Yongjiao Yang’s research while affiliated with Tianjin Medical University and other places

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Publications (41)


Icariside Ii Conditioning Exerts Testicular Germ Cells Protection Against Varicocele, by Targeting Keap1 and Activating Nrf2-Mediated Antioxidant Pathway
  • Preprint

January 2025

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1 Read

Yuhong Feng

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Jiancheng Pan

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Woongjin Bae

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AGD measurement in male patients. AGD anogenital distance, AGDas distance between the anus and posterior base of the scrotum, AGDap distance between the anus and upper penis
Partial regression plots for IPSS score, PVR, TPV, and Qmax in relation to AGDas. AGD anogenital distance, IPSS International Prostate Symptom Score, PVR post-voiding residual volume, TPV total prostate volume, Qmax maximum urine flow rate. (A: IPSS and AGDas; B: TPV and AGDas; C: PVR and AGDas; D: Qmax and AGDas)
Receiver operating characteristic (ROC) curve to test the predictive value of AGDas in the symptom of BPH-LUTS. (A: The AGDas shorter than 27.4 mm predicted mild symptom of BPH-LUTS, AUC = 0.802; B: The AGDas longer than 46.8 mm predicted msevere symptom of BPH-LUTS, AUC = 0.779). AGD anogenital distance, AUC area under curve, BPH-LUTS benign prostatic hyperplasia-lower urinary tract symptom
The association between anogenital distance and benign prostatic hyperplasia related lower urinary tract symptoms in Chinese aging men
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  • Publisher preview available

July 2021

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110 Reads

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6 Citations

World Journal of Urology

Purpose We conducted the study to investigate the relationship between anogenital distance (AGD) and benign prostatic hyperplasia (BPH) related lower urinary tract symptoms (LUTS). Methods From May 2018 to January 2020, 220 subjects: 110 men with BPH-related LUTS (BPH-LUTS group) and 110 men without any urination complaints (control group) were selected. Clinical questionnaires, detailed physical examinations, including AGDas (distance between the anus and posterior base of the scrotum) and AGDap (distance between the anus and upper penis) measurements, and blood tests were all assessed. Results The two groups were similar in terms of basic features (P > 0.05). The AGDap and AGDas in the control group were significantly shorter than the BPH-LUTS group (P < 0.001). Adjusted multivariate analyses showed that AGDas was significantly related to International Prostate Symptom Score (IPSS), post-voiding residual volume (PVR), total prostate volume (TPV) and maximum urine flow rate (Qmax) (P = 0.002, P = 0.009, P = 0.001, P = 0.028, respectively). However, the associations between AGDap and IPSS score, PVR, TPV, Qmax and total testosterone (TT) were all negligible (P > 0.05 for all). The associations between TT and BPH-LUTS related evaluations were also negligible (P > 0.05 for all). Furthermore, the study revealed that the AGDas cut-off values for mild, moderate, and severe symptom (based on IPSS score) in BPH-LUTS cases were 27.4 mm and 46.8 mm [area under curve (AUC): 0.802 and AUC: 0.779, respectively], respectively. Conclusion Longer AGDas was related to more severe BPH related symptoms. It may be useful to consider AGD as a marker for BPH-LUTS. Further well-designed studies are remained to be done to explore the intriguing problem.

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The association between plant‐based diet and erectile function in Chinese young healthy men: A population‐based study

March 2021

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38 Reads

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9 Citations

The study was designed and conducted to evaluate the plant‐based diet status and its association with erectile function (EF) in Chinese young healthy men. From July 2018 to May 2020, 116 objectively proved physically and psychologically healthy men were selected. Clinical questionnaires, detailed physical examinations and blood tests were all assessed. An overall plant‐based diet index (PDI) and a healthful plant‐based diet index (hPDI) were developed from each participant to measure plant‐based diet quantitatively. The EF was measured by both the International Index of Erectile Function‐5 (IIEF‐5) and the surrogated measures of endothelial function, peripheral levels of nitric oxide (NO) and E‐selectin. In subjects, the mean PDI and hPDI were 53.8 ± 8.2 and 54.7 ± 8.9 respectively. Results of multivariate analysis showed that both PDI and hPDI were negatively associated with BMI (all p < .05), but had no relationships with NO, E‐selectin, TT levels and IIEF‐5 scores (all p > .05). In a subgroup of male population, Chinese young healthy men, the plant‐based diet, measured by PDI and hPDI, was not related to erectile function. The population can adhere to plant‐based diet to keep healthy without concerns of negative influence on erectile function.


Adjusted ORs and 95% CIs for the association between MetS and its components and UTUC.
Metabolic Syndrome and Risk of Upper Tract Urothelial Carcinoma: A Case-Control Study From Surveillance, Epidemiology and End Results-Medicare-Linked Database

January 2021

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43 Reads

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7 Citations

Background Metabolic syndrome (MetS) and its components are associated with increased risks of several cancers. However, the relationship between MetS and upper tract urothelial carcinoma (UTUC) has never been investigated before. Methods We identified 3,785 UTUC cases aged over 65 years old within the Surveillance, Epidemiology and End Results-Medicare database between 2007 and 2016. For comparison, non-cancer controls (n = 189,953) were selected from the 5% random sample of individuals residing within regions of SEER registries and matched with cases through diagnosis date and pseudo-diagnosis date. MetS and its components were all defined by using ICD-9-CM codes. Multivariate logistic regression models were conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Time trends for MetS and its components were reported and we also performed dose-response effect analysis to test the concomitant effect of these components. The study was presented following the STROBE reporting checklist. Results UTUC risk was associated with metabolic syndrome (NCEP-III: OR: 1.669, 95% CI: 1.550–1.792; IDF: OR: 1.924, 95% CI: 1.676–2.172) and its component factors: elevated waist circumference/central adiposity (OR: 1.872, 95% CI: 1.693–2.055), impaired fasting glucose (OR: 1.306, 95% CI: 1.133–1.480), high blood pressure (OR: 1.295, 95% CI: 1.239–1.353), high triglycerides (OR: 1.280, 95% CI: 1.222–1.341), and low high-density lipoprotein cholesterol (OR: 1.354, 95% CI: 1.118–1.592). Consistent associations could also be observed in the subgroup analyses by tumor stages, grades, and tumor size. Additionally, the rates of MetS increased over time in both UTUC and control cohort (NCEP-III criterion; EAPC: +18.1%, P <0.001; EAPC: +16.1%, P <0.001, respectively). A significantly gradual increase in UTUC rates could be seen as the No. of the MetS components increase (χ² = 37.239, P trend = 0.000). Conclusions Among people aged over 65, MetS and its components were significant risk factors for UTUC with consistent associations in different tumor stages, grades, and tumor size. Even if a subject who did not meet the criteria for MetS had only one of the components, he (she) still had an elevated risk for UTUC. Strategies to control the epidemic of MetS and its components might contribute to a reduction in the UTUC burden. The findings should be considered tentative until ascertained by more researches.


Figure 1 Mechanism of micro-energy therapy regulating the biological behavior of endogenous stem cells (ESCs).
Progress in studies on pathological changes and future treatment strategies of obesity-associated female stress urinary incontinence: a narrative review

January 2021

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27 Reads

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5 Citations

Translational Andrology and Urology

With the increasing prevalence of obesity worldwide, obesity-related female stress urinary incontinence (FSUI) has become a key health problem. Recent studies indicated that FSUI is primarily caused by obesity-related pathological changes, such as fat droplet deposition, and results in pelvic floor nerve, vascular, and urethral striated muscle injury. Meanwhile, treatments for obesity-associated FSUI (OA-FSUI) have garnered much attention. Although existing OA-FSUI management strategies, including weight loss, pelvic floor muscle exercise, and urethral sling operation, could play a role in symptomatic relief; they cannot reverse the pathological changes in OA-FSUI. The continued exploration of safe and reliable treatments has led to regenerative therapy becoming a particularly promising area of researches. Specifically, micro-energy, such as low-intensity pulsed ultrasound (LIPUS), low-intensity extracorporeal shock wave therapy (Li-ESWT), and pulsed electromagnetic field (PEMF), have been shown to restore the underlying pathological changes of OA-FSUI, which might be related by regulation endogenous stem cells (ESCs) to restore urine control function ultimately in animal experiments. Therefore, ESCs may be a target for repairing pathological changes of OA-FSUI. The aim of this review was to summarize the OA-FSUI-related pathogenesis, current treatments, and to discuss potential therapeutic options. In particular, this review is focused on the effects and related mechanisms of micro-energy therapy for OA-FSUI to provide a reference for future basically and clinical researches.


Identification and verification of hub microRNAs in varicocele rats through high-throughput sequencing and bioinformatics analysis

October 2020

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17 Reads

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11 Citations

Reproductive Toxicology

Varicocele (VC) is the most common treatable cause of infertility, but it is difficult to distinguish fertile from infertile VC populations because the pathogenesis is unclear. In order to study the related mechanism of VC causing male sterility, we made VC rats model by surgery, analyzed the rat epididymal sperm, and use the transcriptome sequencing compared all the miRNA expression differences in testicular tissue between VC rats, surgical treatment rats and control rats. The differentially expressed miRNAs (DEMs) of testicular tissue were also screened by the edgeR package in R software. We found that rno-miR-210-3p, rno-miR-6316, rno-miR-190a-5p and rno-miR-135b-5p were key miRNAs for VC and they were all up-regulated in VC samples and they are enriched in regulation of immune system process (GO:0002683), innate immune system (R-RNO-168,249) and apoptotic signaling pathway (GO:0097190). We hypothesize that negative regulation of immune system and apoptosis play an important role in the occurrence and development of VC, and it is induced the abnormal expression of target genes (such as Kitlg, Cxcl12) may involve in the development of VC associated infertility. Four key miRNAs, rno-miR-210-3p, rno-miR-6316, rno-miR-190a-5p and rno-miR-135b-5p, as well as their target genes are critical in VC, which could have attractive applications to provide new biomarkers for VC.


Development and Validation of a Nomogram to Predict Lymph Node Metastasis in Patients With T1 High-Grade Urothelial Carcinoma of the Bladder

October 2020

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52 Reads

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8 Citations

Purpose: This study aims to develop and validate a nomogram to predict lymph node (LN) metastasis preoperatively in patients with T1 high-grade urothelial carcinoma. Methods: We retrospectively evaluated the data of 2,689 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC) and bilateral lymphadenectomy in two medical centers. Eventually, 412 patients with T1 high-grade urothelial carcinoma were enrolled in the primary cohort to develop a prognostic nomogram designed to predict LN status. An independent validation cohort (containing 783 consecutive patients during the same period) was subjected to validate the predicting model. Binary regression analysis was used to develop the predicting nomogram. We assessed the performance of the nomogram concerning its clinical usefulness, calibration, and discrimination. Results: Overall, 69 (16.75%), and 135 (17.24%) patients had LN metastasis in the primary cohort and external validation cohort, respectively. The final nomogram included information on tumor number, tumor size, lymphovascular invasion (LVI), fibrinogen, and monocyte-to-lymphocyte ratio (MLR). The nomogram showed good predictive accuracy and calibration with a concordance index in the primary cohort of 0.853. The application of the nomogram in the external validation cohort still gave good discrimination (C-index, 0.845) and good calibration. The analysis of the decision curve shows that the nomogram has clinical application value. Conclusion: The nomogram that incorporated the tumor number, tumor size, LVI, fibrinogen, and MLR showed favorable predictive accuracy for LN metastasis. It may be conveniently used to predict LN metastasis in patients with T1 high-grade urothelial carcinoma and be helpful in guiding treatment decisions.


Fig. 1. PRISMA flow chart of the the data search.
Fig. 2. The association between phosphodiesterase type 5 inhibitors use and risk for development of skin cancers. OR: odds ratio, CI: confidence interval, MM: malignant melanoma, DNHR: Danish Nationwide Health Registries, KPNC: Kaiser Permanente Northern California, BCC: basal cell carcinoma, SCC: squamous cell carcinoma.
Fig. 5. Cumulative meta-analysis of the association between phosphodiesterase type 5 inhibitors use and risk for development of malignant melanoma, based on year of publication. OR: odds ratio, CI: confidence interval, DNHR: Danish Nationwide Health Registries, KPNC: Kaiser Permanente Northern California.
Fig. 6. Trial sequential analysis of the association between phosphodiesterase type 5 inhibitors use and the risk of malignant melanoma. The acquired information size (AIS) was calculated based on a two side α=5%, β=15% (power 80%), and a relative risk reduction of 12%. DNHR: Danish Nationwide Health Registries, KPNC: Kaiser Permanente Northern California.
Fig. 7. Overall survival (OS) and disease-free survival (DFS) analysis for different expression levels of phosphodiesterase A (PDE5A) gene. (A) OS analysis and data were obtained from OncoLnc, (B) OS analysis and data was obtained from GEPIA, (C) DFS analysis and data was obtained from GEPIA. TPM: transcripts per million, HR: hazard ratio.
Phosphodiesterase Type 5 Inhibitors and Risk of Skin Cancers in Men: A Meta-Analysis and Trial Sequential Analysis Involving 7,479,852 Subjects

August 2020

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65 Reads

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2 Citations

The World Journal of Men s Health

Purpose: We conducted a systematic review and meta-analysis to quantify the association between phosphodiesterase type 5 inhibitors (PDE5Is) use and skin cancers and we also examined whether down-expression of the PDE5A gene was related to worse prognosis for malignant melanoma (MM) patients. Materials and methods: The PubMed, Cochrane Library, Web of Science, EMBASE, and ClinicalTrails.gov databases were searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between PDE5Is use and risk of skin cancers. Cumulative meta-analysis and trial sequential analysis (TSA) were also conducted. Survival outcomes were analyzed online. Results: After pooling all 8 eligible studies comprising 7,479,852 subjects, we found that PDE5Is use was significantly associated with slightly increased risk of developing MM (OR: 1.13, 95% CI: 1.05 to 1.21, I²=67.1%), basal cell carcinoma (OR: 1.16, 95% CI: 1.13 to 1.19, I²=49.6%), and squamous cell carcinoma (OR: 1.07, 95% CI: 1.01 to 1.13, I²=0.0%). Totally, PDE5Is increased the risk of developing skin cancers (OR: 1.13, 95% CI: 1.09 to 1.17, I²=70.8%). TSA results showed that the sample size was enough to reach a positive conclusion. Conclusions: The use of PDE5Is may be slightly associated with increased risk of developing skin cancers. There should be a balance between drug benefits and potential safety issues. However, the pooled results should be considered tentative until confounding factors such as sun exposure and lifestyle are well-controlled in further studies.


The Prevalence and Prognostic Role of PD-L1 in Upper Tract Urothelial Carcinoma Patients Underwent Radical Nephroureterectomy: A Systematic Review and Meta-Analysis

August 2020

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74 Reads

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20 Citations

Background: Several studies investigating the role of PD-L1 in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU) to predict prognosis had been published and great controversy existed among them. We, therefore, in the meta-analysis, reported the association between PD-L1 and survival in UTUC patients who underwent RNU. Methods: We searched the PubMed, Cochrane Library, EMBASE, and Web of Science by April 1, 2020. Hazard ratio (HR) and odds ratio (OR) were adopted to evaluate relationships between PD-L1 and survival outcomes, and tumor features, respectively. We formulated clinical questions and organized following the PICOS strategy. Results: Eight retrospective studies incorporating 1406 patients were included. The pooled positive rate of PD-L1 in UTUC patients was 21.0% (95% CI = 13.0–30.0%, I² = 95.3%). Furthermore, higher PD-L1 in tumor tissues was related to shorter cancer-specific survival (CSS) in radically resected UTUC patients (HR = 1.63, 95% CI = 1.17–2.26, I² = 0.0%), but was not associated with overall survival (OS) (HR = 1.49, 95% CI = 0.76–2.91, I² = 74.9%). Subgroup analyses indicated associations between higher PD-L1 and shorter CSS in both Caucasus (HR = 1.72, 95% CI = 1.02–2.92, I² = 0.0%) and Asian (HR = 1.57, 95% CI = 1.03–2.39, I² = 23.1%) UTUC patients. Furthermore, PD-L1 was related to tumor grade of UTUC (High vs. Low, OR = 3.56, 95% CI = 1.82–6.97, P = 0.000) and invasive depth (pT3+pT4+pT2 vs. pT1+pTa/pTis, OR = 2.53, 95% CI = 1.07–5.96, P = 0.001). In the cumulative meta-analysis, results indicated that the 95% CIs narrowed as the pooled results gradually moved near the null. Conclusions: PD-L1 overexpression was related to worse survival outcomes in UTUC patients after RNU. It may be useful to incorporate PD-L1 into prognostic tools to select appropriate treatment strategies for UTUC. PD-L1 can also be clinically used for survival anticipation, risk stratification, and patient counseling. However, the pooled findings should be considered tentative until ascertained by more researches.


The association between acquired premature ejaculation and metabolic syndrome in young Chinese men

August 2020

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39 Reads

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3 Citations

We conducted the study to investigate the association between metabolic syndrome (MetS) and acquired premature ejaculation (APE). From January 2017 to December 2019, 1,000 subjects, 500 men with APE (APE group) and 500 men without APE (control group), were selected. Self-estimated intravaginal ejaculatory latency time (IELT) and Premature Ejaculation Diagnostic Tool (PEDT) were recorded from each participant to evaluate APE. Detailed physical examinations, body composition analysis and blood tests were all assessed. The neck circumference, waist circumference, visceral fat rating, fat mass, fasting blood glucose (FBG) and highly sensitive C-reactive protein (hs-CRP) in the APE group were significantly higher than the control group (p <.05 for all). Furthermore, the APE population had a higher prevalence of MetS than the control group (49.4% versus 35.6%, p =.000). Consistent results could also be observed in terms of the number of MetS components and each component of the MetS (both p <.05). Moreover, both the prevalence of APE and the severity of PE increased significantly as the number of MetS components increased. Finally, in the multivariate analysis, we found that both MetS and hs-CRP were independent risk factors for APE (both p <.01). The results indicated that APE was related to MetS but not its components.


Citations (32)


... In two studies, PDI and hPDI were used. The first study included 116 healthy men aged <45 with typical erectile function (IIEF-5 score 23.2 ± 1.5) seen at a single institution 82 . Within this group, increased PDI (β coefficient −0.36, 95% CI −0.40 to −0.31, P = 0.023) and hPDI (β coefficient -0.49, 95% CI −0.50 to −0.39, P = 0.001) were significantly associated with lower body mass index, but no significant relationship was found between PDI, hPDI or any specific food group with IIEF-5 scores or testosterone levels in these young healthy men. ...

Reference:

Plant-based diets and urological health
The association between plant‐based diet and erectile function in Chinese young healthy men: A population‐based study
  • Citing Article
  • March 2021

... Furthermore, low urine pH has been reported to be associated with metabolic syndrome in previous studies [19,20]. Indeed, metabolic syndrome is a significant risk factor for upper tract urothelial cancer and is consistently associated with tumor size and stage [21]. Therefore, we also compared the clinical factors associated with metabolic syndrome according to urine acidity status, such as BMI, history of diabetes mellitus, serum glucose levels, uric acid levels, and serum cholesterol levels. ...

Metabolic Syndrome and Risk of Upper Tract Urothelial Carcinoma: A Case-Control Study From Surveillance, Epidemiology and End Results-Medicare-Linked Database

... Recent research shows strong evidence of a connection between obesity and female SUI. Female SUI is mainly brought on by obesityrelated pathological alterations, especially the deposition of fat droplets, which harm the urethral striated muscle, vascular system, and pelvic floor nerve [14]. Thus, the WWI index adjusted for waist circumference and weight is more standardized and accessible to assess for obesity, which was initially suggested by Park et al. [15,16]. ...

Progress in studies on pathological changes and future treatment strategies of obesity-associated female stress urinary incontinence: a narrative review

Translational Andrology and Urology

... BPH mainly manifests as lower urinary tract symptoms (LUTS), and its incidence has been on the rise in recent years. Epidemiological surveys have reported that this disease affects over 15 million men, particularly those over the age of 50, and is a considerable economic burden on society (2). However, the specific mechanism of BPH is unclear, as multifactorial disease, age, androgen and estrogen interactions, obesity, diabetes, hypertension, hypogonadism, unhealthy lifestyle factors such as smoking, and alcohol consumption may be potential risk factors for the development of BPH (3). ...

The association between anogenital distance and benign prostatic hyperplasia related lower urinary tract symptoms in Chinese aging men

World Journal of Urology

... *, P < 0.05; **, P < 0.01; ***, P < 0.001 LNM, lymph node metastasis; LN, lymph node; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; MLR, monocyte-to-lymphocyte ratio; NPR, neutrophil-to-platelet ratio; SII, systemic immune inflammation index. *, P < 0.05; **, P < 0.01; ***, P < 0.001 nomogram for predicting LNM in T1 high-grade BUC containing MLR and fibrinogen [22]. Another study also demonstrated that systemic inflammatory biomarker such as NLR was an independent risk factor for LNM in BUC [13]. ...

Development and Validation of a Nomogram to Predict Lymph Node Metastasis in Patients With T1 High-Grade Urothelial Carcinoma of the Bladder

... A study showed the upregulation of rno-miR-210-3p, rno-miR-6316, rno-miR-190a-5p, and rno-miR-135b-5p in rats with varicocele compared with healthy and sham-operated rats. The authors also showed that these miRNAs are involved in the expression of genes that regulate the immune response and the apoptotic process, suggesting that the dysregulation of these mechanisms could underlie varicocele-induced sperm damage [20]. ...

Identification and verification of hub microRNAs in varicocele rats through high-throughput sequencing and bioinformatics analysis
  • Citing Article
  • October 2020

Reproductive Toxicology

... Phosphodiesterases are already focussed on tumour research. The expression of PDE5A was increased in colorectal neoplasms [41] and in 2021, a meta-analysis about their effect on the risk of melanoma was investigated [42]. EPM2AIP1 expression correlated with UICC status (p = 0.048), grade (p = 0.089), smoking status (p = 0.036), alcohol abuse status (p = 0.038), and epithelial type of OSCC (p = 0.073). ...

Phosphodiesterase Type 5 Inhibitors and Risk of Skin Cancers in Men: A Meta-Analysis and Trial Sequential Analysis Involving 7,479,852 Subjects

The World Journal of Men s Health

... Immune checkpoint inhibitors (ICIs), such as nivolumab and pembrolizumab, have shown significant survival benefits in specific subgroups, particularly in patients with microsatellite instability (MSI) or Epstein-Barr virus-positive tumors, but most GC patients fail to respond effectively (4). Challenges like identifying reliable predictive biomarkers, such as programmed cell death-ligand 1 (PD-L1) expression and tumor mutational burden, further limit the precision of immunotherapy application (5)(6)(7). Current research focuses on overcoming these hurdles by exploring combination therapies, such as ICIs paired with chemotherapy or targeted agents, which have shown promising results, especially in human epidermal growth factor receptor 2 (HER2)-positive GC patients (2,8). Additionally, novel strategies like chimeric antigen receptor T-cell therapy and cancer vaccines are under development, offering hope for improved outcomes. ...

The Prevalence and Prognostic Role of PD-L1 in Upper Tract Urothelial Carcinoma Patients Underwent Radical Nephroureterectomy: A Systematic Review and Meta-Analysis

... Overall, AhR contributes to the intricate process of sperm cell development, encompassing distinct phases including the Golgi, Cap, Tail, and Maturation phases, as well as being a crucial factor in spermiation since it plays a role in the sequential development of sperm cells and their eventual release during spermiation [14,46,47]. In addition, the AhR is involved in the regulation of Sertoli cells, which are essential for spermatogenesis since Sertoli cells provide nourishment and structural support to developing sperm cells; thus, AhR affects the function of Sertoli cells, thereby influencing spermatogenesis [48,49]. ...

Relationship between aryl hydrocarbon receptor and spermatogenic dysfunction in male patients with varicocele
  • Citing Article
  • August 2020

... In this study, we used PREQIs to evaluate the impact of various residential environment elements on mental health. We also combined the self-rating Depression Scale (SDS) [29] and premature ejaculation diagnostic tool (PEDT) [30] scale to explore the potential impact of residential environment on PE. ...

The association between acquired premature ejaculation and metabolic syndrome in young Chinese men
  • Citing Article
  • August 2020