Serum levels of microRNAs can specifically predict liver injury of chronic hepatitis B

AIM:To investigate whether circulating microRNAs (miRNAs) can serve as molecular markers to predict liver injury resulted from chronic hepatitis B (CHB). METHODS:The profiles of serum miRNA expression were first generated with serum samples collected from 10 patients with CHB and 10 healthy donors (Ctrls) by microarray analysis. The levels of several miRNAs were further quantitated by real-time reverse transcriptionpolymerase chain reaction with serum samples from another 24 CHB patients and 24 Ctrls. Serum samples of 20 patients with nonalcohlic steatohepatitis (NASH) were also included for comparison. The comparison in the levels of miRNAs between groups (CHB, NASH and Ctrl) was analyzed with Mann-Whitney Utest. The correlation between miRNAs and clinical pathoparameters was analyzed using Spearman correlation analysis or canonical correlation analysis. The receiver-operator characteristic (ROC) curves were also generated to determine the specificity and sensitivity of each individual miRNA in distinguishing patients with CHB from Ctrls. RESULTS:miRNA profile analysis showed that 34 miRNAs were differentially expressed between CHB and Ctrl subjects, in which 12 were up-regulated and 22 down-regulated in CHB subject (fold change > 2.0 and P < 0.01). The median levels of miR-122, -572, -575 and -638 were significantly higher (P < 1.00 × 10 -5 ) while miR-744 significantly lower (P < 1.00 × 10 -6 ) in CHB compared with the Ctrl. The levels of miR-122, -572 and -638 were also higher (P < 1.00 × 10 -3 ) while the level of miR-744 lower in CHB (P < 0.05) than in NASH, although the difference between them was not as significant as that between CHB and Ctrl. ROC curve analysis revealed that the levels of miR-122, -572, -575, -638 and -744 in serum were sensitive and specific enough to distinguish CHB, NASH and Ctrl. Multivariate analysis further showed that the levels of these miRNAs were correlated with the liver function parameters. Most significantly, it was the scatter plot of principal component with the levels of these miRNAs, but not the parameters of liver function, which clearly distinguished CHB, NASH and Ctrl subjects. CONCLUSION:Serum levels of miR-122, -572, -575, -638 and -744 are deregulated in patients with CHB or NASH. The levels of these miRNAs may serve as potential biomarkers for liver injury caused by CHB and NASH.

Research advances in traditional Chinese medicine syndromes in cancer patients

Traditional Chinese medicine （TCM） syndrome, also known as TCM ZHENG or TCM pattern, is an integral and essential part of TCM theory that helps to guide the design of individualized treatments. ATCM syndrome, in essence, is a characteristic profile of all clinical manifestations in one patient that can be readily identified by a TCM practitioner. In this article, the authors reviewed the presentations of TCM syndromes in seven common malignancies （liver, lung, gastric, breast, colorectal, pancreatic and esophageal cancers）, the objectivity and the standardization of TCM syndrome differentiation, the evaluation of TCM syndrome modeling in cancer research, and syndrome differentiation-guided TCM treatment of cancers. A better understanding of TCM syndrome theory, as well as its potential biologica basis, may contribute greatly to the clinical TCM diagnosis and the treatment of cancer.

Advances in mesenchymal stem cells combined with traditional Chinese medicine therapy for liver fibrosis

Liver fibrosis is a primary cause of liver cirrhosis, and even hepatocarcinoma. Recently, the usage of mesenchyrnal stem cells （MSCs） has been investigated to improve liver fibrosis. It has been reported that the differentiation, proliferation and migration of MSCs can be regulated by traditional Chinese medicine treatment; however, the mechanisms are still unclear. In this article, the authors review the characteristics of MSCs such as multidirectional differentiation and homing, and its application in animal experiments and clinical trials. The authors also list areas that need further investigation, and look at the future prospects of clinical application of MSCs.

Traditional Chinese Medicine Syndromes Distribution in Colorectal Cancer and its Association with Western Medicine Treatment and Clinical Laboratory Indicators

Objective:The objective of the study is to explore the traditional Chinese medicine (TCM) syndrome distribution in colorectal cancer (CRC) and its correlation with treatment methods and clinical laboratory indicators.Materials and Methods: Using the CRC cases report form of TCM,760 CRC patients with TCM four diagnosis information,western medicine treatment information and clinical laboratory indicators were collected,and TCM syndromes distribution in CRC were summarized.The correlation between TCM syndrome type and western medicine treatments,clinical laboratory indicators such as liver and kidney function,immune function,and tumor biomarkers was analyzed. Results:In 760 cases of CRC, Spleen deficiency syndrome (SDS, 25%),liver and kidney Yin deficiency syndrome (LKYDS, 13%), LKYDS-SDS,12%,spleen deficient Qi stagnation syndrome (SDQSS, 10%),and damp heat syndrome (DHS, 9%) were more common TCM syndrome types.LKYDS, SDS,LKYDS-SDS,and SDQSS were significantly distributed under different treatment methods (P < 0.001).There was no statistically significant difference in the distribution of immune fUnction and cytokine among the five TCM syndromes (P > 0.05),but there was statistically significant difference in the distribution of blood routine,liver and kidney function, and tumor biomarkers (P < 0.05). Conclusion: LKYDS,SDS,LKYDS-SDS, SDQSS,and DHS were the first five TCM syndromes in CRC.There were the significant correlations between the distribution of TCM syndrome and the clinical laboratory indicators,and the distribution of TCM syndromes was affected by surgery, radiotherapy,and chemotherapy.

Ginsenoside Rb1 Pretreatment Attenuates Myocardial Ischemia by Reducing Calcium/Calmodulin-Dependent Protein Kinase Ⅱ-Medicated Calcium Release

Objective:The aim of this study was to investigate the protective effects of ginsenoside Rb1 and assess whether these protective effects are related to calcium/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ).Methods:A myocardial ischemia(IS)rat.model and a myocardial H9 C2 cell hypoxia model were established.MI was induced by occluding the left anterior descending artery for 120 min.Ginsenoside Rb1(10 mg/kg)was administered 30 min before ischemia induction,and the treatment continued for 7 days.Results:In the rat IS injury model,ginsenoside Rb1 reduced myocardial infarct size,mean left ventricular diastolic pressure,incidence of arrhythmia,and levels of serum creatine kinase,lactate dehydrogenase,and malondialdehyde.However,the mean left ventricular systolic pressure,and maximal rising and falling rates of ventricular pressure(±dp/dtmax)increased.In the myocardial H9 C2 cell hypoxia model,ginsenoside Rb1 reduced intracellular calcium concentrations([Ca2+]i)during hypoxia,and markedly reversed the hypoxia-induced decrease in cell survival.Ginsenoside Rb1 was involved in the downregulation of CaMKⅡand the ryanodine receptor,as well as hypoxia-induced H9 C2 cell survival.Conclusion:The findings of the present study suggest that ginsenoside Rb1 attenuates MI injury in rats,partially through the downregulation of CaMKⅡexpression.

DNA Methylation and SNPs in VCX are Correlated with Sex Differences in the Response to Chronic Hepatitis B

The study was conducted to explore the mechanisms of sex differences in the response to chronic hepatitis B(CHB)in terms of DNA methylation,SNP genotype,and gene expression.Genomic DNA was isolated from peripheral blood mononuclear cells(PBMCs)of CHB patients and healthy controls and evaluated using the Human Methylation 450 K Assay.The DNA methylation level at hg37 chromosome(CHR)X:7810800 was further validated using pyrosequencing.SNP genotypes,VCX mRNA expression of PBMCs,and plasma VCX protein concentration were further examined using SNaPshot,RT-qPCR,and Western blot,respectively.Results showed that a total of 5529 CpG loci were differentially methylated between male and female CHB patients.DNA methylation level and CC+CT frequency at CHR X:7810800,VCX mRNA expression of PBMCs,and plasma VCX protein concentration were higher in female than in male CHB patients.The CHR X:7810800 locus was hypermethylated in CHB patients with CC+CT genotypes in comparison with those with the TT genotype.In cases of CC-f CT genotypes,VCX mRNA expression was negatively correlated with the DNA methylation level.CHB patients with higher levels of HBV DNA,AST,and GGT or higher GPRI scores exhibited lower VCX expression.In conclusion,SNPs and DNA methylation at the CHR X:7810800 locus cooperatively regulate VCX expression in CHB.The upregulated VCX expression in female CHB patients might represent a mechanism of protection from more severe liver dysfunction and extensive fibrosis,as observed in male CHB patients.

Therapeutic Effect of Jianpi Decoction Combined with Chemotherapy on Postoperative Treatment of Colorectal Cancer: A Systematic Review and Meta-analysis

Objective:The purpose of this systematic review is to assess the therapeutic effect of Jianpi decoctions in Chinese herbal medicines(CHM)combined with chemotherapy on the postoperative treatment of colorectal cancer.Methods:Literatures were obtained from Wanfang database,CNKI,Pub Med,Cqvip,MEDLINE,Cochrane,CBM,and Springer LINK as well as other conference papers and theses.The search included all documents in English or Chinese published before September 2018.We selected randomized controlled trials based on specific criteria and the most important criteria were that Jianpi decoction should be applied in combination with chemotherapy on the postoperative treatment of colorectal cancer.Results:Publications in eight electronic databases were extensively searched and 20 trials were included for analysis eventually.A total of 1652 patients in total were enrolled in these studies.Among them,879 patients received CHM and Western medicine combination therapy and another 773 participants only got Western medicine therapy.Compared with those patients receiving Western medicine alone,the survival rate of 1-year(odds ratio[OR]=2.35,95%confidence limit[Cl]=1.30–4.28,P<0.05),3-year(OR=2.02,95%Cl=1.49–2.73,P<0.001),and 5-year survival rate(OR=2.32,95%Cl=1.56–3.45,P<0.001)of patients in the group of Jianpi decoctions in CHM and chemotherapy combination has significantly increased.Moreover,results also showed positive effects on immunoregulation such as CD3^+(OR=0.68,95%confidence interval[CI]=0.52–0.85,P<0.0001),CD4^+/CD8^+(OR=0.77,95%CI=0.29–1.26,P<0.05).Side effects caused by chemotherapy such as nausea(OR=0.35,95%CI=0.25–0.50,P<0.0001)and vomiting(OR=0.32,95%CI=0.22–0.46,P<0.0001),diarrhea(OR=0.42,95%CI=0.30–0.60,P<0.0001),as well as metastasis and recurrence(OR=0.38,95%CI=0.24–0.61,P<0.001)were remarkably reduced.The quality of life(OR=4.40,95%Cl=2.86–6.77,P<0.0001)has been improved.Moreover,there was no statistically significant bias in the overall studies.Conclusion:This systematic review suggests that Jianpi decoction in CHM can reduce the chemotherapy toxicity,enhance the patient's immunity,prolong their survival rate,improve their quality of life as well as prevent metastasis,and recurrence for patients in postoperative treatment of colorectal cancer.

Compound-Target-Pathway Network Analysis and Effective Mechanisms Prediction of Bu-Shen-Jian-Pi Formula

Objective: The aim of this study was to predict the active compounds, therapy targets, and diseases of Bu-Shen-Jian-Pi formula(BSJPF) through the system pharmacology-based approach.Methods: Traditional Chinese Medicine Systems Pharmacology(TCMSP) and TCM Database@Taiwan Databases were used to obtain Chinese herbal medicine compounds.Oral bioavailability(OB) and drug-likeness(DL) based on the TCMSP database were used to screen the active compounds of BSJPF and related diseases.Therapy targets were defined according to the DrugBank database.The compounds-targets-disease network was constructed by Cytoscape and function and signaling pathways were also analyzed.Results: A total of 143 of 2106 compounds in BSJPF were screened out(OB ≥30%, DL index ≥0.18).Two hundred and sixty-five targets were found and 334 diseases were enriched.The diseases such as cancer, Alzheimer's disease, inflammation, and asthma were most closely correlated with the formula.BSJPF, Liu-Wei-Di-Huang decoction(LWDHD), and Si-Jun-Zi decoction(SJZD) could regulate cell proliferation and apoptosis; LWDHD also regulated biological processes and cellular processes and regulated stress on chemical stimuli and SJZD focused on the regulation of anabolic reaction.All had enriched the signaling pathways in cancer, nonsmall cell lung cancer, and thyroid cancer pathways.There were more pathways in both BSJPF and LWDHD, mainly including cancer, colorectal cancer pathways, toll-like receptors, T-cell receptors and P53 signaling pathways, and apoptosis.LWDHD was also involved in Wnt, natural killer cell cytotoxicity, and lymphocyte migration signaling pathways.SJZD had no separate pathways.In the tumor-related pathways, targets were more concentrated in the PI3K/Akt pathway and the MAPK/ERK signaling pathway.Conclusions: BSJPF owns multiple targets and pathways to treat various diseases under the guidance of "treating different diseases with the same method."