the detection of biomolecules (ATP, adenosine and thrombin) based on DNA/Ag nanoclusters fluorescence light-up system.

We report here an ultrasensitive strategy based on the recognition-induced conformational alteration of aptamer and fluorescence turn-on abilities of guanine-rich (G-rich) DNA sequence in proximity to silver nanoclusters for adenosine triphosphate (ATP), adenosine (A) and thrombin (TB) detection. Herein, we designed two tailored DNA sequences noted as complementary DNA (abbreviated as c-DNA) and signal probe DNA (abbreviated as s-DNA), respectively. c-DNA is designed as a special structure consisting of a sequence complementary to aptamer at the 3'-end and a guanine-rich DNA sequence at the 5'-end; s-DNA contains a cytosine-rich sequence responsible for Ag NCs templated synthesis at the 3'-end and a link sequence (part of aptamer) complementary to partial of the c-DNA at the 5'-end. In the presence of target, the aptamer associated with the target, resulting in the formation of duplex DNA (dsDNA), the DNA-Ag NCs thereafter could close to the guanine-rich sequence, leading to enhanced fluorescence signal readout. The widespread application of the sensing system is achieved success in the detection of three biomolecules. ATP, adenosine and thrombin in the range of 0.5-8.0 µM, 0.5-7.0 µM and 50-900 nM could be linearly detected with the detection limits of 91.6 nM, 103.4 nM and 8.4 nM, respectively. This label-free and turn-on fluorescent sensing system employing the mechanism proposed here turns out to be sensitive, selective, and convenient for the detection of biomolecules without washing and separation steps.