Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-viral antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

Expanded circulating peripheral helper T cells in primary biliary cholangitis: Tph cells in PBC.

BACKGROUND: Peripheral helper T (TPH) cells, a recently defined subset of Th cells, promote B cell differentiation and antibody production in inflamed tissues. This study investigated whether circulating TPH cells are associated with primary biliary cholangitis (PBC), a typical organ-specific autoimmune disease. METHODS: Twenty PBC patients and 20 age- and sex-matched healthy controls (HCs) were recruited. The circulating TPH cell subsets were analyzed by flow cytometry, and the associations of TPH cells with disease activity and plasma cells were determined. Functional analysis was performed using a TPH and B cell coculture experiment. RESULTS: The frequencies of circulating TPH cells, ICOS+ TPH cells, and CD28+ TPH cells were increased in patients with PBC. Furthermore, the ICOS+ TPH cell level was higher in PBC patients with or without cirrhosis than in HCs, and the level decreased after treatment. Moreover, ICOS+ TPH cell levels correlated positively with specific clinical parameters (including anti-mitochondrial antibodies against M2 antigen (AMA-M2), IgM) and plasma cell levels, suggesting that the TPH cell activation status is associated with the severity of PBC. Coculture results revealed an enhanced ability of TPH cells from PBC patients to induce B cell differentiation. CONCLUSIONS: Elevated numbers of TPH cells may be involved in the pathogenesis of PBC, and the activation status of TPH cells is related to the severity of PBC. Additionally, TPH cells can be used as a useful biomarker for evaluating the progression of PBC and may serve as a therapeutic target for PBC patients in the future.

Research status and challenges in the prognosis of primary biliary cholangitis after liver transplantation / 临床肝胆病杂志

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with unknown etiology, and patients with poor response to ursodeoxycholic acid and obeticholic acid may eventually progress to liver cirrhosis and even liver failure. Liver transplantation is the only effective treatment method for PBC at present. This article elaborates on liver transplantation, survival time after liver transplantation, complications, recurrence of PBC after liver transplantation, and prospects and challenges of liver transplantation in patients with PBC, so as to provide a reference for clinical outcome and treatment after liver transplantation for PBC.

Effect of HSP70 on HBV replication / 中国病理生理杂志

AIM:To investigate the role of heat shock protein 70(HSP70)in hepatitis B virus (HBV) replica-tion.METHODS:The effect of HBV replication on the expression of HSP 70 was analyzed by RT-qPCR.The overexpres-sion efficiency of HSP70 was confirmed by Western blot .The effect of HSP70 overexpression on HBV DNA replicative in-termediates was analyzed by RT-qPCR and Southern blot .The effects of HSP70 overexpression on the expression level of HBV 3.5 kb mRNA and HBV core protein were measured by RT-qPCR and Western blot, respectively.The Effect of HSP70 overexpression on HBV promoter activity was detected by dual luciferase reporter system .RESULTS: The mRNA levels of HSP70 were inhibited by HBV replication .Overexpression of HSP70 repressed the expression of HBV DNA repli-cative intermediates, 3.5 kb mRNA and core protein, as well as HBV core promoter activity .CONCLUSION:HBV rep-lication inhibits the expression of HSP70.Overexpression of HSP70 represses HBV replication.These data suggest that HSP70 repressed HBV replication by inhibiting HBV core promoter activity .

IL28B Is Associated with Outcomes of Chronic HBV Infection

PURPOSE: The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. MATERIALS AND METHODS: IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. RESULTS: Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001). CONCLUSION: Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.

Relationship between serum aminotransferase levels and metabolic disorders in northern China.

BACKGROUND/AIMS: Increasing evidence suggests an association between elevated serum aminotransferase levels and metabolic disorders (metabolic syndrome, hyperlipidemia and diabetes mellitus). However, the significance of relatively low levels of aminotransferases in relation to metabolic disorders has not been fully investigated in the general population. We investigated the association between serum aminotransferase levels and metabolic disorders using data from a survey in Jilin Province, China. MATERIALS AND METHODS: In 2007, a prospective survey was conducted throughout Jilin, China, covering both urban and rural areas. A total of 3835 people, 18-79 years old, were undergoing real-time ultrasonography, blood tests, and interviews with a structured questionnaire. RESULTS: Serum aminotransferase levels within the normal range were associated with metabolic syndrome independent of age, occupation, cultural and educational level, income, body mass index, waist circumference, smoking, and alcohol intake. Compared with the lowest level (< 20 IU/L), the adjusted odds ratios for alanine aminotransferase levels of 20-29, 30-39, 40-49, and >50 IU/L were 1.92, 2.50, 2.97, and 3.52 in men, and 1.38, 1.54, 3.06, and 2.62 in women, respectively. Near-normal serum aminotransferase levels associated with hyperlipidemia, non-alcoholic fatty liver disease, and diabetes mellitus were also found in the study. CONCLUSIONS: Normal to near-normal serum aminotransferase levels are associated with metabolic disorders. Serum alanine aminotransferase levels of 21-25 IU/L for men and 17-22 IU/L for women are suggested as cut-off levels that detect metabolic disorders affecting the liver.

HPLC determination of catalpol in cerebrospinal fluid of rats / 中国中药杂志

<p><b>OBJECTIVE</b>To establish an HPLC method for determination of catalpol in CSF (cerebrospinal fluid) of rats.</p><p><b>METHOD</b>Rats were intravenously injected 1.0 g x L(-1) catalpol physiological saline, and the sample of CSF from subarachnoid space of the cerebrum 40 minutes of injection. The sample of CSF from normal rats was used for blank control, the all samples were preserved in a refrigerator of - 20 degrees C, and use HPLC was employed to determine the catalpol content. The separation of catalpol was performed on Hypersil C18 reversion phase chromatographic column. The mobile phase consisted of water-acetonitrile (99.5: 0.5) with a flow rate of 1.0 mL x min(-1) and detection wavelength of 210 nm.</p><p><b>RESULT</b>The linear range of catalpol in CSF was 0.5-40 mg x L(-1) (r = 0.999 7). The absolute recoveries were (90.2 +/- 1.71)%, (89.1 +/- 1.17)% and (86.9 +/- 0.98)%; and the methodological recoveries were (99.8 +/- 1.98)%, (101.1 +/- 3.04)%, (100.1 +/- 2.30)% respectively. The within-day and between-day derivation RSD were less than 4%. Catalpol was stable in a refrigerator of -20 degrees C for 15 days.</p><p><b>CONCLUSION</b>The method is simple and accurate for the determination of the content of catalpol in CSF.</p>

Expression levels of CD4~+CD25~+ regulatory T cells in peripheral blood of patients with chronic hepatitis B and clinical significance / 吉林大学学报(医学版)

Objective To investigate the proportion of CD4+CD25highTreg and CD4+CD25+CD127low/-Treg in peripheral blood in patients with chronic hepatitis B(CHB) and determine the relationship between the proportion of CD4+CD25+Treg and clinical parameters.Methods Fresh isolated peripheral blood mononuclear cells(PBMCs) of 28 patients with CHB and 24 healthy donors were analyzed for the proportion of CD4+CD25+Treg using flow cytometry by surface staining for CD4-PC5,CD25-FITC,CD127-PE.HBsAg,HBsAb,HBeAg,HBeAb and HBcAb were evaluated.HBV DNA levels were measured using real-time RT-PCR.Results The proportions of CD4+CD25highTreg to CD4+ T cells(3.36%?2.59%) and CD4+CD25+CD127low/-Treg(4.05%?1.63%) to CD4+ T cells in patients with CHB were higher than those in health controls(1.60%?0.66%,1.75%?0.83%,P100U?L-1) had a higher fraction(4.26%?3.10%) of CD4+CD25highTreg in peripheral blood than those patients with low level ALT(ALT

Researches and Thinking to Train Students' Innovative Spirit and Ability in Pharmaceutics Teaching / 中华医学教育探索杂志

This article manages to find some methods to improve students' innovative spirit and ability with some pharmaceutical teaching practice

Investigation of speed of dissolving out situation on domestic carbamazepine tablets produced by different pharmaceutical factories / 重庆医科大学学报

Objective:To acquaint with situation of drug quantity of dissolving out of pharmacy tablet,we investigated the speed of dissolving out situation of domestic carbamazepine tablets(0.1?100) produced by six pharmaceutical factories.Methods:Refer to testing second methods of degree of dissolving out of pharmacy tablet in 《Pharmacopeia of China》2000 year edition,second portion.Results:Speed of dissolving out of the carbamazepine tablets(0.1g?100)produced by six pharmaceutical factories are greatly different among them,even in same one.Some accord with stipulation of degree of dissolving out of the drug within 30 minutes;while some accord with stipulation of degree of dissolving out of the drug within 60 minutes.Conclusion:speed of dissolving out of the domestic carbamazepine tablets(0.1g?100) produced by six pharmaceutical factories is quite different.