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.     

An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases

Aim:

SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases.

Methods:

Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells.

Results:

Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells.

Conclusion:

NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.     

Risk factors for post-traumatic stress disorder in acute trauma patients: A protocol for systematic review and meta-analysis

Background:Post-traumatic stress disorder (PTSD) is one of the most commonly reported mental health consequences, followed by disasters and traumatic events, either natural or man-made. At present, there are no unified results for the prevalence rate of PTSD in patients suffering from acute trauma and related influencing factors. Therefore, the purpose of this study is to systematically evaluate the existing literatures, thus obtaining a comprehensive estimation of the combined prevalence rate of PTSD and related factors in trauma patients, so as to provide evidence support for clinical disease prediction models and intervention strategies.Methods:Published articles will be retrieved from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database. Research reports will be searched in March 2021. STATA 14.0 software will be applied for data analysis. Mantel–Haenszel fixed effect model or DerSimonian–Laird random effect model will be selected to estimate the pooled prevalence of PTSD in patients with acute trauma and associated factors.Results:We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals.Conclusions:The results of this analysis can be used to establish a risk prediction model of PTSD in patients experiencing acute trauma, so as to provide intervention strategies.OSF Registration Number:DOI 10.17605/OSF.IO/Z275U.     

Differences in clinical characteristics and liver injury between suspected and confirmed COVID-19 patients in Jingzhou,Hubei Province of China

To evaluate the clinical characteristics and liver injury in coronavirus disease 2019 (COVID-19) patients, and analyze the differences between suspected and confirmed COVID-19 patients, this retrospective study was performed on 157 COVID-19 patients and 93 suspected patients who were ultimately excluded from COVID-19 (control patients). Differences in clinical characteristics and liver injury between suspected and confirmed COVID-19 patients were analyzed. Age, male sex, fever, chest tightness and dyspnea were related to the severity of COVID-19. C-reactive protein (CRP) and D-dimer may be predictors of the severity of COVID-19. Computed tomography (CT) played an important role in the screening of COVID-19 and the evaluation of disease severity. Multiple factors may cause liver injury in COVID-19 patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be more likely to cause liver injury than common respiratory infectious diseases. Age, temperature (T), white blood cell (WBC), lymphocytes (LY), hematocrit (HCT), CRP, and finger pulse oxygen saturation (SpO₂₎ may correlate with liver function impairment and may predict the occurrence and severity of liver function impairment. Some therapeutic drugs (like glucocorticoid) may be involved in the liver function impairment of COVID-19 patients. Most liver function indices improved significantly after active treatment. Although COVID-19 and other common respiratory infectious diseases share some clinical characteristics, COVID-19 has its own characteristics.     

Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, P_Adj?=?2.75?×?10^?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.