3 CpG Methylation Biomarkers for the Diagnosis of Polycystic Ovary Syndrome (PCOS) in Blood Samples.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease in women that seriously interferes with patient's metabolic and reproductive functions. The current diagnostic criteria for PCOS are expert-based and still disputed. Previous studies have identified changes in DNA methylation in peripheral blood of women with PCOS, but their diagnostic potential for PCOS remains to be studied. OBJECTIVE: The present study aimed to identify potential methylation biomarkers for the diagnosis of PCOS in blood. METHODS: Methylation profiling of peripheral blood was downloaded from a public database, Gene Expression Omnibus (GEO), including 30 PCOS patients (diagnosed with the revised 2003 Rotterdam consensus criteria) and 30 age-matched healthy women recruited from Centre of Reproductive Medicine, Linyi People's Hospital, Shandong, China. Weighted gene co-expression network analysis (WGCNA) was utilized to identify PCOS-related co-methylation CpG sites (co- MPs). Functional enrichment analysis was performed on the localized genes of PCOS-related co- MPs. The least absolute shrinkage and selection operator (LASSO) regression was used to screen out CpG methylation signatures for PCOS diagnosis, and receiver operating characteristic (ROC) analysis was conducted to evaluate their diagnostic accuracy. To assess the accuracy of the combination of the investigated indicators, multivariate ROC analysis was performed on the predicted probability values obtained using binary logistic regression on the methylation levels of selected CpGs. RESULTS: Seven co-methylation modules were obtained, among which the turquoise module is the most relevant to PCOS, containing 194 co-MPs. The genes that these co-MPs located in were mainly associated with the immune-related pathway. According to LASSO regression, three Co- MPs (cg23464743, cg06834912, cg00103771) were identified as potential diagnostic biomarkers of PCOS. ROC analysis showed an AUC (area under curve) of 0.7556 (sensitivity 60.0%, specificity 83.3%) for cg23464743, 0.7822 (sensitivity 70.0%, specificity 80.0%) for cg06834912, and 0.7611 (sensitivity 63.3%, specificity 83.3%) for cg00103771. The diagnostic accuracy of the combination of these 3 indicators presented to be higher than any single one of them, with the AUC of 0.8378 (sensitivity 73.3%, specificity 93.3%). CONCLUSION: The combination of 3 CpG methylation signatures in blood was identified with a good diagnostic accuracy for PCOS, which may bring new insight into the development of PCOS diagnostic markers in the future.

A Comprehensive Network Pharmacology-Based Strategy to Investigate Multiple Mechanisms of HeChan Tablet on Lung Cancer.

BACKGROUND: HeChan tablet (HCT) is a traditional Chinese medicine preparation extensively prescribed to treat lung cancer in China. However, the pharmacological mechanisms of HCT on lung cancer remain to be elucidated. METHODS: A comprehensive network pharmacology-based strategy was conducted to explore underlying mechanisms of HCT on lung cancer. Putative targets and compounds of HCT were retrieved from TCMSP and BATMAN-TCM databases; related genes of lung cancer were retrieved from OMIM and DisGeNET databases; known therapeutic target genes of lung cancer were retrieved from TTD and DrugBank databases; PPI networks among target genes were constructed to filter hub genes by STRING. Furthermore, the pathway and GO enrichment analysis of hub genes was performed by clusterProfiler, and the clinical significance of hub genes was identified by The Cancer Genome Atlas. RESULT: A total of 206 compounds and 2,433 target genes of HCT were obtained. 5,317 related genes of lung cancer and 77 known therapeutic target genes of lung cancer were identified. 507 unique target genes were identified among HCT-related genes of lung cancer and 34 unique target genes were identified among HCT-known therapeutic target genes of lung cancer. By PPI networks, 11 target genes AKT1, TP53, MAPK8, JUN, EGFR, TNF, INS, IL-6, MYC, VEGFA, and MAPK1 were identified as major hub genes. IL-6, JUN, EGFR, and MYC were shown to associate with the survival of lung cancer patients. Five compounds of HCT， quercetin, luteolin, kaempferol, beta-sitosterol, and baicalein were recognized as key compounds of HCT on lung cancer. The gene enrichment analysis implied that HCT probably benefitted patients with lung cancer by modulating the MAPK and PI3K-Akt pathways. CONCLUSION: This study predicted pharmacological and molecular mechanisms of HCT against lung cancer and could pave the way for further experimental research and clinical application of HCT.

Oral oxymatrine for hepatitis B cirrhosis: A systematic review protocol.

BACKGROUND: Characterized by diffuse hepatic fibrosis and nodule formation, hepatitis B cirrhosis (HBC), an important result of chronic hepatitis B development, mainly contains compensated and decompensated stage. Compensated cirrhosis can further develop into decompensated stage and hepatocellular carcinoma with serious complications and high mortality. Antiviral therapy using interferon (IFN) or nucleos(t)ide analogs (NUCs) is essential for improving the prognosis of the disease but IFN has large side effects while NUCs often develop drug resistance. Antifibrosis is also an important strategy, but currently there is no effective antifibrosis drug. Pharmacologic studies have demonstrated that oxymatrine (OM) exhibits anti-hepatitis B virus (HBV) and antifibrosis effects. An increasing number of clinical controlled studies also have found that OM combined with conventional therapy could improve the curative effect and reduce adverse events incidence in treating HBC but there is no systematic review of it. Based on the extensive collection of literature, we will use meta-analysis to assess the efficacy and safety of OM for HBC. METHODS: PubMed, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang data, Chinese Scientific Journals Database (VIP), and China biomedical literature database will be searched to obtain the eligible studies published up to July 15, 2018. The primary outcome will be liver function indexes, liver fibrosis indexes, and Child-Pugh score. The secondary outcome will be hepatitis B virus DNA quantification, HBV DNA seroconversion rate, hepatitis B e antigen (HBeAg) seroconversion rate, and adverse events incidence. Data analysis will be conducted using RevMan 5.3 and Stata V.9.0 software. Trial sequential analysis (TSA) will be performed to assess the risk of random error and the validity of conclusion using TSA program version 0.9 beta. RESULTS: This systematic review will provide a high quality synthesis of OM for HBC from various evaluation aspects including liver function indexes, liver fibrosis indexes and Child-Pugh score, HBV DNA quantification, HBV DNA seroconversion rate, HBeAg seroconversion rate and adverse events incidence. CONCLUSION: The systematic review will provide evidence to assess the efficacy and safety of OM in the treatment of HBC. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018095275.

Berberine Combined with Triple Therapy versus Triple Therapy for Helicobacter pylori Eradication: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To assess the effects and safety of berberine combined with triple therapy on Helicobacter pylori (H. pylori) eradication in adults. METHODS: PubMed, MEDLINE, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure (CNKI), Wanfang data, Chinese Technology Journal Full-text Database (VIP), and China biomedical literature database (CBM) were searched to obtain the eligible studies published up to October 10, 2017. The primary outcome was eradication rate of H. pylori. The secondary outcome was incidence of adverse effects. Data analysis was conducted by RevMan5.2 and Stata V.9.0 software. Trial sequential analysis (TSA) was performed to assess the risk of random error and the validity of conclusion with TSA program version 0.9 beta. RESULTS: The meta-analysis results indicated berberine combined with triple therapy could improve the eradication rates of H. pylori (urea breath test subgroup: RR=1.18, 95%CI=(1.12,1.24), P < 0.00001, biopsy subgroup: RR=1.23, 95%CI=(1.13,1.34), P < 0.00001) and reduce the total occurrence of adverse effects (OR=0.59, 95%CI(0.46, 0.75), P < 0.0001) when compared with only using triple therapy. Besides, the incidence of nausea (OR=0.59, 95%CI(0.41, 0.86), P < 0.05) and diarrhea (OR=0.41, 95%CI(0.24, 0.71) was remarkably lower in experimental group while that of abdominal distention (OR=0.64, 95%CI(0.40,1.04), P > 0.05) and vomiting (OR=0.65, 95%CI(0.37, 1.15), P > 0.05) had no significant change. TSA of H. pylori eradication rates and adverse effects incidence illustrated that the cumulative value of Z-curve went across the conventional boundary value, trial sequential monitoring boundary for benefit, and required information size, suggesting the results were stable. CONCLUSION: Evidence from meta-analysis suggested that berberine combined with triple therapy can be an option for increasing H. pylori eradication rates and reducing overall therapy-related adverse effects incidence, particularly nausea and diarrhea, whereas more randomized controlled trials designed according to CONSORT statement are demanded to support the efficacy in further studies.