The Role of Gut Microbiota in Some Liver Diseases: From an Immunological Perspective.

Gut microbiota is a microecosystem composed of various microorganisms. It plays an important role in human metabolism, and its metabolites affect different tissues and organs. Intestinal flora maintains the intestinal mucosal barrier and interacts with the immune system. The liver is closely linked to the intestine by the gut-liver axis. As the first organ that comes into contact with blood from the intestine, the liver will be deeply influenced by the gut microbiota and its metabolites, and the intestinal leakage and the imbalance of the flora are the trigger of the pathological reaction of the liver. In this paper, we discuss the role of gut microbiota and its metabolites in the pathogenesis and development of autoimmune liver diseases((including autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), metabolic liver disease such as non-alcoholic fatty liver disease, cirrhosisits and its complications, and liver cancer from the perspective of immune mechanism. And the recent progress in the treatment of these diseases was reviewed from the perspective of gut microbiota.

YinQiSanHuang Jiedu decoction for the treatment of hepatitis B-related compensated liver cirrhosis: study protocol for a multi-center randomized controlled trial.

INTRODUCTION: Hepatitis B-related compensated liver cirrhosis is related to a higher risk of hepatocellular carcinoma, and antiviral therapy is the preferred method. As the pathological mechanisms of liver fibrosis are complex, drugs developed for a single target are difficult to be effective in clinical practice, so there are no chemical drugs or biological drugs with clear efficacy available for clinical application at present. Traditional Chinese medicine is a kind of medical science that has been gradually formed during thousands of years and continuously enriched by the people of all ethnic groups in China. Traditional Chinese medicine shows curative effects in the treatment of liver diseases, especially in the field of liver fibrosis prevention and treatment. This study aims to test the integrative medicine (Chinese medicine plus antiviral therapy) effective on lowing hepatocellular carcinoma risk among patients with hepatitis-related compensated liver cirrhosis. METHODS AND ANALYSIS: This is a multi-center randomized controlled trial, and a total of 5 hospitals and 802 patients will be involved in. All the subjects are randomly allocated to the YinQiSanHuang Jiedu decoction (YQSHD) group (n = 401) or the placebo group (n = 401). The YQSHD group receives YQSHD granule with entecavir (ETV), and the placebo group receives YQSHD placebo with ETV. The treatment period will last for 52 weeks, and the follow-up period for 52 ± 2 weeks. The primary outcome measure is the annual incidence of HCC. Outcomes will be assessed at baseline and after treatment. The objective of this trial is "the integrative of YQSHD with ETV reduce the annual incidence of HCC to 1%." ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Committee of Guang'anmen Hospital, China (No.2019-006-KY), and the other centers in the trial will not begin recruiting until the local ethical approval has been obtained. Trial final results will be disseminated via publication. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900021532 . Registered on February 26, 2019.

Efficacy and safety of YinQiSanHuang-antiviral decoction in chronic hepatitis B: study protocol for a randomized, placebo-controlled, double-blinded trial.

INTRODUCTION: Chronic hepatitis B (CHB) is a global public health problem. Antiviral therapy is the primary treatment. Studies have shown that a combined therapy of traditional Chinese medicine (TCM) and conventional antiviral drugs has better efficacy than conventional antiviral for treatment of CHB. YinQiSanHuang-antiviral decoction (YQSH) is a TCM compound preparation that has shown an effect on anti-hepatitis B virus and on slowing progression of hepatitis B-related liver diseases. To evaluate the efficacy and safety of YQSH combined with entecavir and its preventive effect on hepatitis B cirrhosis, we designed this randomized, double-blind and placebo-controlled trial. The objective is that the combination of YinQiSanHuang-antiviral decoction with entecavir will reduce the annual incidence of liver fibrosis/cirrhosis to 1%. METHODS: This is a multicenter, randomized, placebo-controlled, double-blinded trial involving five hospitals. A total of 802 patients are randomly allocated to two groups: the YQSH group (n = 401) or the placebo group (n = 401). The YQSH group receives YQSH with entecavir; the placebo group receives granules of placebo with entecavir. Patients receive treatment for 52 weeks and then are followed up for 52 ± 2 weeks. The primary outcome measure is the annual incidence of cirrhosis. The secondary outcome measures are hepatitis B virus DNA negative rate, hepatitis B surface antigen negative rate, hepatitis B e antigen seroconversion rate, liver function (alanine aminotransferase, aspartate aminotransferase , gamma-glutamyl transferase , alkaline phosphatase , serum albumin, and total bilirubin), spleen thickness, evaluation scores of patients' clinical symptoms, and safety assessment. Outcomes will be assessed at baseline and after treatment. DISCUSSION: Combination therapy could become a trend for treatment of CHB, and this trial expects to provide credible clinical evidence for the future combination of TCM and conventional antiviral drugs for the treatment of CHB. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900021521. Registered on 25 February 2019.

Effects of Astragalus Polysaccharide on Mechanical Characterization of Liver Sinusoidal Endothelial Cells by Atomic Force Microscopy at Nanoscale.

OBJECTIVE: To study the effects of Astragalus polysaccharide (APS), the primary effective component of the Chinese herb medicine Astragalus membranaceus (frequently used for its anti-hepatic fibrosis effects), on nanoscale mechanical properties of liver sinusoidal endothelial cells (SECs). METHODS: Using endothelial cell medium as the control, 5 experimental groups were established utilizing different concentrations of APS, i.e. 12.5, 25, 50, 100, and 200 µg/mL. By using atomic force microscopy along with a microcantilever modified with a silicon dioxide microsphere as powerful tools, the value of Young's modulus in each group was calculated. SAS 9.1 software was applied to analyze the values of Young's modulus at the pressed depth of 300 nm. Environmental scanning electron microscopy was performed to observe the surface microtopography of the SECs. RESULTS: The value of Young's modulus in each APS experimental group was significantly greater than that of the control group: as APS concentration increased, the value of Young's modulus presented as an increasing trend. The difference between the low-concentration (12.5 and 25 µg/mL) and high-concentration (200 µg/mL) groups was statistically significant (P<0.05), but no significant differences were observed between moderateconcentration (50 and 100 µg/mL) groups versus low- or high-concentration groups (P>0.05). Surface topography demonstrated that APS was capable of increasing the total area of fenestrae. CONCLUSIONS: The values of Young's modulus increased along with increasing concentrations of APS, suggesting that the stiffness of SECs increases gradually as a function of APS concentration. The observed changes in SEC mechanical properties may provide a new avenue for mechanistic research of anti-hepatic fibrosis treatments in Chinese medicine.

Pathological process of liver sinusoidal endothelial cells in liver diseases.

Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix, which is closely related to liver sinusoidal endothelial cells (LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor, which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein, we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.

Association of platelet-activating factor receptor gene rs5938 (G/T) and rs313152 (T/C) polymorphisms with coronary heart disease and blood stasis syndrome in a Chinese Han population / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the association of the platelet-activating factor receptor (PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease (CHD) and blood stasis syndrome (BSS) of CHD in Chinese Han population.</p><p><b>METHODS</b>A total of 570 CHD patients (299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaPshot technology. The statistical analysis was conducted using a multiple variable logistic regression model.</p><p><b>RESULTS</b>Significant differences were detected in the genotypes frequency distributions of the rs5938 (P<0.01), but not the rs313152 (P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio (aOR)=0.35, 95% confidence interval (CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD (aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD (aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS (aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS (aOR=1.22, 95% CI: 0.81 to 1.85, P<0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27 (95% CI: 0.1 to 0.7, P<0.01).</p><p><b>CONCLUSION</b>The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population.</p>

A case control study of influential factors or the Han population with coronary heart disease of blood stasis syndrome in Fuzhou area / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study main factors and the influencing extent of the susceptibility of the Han population with coronary heart disease (CHD) of blood stasis syndrome (BSS) in Fuzhou area.</p><p><b>METHODS</b>A case control study was employed in Fujian People's Hospital from August 2009 to January 2010. Patients with recent attack of CHD of BSS and of CHD of non-BSS, as well as patients without CHD of non-BSS were recruited as subjects. Correlated factors with CHD were collected using questionnaire and laboratory examinations. The correlation and the correlation strength between each factor and CHD of BSS were analyzed using one-way and multiple-factor unconditional Logistic regression methods.</p><p><b>RESULTS</b>Of the 403 patients in line with inclusion criteria, there were 176 patients with CHD of BSS, 123 with CHD of non-BSS, and 104 without CHD of non-BSS. Results of one-way analysis were reported as follows. Senility, mental labors, hypertension, excessive consumption of oil and salt, depression, stress, past relevant medical history, abnormal prothrombin time (PT), and abnormal hematocrit (HCT) were high-risk factors for CHD of BSS. Regular physical exercise and adequate sleep were protective factors. Except for the effects by age and sex, mental labors, hypertension, excessive consumption of oil and salt, depression, stress, past relevant medical history were still risk factors for CHD of BSS, with the correlation strength (OR value, 95% CI) being 1.902 (95% CI 1.222-2.959), 2.221 (95% CI 1.181-4.176), 2.945 (95% CI 1.781 4.871), 1.794 (95% CI 1.114-2.890), 3.462 (95% CI 1.555-7.712), 1.517 (95% Cl 1.082-2.128), and 3.159 (95% CI 1.732-5.764). In the comparison between those with CHD of BBS and those with CHD of non-BBS, excessive consumption of salt and meat, and stress were the risk factors for BSS. After the effects by age and sex were adjusted, the OR value were still 1.586 (95% CI 1.051-2.393), 1.801 (95% CI 1.191-2.723), and 1.386 (95% CI 1.024-1.876).</p><p><b>CONCLUSIONS</b>When compared with the population of non-BSS, the predisposing factors for the Han population with CHD of BSS in Fuzhou area covered mental labors, hypertension, excessive consumption of oil and salt, depression, stress, and past relevant medical history. Compared with other syndrome types in Chinese medicine, positive correlation existed between BSS and excessive consumption of salt and meat, as well as stress.</p>

[Platelet count of peripheral blood is associated with invasion and metastasis of esophageal carcinoma].

OBJECTIVE: To analyze the association between the platelet count of peripheral blood and clincopathologic parameters of esophageal carcinoma. METHODS: Platelets of peripheral blood were measured in 415 cases of esophageal carcinoma and 325 healthy subjects as control. The correlation of platelet counts and clinicopathological features of cancer was analyzed. RESULT: Platelet count in patients with esophageal carcinomas (286+/-88)x10(9)/L was significantly higher than that in the control subjects [(204+/-114)x10(9)/L, P<0.05 ]. Increased platelet counts (>300 x 10(9)/L) was significantly associated with tumor infiltration and lymph node metastasis in patients with esophageal cancer (P<0.05). CONCLUSION: Platelet count of peripheral blood might be associated with the development and progression of esophageal cancer.