Mulati Rexiati

Background: While peptidyl-prolyl cis-trans isomerase B (PPIB) has been implicated in tumorigenesis and RNA metabolism, its specific function in prostate cancer is poorly understood. Methods: PPIB expression was assessed in clinical prostate adenocarcinoma samples and the TCGA-PRAD cohort. In PC-3 cells, stable PPIB knockdown was achieved via lentiviral shRNA. Subsequent in vitro assays measured proliferation, apoptosis, migration, and invasion, and tumor growth was evaluated in nude mouse xenograft models. We conducted strand-specific RNA sequencing to identify differentially expressed genes (DEGs) and PPIB-associated alternative splicing events (ASEs), followed by functional enrichment analyses (GO, KEGG, and GSEA). In addition, an shRNA-resistant PPIB cDNA carrying synonymous substitutions within the sh-PPIB-275 target sequence was re-expressed in PPIB-depleted cells, followed by Transwell rescue assays. Results: TCGA-PRAD analysis showed significantly higher PPIB mRNA expression in tumors. In the paired IHC cohort, an exploratory ROI-level comparison showed higher PPIB H-scores in tumor regions than in adjacent non-tumor regions (P < 0.05). Because multiple ROIs were obtained from the same patients, patient-level inference was based on ROI-averaged paired values; the mean tumor H-score was higher, but the paired difference was not statistically significant. PPIB knockdown inhibited cell proliferation, migration, invasion, and xenograft tumor growth. A modest increase in apoptotic cells was observed after PPIB depletion. Transcriptomic analysis revealed 570 differentially expressed genes and 873 altered splicing events, with enriched pathways involving DNA repair, the cell cycle, and amino acid metabolism. Integrating DEG and ASE data identified 22 overlapping genes, including the metabolic regulators PHGDH and SHMT2. Re-expression of shRNA-resistant PPIB significantly reversed the reductions in migration and invasion caused by PPIB knockdown. Conclusions: PPIB promotes prostate cancer progression and is associated with broad transcriptional and alternative splicing alterations. These results indicate a role for PPIB in prostate cancer progression and establish a foundation for investigating its post-transcriptional functions.

Prostate-specific membrane antigen (PSMA) is a protein primarily overexpressed on the surface of prostate cancer (PCa) cells, making it a key target for PSMA-based theranostics, which combine diagnostic imaging and therapy. PSMA-based molecular probes, conjugated tracers and isotopes, and multifunctional imaging technologies have significantly advanced the landscape of high-risk PCa management, particularly during initial diagnosis and treatment planning. This tool is especially crucial as the ratio of mortality to incidence of PCa in Asian populations is higher, and the overall prognosis is significantly worse compared to Western countries. Furthermore, prostate-specific antigen (PSA) screening using multiparametric magnetic resonance imaging (MRI) and pathological examination shows that only a small percentage of men (below 30%) with PSA levels between 4–10 ng/ml in China, considered low risk, actually test positive for PCa when biopsied. Therefore, PSMA ligand-based positron emission tomography (PET) has been increasingly utilized for the accurate diagnosis, clinical staging, dynamic monitoring, treatment guidance, and prognosis evaluation of PCa. Moreover, PSMA-targeted radioligand therapy (RLT), antibody-drug conjugate (ADC) therapy, cellular immunotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT), along with PSMA radioguided surgery (PSMA-RGS) intervention, have shown substantial advantages and promising potential. The field of PSMA ligands in PCa management has seen remarkable advancements in recent years, impacting both diagnostic and therapeutic approaches. This review discusses and summarizes the recent research progress and application prospects of PSMA-based theranostics in the clinical management of PCa in Asian populations.

Objective We aimed to investigate the relationship between serum neurofilament light chain (NfL) and grip strength using data from the 2013–2014 US National Health and Nutrition Examination Survey (NHANES). Design Secondary analysis of cross-sectional, population-based data. Setting NHANES sample, 2013–2014. Participants We studied 1925 participants aged 20–75 years. Outcome measures and analysis We applied a multivariable generalised linear regression model, adjusted for several potential confounders, and restrictive cubic spline models to evaluate the association between serum NfL and grip strength. Subgroup analyses were conducted using stratified multivariable linear regression analysis. Results We included 1925 participants (average age: 44.8±0.44 years) from the NHANES database. Participants with higher serum NfL levels had a significantly higher prevalence of medical conditions (hypertension, diabetes, cardiovascular disorder, chronic kidney disease (CKD) and cancer) compared with those with lower NfL levels (all pConclusion Our study demonstrates a strong, negative and linear correlation between elevated serum NfL levels and grip strength. Notably, our findings indicate that individuals aged between 60 and 75 years, those with physical inactivity and those with CKD exhibit a more pronounced reduction in grip strength with increasing serum NfL levels.

First and foremost, we extend our sincere gratitude to Zhang et al for their dedication to advancing scientific knowledge. True scientific progress is achieved through iterative research, critical discourse, and persistent pursuit of accurate solutions. We are deeply inspired by the commitment demonstrated by Zhang et al and aspire to emulate their dedication in our future endeavors. It is imperative to acknowledge, however, that while we hold great respect for the perspectives presented by Zhang et al, endorsing them may pose challenges. Whether considering contemporary methodological standards or the findings of previously published Mendelian randomization (MR) studies, convincing a broad audience presents inherent complexities. Their letter lacks sufficient evidence to support their views and urges us, along with many other researchers who have published ED-related MR studies, to reconsider and update our methodologies and article content.

Objective We aimed to explore the association between the leucocyte telomere length (LTL) and erectile dysfunction (ED) among a nationally representative sample of US adults. Design Secondary population-based study. Setting The National Health and Nutrition Examination Survey (NHANES) (2001–2002). Participants A total of 1694 male participants were extracted from the NHANES database for 2001–2002. Primary and secondary outcome measures The primary focus of the study was to determine the association between the LTL and ED, using multivariate logistic regression and restricted cubic spline models for examination. The secondary outcome measures involved conducting stratified subgroup analyses to exclude interactions of different variables with the LTL. Results Participants with ED had shorter LTLs than those without ED (pConclusion Our results demonstrated an inverted J-curve relationship between the LTL and ED. When the LTL was ≥1.037, the incidence of ED decreased with increasing LTL.

Background: Previous studies have established that diabetes mellitus (DM) markedly raises the risk of developing erectile dysfunction (ED). Despite extensive investigations, the risk factors associated with ED in diabetic men have yet to be unequivocally determined, owing to incongruent and inconclusive results reported in various studies.Objective: The objective of this systematic review and meta-analysis was to assess the risk factors for ED in men with DM.Methods: A comprehensive systematic review was conducted, encompassing studies published in the PubMed, Scopus and Embase databases up to August 24th, 2023. All studies examining the risk factors of ED in patients with DM were included in the analysis. To identify significant variations among the risk factors, odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were employed. The risk of bias was evaluated using the Newcastle-Ottawa Scale(NOS) for longitudinal studies and the Agency for Healthcare Research and Quality Scale(AHRQ) for cross-sectional studies.Results: A total of 58 studies, including a substantial participant pool of 66,925 individuals diagnosed with DM, both with or without ED, were included in the meta-analysis. Mean age (OR: 1.31, 95% CI=1.24-1.37), smoking status (OR: 1.32, 95% CI=1.18-1.47), HbA1C (OR: 1.44, 95% CI=1.28-1.62), duration of DM (OR: 1.39, 95% CI=1.29-1.50), diabetic neuropathy (OR: 3.47, 95% CI=2.16-5.56), diabetic retinopathy (OR: 3.01, 95% CI=2.02-4.48), diabetic foot (OR: 3.96, 95% CI=2.87-5.47), cardiovascular disease (OR: 1.92, 95% CI=1.71-2.16), hypertension (OR: 1.74, 95% CI=1.52-2.00), microvascular disease (OR: 2.14, 95% CI=1.61-2.85), vascular disease (OR: 2.75, 95% CI=2.35-3.21), nephropathy (OR: 2.67, 95% CI=2.06-3.46), depression (OR: 1.82, 95% CI=1.04-3.20), metabolic syndrome (OR: 2.22, 95% CI=1.98-2.49), and diuretic treatment (OR: 2.42, 95% CI=1.38-4.22) were associated with increased risk factors of ED in men with DM.Conclusion: Our study indicates that in men with DM, several risk factors for ED have been identified, including mean age, HbA1C, duration of DM, diabetic neuropathy, diabetic retinopathy, diabetic foot, cardiovascular disease, hypertension, microvascular disease, vascular disease, nephropathy, depression, metabolic syndrome, and diuretic treatment. By clarifying the connection between these risk factors and ED, clinicians and scientific experts can intervene and address these risk factors, ultimately reducing the occurrence of ED and improving patient management.

Previous observational studies have found a potential link between prostate disease, particularly prostate cancer (PCa), and kidney disease, specifically chronic renal disease (CKD), in relation to erectile dysfunction (ED), yet the causal relationship between these factors remains uncertain. The study sought to explore the potential causal association between prostate diseases, renal diseases, renal function, and risk of ED. In this study, 5 analytical approaches were employed to explore the causal relationships between various prostate diseases (PCa and benign prostatic hyperplasia), renal diseases (CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, and kidney ureter calculi), as well as 8 renal function parameters, with regard to ED. All data pertaining to exposure and outcome factors were acquired from publicly accessible genome-wide association studies. The methods used encompassed inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode residual sum and outlier techniques. The MR-Egger intercept test was utilized to assess pleiotropy, while Cochran’s Q statistic was employed to measure heterogeneity. We employed inverse variance weighting MR as the primary statistical method to assess the causal relationship between exposure factors and ED. Genetically predicted PCa demonstrated a causal association with an elevated risk of ED (odds ratio, 1.125; 95% confidence interval, 1.066-1.186; P < .0001). However, no compelling evidence was found to support associations between genetically determined benign prostatic hyperplasia, CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, kidney ureter calculi, and the renal function parameters investigated, and the risk of ED. The risk of ED is considerably amplified in patients diagnosed with PCa, thereby highlighting the importance of addressing ED as a significant concern for clinicians treating individuals with PCa. This study’s strength lies in validating the PCa-ED association using genetic analysis, while its limitation is the heterogeneity in study results. The results of this study suggest a potential link between PCa and a higher risk of ED.

Aims: Female sexual dysfunction (FSD) is a considerably underestimated condition. It has been repeatedly reported that patients with cardiovascular diseases (CVD) may suffer from an increased risk of FSD. However, there is still a lack of comprehensive and systematic evaluation of various CVD and FSD. We aimed to elucidate the association between CVD and FSD through a comprehensive literature review and meta-analysis. Methods and results: The PubMed, Scopus, Embase, and Cochrane Library databases were systematically searched from inception to 28 February 2023. We identified all relevant studies reporting the risk of FSD in subjects with or without CVD. The associations between CVD and the risk of FSD were assessed by calculating pooled odds ratios (ORs) (cross-sectional studies) and risk ratios (RRs) (longitudinal studies) with 95% CIs. We employed random-effects models to account for potential heterogeneity, and the quality of the included studies was assessed using the Newcastle–Ottawa Scale. Fifty-four articles with 148 946 individuals were included in our meta-analysis. Compared with control subjects, subjects with CVD had a 1.51-fold increased risk of FSD (OR 1.51 95% CI, 1.34–1.69, P < 0.001, heterogeneity I2 = 91.4%, P < 0.001). Subgroup analyses indicated that the association between CVD and FSD remained significant in longitudinal studies (RR 1.50 95% CI, 1.21–1.86, P < 0.001, heterogeneity I2 = 86.7%, P < 0.001). Particularly, hypertension (OR 1.41 95% CI, 1.23–1.62, P < 0.001, heterogeneity I2 = 82.7%, P < 0.001), stroke (OR 1.81 95% CI, 1.54–2.12, P < 0.001, heterogeneity I2 = 0%, P < 0.423), and myocardial infarction (OR 2.07 95% CI, 1.60–2.67, P < 0.001 heterogeneity I2 = 82.4%, P < 0.001) were significantly associated with FSD. Meta-regression revealed that the primary sources of heterogeneity in FSD are attributable to adjustments for covariates, study design, and study population. Conclusion: Our meta-analysis indicated that patients with CVD suffer from a greater risk of developing FSD. Meanwhile, we validated these findings in longitudinal queues. Notably, conditions such as hypertension, stroke, and myocardial infarction demonstrated a significant association with the incidence of FSD.

The associations between sexual dysfunction (SD) and sleep disorders, sleep quality, and sleep duration remain unclear. To assess the relationship between sleep and SD through a literature review and meta-analysis. The PubMed, Scopus, Embase, Ovid MEDLINE, and Cochrane Library databases were systematically searched from inception to November 10, 2022. Pooled relative risks and 95% CIs were used to examine the association of sleep disorders with SD in longitudinal studies. Pooled odds ratios (ORs) and 95% CIs were used to examine the associations between SD and sleep disorders, sleep quality, and sleep duration in cross-sectional studies. Forty-three articles, including 11 longitudinal studies and 32 cross-sectional studies, were included in the quantitative analysis. The pooled relative risk of SD in patients with sleep disorders was 1.97 in longitudinal studies (95% CI, 1.46-2.67, P < .001; heterogeneity: I² = 95.0%, P < .001), while the pooled OR of SD in patients with sleep disorders was 2.05 in cross-sectional studies (95% CI, 1.76-2.39, P < .001; heterogeneity: I² = 91.4%, P < .001). When compared with controls, subjects with poor sleep quality had a 1.49-fold increased risk of SD (OR, 1.49; 95% CI, 1.31-1.71, P < .001; heterogeneity: I² = 73.4%, P < .001). In addition, short sleep duration was associated with the risk of SD (OR, 1.14; 95% CI, 1.06-1.22, P < .001; heterogeneity: I² = 0.0%, P = .849). The risk of SD is significantly increased in patients with sleep disorders and poor sleep quality, indicating that clinicians should monitor sleep among patients with SD. This study is the most comprehensive meta-analysis of the association between sleep and SD to date. However, different sleep disorders may have varying associations with sleep duration and sleep quality; thus, we could not identify the independent effects across the studies. Our systematic review and meta-analysis results suggest that sleep disorders, especially obstructive sleep apnea, increase the risk of SD in men and women. Poor sleep quality is significantly associated with SD. Short sleep duration is associated with an increased risk of SD.

Whether there is a connection between sexual dysfunction (SD) and prostate cancer (PCa) is controversial. We sought to review the interrelationship between SD and PCa and to determine whether there is a definitive risk of men developing PCa after suffering from SD. A complete search of the PubMed, Web of Science, Ovid MEDLINE, Embase, and Cochrane Library databases was performed to search for eligible studies published up to October 2022. The protocol for this meta-analysis is available from PROSPERO (ID: CRD42022342381). The associations between SD and the risk of PCa were assessed by calculating pooled ORs with 95% CIs, and the standard mean difference (SMD) and its 95% CI were used to assess the relationship between SD and prostate-specific antigen (PSA) levels or prostate volume (PV). Random-effects models were used to account for potential heterogeneity, and the Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of the included studies. Twenty studies involving 215,626 individuals were included in our meta-analysis. Compared with controls, subjects with SD had a 1.62-fold increased risk of PCa (OR = 1.62, 95% CI, 1.77-2.23, P = .003; heterogeneity: I² = 97.8%, P < .001). Patients with SD had higher PSA levels than controls (SMD =0.07, 95% CI, 0.00 to 0.13, P = .041; heterogeneity: I² = 55.6%, P = .027). However, there was no association between SD and PV (SMD = 0.03, 95% CI, −0.05 to 0.11, P = .122; heterogeneity: I² = 48.5%, P = .100). Current evidence confirms a potential link between SD and the risk of PCa and that SD in PCa patients should be of concern to clinicians. The strength of this study is that it is to our knowledge the first meta-analysis of studies on the risk of PCa in men with SD. A limitation is that most of the studies included in this meta-analysis focused on ED. Our systematic review and meta-analysis results suggest that men with SD have a higher risk of PCa and higher PSA levels than men without SD. However, this is merely inferential, and causality cannot be determined based on the current data. Further longitudinal studies should be performed to validate our preliminary findings.