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To assess the clinical applicability of a semi-quantitative luciferase immunosorbent assay (LISA) for detecting antibodies against Treponema pallidum antigens TP0171 (TP15), TP0435 (TP17), and TP0574 (TP47) in diagnosing and monitoring syphilis. LISA for detection of anti-TP15, TP17, and TP47 antibodies were developed and evaluated for syphilis diagnosis using 261 serum samples (161 syphilis, 100 non-syphilis). Ninety serial serum samples from 6 syphilis rabbit models (3 treated, 3 untreated) and 110 paired serum samples from 55 syphilis patients were used to assess treatment effects by utilizing TRUST as a reference. Compared to TPPA, LISA-TP15, LISA-TP17, and LISA-TP47 showed a sensitivity of 91.9%, 96.9%, and 98.8%, specificity of 99%, 99%, and 98%, and AUC of 0.971, 0.992, and 0.995, respectively, in diagnosing syphilis. Strong correlations (rs = 0.89–0.93) with TPPA were observed. In serial serum samples from rabbit models, significant differences in the relative light unit (RLU) were observed between the treatment and control group for LISA-TP17 (days 31–51) and LISA-TP47 (day 41). In paired serum samples from syphilis patients, TRUST titres and the RLU of LISA-TP15, LISA-TP17, and LISA-TP47 decreased post-treatment (P

Abstract Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as “the great imitator,” NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients.

Abstract The usage of antiretroviral treatment (ART) has considerably decreased the morbidity and mortality related to HIV-1 (human immunodeficiency virus type 1) infection. However, ART is ineffective in eradicating the virus from the persistent cell reservoirs (e.g., microglia), noticeably hindering the cure for HIV-1. Microglia participate in the progression of neuroinflammation, brain aging, and HIV-1-associated neurocognitive disorder (HAND). Some methods have currently been studied as fundamental strategies targeting microglia. The purpose of this study was to comprehend microglia biology and its functions in HIV-1 infection, as well as to look into potential therapeutic approaches targeting microglia.

Summary: Background: The ability to accurately identify the absolute risk of neurosyphilis diagnosis for patients with syphilis would allow preventative and therapeutic interventions to be delivered to patients at high-risk, sparing patients at low-risk from unnecessary care. We aimed to develop, validate, and evaluate the clinical utility of simplified clinical diagnostic models for neurosyphilis diagnosis in HIV-negative patients with syphilis. Methods: We searched PubMed, China National Knowledge Infrastructure and UpToDate for publications about neurosyphilis diagnostic guidelines in English or Chinese from database inception until March 15, 2023. We developed and validated machine learning models with a uniform set of predictors based on six authoritative diagnostic guidelines across four continents to predict neurosyphilis using routinely collected data from real-world clinical practice in China and the United States (through the Dermatology Hospital of Southern Medical University in Guangzhou [659 recruited between August 2012 and March 2022, treated as Development cohort], the Beijing Youan Hospital of Capital Medical University in Beijng [480 recruited between December 2013 and April 2021, treated as External cohort 1], the Zhongshan Hospital of Xiamen University in Xiamen [493 recruited between November 2005 and November 2021, treated as External cohort 2] from China, and University of Washington School of Medicine in Seattle [16 recruited between September 2002 and April 2014, treated as External cohort 3] from United States). We included all these patients with syphilis into our analysis, and no patients were further excluded. We trained eXtreme gradient boosting (XGBoost) models to predict the diagnostic outcome of neurosyphilis according to each diagnostic guideline in two scenarios, respectively. Model performance was measured through both internal and external validation in terms of discrimination and calibration, and clinical utility was evaluated using decision curve analysis. Findings: The final simplified clinical diagnostic models included neurological symptoms, cerebrospinal fluid (CSF) protein, CSF white blood cell, and CSF venereal disease research laboratory test/rapid plasma reagin. The models showed good calibration with rescaled Brier score of 0.99 (95% CI 0.98–1.00) and excellent discrimination (the minimum value of area under the receiver operating characteristic curve, 0.84; 95% CI 0.81–0.88) when externally validated. Decision curve analysis demonstrated that the models were useful across a range of neurosyphilis probability thresholds between 0.33 and 0.66 compared to the alternatives of managing all patients with syphilis as if they do or do not have neurosyphilis. Interpretation: The simplified clinical diagnostic models comprised of readily available data show good performance, are generalisable across clinical settings, and have clinical utility over a broad range of probability thresholds. The models with a uniform set of predictors can simplify the sophisticated clinical diagnosis of neurosyphilis, and guide decisions on delivery of neurosyphilis health-care, ultimately, support accurate diagnosis and necessary treatment. Funding: The Natural Science Foundation of China General Program, Health Appropriate Technology Promotion Project of Guangdong Medical Research Foundation, Department of Science and technology of Guangdong Province Xinjiang Rural Science and Technology（Special Commissioner）Project, Southern Medical University Clinical Research Nursery Garden Project, Beijing Municipal Administration of Hospitals Incubating Program.

Abstract Objective Men who have sex with men (MSM) living with HIV are more likely to suffer from mental health problems. They should be given adequate attention to treat and improve their mental health disorders. This meta-analysis aimed to assess whether psychosocial interventions reliably improve psychological well-being among MSM living with HIV. Method Cochrane Library, EMBASE, PsycINFO, and PubMed were searched for psychosocial intervention randomized controlled trials evaluating mental health (e.g., depression, anxiety, self-efficacy). The effect size was pooled using the random-effects model, and continuous outcomes were reported using standardized mean difference (SMD) values . Results A total of 12 studies including 1782 participants were included in the meta-analysis. Psychosocial interventions in contrast to control groups significantly reduced depression (SMD, − 0.28; 95% CI − 0.52 – − 0.03) at the follow-up assessment and improved quality of life (SMD 0.43, 95% CI 0.23–0.63) after treatment. Psychosocial interventions also had a significant effect on measures of self-efficacy (SMD 2.22, 95% CI 0.24–4.20), and this effect was sustained until long-term follow-up (SMD 0.55, 95% CI 0.02–1.08). Subgroup analyses revealed that improvements in depression were more significant when participants possessed higher education and treatment providers used cognitive behavioral therapy (CBT). Conclusions The findings of this study indicate that psychosocial interventions benefit the mental health of MSM living with HIV. It is necessary to conduct more research to explore characteristics that may affect treatment outcomes in the future. Trial registration This research was prospectively registered in PROSPERO ( CRD42021262567 ).

BackgroundIn recent years, the incidence of syphilis has increased year by year. Our study is to explore the risk factors for the development of neurosyphilis in patients who failed syphilis treatment.MethodsA total number of 165 patients with complete medical records and who agreed to undergo lumbar puncture were divided into 47 neurosyphilis cases and 118 non-neurosyphilis cases according to the diagnostic criteria of neurosyphilis, and the differences in clinical characteristics and laboratory features between the two groups were analyzed. Significant variables were entered into multivariable logistic regression models.Results(1) There were statistical differences (p < 0.05) between the neurosyphilis (NS) group and the non-neurosyphilis (NNS) group in terms of the higher proportion of male and serum rapid plasma reagin (RPR) > 1:32 and the elevated cerebrospinal fluid white blood cell (CSF WBC) and CSF protein in the neurosyphilis group compared with the non-neurosyphilis group. (2) Male gender, serum RPR titers >1:32 at lumbar puncture, CSF WBC >8 × 106/L were significantly associated with neurosyphilis.ConclusionFor patients who have failed syphilis treatment, lumbar puncture should be performed to exclude neurosyphilis, to enable early diagnosis and treatment, and to prevent irreversible damage of neurosyphilis, especially if the patient is male and has a serum RPR>1:32 and elevated CSF WBC at lumbar puncture, which are risk factors for neurosyphilis.

Objectives: To investigate the acceptability of human papillomavirus (HPV) vaccination among men who have sex with men (MSM) and its associated factors.Methods: We searched studies written in English in PubMed, EMBASE, and Web of Science with no geographical or time restrictions. We evaluated the quality of the included literature. We calculated the pooled acceptability and performed meta-analysis of selected studies, including factors associated with the acceptability among MSM, using Review Manager (v5.3).Results: The acceptability among the 15 studies (n = 8,658) was 50% (95% CI: 0.27–0.72). The meta-analysis of seven articles (n = 4,200) indicated that having a college or higher degree (OR = 1.62, 95% CI: 1.35–1.95), disclosure of sexual orientation to healthcare professionals (HCPs; OR = 2.38, 95% CI: 1.47–3.86), vaccination with at least one dose for hepatitis A or B (OR = 2.10, 95% CI: 1.42–3.10), awareness of HPV (OR = 1.85, 95% CI: 1.21–2.83), knowledge of HPV (SMD = 0.28, 95% CI: 0.16–0.39), perceived susceptibility to HPV infection (SMD = 0.31, 95% CI: 0.11–0.50), and perceived severity of HPV-related disease (SMD = 0.40, 95% CI: 0.28–0.51) can promote acceptance of HPV vaccines. Meanwhile, people who have had unprotected anal sex or have more sex partners tend to have low acceptance of HPV vaccines.Conclusions: HPV education should be actively promoted according to the factors that influence the acceptability of HPV vaccines among the MSM population. HPV education should be especially aimed at people with low academic qualifications and people with risky sexual behaviors, and should emphasize the aspects of susceptibility to and severity of HPV-related disease. More intervention trials should be conducted to increase the credibility of the results.

Syphilis is an important health problem worldwide; however, few studies have probed the impact of syphilitic infection on T cell turnover. The mechanisms behind the frequency of T cell subset changes and the associations between these subsets during syphilitic infection remain unclear. Herein, we used a cell-staining method and flow cytometry to explore changes in T cell subpopulations and potential contribution of apoptosis and pyroptosis that triggered therein. We investigated caspase-1-mediated pyroptosis and caspase-3-mediated apoptosis of CD4 + and CD8 + T cells, the major effector lymphocytes with pivotal roles in the pathogenesis of infectious diseases. We found that the levels of caspase-1 and caspase-3 increased in both the circulation and intracellularly in CD4 + and CD8 + T cells. Caspase-1 showed a continual increase from early latent stage infection through to phase 2 disease, whereas caspase-3 increased through to phase 1 disease but declined during phase 2. In addition, serum levels and intracellular expression of caspase-1 and caspase-3 were positively correlated. Overall, this study increases our understanding of how syphilitic infection influences CD4 + and CD8 + T-cell turnover, which may help with designing novel and effective strategies to control syphilis infection and prevent its transmission.