Evaluation of association between methylenetetrahydrofolate reductase and azoospermia: A meta-analysis

Background:Infertility affects childbearing age couples all over the world. One of the important reasons for infertility is genetic factors. Our study evaluated the association between methylenetetrahydrofolate reductase (MTHFR) and azoospermia.Methods:Multiple databases like MEDLINE, EMBASE, Cochrane library, and China journal full-text database were used to search for relevant studies, and full-text articles involved in the evaluation of MTHFR and azoospermia. The results were evaluated using STATA 12.0. Heterogeneity analysis, sensitivity analysis, and bias analysis were also performed on the data.Results:Thirteen related studies eventually met the inclusion criteria. Significant association between C677T polymorphism and azoospermia (relative risk [RR] = 0.94 [0.90, 0.99], I² = 60.9%, P = .002), and between A1298C polymorphism and azoospermia (RR = 0.98 [0.94, 1.02], I² = 56.3%, P = .011) was observed. Meanwhile, in subgroup analysis, Caucasians had higher risk than Mongolians in association between MTHFR and azoospermia.Conclusion:There was association between MTHFR polymorphism and azoospermia. Caucasian populations had higher risk than Mongolian populations in association between MTHFR and azoospermia.     

Azathioprine-induced toxoplasma gondii infection in a patient with Crohn's disease with NUDT15 variation: A case report

Introduction:Azathioprine (AZA) has been widely used for the treatment of various immune-related diseases and has become a mainstay in the treatment of inflammatory bowel disease. However, patients with genetic mutations may experience severe adverse events when treated with azathioprine. Most of the previous literature focused on the TPMP gene-related adverse reactions, herein, we report a case of Crohn''s disease patient with nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) variation and wild-type TPMP gene who developed toxoplasma gondii infection after azathioprine treatment.Patient concerns:A 56-year-old Crohn''s disease patient developed toxoplasma gondii infection within 2 months after the administration of azathioprine; however, he had no relevant high-risk factors.Diagnosis:Subsequent genetic testing revealed that the patient was heterozygous for NUDT15. Therefore, it was reasonable to consider that the patient''s genetic mutation resulted in reduced tolerance to azathioprine, leading to low immunity and eventually toxoplasma infection.Interventions:AZA was then discontinued; after anti-infection, antipyretic and other supportive treatments were administered, the patient''s condition gradually improved.Outcomes:The patient was followed up at 1, 3, and 6 months after discharge; fortunately, he was in good health.Conclusion:We report a case of Crohn''s disease in a patient who developed severe pneumonia caused by toxoplasma gondii infection due to the administration of AZA, with normal TPMP gene but NUDT15 gene mutation. This indicates that NUDT15 variation may contribute to severe adverse events in patients treated with azathioprine, and we suggest that NUDT15 genotype be detected before the use of azathioprine in order to provide personalized therapy and reduce side effects.     

Treatment strategies for central nervous system infections: an update

Introduction: Central nervous system infection continues to be an important cause of mortality and morbidity worldwide. Our incomplete knowledge on the pathogenesis of how meningitis-causing pathogens cause CNS infection and emergence of antimicrobial resistance has contributed to the mortality and morbidity. An early empiric antibiotic treatment is critical for the management of patients with bacterial meningitis, but early recognition of bacterial meningitis continues to be a challenge.

Areas covered: This review gives an overview on current therapeutic strategies for CNS infection with a focus on recent literature since 2010 on bacterial meningitis. Bacterial meningitis is a medical emergency, requiring early recognition and treatment. The selection of appropriate empiric antimicrobial regimen, after incorporating the epidemiology of bacterial meningitis, impact of vaccination, emergence of antimicrobial-resistant bacteria, role of adjunctive therapy and the current knowledge on the pathogenesis of meningitis and associated neuronal injury are covered.

Expert opinion: Prompt treatment of bacterial meningitis with an appropriate antibiotic is essential. Optimal antimicrobial treatment of bacterial meningitis requires bactericidal agents able to penetrate the blood–brain barrier, with efficacy in cerebrospinal fluid. Emergence of CNS-infecting pathogens with resistance to conventional antibiotics has been increasingly recognized, but development of new antibiotics has been limited. More complete understanding of the microbial and host factors that are involved in the pathogenesis of bacterial meningitis and associated neurologic sequelae is likely to help in developing new strategies for the prevention and therapy of bacterial meningitis.     

High-dose vitamin C intravenous infusion in the treatment of patients with COVID-19: A protocol for systematic review and meta-analysis

Background:Patients infected with a virus usually lack vitamin C. High-dose vitamin C has an antiviral effect, and has been used by several researchers to treat COVID-19 by intravenous infusion, achieving good results. However, the efficacy and safety of vitamin C in the treatment of patients with COVID-19 remain unclear. Thus, the aim of the present study was to investigate the efficacy of high-dose vitamin C infusion in the treatment of patients with COVID-19.Methods:Electronic databases were searched, including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, China National Knowledge Infrastructure database, Chinese Wanfang database, and Chinese Biomedical Literature database. The aim was to collect randomized controlled trials of high-dose vitamin C infusion in the treatment of patients with COVID-19, with the retrieval time being from the establishment of the database to March 2021. In accordance with the pre-designed inclusion/exclusion criteria, all data were extracted independently by 2 researchers. To assess the risk bias in the studies, the Cochrane collaboration''s tool for assessing risk of bias was used to assess the risk bias in the studies, while meta-analysis was performed using Revman 5.3 software.Results:In the present study, a high-quality comprehensive evaluation is provided of high-dose vitamin C infusion in the treatment of patients with COVID-19.Conclusion:Further convincing evidence for the clinical treatment of COVID-19 is provided, in addition to evidence-based guidance for clinical practice.PROSPERO Registration Number:CRD42021246342.     

Efficacy and safety of Xihuang pill for gastric cancer: A protocol for systematic review and meta-analysis

Background:Xihuang pill has been widely applied as a promising adjunctive drug for gastric cance. However, the exact effects and safety of Xihuang pill have yet to be systematically investigated. We aimed to summarize the effificacy and safety of Xihuang pill for the treatment of advanced GC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials.Methods:The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Relevant randomized controlled trials were searched from PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and echnology Periodical Database, and Chinese Biomedical Literature Database. Papers in English or Chinese published from their inception to October 2020 will be included without any restrictions. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I² tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger test. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluate system.Results:The results of our research will be published in a peer-reviewed journal.Conclusion:The conclusion of this study will provide helpful evidence of the effect and safety of Xihuang pill for the treatment of GC in clinical practice.OSF registration number:10.17605/OSF.IO/VFJAK.