Association between proton pump inhibitors and risk of hepatic encephalopathy in patients undergoing transjugular intrahepatic portosystemic shunt: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Hepatic encephalopathy (HE) is a major complication of acute liver failure, cirrhosis and transjugular intrahepatic portosystemic shunt (TIPS) placement. Its clinical manifestations range from mild cognitive deficits to coma. Furthermore, HE is a financial burden to a patient's family and significantly affects the patient's quality of life. In clinical practice, proton pump inhibitors (PPIs) are widely used for the treatment of HE. The use of PPIs is associated with an increased risk of post-TIPS HE; however, findings on the risk relationship between PPIs and post-TIPS HE are inconsistent. Therefore, a systematic evaluation of the relationship is needed to further provide valid evidence for the rational use of PPIs in patients who undergo TIPS. METHODS AND ANALYSIS: PubMed, Web of Science, Cochrane Library and Embase will be searched extensively for relevant information. Information from 1 July 2023 to 31 July 2023 in these databases will be included. Primary outcomes will be the use of PPIs and incidence of HE after TIPS; secondary outcomes will be survival, dose dependence and adverse events. This meta-analysis will be reported in accordance with the 50 Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The risk of bias, heterogeneity and quality of evidence of the included studies will be evaluated prior to the data analysis. All data will be analysed using Review Manager (V.5.4.1) and Stata (V.17.0) statistical software. ETHICS AND DISSEMINATION: Ethical approval will not be necessary for this review and meta-analysis. The results of the study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022359208.

Live-cell imaging of human apurinic/apyrimidinic endonuclease 1 in the nucleus and nucleolus using a chaperone@DNA probe.

Human apurinic/apyrimidinic endonuclease 1 (APE1) plays crucial roles in repairing DNA damage and regulating RNA in the nucleus. However, direct visualization of nuclear APE1 in live cells remains challenging. Here, we report a chaperone@DNA probe for live-cell imaging of APE1 in the nucleus and nucleolus in real time. The probe is based on an assembly of phenylboronic acid modified avidin and biotin-labeled DNA containing an abasic site (named PB-ACP), which cleverly protects DNA from being nonspecifically destroyed while enabling targeted delivery of the probe to the nucleus. The PB-ACP construct specifically detects APE1 due to the high binding affinity of APE1 for both avidin and the abasic site in DNA. It is easy to prepare, biocompatible and allowing for long-term observation of APE1 activity. This molecular tool offers a powerful means to investigate the behavior of APE1 in the nuclei of various types of live cells, particularly for the development of improved cancer therapies targeting this protein.

Comparative efficacy and tolerability of first-line treatments for untreated, HER2-negative, advanced gastric cancer: systematic review and network meta-analysis.

INTRODUCTION: This article provided direct comparisons across first-line regimens for patients with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer. We performed a network meta-analysis (NMA) of phase III trials to compare the efficacy and safety of first-line treatments for gastric cancer. METHODS: We conducted a systematic review and Bayesian or Frequentist network meta-analysis by searching relevant literature from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences from January 1, 2000 to May 1, 2023. This study was registered in the Prospective Register of Systematic Reviews (PROSPERO CRD42023414357) to ensure transparency. Randomized clinical trials (RCTs) that qualified the inclusion criteria were subjected to network meta-analysis and systematically reviewed. RESULTS: We included a total of 25 studies including 14389 patients and 23 first-line treatments. Overall, sintilimab plus capecitabine plus oxaliplatin (Sint-XELOX) appeared to confer the best overall survival (OS) (calculated using surface under the cumulative ranking curve [SUCRA], 81%), with significant differences versus fluorouracil plus cisplatin (PF) (HR [hazard ratios] = 0.71, 95% credible interval [CI]: 0.51-0.99). Nivolumab plus tegafur (S-1) plus oxaliplatin (Nivo-SOX) and tislelizumab plus capecitabine plus oxaliplatin (Tisle-XELOX) were also found to be better than PF in providing OS benefit (HR = 0.73, 95%CI: 0.57-0.93 and HR = 0.74, 95%CI: 0.59-0.93, respectively). Sint-XELOX still provided the best progression-free survival (PFS) (SUCRA, 96%), with significant differences versus PF (HR = 0.47, 95%CI: 0.31-0.69). Nivo-SOX and Tisle-XELOX were also found to be better to PF in providing PFS benefit (HR = 0.58, 95%CI: 0.42-0.80 and HR = 0.67, 95%CI: 0.54-0.82, respectively). CONCLUSIONS: These results indicated that immunotherapy plus chemotherapy was associated with greater progression-free survival and overall survival benefits for patients with HER2-negative advanced gastric cancer, compared with other first-line treatments. In particular, sintilimab combined with chemotherapy showed the best PFS and OS benefits.

Establishment and validation of a nomogram model for riskprediction of hepatic encephalopathy: a retrospective analysis.

To establish a high-quality, easy-to-use, and effective risk prediction model for hepatic encephalopathy, to help healthcare professionals with identifying people who are at high risk of getting hepatic encephalopathy, and to guide them to take early interventions to reduce the occurrence of hepatic encephalopathy. Patients (n = 1178) with decompensated cirrhosis who attended the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were selected for the establishment and validation of a nomogram model for risk prediction of hepatic encephalopathy. In this study, we screened the risk factors for the development of hepatic encephalopathy in patients with decompensated cirrhosis by univariate analysis, LASSO regression and multifactor analysis, then established a nomogram model for predicting the risk of getting hepatic encephalopathy for patients with decompensated cirrhosis, and finally performed differentiation analysis, calibration analysis, clinical decision curve analysis and validation of the established model. A total of 1178 patients with decompensated cirrhosis who were hospitalized and treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were included for modeling and validation. Based on the results of univariate analysis, LASSO regression analysis and multifactor analysis, a final nomogram model with age, diabetes, ascites, spontaneous peritonitis, alanine transaminase, and blood potassium as predictors of hepatic encephalopathy risk prediction was created. The results of model differentiation analysis showed that the AUC of the model of the training set was 0.738 (95% CI 0.63-0.746), while the AUC of the model of the validation set was 0.667 (95% CI 0.541-0.706), and the two AUCs indicated a good discrimination of this nomogram model. According to the Cut-Off value determined by the Jorden index, when the Cut-Off value of the training set was set at 0.150, the sensitivity of the model was 72.8%, the specificity was 64.8%, the positive predictive value was 30.4%, and the negative predictive value was 91.9%; when the Cut-Off value of the validation set was set at 0.141, the sensitivity of the model was 69.7%, the specificity was 57.3%, the positive predictive value was 34.5%, and the negative predictive value was 84.7%. The calibration curve and the actual events curve largely overlap at the diagonal, indicating that the prediction with this model has less error. The Hosmer-Lemeshow test for goodness of fit was also applied, and the results showed that for the training set, χ2 = 1.237587, P = 0.998, and for the validation set, χ2 = 31.90904, P = 0.0202, indicating that there was no significant difference between the predicted and actual observed values. The results of the clinical decision curve analysis showed that the model had a good clinical benefit, compared with the two extreme clinical scenarios (all patients treated or none treated), and the model also had a good clinical benefit in the validation set. This study showed that aged over 55 years, complications of diabetes, ascites, and spontaneous bacterial peritonitis, abnormal glutamate aminotransferase and abnormal blood potassium are independent risks indicators for the development of hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model based on the indicators mentioned above can effectively and conveniently predict the risk of developing hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model established on this study can help clinical healthcare professionals to timely and early identify patients with high risk of developing hepatic encephalopathy.

Correlation Analysis of Prognostic Gene Expression, Tumor Microenvironment, and Tumor-Infiltrating Immune Cells in Ovarian Cancer.

Objective: Tumor microenvironment (TME) research can provide a crucial direction for the innovation and continuous improvement of novel biologic therapies for cancer. This study examined the relationship between the TME, expression profiles of the tumor-infiltrating immune cell, and prognostic gene expression in ovarian cancer (OC). Materials and Methods: Screening of CD3E, CD3G, CD2, CD3D, CCL19, and IL2RG was performed using the bioinformatics methods. Results: All six genes were found to participate in immune-related molecular mechanisms and could regulate the expression of tumor-infiltrating cells. A Kaplan-Meier survival analysis results demonstrated a strong association between overall survival and all gene expressions in patients with OC. CIBERSORT analysis results showed that the expression level of all genes was positively correlated with γδ T cell proportions. Conclusion: Therefore, in the OC microenvironment, CD3E, CD3G, CD2, CD3D, CCL19, and IL2RG can be potential immunotherapy targets and prognostic markers.

Visualization and Comparison of the Level of Apurinic/Apyrimidinic Endonuclease 1 in Live Normal/Cancerous and Neuron Cells with a Fluorescent Nanoprobe.

As a major apurinic/apyrimidinic endonuclease and a redox signaling protein in human cells, APE1 plays a crucial role in cellular function and survival. The relationship between alterations of APE1 expression and subcellular localization and the initiation, development and treatment of various cancers has received extensive attention. However, comparing the in-vivo activity of APE1 in normal and cancerous breast live cells remains challenging due to the low efficiency of commonly used liposome transfection methods in delivering DNA substrate probes into human normal breast epithelial cells (MCF-10A). In this work, we develop a DNA/RNA hybrid-based small magnetic fluorescent nanoprobe (25 ± 3 nm) that can be taken up by various live cells under magnetic transfection. The D0/R-nanoprobe demonstrates an outstanding specificity toward APE1 and strong resistance to the cellular background interference. Using this nanoprobe, we are not only able to visualize the intracellular activity of APE1 in breast ductal carcinoma (MCF-7) live cells, but also demonstrate the APE1 activity in MCF-10A live cells for the first time. The method is then extended to observe the changes in APE1 levels in highly metabolically active neuroendocrine cells under normal conditions and severe attacks by reactive oxygen species in real-time. The fluorescent nanoprobe provides a useful tool for studying the dynamic changes of intracellular APE1 in normal or cancerous live cells. It also displays the potential for visible and controllable release of miRNA drugs within live cells for therapeutic purposes.

Gut microbiota in Chinese and Japanese patients with cardiovascular diseases: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) is a major threat to public health. OBJECTIVE: Compare the gut microbial composition between Chinese and Japanese patients with cardiovascular diseases and healthy subjects. STUDY SELECTION: Observational studies with Chinese and Japanese populations. Reviews, duplicate, book chapters, and other irrelevant studies were excluded. DATA EXTRACTION: Independent searching by two investigators (LLJ, HJL). DATA SYNTHESIS: Data from eleven studies (with 960 subjects) were included for the meta-analysis. The meta-analysis showed that the abundance of Firmicutes in patients with cardiovascular disease was [ES=0.42, 95%CI, (0.34, 0.50), P<.01], while the abundance of Firmicutes in control subjects was [ES=0.36, 95%CI, (0.23, 0.49), P<.01] (ES: effect size). When compared to control subjects, the differential expression of Firmicutes abundance in patients with CVDs was [MD = 15.21, 95%CI (8.95, 21.48), P<.01] (MD: mean difference). The ratio of Firmicutes abundance in patients with CVDs to the control subjects was [RR=1.28, 95%CI (0.98, 1.67), P=.07]. The ratio of Firmicutes in coronary heart disease (CHD) patients and controls was [RR=1.42, 95%CI (1.05, 1.94), P=.02]. Firmicutes/Bacteroidetes ratio is [OR=1.64 95%CI (1.11, 2.42), P=.01]. CONCLUSION: Our data show that patients with cardiovascular disease had higher levels of gut Firmicutes when compared to healthy controls. In addition, gut microbial dysbiosis was present in patients with cardiovascular diseases. LIMITATIONS: Due to limited quality and quantity of selected studies, conclusions from the current study need to be validated by future studies. CONFLICT OF INTEREST: None.

Comparative Transcriptome Sequencing Analysis of Hirudo nipponia in Different Growth Periods.

Hirudo nipponia is the only blood-sucking leech included in Chinese Pharmacopoeia having distinct features of anticoagulation, exorcizing blood stasis, and promoting menstruation. Despite such significant characteristics, very little is known about its molecular genetics and related physiological mechanisms. In this study, the transcriptomes of H. nipponia at three developmental stages (larvae, young, and adults), revealed a total of 1,348 differentially expressed genes (DEGs), 223 differentially expressed lncRNAs, and 88 novel mRNAs. A significant diverse gene expression patterns were observed at different developmental stages which were analyzed by differential gene expression trends, and the overall gene expression trends consist of three overall down-regulated trends, and two overall up-regulated trends. Furthermore, the GO and KEGG enrichment functional annotation analysis revealed that these DEGs were mainly associated with protein hydrolysis, signal transduction, energy metabolism, and lipid metabolism while growth, development, metabolism, and reproduction-related DEGs were also found. Additionally, real-time quantitative PCR results confirmed deep sequencing results based on the relative expression levels of nine randomly selected genes. This is the first transcriptome-based comprehensive study of H. irudo nipponia at different developmental stages which provided considerable deep understanding related to gene expression patterns and their relevant developmental pathways, neurodevelopmental and reproductive characteristics of the leech.

Comprehensive Transcriptome Sequencing Analysis of Hirudinaria manillensis in Different Growth Periods.

Medical leeches are widely been used in biochemical and clinical medical studies, helping to restore blood circulation to grafted or severely injured tissue. Mostly, adult leeches are being used in the traditional pharmacopeia, but the gene expression profiling of leeches in different growth periods is not well-reported. So, in this study, we used transcriptome analysis to analyze the comparative gene expression patterns of Hirudinaria manillensis (H. manillensis) in different growth periods, including larval, young, and adult stages. We constructed 24 cDNA libraries from H. manillensis larval, young, and adult stages, and about 54,639,118 sequences were generated, 18,106 mRNA transcripts of which 958 novel mRNAs and 491 lncRNAs were also assembled as well. Furthermore, the results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the differentially upregulated genes from the larval to adult stages were enriched in pathways such as cilium, myofibril, contractile fiber, cytoskeleton proteins, dilated cardiomyopathy, adrenergic signaling in cardiomyocytes, etc. Moreover, in the adult stages, a significant increase in the expression of the Hirudin-HM (HIRM2) genes was detected. In addition, our comparative transcriptome profiling data from different growth stages of H. manillensis also identified a large number of DEGs and DElncRNAs which were tentatively found to be associated with the growth of H. manillensis; as it grew, the muscle-related gene expression increased, while the lipid metabolism and need for stimulation and nutrition-related genes decreased. Similarly, the higher expression of HIRM2 might attribute to the high expression of protein disulfide isomerase gene family (PDI) family genes in adulthood, which provides an important clue that why adult leeches rather than young leeches are widely used in clinical therapeutics and traditional Chinese medicine.

Association of MTHFR Polymorphisms with H-Type Hypertension: A Systemic Review and Network Meta-Analysis of Diagnostic Test Accuracy.

Purpose: An association between MTHFR polymorphisms and H-type hypertension (H-HTN) has been investigated by epidemiological studies, but results have been inconsistent. Thus, a systematic assessment of the association was performed based on a literature review and pooled analysis, to provide stronger evidence on the effects of single nucleotide polymorphisms on H-HTN risk. Methods: Three investigators independently retrieved relevant studies in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and China Biomedical Literature Database (CBM). A fixed or random effects model was selected to calculate pooled odds ratio (OR) and 95% confidence intervals (CIs). A network meta-analysis of diagnostic test and Thakkinstian's algorithm were used to select the most appropriate genetic model, along with false-positive report probability (FPRP) for noteworthy associations. All data were processed using Stata 15.0 and Meta-Disc. Results: A total of 14 studies involving 1759 cases and 1581 controls for MTHFR were included in our meta-analysis. In a direct meta-analysis, we found that MTHFR C667T rs1801133 significantly increased the risk of H-HTN susceptibility except for an overdominant model. However, MTHFR A1298C rs1801131 polymorphism had no significant correlation with H-HTN risk. Besides, MTHFR C667T rs1801133 is a potential diagnostic biomarker for estimating H-HTN risk. The results indicated that the dominant model was an optimal diagnosis model for excluding diseases, which could reduce a missed diagnosis rate and further improve the accuracy of disease diagnosis. Conclusion: The present result suggests that MTHFR C667T rs1801133 polymorphism is associated with H-HTN risk and may act as a promising predictive biomarker for H-HTN risk. However, further well-designed studies are warranted to confirm these results.

Molecular mechanisms underlying hematophagia revealed by comparative analyses of leech genomes.

BACKGROUND: Leeches have been used in traditional Chinese medicine since prehistoric times to treat a spectrum of ailments, but very little is known about their physiological, genetic, and evolutionary characteristics. FINDINGS: We sequenced and assembled chromosome-level genomes of 3 leech species (bloodsucking Hirudo nipponia and Hirudinaria manillensis and nonbloodsucking Whitmania pigra). The dynamic population histories and genome-wide expression patterns of the 2 bloodsucking leech species were found to be similar. A combined analysis of the genomic and transcriptional data revealed that the bloodsucking leeches have a presumably enhanced auditory sense for prey location in relatively deep fresh water. The copy number of genes related to anticoagulation, analgesia, and anti-inflammation increased in the bloodsucking leeches, and their gene expressions responded dynamically to the bloodsucking process. Furthermore, the expanded FBN1 gene family may help in rapid body swelling of leeches after bloodsucking, and the expanded GLB3 gene family may be associated with long-term storage of prey blood in a leech's body. CONCLUSIONS: The high-quality reference genomes and comprehensive datasets obtained in this study may facilitate innovations in the artificial culture and strain optimization of leeches.

The prescription rule analysis of the New Theory on Spleen Dampness Syndrome by Academician TONG Xiaolin / 数字中医药（英文）

@#Objective To analyze the basic characteristics, drug features, prescription rules, and drug-symptom relationships of patients in the splenic deficiency and impairment stage, by data mining of medical records under the New Theory on Spleen Dampness Syndrome (Pi Dan Xin Lun, 《脾瘅新论》). Methods Medical records listed in the “New Theory on Spleen Dampness Syndrome – Understanding and Treatment of Metabolic Syndrome from the Perspective of Traditional Chinese Medicine”, and which were diagnosed with the spleen dampness syndrome at the splenic deficiency and impairment stage, during January 2004 and December 2016 were selected. These patients’ data, including basic information, clinical symptoms, laboratory examination results, traditional Chinese medicine (TCM) and western medicine diagnoses, treatment methods, prescriptions, etc., were collected. The collected data were subsequently compiled into a medical record database using the Epidata 3.1 data management software, followed by the use of Apriori algorithm provided in the SPSS Modeler 14.2 statistical software to investigate the association rules between drug-drug, drug-symptom, and drug-western medicine indices. Results (i) A total of 51 medical records were included, involving 17 types of syndromes. Among them, the top three with frequency ≥ 3 included “Phlegm and blood stasis, and thoracic obstruction” “Deficiency-weakness of the spleen Qi, and static blood blocking collaterals”, and “Deficiency-weakness of the spleen Qi, and static blood blocking collaterals”. Alternatively, of the 14 treatment methods, the top three treatments with frequency of ≥ 3 included “Activating Yang and eliminating turbidity, and removing phlegm and dredging channel blockage” “Strengthening the spleen and benefiting Qi, and eliminating phlegm to activate the channels”, and “Warming Yang and benefiting Qi, and expelling cold to remove obstructions”. Among the 15 prescriptions, the top three used with frequency ≥ 3 included Huangqi Guizhi Wuwu Tang (黄芪桂枝五物汤), Gualou Xiebai Banxia Tang (瓜蒌薤白半夏汤), and Ganjiang Huangqin Huanglian Renshen Tang (干姜黄芩黄连人参汤). Lastly, of the 83 drugs used for a total of 476 times, those with frequency ≥ 15 included Huanglian (Coptidis Rhizoma), Huangqi (Astragali Radix), Jiudahuang (Wine-processed Rhei Radix et Rhizoma), Jixueteng (Spatholobi Caulis), Shengjiang (Zingiberis Rhizoma Recens), Huangqin (Scutellariae Radix), and Guizhi (Cinnamomi Ramulus). (ii) For the drug-drug associations, under the criteria of support ≥ 15% and confidence = 100%, seven second-order association rules, seven third-order rules, and six fourth-order roles were identified. The top-ranking rule of each was “Huangqin (Scutellariae Radix) → Huanglian (Coptidis Rhizoma)” “Ganjiang (Zingiberis Rhizoma) + Huangqin (Scutellariae Radix) → Huanglian (Coptidis Rhizoma)”, and “Baishao (Paeoniae Radix Alba) + Guizhi (Cinnamomi Ramulus) + Jixueteng (Spatholobi Caulis) → Huangqin (Scutellariae Radix)”, respectively. Alternatively, the drug-symptom associations were analyzed under the criteria of support ≥ 5% and confidence = 100%, which derived eight second-order association rules, 31 third-order rules, and 30 fourth-order rules. The top-ranking association rule of each order was “Huangqi (Astragali Radix) → Limb edema” “Guizhi (Cinnamomi Ramulus) + Jixueteng (Spatholobi Caulis) → Limb numbness and pain”, and “Guizhi (Cinnamomi Ramulus) + Jixueteng (Spatholobi Caulis) + Huangqi (Astragali Radix) → Limb numbness and pain”, respectively. Similarly, the drug-western medicine index associations were investigated under the criteria of support ≥ 5% and confidence = 100%, and five second-order association rules, 16 third-order rules, and 16 fourth-order rules were identified. In this category, the top-ranking association rule of each order was “Qinpi (Fraxini Cortex) → Uric acid” “Huanglian (Coptidis Rhizoma) + Ganjiang (Zingiberis Rhizoma) → Glycated hemoglobin”, and “Huanglian (Coptidis Rhizoma) + Ganjiang (Zingiberis Rhizoma) + Huangqin (Scutellariae Radix) → Glycated hemoglobin”, respectively. Conclusion Through association rule mining, this study objectively and quantitatively demonstrated the drug-drug, drug-symptom, and drug-physicochemical index associations of patients with the spleen dampness syndrome at the splenic deficiency and impairment stage treated by Academician TONG Xiaolin. The results indicated that treatment for these patients adopted the “state-target” syndrome differentiation method. The drug combination was characterized by “small prescriptions”, targeting both the patient’s symptoms and signs (syndrome target) and western medicine indices (treatment target). This study could provide references for future research on the academic thoughts and medical experience of Academician TONG Xiaolin.

Exploring the mechanisms underlying the therapeutic effect of Salvia miltiorrhiza in diabetic nephropathy using network pharmacology and molecular docking.

The mechanisms underlying the therapeutic effect of Salvia miltiorrhiza (SM) on diabetic nephropathy (DN) were examined using a systematic network pharmacology approach and molecular docking. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of SM. Targets were obtained using the SwissTargetPrediction and TCMSP databases. Proteins related to DN were retrieved from the GeneCards and DisGeNET databases. A protein-protein interaction (PPI) network was constructed using common SM/DN targets in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The Metascape platform was used for Gene Ontology (GO) function analysis, and the Cytoscape plug-in ClueGO was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was performed using iGEMDOCK and AutoDock Vina software. Pymol and LigPlos were used for network mapping. Sixty-six active ingredients and 189 targets of SM were found. Sixty-four targets overlapped with DN-related proteins. The PPI network revealed that AKT serine/threonine kinase 1 (AKT1), VEGFA, interleukin 6 (IL6), TNF, mitogen-activated protein kinase 1 (MAPK1), tumor protein p53 (TP53), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 14 (MAPK14), and JUN were the ten most relevant targets. GO and KEGG analyses revealed that the common targets of DN and SM were mainly involved in advanced glycation end-products, oxidative stress, inflammatory response, and immune regulation. Molecular docking revealed that potential DN-related targets, including tumor necrosis factor (TNF), NOS2, and AKT1, more stably bound with salvianolic acid B than with tanshinone IIA. In conclusion, the present study revealed the active components and potential molecular therapeutic mechanisms of SM in DN and provides a reference for the wide application of SM in clinically managing DN.

A systematic review and network meta-analysis of single nucleotide polymorphisms associated with pancreatic cancer risk.

In this meta-analysis, we systematically investigated the correlation between single nucleotide polymorphisms (SNPs) and pancreatic cancer (PC) risk. We searched PubMed, Network Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP), and Wanfang databases up to January 2020 for studies on PC risk-associated SNPs. We identified 45 case-control studies (36,360 PC patients and 54,752 non-cancer individuals) relating to investigations of 27 genes and 54 SNPs for this meta-analysis. Direct meta-analysis followed by network meta-analysis and Thakkinstian algorithm analysis showed that homozygous genetic models for CTLA-4 rs231775 (OR =0.326; 95% CI: 0.218-0.488) and VDR rs2228570 (OR = 1.976; 95% CI: 1.496-2.611) and additive gene model for TP53 rs9895829 (OR = 1.231; 95% CI: 1.143-1.326) were significantly associated with PC risk. TP53 rs9895829 was the most optimal SNP for diagnosing PC susceptibility with a false positive report probability < 0.2 at a stringent prior probability value of 0.00001. This systematic review and meta-analysis suggest that TP53 rs9895829, VDR rs2228570, and CTLA-4 rs231775 are significantly associated with PC risk. We also demonstrate that TP53 rs9895829 is a potential diagnostic biomarker for estimating PC risk.

Tai Chi Chuan for Subjective Sleep Quality: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: This review aims to investigate the efficacy of Tai Chi Chuan on subjective sleep quality among adults. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Scopus, CNKI (China National Knowledge Infrastructure), and the Wanfang Database from their inception to August 2019 and identified 25 eligible studies that were published in both English and Chinese. RESULTS: 24 out of 25 studies were identified to be high-quality studies according to the PEDro scale. The pooled results confirmed that Tai Chi Chuan elicited moderate improvements in subjective sleep quality (SMD = -0.512, 95% CI [-0.767, -0.257], P < 0.001). Notably, Tai Chi Chuan yielded more significant effects on sleep quality among the healthy population (SMD = -0.684, 95% CI [-1.056, -0.311], P < 0.001) than the clinical population (SMD = -0.395, 95% CI [-0.742, -0.047], P=0.026) and more benefits among the Asian population (SMD = -0.977, 95% CI [-1.446, -0.508], P < 0.001) than the American population (SMD = -0.259, 95% CI [-0.624, 0.105], P=0.164). After controlling the methodological quality of studies, it has been noted that Asians could achieve the most significant sleep-promoting benefit when Tai Chi Chuan was practiced between 60 and 90 min per session. CONCLUSIONS: Available data implied that subjective sleep quality was improved via Tai Chi training, but more thorough studies must be executed to ascertain our findings and optimize Tai Chi practices accordingly toward various populations.

Traditional Chinese medicine for the treatment of pulmonary fibrosis: A protocol for systematic review and meta-analysis of overview.

BACKGROUND: Since December 2019, there have been many cases of viral pneumonia of unknown causes in Wuhan City, Hubei Province. During the period of novel coronavirus, according to the observation of limited autopsy and biopsy pathological results, pulmonary interstitial fibrosis appeared in some pathological changes of lung. Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia with unknown etiology and pathological changes limited to the lung. At present, there is still a lack of reevaluation of systematic evaluation of traditional Chinese medicine treatment IPF. Therefore, a systematic re-evaluation of the systematic evaluation of traditional Chinese medicine in the treatment of pulmonary fibrosis may help to understand the effective treatment scheme of traditional Chinese medicine in the treatment of pulmonary fibrosis and provide more reliable evidence for the first-line clinicians to treat novel coronavirus. METHODS: We will search 3 foreign electronic databases (Cochrane Library, Embase, PubMed) and 4 Chinese electronic databases (China National Knowledge Infrastructure [CNKI], WangFang Database, Chinese Biomedical Literature Database [CBM], and Chinese Scientific Journal Database [VIP]) to collect potential systematic reviews from their inceptions to February 2020. The language of publication is limited to Chinese or English. We will consider SRs and meta-analysis of Traditional Chinese Medicine for the Treatment of pulmonary fibrosis. Two reviewers will identify relevant studies, and then assess the methodological quality by assessment of multiple systematic reviews-2 tool. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) report checklist to assess the quality of reports included in the study. In order to better evaluate the systematic evaluation included in this research, risk of bias in systematic review tool is included in this research to evaluate the methodological quality. The quality of evidence of the included systematic reviews was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The Primary outcomes include: Clinical total effective rate, curative effect of TCM symptoms, pulmonary function and blood gas analysis. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSIONS: We expect to obtain reliable evidence from systematic analysis of traditional Chinese medicine treatment of pulmonary fibrosis in an available and useful document. REGISTRATION NUMBER: INPLASY202060029.

A comprehensive evaluation of single nucleotide polymorphisms associated with atrophic gastritis risk: A protocol for systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with atrophic gastritis (AG) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with AG. METHODS: To identify all associated studies of SNPs and AG published, databases had been searched through January 2020 from the databases of PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, Embase, the Chinese Science and Technology Periodical Database (VIP), Cochrane Library, and Wanfang databases. With the help of network meta-analysis and Thakkinstian algorithm, the best genetic model with the strongest correlation with AG was selected, the final result - matching to the noteworthy correlation - was obtained by referring to the false positive reporting rate (false positive report probability, FPRP). Based on STREGA's stated criteria, the methodological quality of the data we collected was valued. Both Stata 14.0 and GeMTC will be used for a comprehensive review of the system and will be used in our meta-analysis. RESULTS: This study will provide a high-quality evidence to find the SNP most associated with AG susceptibility and the best genetic model. CONCLUSIONS: This study will explore which SNP is most associated with AG susceptibility. REGISTRATION: INPLASY202050016.

Tianma Gouteng Decoction combined with Qiju Dihuang Pill for the treatment of essential hypertension: A protocol for systematic review and meta-analysis.

BACKGROUND: Essential hypertension is one of the risk factors of cardiovascular and cerebrovascular diseases, which can cause target organ damage such as heart, brain and kidney, and has extremely high disability rate and death rate. With the development of economy and society, the prevalence rate of hypertension in China has increased rapidly from 9.8% in the 1980s to over 30% in the 21st century. According to the data published in "China Cardiovascular Disease Report 2018," China currently has 245 million hypertension patients. Comprehensive prevention and treatment of hypertension has become one of the major public health problems in China. The clinical practice and theoretical innovation of traditional Chinese medicine in the prevention and treatment of hypertension have been carried out for decades. Relevant literature points out that Tianma Gouteng Decoction combined with Qiju Dihuang Pill has ideal effect in the treatment of primary hypertension. However, most of the literatures are small sample studies, with uneven quality and clinical evidence, and lack of evidence-based medical evidence for clinical efficacy. Therefore, this study makes further meta-analysis of Tianma Gouteng Decoction combined with Qiju Dihuang Pill in the treatment of primary hypertension, with a view to providing evidence-based medical evidence for the treatment of primary hypertension. METHODS: We will search 3 foreign electronic databases (Cochrane Library, Embase, PubMed) and 4 Chinese electronic databases (China National Knowledge Infrastructure, WangFang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database) to collect potential systematic reviews from their inceptions to February 2020. The language of publication is limited to Chinese or English. First, the quality of randomized controlled trials documents included in this study was evaluated by using the improved Jadad scoring scale. Then, the 2 researchers conducted the evaluation independently according to Cochrane bias risk tools. The evidence level of the results will be evaluated by using the recommended evaluation, development and evaluation grading of recommendations assessment, development, and evaluation method. Statistical analysis will be conducted using Revman 5.3. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSIONS: The conclusion of this study will provide evidence for the efficacy of Tianma Gouteng Decoction combined with Qiju Dihuang Pills in the treatment of primary hypertension due to the efficacy of western medicine alone in treating primary hypertension. REGISTRATION NUMBER PROSPERO: INPLASY202050088.

Effects of salvianolic acid B on liver fibrosis: A protocol for systematic review and meta analysis.

BACKGROUND: Liver fibrosis is a pathological change existing in most chronic liver diseases, which leads to abnormal changes in liver tissue structure and affects the normal physiological function of liver. Without effectively control, liver fibrosis can develop into cirrhosis and increase the risk of liver cancer. Salvianolic acid B (Sal B) is the main active component in the water-soluble extract from Salvia miltiorrhiza, which is a traditional Chinese medicine usually used for treating cardiovascular and liver diseases. It is reported that Sal B shown a good action against liver fibrosis via numerous signaling pathways, which indicate that Sal B is a potential candidate drug for the treatment of liver fibrosis. METHODS: We searched the related researches from the following electronic databases: PubMed, EMBASE, Web of science, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wan fang Database for Chinese Technical Periodicals and VIP Database. All the databases were searched from inception to December 2019. No restriction of language, publication date, or publication status. PICO of this systematic review are shown as flowing: P, preclinical studies which evaluated the effects of Sal B on the animal models of liver fibrosis with controlled studies; I, received Sal B as only treat in any dose; C, received normal saline, distilled water, or no treatment; O, the primary outcome include measure will be the decrease in liver fibrosis score, and the secondary outcomes include the index of liver fibrosis. All the included data will be analyzed with the software of Review Manager 5.2 and STATA 14.2. DISCUSSION: The purpose of this study is to conduct a systematic review and meta-analysis to assess the effects on anti-liver fibrosis of Sal B, and this will be contribute to drug development and pathological mechanisms of clinical research. TRIAL REGISTRATION: INPLASY202050101, registered on 28/5/2020.

A comprehensive evaluation of single nucleotide polymorphisms associated with gastric cancer risk: A protocol for systematic review and network meta-analysis.

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been inconsistently associated with gastric cancer (GC) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with GC. METHODS: Databases were searched to identify association studies of SNPs and GC published through January 2020 from the databases of PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and Wan fang databases. Network meta-analysis and Thakkinstian algorithm were used to select the most appropriate genetic model, along with false positive report probability for noteworthy associations. The methodological quality of data was assessed based on the STrengthening the REporting of Genetic Association Studies statement Stata 14.0 will be used for systematic review and meta-analysis. RESULTS: This study will provide a high-quality evidence to find the SNP most associated with GC susceptibility and the best genetic model. CONCLUSIONS: This study will explore which SNP is most associated with GC susceptibility. REGISTRATION: INPLASY202040132.