ObjectiveTo analyze the antidepressant quality markers（Q-Marker） of Bupleuri Radix（BP） before and after vinegar-processing by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， multivariate statistical analysis and network pharmacology. MethodUPLC-Q-TOF-MS was used to analyze the chemical basis of raw and vinegar-processed products of BP， and principal component analysis（PCA） orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to identify the differential components in BP that changed significantly before and after vinegar-processing， which were regarded as candidate quality markers（Q-Marker）. Then the disease-drug-component-target network related to antidepressant effect of BP was constructed by network pharmacology， and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined. Rats were randomly divided into blank group， model group， fluoxetine group（2.67 mg·kg^-1） and total saponin group（0.72 mg·kg^-1）， except the blank group， rats in the other groups were subjected to chronic unpredictable mild stress（CUMS）. Three weeks after the start of modeling， rats in each administration group were given the corresponding dose of drugs once a day for 4 weeks， and rats in the blank and model groups were given normal saline with dose of 10 mL·kg^-1. At 1 day before modeling， 21 days and 28 days after administration， body mass weighing， sucrose preference test and open field test were performed on each group . After 28 days of administration， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression levels of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（Akt）， mammalian target of rapamycin（mTOR）， glycogen synthase kinase-3β（GSK-3β）， forkhead box transcription factor O3a（FoxO3a） and β-catenin in hippocampal tissues of rats in each group， while protein expression levels of PI3K， Akt， mTOR and FoxO3a in hippocampal tissues of rats in each group were detected by Western blot. ResultThere were 19 components in BP showed significant changes before and after vinegar-processing， and 9 components such as saikosaponin A， saikosaponin B₁， saikosaponin B₂， saikosaponin C and saikosaponin D were identified as potential Q-Marker through S-plot differential marker screening. Combined with the disease-drug-component-target network， saikosaponin A， saikosaponin B₁， saikosaponin B₂ and saikosaponin D were identified as antidepressant Q-Marker of raw and vinegar-processed products of BP. According to the results of pharmacodynamic tests， after 28 d of administration， compared with the blank group， the body mass， sucrose preference index and open field total score of rats in model group， fluoxetine group and total saponin group decreased significantly（P<0.01）. Compared with the model group， the body mass， sucrose preference index and open field total score in total saponin group increased significantly（P<0.01）. Compared with the blank group， mRNA expression levels of PI3K， Akt， mTOR and β-catenin in hippocampus of rats in the model group decreased significantly（P<0.05）， while mRNA expression levels of GSK-3β and FoxO3a increased significantly（P<0.05）. Compared with the model group， mRNA expression levels of PI3K， Akt， mTOR and β-catenin in hippocampus of rats in the total saponin group were increased significantly（P<0.05）， while mRNA expression levels of GSK-3β and FoxO3a decreased significantly（P<0.05）. Compared with the blank group， the protein expression levels of Akt and mTOR in hippocampus of the model group decreased significantly（P<0.01）， while the protein expression levels of PI3K and FoxO3a increased significantly（P<0.01）. Compared with the model group， the expression level of Akt in hippocampus of the total saponin group increased significantly（P<0.01）， the mTOR expression level was increased but not statistically significant， while the protein expression levels of PI3K and FoxO3a decreased significantly（P<0.01）. ConclusionThe chemical constituents of BP changed greatly after vinegar-processing， and the antidepressant Q-Marker of raw and vinegar-processed products of BP was determined by chemical basis， pharmacodynamics， network pharmacology and signaling pathway， which provided a reference for further research on quality control， pharmacodynamic substance basis and processing mechanism of BP.

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Objective: To understand the relations between high risk sexual behavior and HIV infection among MSM in ways of finding male partners in Ningbo. Methods: A cross-sectional study was conducted in Ningbo between April and November in 2018. Data related to socio-demographics, ways of finding male partners, adoption of gay apps and sexual behaviors were collected by snowball method. Blood samples were drawn for HIV antibody testing. Classified data was evaluated by chi-square test. Related factors on HIV infection were analyzed by multivariate logistic regression. Results: A total of 735 participants were included in this study. Ways of finding male partners would through gay apps (60.8%, 447/735), QQ/Wechat (32.3%, 237/735) and gay-places (6.9%, 51/735). Related information on high risk sexual behavior and HIV infection among gay apps users were found as: 16.8%(75) had sexual behavior once per week in the past 6 months, 41.8% (187/447) had multiple sexual partners, 12.1% (54/447) had unprotected anal intercourse in the last time, 52.3% (234/447) having had unprotected anal intercourse in the past 6 months. The overall HIV prevalence rate was 12.1%(54/447). Among the HIV cases who got infected within the two years, 68.6%(24/35) of them had used gay apps for less than two years. Results from the, multivariate logistic regression analysis showed that gay apps users were more susceptible to infected HIV than those who used the QQ/Wechat (OR=3.03, 95%CI: 1.30-7.07). Conclusions Gay apps was popularly known among the Ningbo MSM, and was associated with the high risk sexual behaviors and HIV infection. HIV control and prevention programs should be strengthened in the MSM population who used the gay apps. Related surveillance and intervention programs for MSM, who use the gay apps, need to be further reinforced.

Objectives To investigate the markers of endothelial injury, adipocytokine and thrombotic activity and explore whether there are cardiovascular disease risk factors in antiretroviral-naive HIV patients. Methods Clinical data and venous blood samples were collected from 43 anti-retroviral naive HIV-infected patients during February -October 2009 in our center, and compared with 17 healthy subjects.Plasma leptin, adiponectin, soluble intercellular adhesion molecule-1 ( sICAM-1 ), D-dimer were measured by ELISA. Four markers and cholesterol, triglyceride, fasting plasma glucose were compared between the two groups. The CD4+ T cells and percentages of CD38, HLA-DR on CD8+ T were determined by flow cytometry and plasma HIV copies were detected with bDNA analyzer among HIV-infected participants.Spearman correlations between the significant markers and CD4+ T cells, CD8+ CD38+/CD8+, CD8+ HLA-DR +/CD8+, HIV viral load were examined among HIV-infected participants. Analyses were conducted by using Stata version 7. Results Thirty-eight of the 43 patients were sexually infected by HIV and the median absolute CD4+ T cell count was ( 133 ± 82 ) cells/μl, HIV RNA was (4. 42 ± 0. 66 ) lg copies/ml. HIV-infected patients, compared with healthy subjects, had lower leptin [11.41 (7.91,14. 53 )μg/L vs 55.31( 16. 49,229.65 ) μg/L, P= 0. 0005], adiponectin [1.79 ( 1.40,4. 00 ) mg/L vs 3.36 ( 2. 92,4. 18 ) mg/L,P =0. 003] and higher sICAM-1 [1.71 (1.11,2.40) mg/L vs 0. 69 ( 0. 57, 0. 80 ) mg/L, P = 0. 0000].No significant differences exist in cholesterol, triglyceride, fasting plasma glucose. For HIV-infected participants, sICAM-1 tended to correlate with CD8+ CD38+/CD8+ and HIV viral load ( r= 0.3378, P= 0.0267;r = 0.3904,P = 0.0096). Conclusion Patients with untreated HIV infection have lower leptin, adiponectin and higher sICAM-1 levels and the relationship of these markers to HIV-mediated atherosclerotic risk requires further study.