Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial / 中华医学杂志(英文版)

BACKGROUND@#Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.@*METHODS@#A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.@*RESULTS@#V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.@*CONCLUSIONS@#The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

Mechanism of Modified Erzhiwan Combined with Epimedium for Atherosclerosis Based on Network Pharmacology / 中国实验方剂学杂志

Objective::In this study, a network pharmacology-based method was applied to analyze the mechanism of modified Erzhiwan combined with epimedium in treatment of atherosclerosis. Method::The compounds and targets of modified Erzhiwan combined with epimedium were screened in traditional Chinese medicine(TCM) systems pharmacology database and analysis platform (TCMSP) and bioinformatics analysis tool for molecular mechanism of TCM (BATMAN-TCM). Mang related databases were applied to find the target-related to atherosclerosis.The common targets of modified Erzhiwan combined with epimedium and atherosclerosis were got by venn diagrams.Cytoscape 3.6.1 was used to construct ingredients-disease-targets networks.Then protein-protein interaction (PPI) analysis of ingredients-disease-targets was builed in STRING database, and was visualized by Cytoscape 3.6.1, then important modules were analyzed with Moleculaar complex detection(MCODE). Biological information annotation databases (DAVID) was used to carry on gene ontology (GO) analysis and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes (KEGG) pathway. Result::A total of 38 active ingredients and 266 potential targets of modified Erzhiwan combined with epimedium were obtained from TCMSP and BATMAN-TCM, 254 atherosclerosis-related targets were retrieved from disease database.Then 52 common targets were obtained and 14 core genes were screened.Biological processes were related to inflammatory response, regulation of insulin secretion, positive regulation of nitric oxide biosynthetic process, etc.The biological pathways mainly included tumor necrosis factor signaling pathway, NF-kappa B(NF-κB)signaling pathway, peroxisome proliferators-activated receptors signaling pathway and so on. Conclusion::Modified Erzhiwan combined with epimedium may play the anti-atherosclerosis role by estrogen-like effect through attach estrogen receptor, inhibiting inflammation and improving insulin resistance, which may provide guidance for further experimental research.

Research advances in diagnosis and treatment of primary biliary cirrhosis / 临床肝胆病杂志

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, characterized by progressive non-pyogenic inflammation in the small intrahepatic bile ducts, and can cause hepatic fibrosis and liver cirrhosis. The etiology and pathogenesis of PBC remain unknown. The development and progression of PBC are caused by various factors, and the major factor is environmental factors acting on patients with genetic susceptibility. Ursodesoxycholic acid is thought to be the only effective drug, but the complete response rate remains low. This article reviews the diagnosis and treatment of PBC with reference to the literature in the world.

Effect of Qianggan capsules on insulin resistance index and liver fibrosis score in patients with nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the effect of Qianggan capsules on liver fibrosis score and insulin resistance index in patients with nonalcoholic fatty liver disease (NAFLD). MethodsA total of 85 NAFLD patients who were treated in the Eighth People′s Hospital of Shanghai from August 2014 to July 2015 were enrolled and randomly divided into treatment group (45 patients) and control group (40 patients). The patients in the treatment group were given Qianggan capsules, and those in the control group were given polyene phosphatidylcholine capsules. The course of treatment was 24 weeks for both groups. The changes in serum aminotransferases ［aspartate aminotransferase (AST) and alanine aminotransferase (ALT)］, homeostasis model assessment of insulin resistance (HOMA-IR), and NAFLD fibrosis score (NAFLDFS) after treatment were observed in both groups. The t-test was used for comparison of continuous data between groups, before-after comparison within each group was made by paired t-test; and the chi-square test was used for comparison of categorical data between groups. ResultsBoth groups showed significant improvements in ALT and AST levels after treatment (all P＜001). After treatment the treatment group showed significant reductions in HOMA-IR and NAFLDFS (358±085 vs 248±078，t=640，P＜001; -178±124 vs -235±098,t=240,P＜001) and the treatment group had significantly lower HOMA-IR and NAFLDFS than the control group(1248±078 vs 309±089,t=336,P＜001;-235±098 vs -148±108,t=380,P＜001). No serious adverse events were observed during the course of treatment. ConclusionQianggan capsules not only reduce the levels of serum aminotransferases, but also improve insulin resistance and reduce fibrosis degree in NAFLD patients.

Multivariate analysis on risk factors for hepatitis B virus infection / 中华全科医师杂志

To explore the major risk factors for hepatitis B (HBV) in Shanghai Jinshan district.A one-to-two matched case control study was performed among the residents of Shanghai Jinshan district in 2010.The data were analyzed by single factor and multivariate analysis performed with SAS 9.13.Single factor analysis showed that the risk factors for hepatitis B were family member with hepatitis B,no vaccination history of hepatitis B virus vaccine and oral treatment.Muhivariable analysis showed that family member with hepatitis B (OR =1.91),no vaccination history of HBV vaccine (OR =0.49) and oral treatment (OR =2.06) were independent risk factors for HBV infection in Shanghai Jinshan district.Strengthening health education for HBV prevention,modifying unhealthy living habits and standardizing the treatment of oral diseases are important measures for lowering infectious rate of HBV.

Clinical characteristics of mild and severe types of influenza A/H1N1 / 中华全科医师杂志

Clinical data of 150 patients with mild and 38 patients with severe confirmed influenza A/H1N1 were collected and retrospectively analyzed in this paper with descriptive epidemiology. Mild patients mainly presented with symptoms similar to seasonal influenza with few complications, however,persistent high fever, cough with bloody sputum expectoration, chest distress and short of breath manifested in severe patients with respiratory failure and acute respiratory distress syndrome in some cases. Proportion of obesity and underlying diseases in severe patients, who were at high risk for severe influenza A/H1N1, was higher than that in mild ones (P＜0. 05). Average course of the illness spanned five to 11 days in patient with mild influenza A/H1N1 with all cured, and 34 of severe cases discharged with better recovery and other four died with a case-fatality of 10. 5 percent.

Hospitalized patients with novel influenza A (H1N1) virus infection: Shanghai, June - July 2009 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>From late May 2009, sporadic imported cases of novel influenza A (H1N1) were continuously confirmed in Shanghai, but there were few reports on its clinical presentation in China. The aim of the study was to investigate the demographic and clinical features of the laboratory-confirmed cases and the treatment with oseltamivir.</p><p><b>METHOD</b>We performed a retrospective study in the Shanghai Public Health Clinical Center (SHAPHC), reviewing the medical records of the laboratory-confirmed patients derived from June 10 to July 20, 2009.</p><p><b>RESULTS</b>A total of 156 cases were enrolled, of whom 152 had a history of recent travel. The mean age was 22.6 years and 89 cases (57.1%) were males. The most common symptoms were fever, cough, and sore throat, with children more likely to run a temperature above 38.5 degrees C than adults. The mean leucocyte count was 5.4 x 10(9)/L, the mean neutrophil count 3.2 x 10(9)/L and the mean lymphocyte count 1.4 x 10(9)/L. Other findings included a normal range or elevated level of C-reactive protein (CRP) and glutamic-pyruvic transaminase and a normal or decreased level of prealbumin; the levels of prealbumin and CRP were significantly lower in the children than in the adults. Fifty-two patients had abnormal chest CT results, with small unilateral or bilateral pulmonary infiltrates, axillary and mediastinal lymphadenopathy and local pleural thickening, while no cases showed symptoms of hypoxia. All the patients received oseltamivir and recovered without complications, but the duration of fever and virus shedding were significantly longer in the children than in the adults.</p><p><b>CONCLUSIONS</b>Travel-related circulation may be an important reason for the H1N1 epidemic in the non-epidemic areas, and the virus caused mild respiratory symptoms. The infection in children was more severe in terms of prealbumin levels, temperature, the duration of fever and virus shedding. Oseltamivir was effective for H1N1, but more effective in the adults than in the children.</p>