Objective Autoimmune diseases (ADs) result from an aberrant immune response, in which the body mistakenly targets its own tissues. The association between TGF-β1 gene polymorphisms and risk of developing autoimmune diseases remains to be established. This meta-analysis aimed to reassess the relationship between TGF-β1 T869C gene polymorphisms and susceptibility to autoimmune diseases. Methods We conducted a comprehensive search of seven electronic databases for case-control studies investigating the TGF-β1 T869C polymorphism in relation to autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, and juvenile idiopathic arthritis. The search encompassed publications published up to June 2024. Studies were categorized by ethnicity into three groups: Asian, Caucasian, and mixed-ethnicity groups. Five different genetic models were assessed, and the quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed using Stata 14.0, by calculating the odds ratio (OR) and 95% confidence interval (CI). Results A total of 32 case-control studies (31 articles), comprising 4,304 cases and 4,664 controls, were included in this meta-analysis. The overall analysis indicated no significant association between TGF-β1 T869C gene polymorphism and susceptibility to autoimmune diseases. However, subgroup analyses based on race and disease status revealed significant associations. Ethnic subgroup analysis showed that the TGF-β1 T869C allele model (T vs C: OR = 1.422, 95% CI = 1.109–1.824, P = 0.006), homozygous model (TT vs CC: OR = 1.923, 95% CI = 1.232–3.004, P = 0.004), and dominant model (TT + TC vs CC: OR = 1.599, 95% CI = 1.164–2.196, P = 0.004) were associated with autoimmune disease susceptibility in Asians. In the disease subgroup analysis, the results showed that the TGF-β1 T869C allele model (T vs C: OR = 1.468, 95% CI = 1.210–1.781, P = 0.000), recessive model (TT vs TC + CC: OR = 1.418, 95% CI = 1.097–1.832, P = 0.008), dominant model (TT + TC vs CC: OR = 1.747, 95% CI = 1.330–2.295, P = 0.000), homozygous model (TT vs CC: OR = 1.937, 95% CI = 1.373–2.734, P = 0.000), and heterozygous model (TC vs CC: OR = 1.555, 95% CI = 1.199–2.016, P = 0.001) were associated with rheumatoid arthritis susceptibility. Conclusion The findings of this meta-analysis suggest that carrying the T allele of the TGF-β1 T869C polymorphism increases the risk of autoimmune diseases in Asian populations. Moreover, individuals carrying the T allele are at higher risk of developing rheumatoid arthritis.
Background: Though children infected by SARS-CoV-2 generally experience milder symptoms compared to adults, severe cases can occur. Additionally, children can transmit the virus to others. Therefore, the availability of safe and effective COVID-19 vaccines for children and adolescents is crucial. Method: A single-center, randomized, double-blind clinical trial was conducted in Funing County, Yancheng City, Jiangsu Province, China. Healthy children and adolescents were divided into two subgroups (6–12 years old or 13–17 years old) and randomly assigned to one of three groups to receive one dose of Ad5-nCoV (3 × 1010 vp/dose). Another group, aged 18–59, received one dose of Ad5-nCoV (5 × 1010 vp/dose) as the control group. At 28, 90, 180, and 360 days post-vaccination, we measured the geometric mean titer (GMT)/concentration (GMC) of neutralizing and binding antibodies against the prototype SARS-CoV-2 strain, as well as serum antibody levels against the BA.4/5 variant. We also evaluated the incidence of adverse events within 28 days post-vaccination. Results: A total of 2413 individuals were screened from 3 June 2021 to 25 July 2021, of whom 2021 eligible participants were enrolled, including 1009 aged 6~17 years in the children and adolescent group and 1012 aged 18–59 years in the adults group. The GMT of anti-wild SARS-CoV-2 neutralizing antibodies was 18.6 (95% CI, 16.6–20.9) in children and adolescents and 13.2 (95% CI, 11.6–15.0) in adults on day 28. The incidence of solicited adverse reactions between the adult group (49.4% [124/251]) and the children and adolescent group (46.3% [156/337]) was not statistically significant. The neutralizing antibody levels decreased by a factor of 3.29 from day 28 to day 360 post-vaccination. Conclusions: A single dose of Ad5-nCoV at 3 × 1010 virus particles/dose is safe in children and adolescents, and it elicited significant immune response, which was not only non-inferior but also superior to that in adults aged 18–59 years.
More than 300 COVID-19 vaccine candidates have been developed or are currently in development. COVID-19 vaccines on the World Health Organization’s Emergency Use Listing and other COVID-19 vaccine products conditionally approved by national regulatory authorities are already in large-scale use, thus preventing severe illness or death and inducing herd immunity at the population level in the SARS-CoV-2 pandemic. In this review, we systemically assess the efficacy and effectiveness of COVID-19 vaccines in clinical trials or real-world studies, in various populations, including healthy adults, children, older people, pregnant people, people with cancer, and people receiving long-term hemodialysis or solid organ transplantation. In addition, we review available evidence regarding the effectiveness of COVID-19 vaccine immunization strategies in people with a history of SARS-CoV-2 infection, and the enhanced effectiveness conferred by various booster immunizations. We also discuss knowledge gaps in the persistence and spectrum of vaccine protection of currently available COVID-19 vaccines.
This randomized, double-blind, placebo-controlled phase 1/2 trial aimed at evaluating the safety and immunogenicity of Ad5-nCoV via aerosolized or intramuscular or intramuscular–aerosolized routes in SARS-CoV-2-negative adults aged over 18 years. In the phase 1 trial, participants were sequentially enrolled into one of five regimen cohorts: Low-Dose (two doses of aerosolized Ad5-nCoV with 0.5 × 1010 viral particles [vps] per dose), Middle-Dose (two doses of aerosolized Ad5-nCoV with 1.0 × 1010 vps per dose), High-Dose (two doses of aerosolized Ad5-nCoV with 2.0 × 1010 vps per dose), Mixed (intramuscular Ad5-nCoV with 5.0 × 1010 vps [first dose] and aerosolized Ad5-nCoV with 2.0 × 1010 vps [second dose]), and Single-Dose (one dose of aerosolized Ad5-nCoV with 1.0 × 1010 vps). Eligible participants in the phase 2 trial were stratified by 18–59 years old or ≥60 years old and then were sequentially enrolled into one of six regimen cohorts: Low-Dose, Middle-Dose, High-Dose, Mixed, Single-Dose, and Intramuscular (one dose of intramuscular Ad5-nCoV with 1.0 × 1010 vps). The intervals between the two doses were 56 days. Participants were randomly allocated in 3:1 (phase 1) and 5:1 (phase 2) ratios to receive either Ad5-nCoV or the placebo in each cohort. This study is registered on ClinicalTrials.gov, NCT04840992. Most adverse reactions that occurred during the solicited period were mild and moderate. One serious adverse event (myelodysplastic syndrome) was considered potentially related to the aerosolized Ad5-nCoV. The GMTs of neutralizing antibodies in the Mixed group were the highest with 57.03 (95% CI: 23.95, 135.80) and 97.37 (95% CI: 74.30, 127.59) in phase 1 and 2 trials, respectively, 28 days after the second dose (p < 0.0001), which showed significantly higher immune responses compared to other regimens with aerosolized or intramuscular Ad5-nCoV alone.
To exploit hepatocellular carcinoma (HCC) diagnostic substances, we identify potential predictive markers based on machine learning and to explore the significance of immune cell infiltration in this pathology.
To provide the anatomical basis for surgical treatment of extraforaminal lumbar disc herniation (EFLDH) by paraspinous muscle splitting approach and to investigate the effect of its application.The relationship among the intertransverse processes, lateral margin of the pars interarticularis, anterior ramus of the lumbar nerve, and anterior ramus of the lumbar artery was studied in 34 cadaveric specimens. From October 1993 to October 1999, eleven cases of extraforaminal lumbar disc herniation were treated by paraspinous muscle splitting approach and retroperitoneal approach.In the extraforaminal region, the anterior ramus of the lumbar artery and venus locate ventrally to the superior half of the intertransverse space, and the anterior ramus of the lumbar artery runs downward behind the nerve. The distance from the lateral margin of the pars interarticularis to the nerve root and the angle between the nerve root and midline sagittal plane were 1.0 - 2.0 cm and 7 degrees - 25 degrees respectively which increased gradually from L(1) to L(5). The period of follow up in 10 of 11 cases was 23 - 98 months. Evaluation according to Low Back Outcome Score showed excellent results in 8 cases, and good in 2.Surgical treatment of EFLDH by paraspinous muscle splitting approach is safe, effective and minimal invasive.
Background To assess the immunogenicity and safety of two-dose regimen of inactivated COVID-19 vaccines in patients with pulmonary tuberculosis (PTB) and explored the potential benefits of additional dose.
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