CD4+ Effective Memory T Cell Markers GBP2 and LAG3 Are Risk Factors for PTB and COVID-19 Infection: A Study Integrating Single-Cell Expression Quantitative Trait Locus and Mendelian Randomization Analyses.

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4+ Effective Memory T Cell (CD4+ TEM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4+ TEM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10-15) and LAG3 (rs67706382, p = 6.16× 10-16). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4+ TEM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4+ TEM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find.

Cellular and Molecular Network Characteristics of TARM1-Related Genes in Mycobacterium tuberculosis Infections.

Tuberculosis (TB) is a global infectious threat, and the emergence of multidrug-resistant TB has become a major challenge in eradicating the disease that requires the discovery of new treatment strategies. This study aimed to elucidate the immune infiltration and molecular regulatory network of T cell-interacting activating receptors on myeloid cell 1 (TARM1)-related genes based on a bioinformatics analysis. The GSE114911 dataset was obtained from the Gene Expression Omnibus (GEO) and screened to identify 17 TARM1-related differentially expressed genes (TRDEGs). Genes interacting with the TRDEGs were analyzed using a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A gene set enrichment analysis (GSEA) was used to identify the biological pathways significantly associated with a Mycobacterium tuberculosis (Mtb) infection. The key genes were obtained based on Cytoscape's cytoHubba plug-in. Furthermore, protein-protein interaction (PPI) networks were analyzed through STRING, while mRNA-RNA-binding protein (RBP) and mRNA-transcription factor (TF) interaction networks were developed utilizing the StarBase v3.0 and ChIPBase databases. In addition, the diagnostic significance of key genes was evaluated via receiver operating characteristic (ROC) curves, and the immune infiltration was analyzed using an ssGSEA and MCPCounter. The key genes identified in the GSE114911 dataset were confirmed in an independent GSE139825 dataset. A total of seventeen TRDEGs and eight key genes were obtained in a differential expression analysis using the cytoHubba plug-in. Through the GO and KEGG analysis, it was found that these were involved in the NF-κB, PI3K/Akt, MAPK, and other pathways related to inflammation and energy metabolism. Furthermore, the ssGSEA and MCPCounter analysis revealed a significant rise in activated T cells and T helper cells within the Mtb infection group, which were markedly associated with these key genes. This implies their potential significance in the anti-Mtb response. In summary, our results show that TRDEGs are linked to inflammation, energy metabolism, and immune cells, offering fresh insights into the mechanisms underlying TB pathogenesis and supporting further investigation into the possible molecular roles of TARM1 in TB, as well as assisting in the identification of prospective diagnostic biomarkers.

Resonant MEMS Accelerometer with Low Cross-Axis Sensitivity-Optimized Based on BP and NSGA-II Algorithms.

This article proposes a low cross-axis sensitivity resonant MEMS(Micro-Electro-Mechanical Systems) accelerometer that is optimized based on the BP and NSGA-II algorithms. When resonant accelerometers are used in seismic monitoring, automotive safety systems, and navigation applications, high immunity and low cross-axis sensitivity are required. To improve the high immunity of the accelerometer, a coupling structure is introduced. This structure effectively separates the symmetric and antisymmetric mode frequencies of the DETF resonator and prevents mode coupling. To obtain higher detection accuracy and low cross-axis sensitivity, a decoupling structure is introduced. To find the optimal dimensional parameters of the decoupled structure, the BP and NSGA-II algorithms are used to optimize the dimensional parameters of the decoupled structure. The optimized decoupled structure has an axial stiffness of 6032.21 N/m and a transverse stiffness of 6.29 N/m. The finite element analysis results show that the sensitivity of the accelerometer is 59.1 Hz/g (Y-axis) and 59 Hz/g (X-axis). Cross-axis sensitivity is 0.508% (Y-axis) and 0.339% (X-axis), which is significantly lower than most resonant accelerometers. The coupling structure and optimization method proposed in this paper provide a new solution for designing resonant accelerometers with high interference immunity and low cross-axis sensitivity.

Serological and molecular epidemiological investigation of Mediterranean spotted fever in Yunnan Province, China.

OBJECTIVES: Given the limited research and its potential hazards, the study aimed to determine the prevalence of Mediterranean spotted fever (MSF) caused by Rickettsia conorii (R. conorii), a tick-borne disease, in Yunnan Province, China. METHODS: Through stratified sampling across five distinct regions in Yunnan, 5358 blood samples were obtained from the general healthy population. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Polymerase chain reaction (PCR) were employed for analysis. RESULTS: IFA identified 27 (0.50%) subjects with immunoglobulin G (IgG) positivity; none were positive for immunoglobulin M (IgM) via ELISA. PCR detected one individual with R. conorii outer membrane protein A (ompA). Significant seroprevalence variation was observed, particularly in Southern Yunnan (P = 0.032), with R. conorii subsp. conorii confirmed in the PCR-positive sample. CONCLUSIONS: This research reveals a correlation between MSF prevalence, geography, and climate in Yunnan. The paucity of prior studies underscores MSF's potential diagnostic challenges in the region. Comprehensive understanding of the pathogen's distribution is pivotal for intervention. Given the study's scope and Yunnan's unique setting, additional research is advocated.

Global prevalence of Borrelia burgdorferi and Anaplasma phagocytophilum coinfection in Ixodes tick populations: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ixodes ticks are pivotal in transmitting diseases like Lyme disease and human granulocytic anaplasmosis, caused by Borrelia burgdorferi and Anaplasma phagocytophilum, respectively. These pathogens not only affect humans through single or multiple tick bites but also pose risks to animal hosts, leading to potential coinfections. Despite regional studies indicating significant prevalence, their global coinfection data remain sparse. This study aims to bridge this gap through a systematic review and meta-analysis of B. burgdorferi and A. phagocytophilum coinfections in Ixodes ticks worldwide. Addressing data limitations and study variability, it seeks to provide a nuanced understanding of coinfection patterns, their epidemiological implications and inform targeted prevention strategies. METHODS AND ANALYSIS: Following Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015 guidelines and PROSPERO registration, this study will undertake a thorough database search without constraints on language or publication date, using standardised screening and data extraction protocols. The quality and bias of studies will be evaluated using Joanna Briggs Institute tools. In the statistical analysis phase, conducted in R, we will initially determine the use of fixed or random-effects models based on the assessment of data heterogeneity. This choice will guide the framework for subsequent analyses. Within the selected model's framework, we will perform subgroup analyses and meta-regression to investigate the effects of various factors, ensuring that each step is tailored to the initial model selection to maintain analytical consistency. ETHICS AND DISSEMINATION: As this study does not involve clinical research or data collection from subjects, ethical approval is not required. We will uphold ethical standards in synthesising and reporting data. Study outcomes will be published in peer-reviewed journals, communicating findings to the scientific community and contributing to the understanding of Ixodes tickborne diseases. PROSPERO REGISTRATION NUMBER: CRD42023449735.

Efficacy and safety of antibiotics for treatment of leptospirosis: a systematic review and network meta-analysis.

BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.

The intricate role of CCL5/CCR5 axis in Alzheimer disease.

The morbidity and mortality associated with Alzheimer disease (AD), one of the most common neurodegenerative diseases, are increasing each year. Although both amyloid ß and tau proteins are known to be involved in AD pathology, their detailed functions in the pathogenesis of the disease are not fully understood. There is increasing evidence that neuroinflammation contributes to the development and progression of AD, with astrocytes, microglia, and the cytokines and chemokines they secrete acting coordinately in these processes. Signaling involving chemokine (C-C motif) ligand 5 (CCL5) and its main receptor C-C chemokine receptor 5 (CCR5) plays an important role in normal physiologic processes as well as pathologic conditions such as neurodegeneration. In recent years, many studies have shown that the CCL5/CCR5 axis plays a major effect in the pathogenesis of AD, but there are also a few studies that contradict this. In short, the role of CCL5/CCR5 axis in the pathogenesis of AD is still intricate. This review summarizes the structure, distribution, physiologic functions of the CCL5/CCR5 axis, and the progress in understanding its involvement in the pathogenesis of AD.

Seventy years of evidence on the efficacy and safety of drugs for treating leprosy: a network meta-analysis.

OBJECTIVE: The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations. METHOD: All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score. RESULTS: Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens. CONCLUSIONS: The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction. AVAILABILITY OF DATA AND MATERIALS: All data generated or analyzed during this study are included in this published article [and its supplementary information files].

Axillary uniportal video-assisted thoracoscopic surgery for bullae is a cosmetically superior approach to primary spontaneous pneumothorax: a case report.

BACKGROUND: Bulla is a common cause of primary spontaneous pneumothorax. Video-assisted thoracoscopic surgery (VATS) through the lateral chest wall is a common surgical approach and an effective treatment for this condition, but postoperative incision scars affect the aesthetic outcome. VATS via axillary approach can hide the scar in the axilla, and the wound in its natural state is invisible; this greatly improves the cosmetic appearance. To our knowledge, this is the first report of VATS-based bullectomy via the axillary approach in a patient with spontaneous pneumothorax. CASE PRESENTATION: A 20-year-old female patient was admitted to the hospital with a 2-day history of chest tightness and chest pain. Plain chest computed tomography showed right spontaneous pneumothorax, lung compression of 75%, and right pulmonary bulla. After complete preoperative examination, VATS bullectomy via right axillary approach was performed. During the operation, a bulla measuring about 4 × 4 cm was found at the apex of the right lung and resected. The incision healed well, and the patient was discharged after surgery. CONCLUSIONS: VATS bullectomy via axillary approach is safe and feasible, with the incision hidden in the axilla and not visible in the natural state. This method leaves no scar on the chest wall and has good cosmetic outcome.

Madelung's disease and pulmonary aspergillosis: a case report and literature review.

BACKGROUND: Madelung's disease (MD) is a rare disorder of fat metabolism, which is usually associated with diabetes, hyperuricemia, liver disease, nevertheless there is no report of a patient with MD and pulmonary aspergillosis (PA). This article aimed to enhance the awareness of this two diseases and discuss the possible mechanism of the combination of them preliminarily. CASE PRESENTATION: In this case, we described a 56-year-old male patient with cough, expectoration and dyspnea. His neck has a very peculiar appearance. Chest enhanced CT scan showed there were multiple nodules in both lungs, some of which had cavities and the mediastinal lymph nodes were swollen. Ultrasound scan of the neck showed diffuse hyperplasia of subcutaneous fat in neck and bilateral supraclavicular fossa. Fortunately, after performing pulmonary wedge resection aimed at pathological examination and giving relevant treatments, this patient was finally diagnosed as MD with PA, and his symptoms were significantly relieved. CONCLUSIONS: MD is rare, the phenomenon that MD combined with PA is rarer. Immune disorder may be the possible mechanism.