Thiolutin, a selective NLRP3 inflammasome inhibitor, attenuates cyclophosphamide-induced impairment of sperm and fertility in mice.

OBJECTIVE: The activation of the NLRP3 inflammasome has been implicated in male infertility. Our study aimed to investigate the therapeutic role of Thiolutin (THL), an inhibitor of the NLRP3 inflammasome, on oligoasthenospermia (OA) and to elucidate its mechanisms. MATERIALS AND METHODS: Semen from 50 OA and 20 healthy males were analyzed to assess the sperm quality and levels of inflammatory markers. Their correlation was determined using Pearson's correlation coefficient. The BALB/c mice were intraperitoneal injected by cyclophosphamide at 60 mg/kg/day for five days to induce OA, followed by a two-week treatment with THL or L-carnitine. Reproductive organ size and H&E staining were determined to observe the organ and seminiferous tubule morphology. ELISA and western blotting were utilized to measure sex hormone levels, inflammatory markers, and NLRP3 inflammasome levels. Furthermore, male and female mice were co-housed to observe pregnancy success rates. RESULTS: OA patients exhibited a decrease in sperm density and motility compared to healthy individuals, along with elevated levels of IL-1ß, IL-18 and NLRP3 inflammasome. In vivo, THL ameliorated OA-induced atrophy of reproductive organs, hormonal imbalance, and improved sperm density, motility, spermatogenesis and pregnancy success rates with negligible adverse effects on weight or liver-kidney function. THL also demonstrated to be able to inhibit the activation of NLRP3 inflammasome and associated proteins in OA mice. DISCUSSION: THL can improve sperm quality and hormonal balance in OA mice through the inhibition of NLRP3 inflammasome activation. Thus, THL holds promising potential as a therapeutic agent for OA.

Virologic status and pattern of drug resistance mutation among ART-experienced HIV-infected patients in Butuo County, China.

OBJECTIVES: To assess the virological outcomes, prevalence of HIV drug resistance mutation (DRM), and correlates in Butuo County. METHODS: We conducted a cross-sectional study. Virological failure (VF) was defined as HIV-1 RNA ≥1000 copies/mL and on antiretroviral therapy (ART) for ≥6 months. Genotypic drug resistance was performed among VF cases. Correlates of DRM were identified using multivariate logistic regression. RESULTS: The overall virological suppression rate was 85.3%; DRM was detected in 42.6% (517/1215) VF cases and 6.2% of the sample patients. A total of 90.9% of patients were infected with HIV-1 CRF07_BC subtype. The prevalence of DRM to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) were 46.0% and 96.9%, respectively. The most prevalent mutation for NRTI was M184V (84.5%). Lamivudine (3TC), emtricitabine (FTC), and abacavir (ABC) had the highest resistance rates. For NNRTI, K103N (60.7%), nevirapine (NVP), and efavirenz (EFV) had the highest resistance rates and cross resistance to rilpivirine (RPV), doravirine (DOR), and etravirine (ETR). Ritonavir boosted lopinavir (LPV/r) resistance rate was extremely low. The occurrence of DRM was associated with age at ART ≤18 years, baseline CD4 count ≤200 cells/mL, NVP-based regimen, and ART duration >3 years. CONCLUSION: A relatively high proportion of VF and broad DRM for NRTI and NNRTI were observed, causing high-level resistance to first-line NRTI, NNRTI, and next generation NNRTI. Our findings necessitate the implementation of scaling up virological monitoring, adherence support, and timely switching to an LPV/r-containing regimen when patients with VF to reduce the occurrence of DRM.

A risk prediction model for evaluating thrombosis extension of muscle calf venous thrombosis after craniotomy.

Objective: To explore the risk factors of muscle calf venous thrombosis (MCVT) after craniotomy and construct a risk prediction model, so as to provide tool for evaluating the prognosis of MCVT after craniotomy. Methods: Retrospective analysis was performed on the data of patients undergoing craniotomy complicated with MCVT from January 1, 2018 to December 31, 2020. A prediction model was established by Logistic regression, and the predictive efficacy of the model was tested by ROC curve. The accuracy of the risk model was evaluated by Hosmer-Lemeshow (H-L) test, and the model was verified internally by cross validation. Results: Among the 446 patients who underwent craniotomy complicated with MCVT, 112 cases (25.11%) had thrombosis extension. D-dimer, Capirini scores, length of hospital stay, malignant tumor, fracture, use of dehydrating agents and hemostatic agents were independently related to thrombosis extension after craniotomy. The area under ROC curve (AUROC) of the prediction model was 0.918 (0.888, 0.942), and the sensitivity and specificity of the maximum Youden index were 85.3% and 78.2%, respectively. H-L test showed that the prediction model was accurate (χ 2 = 12.426, P = 0.133). The internal verification results of the prediction model showed that the AUROC value of the prediction model is 0.892. Conclusion: The prediction model has a good prediction efficacy on the prognosis of post-craniotomy patients complicated with MCVT, and can be used as a tool to evaluate the risk of thrombosis extension.

PPARD May Play a Protective Role for Major Depressive Disorder.

Activation of PPARD has been shown to inhibit depressive behaviors and enhances neurogenesis. However, whether PPARD is involved in the pathological development of major depressive disorder (MDD) is largely unknown. To explore the potential connection between PPARD and MDD, we first conducted a literature-based data mining to construct a PPARD-driven MDD regulating network. Then, we tested the PPARD expression changes in MDD patients from 18 independent MDD RNA expression datasets, followed by coexpression analysis, multiple linear regression analysis, and a heterogeneity analysis to study the influential factors for PPARD expression levels. Our results showed that overexpression of PPARD could inhibit inflammatory cytokine signaling pathways and the ROS and glutamate pathways that have been shown to play important roles in the pathological development of MDD. However, PPARD could also activate nitric oxide formation and ceramide synthesis, which was implicated as promoters in the pathogenesis of MDD, indicating the complexity of the relationship between PPARD and MDD. PPARG presented significant within- and between-study variations in the 18 MDD datasets (p value = 0.97), which were significantly associated with the population region (country) and sample source (p < 2.67e - 5). Our results suggested that PPARD could be a potential regulator rather than a biomarker in the pathological development of MDD. This study may add new insights into the understanding of the PPARD-MDD relationship.

Clinical Predictive Factors of Lower Extremity Deep Vein Thrombosis in Relative High-Risk Patients after Neurosurgery: A Retrospective Study.

INTRODUCTION: It is acknowledged that patients undergoing neurosurgery with neurological illness are at higher risk of lower extremity deep vein thrombosis (DVT). As an underlying life-threatening complication, the incidence and risk factors for high-risk patients with lower extremity deep vein thrombosis are still controversial in relative high-risk patients after neurosurgery. MATERIALS AND METHODS: A total of 204 patients who underwent neurosurgery and were considered as a high-risk group of DVT according to times of stay in bed more than 3 days were enrolled in this study. We evaluated the lower extremity DVT by using Color Doppler Ultrasound System (CDUS). Clinical parameters of patients at the time of admission and postoperation were recorded and prepared for further analysis. Early predictive factors for postoperative lower extremity DVT were established. Diagnostic performance of predictive factors was evaluated by using receiver operating characteristic (ROC) curve analysis. RESULTS: The overall incidence rate of DVT in 204 enrolled patients was 30.9%. Multivariate logistic regression indicated that hypertension (OR 3.159, 95% CI 1.465-6.816; P = 0.003), higher postoperative D-dimer (OR 1.225, 95% CI 1.016-1.477; P = 0.034), female (OR 0.174, 95% CI 0.054-0.568; P = 0.004), and lower GCS score (OR 0.809, 95% CI 0.679-0.965; P = 0.013) were independently associated with incidence of DVT in patients after neurosurgery. The logistic regression function (LR model) of these four independent risk factors had a better performance on diagnostic value of DVT in patients after neurosurgery. CONCLUSION: The combined factor was constructed by hypertension, postoperative D-dimer, gender, and GCS score, and it might be a more handy and reliable marker to stratify patients at risk of DVT after neurosurgery.

Antiviral therapy for HCV in hemophilia A patients with HIV-1 co-infection.

Anti-hepatitis C virus (HCV) treatment for human immunodeficiency virus (HIV)/HCV co-positive patients with hemophilia A presents numerous problems in terms of safety and effectiveness. The emergence of direct-acting antiviral (DAA) regimens has led to tremendous changes in the management of HIV/HCV co-infection over the past few years, but the application of DAA in patients with hemophilia complicated with HIV/HCV co-infection has rarely been reported.We retrospectively analyzed the clinical course and outcome of hemophilia A patients with HIV/HCV co-infection receiving DAA with a focus on the virological response, changes in cluster of differentiation 4 lymphocyte (CD4) count, side effects, and impact on bleeding before and after DAA therapy.A total of 12 hemophilia A patients with HIV/HCV co-infection were included, 9 of which were severe. All the patients were in stable states with CD4 counts >200/mm and plasma HIV ribonucleic acid (RNA) suppressed (<40 IU/mL) while taking the antiretroviral regimen. Majority of the patients (n = 9, 75.0%) were infected with HCV genotype (GT) 1b, while 2 and 1 was infected with HCV GT 2i and HCV GT 3, respectively.After 12 weeks of DAA treatment, 11 patients (91.7%) obtained sustained virologic response within 24 weeks of discontinuation of treatment (SVR24), except 1 patient who was treated with sofosbuvir (SOF) + pegylated interferon + ribavirin (PR), which was then switched to daclatasvir (DCV) + asunaprevir (ASV) for 12 weeks; this patient then achieved SVR24. During DAA treatment, HIV RNA in all the patients was constantly suppressed, while CD4 counts showed no obvious change.The most common treatment-emergent adverse events were weakness and loss of appetite (generally mild). There was no evidence of an increased tendency of bleeding, and changes in response to replacement.DAA therapy offered a safe and well-tolerated management strategy for HIV/HCV co-infected patients with hemophilia A. An awareness of the potential drug-drug interactions (DDI) between DAA and combination antiretroviral therapy (cART) by clinicians is important for optimal management of co-infected patients.

Duration of empirical therapy in neonatal bacterial meningitis with third generation cephalosporin: a multicenter retrospective study.

INTRODUCTION: The duration of treatment is not well established, especially in the negative cerebrospinal fluid (CSF) culture. The aim of this study is to explore the influence of duration of treatment in neonatal bacterial meningitis. MATERIAL AND METHODS: This is a retrospective analysis of 200 CSF specimens. Two hundred full-term neonates with bacterial meningitis admitted to the clinical status were evaluated using the Glasgow Outcome Scale (GOS) on the day of discharge. RESULTS: Neonates were identified as having bacterial meningitis based on the results of CSF culture tests of all suspected cases. According to the GOS, neonates were divided into two outcome groups: 77.5% good (GOS = 5) (shorter than 3 weeks' administration) and 22.5% unfavorable (GOS = 1-4) (longer than 3 weeks' administration). The duration of antibiotic treatment ranged from 4 to 43 days, and the mean therapy time was 19.74 ±7.32 days. Duration longer than 3 weeks for neonatal bacterial meningitis with negative CSF culture had no impact on prognosis. The unfavorable outcome group had more prenatal infections and premature rupture of membranes cases than the good outcome group. High CSF protein and CSF glucose and CSF cell count increase were associated with unfavorable outcome in 167 non-prenatal infection infants. High CSF cell count increase was associated with unfavorable outcome in 33 prenatal infection infants. In term infants, the positive rate of blood cultures was 24.5%. CONCLUSIONS: Third generation cephalosporin therapy does not have a different prognosis for negative CSF culture of neonatal bacterial meningitis in term infants in this study.

Five-Year Multicenter Study of Clinical Tests of Neonatal Purulent Meningitis.

This study aimed to provide more data support for early diagnosis and treatment of neonatal purulent meningitis through retrospective analysis of its clinical diagnosis and treatment, pathogen distribution, and drug resistance in 5 third-class A hospitals in Southwest and Northwest China from January 2011 to December 2015. It was found that both the positive rates of blood and cerebrospinal fluid culture were low, and Escherichia coli should be the main pathogenic bacteria. Drug-resistant strains with varying degrees to the third generation of cephalosporin antibiotics have appeared currently.