OBJECTIVETo compare the liver pathohistological and clinical features between chronic HBV carriers and chronic hepatitis B patients with mild elevated in ALT.

METHODS128 patients were divided into 3 groups according to the ALT: group A: ALT is less than or equal to 0.5*ULN, group B: 0.5*ULN less than ALT is less than or equal to 1*ULN, group C: 1*ULN less than ALT less than 2*ULN. The age, sex, serum HBV DNA, HBeAg status, expression of HBcAg in liver, thickness of spleen, breadth of portal vein ,blood stream speed of protal vein, right liver obliqua diameter, grade of liver inflammation and stage of liver fibrosis were compared in the three groups.

RESULTSAmong 128 patients, 57(44.5%) patients had G1 hepatitis and 71 (55.5%) had G2 hepatitis, no G0 hepatitis was found in these patients; 72 patients (56.3%) had S1 fibrosis, 30 (23.4%) patients had S2 fibrosis, and 26 (20.3%) patients did not have liver fibrosis. The liver inflammation in group C was more aggravated than that in group A (P less than 0.05). And there were significant differences in thickness of spleen and right liver obliqua diameter between group C and group A, as well as between group C and B (P all less than 0.01). With the aggravating of liver inflammation, the serum ALT, thickness of spleen, breadth of portal vein and expression of HBcAg in liver were increased obviously (P less than 0.05). With the aggravating of liver fibrosis, the thickness of spleen, breadth of portal vein, right liver obliqua diameter and HBeAg negative patients were increased obviously, while the blood stream speed of portal vein was decreased obviously (P less than 0.01).

CONCLUSIONAmong the chronic HBV infection patients whose ALT less than 2*ULN, there were 55.5% patients had G2 of liver inflammation and 23.4% patients had S2 of liver fibrosis. The serum ALT, thickness of spleen, breadth and blood stream speed of portal vein, right liver obliqua diameter and expression of HBcAg in liver are associated with pathohistological changes in these patients.

Adult ; Alanine Transaminase ; blood ; Biopsy, Needle ; Carrier State ; blood ; pathology ; virology ; DNA, Viral ; blood ; Female ; Hepatitis B Core Antigens ; metabolism ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Humans ; Liver ; metabolism ; pathology ; virology ; Liver Cirrhosis ; pathology ; Male ; Polymerase Chain Reaction ; methods ; Retrospective Studies ; Virus Replication

OBJECTIVETo perform meta-analyses evaluating the efficacy of adding Liuwei Dihuang Pills (, LDP) to Western medicine in improving treatment outcomes for type 2 diabetes.

METHODSMedline, PubMed, Cochrane Library, and Chinese databases, including the Chinese National Knowledge Infrastructure were searched to identify eligible studies; i.e., if the study involved a randomized clinical trial in which the experimental group combined LDP with Western drugs and the control group used the corresponding Western drugs alone to treat type 2 diabetes. Outcomes were measured in terms of fasting blood glucose (FBG), postprandial blood glucose (2hPG) and HbA1c level. Efficacy was also measured by using control and response rates. The combined odds ratio (OR), mean difference (MD), and 95% confidence intervals (95% CI) were calculated.

RESULTSStudies included in the analysis were less adequate than expected in terms of methodological quality. A total of 1,609 patients from 18 studies were included. We found that adding LDP can lower patients' FBG (MD=0.54 mmol/L, 95% CI [0.15, 0.93], P=0.007), 2hPG (MD=1.05 mmol/L, 95% CI [0.29, 1.81], P<0.01) and HbA1c (MD=0.23, 95% CI [0.02, 0.45], P=0.008). There were also improvements in treatment response rates (OR=3.41, 95% CI [2.38, 4.90], P<0.01) and control rates (OR=2.47, 95% CI [1.91, 3.20], P<0.01).

CONCLUSIONAdding LDP to Western medicine might improve treatment outcomes of diabetes, including FBG, 2hPG, response rates and control rates.

Blood Glucose ; metabolism ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Fasting ; blood ; Gliclazide ; adverse effects ; therapeutic use ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Metformin ; adverse effects ; therapeutic use ; Publication Bias ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Western World

OBJECTIVETo determine the relative resistance to HIV-1 infection of CD4 + T lymphocytes in HIV-exposed seronegative individuals (ESNs) in China.

METHODSHIV primary isolates were obtained from peripheral whole blood of HIV-infected persons. CD4 + T lymphocytes of Chinese ESNs were separated from peripheral blood mononuclear cells with magnetic cell sorting (MACS). The purified CD4 + T lymphocytes were cocultured with HIV primary isolates. The p24 level was detected and the culture medium was refreshed every 3 days within 2 weeks.

RESULTSFor M tropic HIV strains, p24 level was significantly lower in ESN group than in control group (P < 0.05); for some M tropic HIV strains, even no p24 replicated in ESN group. However, T tropic virus strains had no significant difference between these two groups (P > 0.05).

CONCLUSIONCD4 + T lymphocytes of Chinese ESNs may possess relative resistance to M tropic HIV strains, which may be one of the main influencing factors that result in ESN.

Adult ; CD4-Positive T-Lymphocytes ; immunology ; virology ; China ; Female ; HIV ; classification ; isolation & purification ; pathogenicity ; HIV Infections ; virology ; HIV Seronegativity ; immunology ; Humans ; In Vitro Techniques ; Male ; Sexual Partners

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

Objective: To explore the mechanism of exosome-derived LncRNA ESCCAL-1 regulating the miR-874 /ITGBL1 axis in the progression of colorectal cancer ( CRC) ． Methods : The differentially expressed genes in CRC were analyzed using the Gene Expression Omnibus( GEO) database．Expressions of LncRNA ESCCAL-1，miR-874 and ITGBL1 in CRC tissues and cell lines (SW480，SW620，HCT116 and HT29) and adjacent normal tissues and NCM460 cell lines were detected by qRT-PCR ; 3-( 4，5-dimethylthiazol-2-yl ) -2，5diphenyltetrazoliumbromide (MTT) ，clone formation and flow cytometry was used to detect cell proliferation，colony formation and apoptosis ; dual luciferase reporter assays were used to verify the interaction between miR-874 and ESCCAL-1，ITGBL1 ; fluorescence in situ hybridization was used to determine the subcellular localization of LncRNAESCCAL-1 ．Exosomes were isolated from serum using the Exosome extraction kit. Results : The expressions of ESCCAL-1 and ITGBL1 in CRC tissues and cell lines were higher than those in adjacent normal tissues and NCM460 cell lines，while the opposite was true for miR-874 (P＜0. 05) ．Knockdown of ESCCAL-1 can inhibit CRC cell proliferation and colony formation and promote apoptosis．There are specific binding sites formiR-874 and ESCCAL-1，and miR-874 inhibitor could partially reverse the effect of knockdown ESCCAL-1 in CRC (P＜0. 05) ．ESCCAL-1 upregulates ITGBL1 by adsorbing miR-874．The serum levels of ESCCAL-1 and exo-ESCCAL-1 in CRC patients were higher than those in the control group．Serum exo-ESCCAL-1 may be a valuable diagnostic indicator for CRC treatment (P＜0. 05) . Conclusion ESCCAL-1 promotes CRC progression by regulating the miR-874/ ITGBL1 axis，and ESCCAL-1 may be an effective molecular target for CRC therapy.