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"Cui, Yuanshan"
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Bladder cancer immunotherapy parallel advances in BCG optimization and next-generation vaccine platforms
2025
Bladder cancer (BCa) remains a significant global health challenge with rising incidence and suboptimal outcomes in advanced stages. Although immunotherapy for urological cancers is not a new treatment, recent clinical advances have confirmed the value of immunotherapy as a urological cancer treatment. In the field of cancer immunotherapy, increasing attention has been focused on the use of cancer vaccines that activate T cells to target growing tumors. Despite Bacillus Calmette-Guérin (BCG) intravesical immunotherapy serving as the first-line treatment for non-muscle-invasive bladder cancer (NMIBC), its limitations, including systemic toxicity, BCG unresponsiveness, and rapid bladder clearance-necessitate novel therapeutic strategies. This descriptive review synthesizes recent advances in BCG optimization and emerging cancer vaccines for BCa, including peptides, antigen-presenting cells, viruses, or nucleic acids, that seeks to stimulate the patient’s immune response targeting tumor cells. Our study underscores the transformative potential of next-generation vaccines in redefining BCa management while addressing critical barriers to implementation.
Journal Article
Integrative analysis identifies STX16 as a prognostic and immune-associated biomarker in ccRCC
2025
STX16 has been studied in various cancers, where it is suggested to regulate tumor cell proliferation, migration, and invasion by affecting vesicle trafficking and signal transduction pathways. However, its specific role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aims to systematically investigate the expression patterns, clinical significance, prognostic value and functional role of STX16 in ccRCC. Bioinformatics analyses using TCGA, CTPAC, TIMER, and UALCAN databases evaluated STX16 expression, clinical correlations, prognosis, and immune infiltration. Functional enrichment, co-expression, and PPI analyses explored STX16-associated pathways. Single-cell sequencing elucidated tumor microenvironment heterogeneity. Laboratory validation included Western blot, immunohistochemistry, and functional assays with siRNA-mediated STX16 knockdown in ccRCC cell lines. STX16 was significantly upregulated at mRNA and protein levels in ccRCC tissues. High STX16 expression correlated with advanced tumor stages, poor overall survival (OS), and disease-specific survival (DSS). Multivariable Cox regression identified STX16 as an independent prognostic factor. STX16 influenced immune infiltration, particularly involving CD4 + T cells, macrophages, and neutrophils, and was associated with immune pathways. Single-cell sequencing revealed heterogeneous STX16 expression across tumor microenvironment cell types. STX16 knockdown inhibited proliferation, migration, and invasion of ccRCC cell lines. STX16 is upregulated in ccRCC and acts as an independent prognostic factor associated with poor outcomes. Its role in promoting tumor progression and modulating immune infiltration highlights STX16 as a potential biomarker and therapeutic target in ccRCC.
Journal Article
Upregulated GSDMB in Clear Cell Renal Cell Carcinoma Is Associated with Immune Infiltrates and Poor Prognosis
by
Zhou, Zhongbao
,
Chai, Yumeng
,
Cui, Yuanshan
in
Apoptosis
,
Biomarkers, Tumor
,
Cancer therapies
2021
Gasdermin B (GSDMB) is part of the gasdermin (GSDM) family, and they use varying means of domain interactions in molecules to adjust their pore-forming and lipid-binding actions. The GSDM family has roles in the regulation of cell differentiation and proliferation, particularly in the process of pyroptosis. Nonetheless, the correlation of GSDMB with immune infiltrates and its prognostic values in clear cell renal cell carcinoma (ccRCC) are still undefined. Therefore, we assessed the correlation of GSDMB with immune infiltrates and its prognostic role in ccRCC. The transcriptional expression profiles of GSDMB in ccRCC tissues in addition to normal tissues were retrieved from The Cancer Genome Atlas (TCGA) and additionally verified in a different independent cohort, which was obtained from the Gene Expression Omnibus (GEO) database. The Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to assess the protein expression of GSDMB. To assess the effectiveness of GSDMB in distinguishing ccRCC from normal samples, the receiver operating characteristic (ROC) curve analysis was performed. Relationships between GSDMB expression, clinicopathological variables, and overall survival (OS) were evaluated with multivariate methods as well as Kaplan-Meier survival curves. Protein-protein interaction (PPI) networks were created with STRING. Functional enrichment analyses were conducted by utilizing the “ClusterProfiler” package. The Tumor Immune Estimation Resource (TIMER) and tumor-immune system interaction database (TISIDB) were utilized to determine the association between the mRNA expression of GSDMB and immune infiltrates. GSDMB expression was significantly more upregulated in ccRCC tissues compared to surrounding normal tissues. An increase in the mRNA expression of GSDMB was related to the high pathologic stage and advanced TNM stage. The analysis of the ROC curve indicated that GSDMB had an AUC value of 0.820 to distinguish between ccRCC tissues and adjacent normal controls. Kaplan-Meier survival analysis indicated that ccRCC patients with high GSDMB had a poorer prognosis compared to those with low GSDMB (P<0.001). Correlation analysis showed that the mRNA expression of GSDMB was associated with immune infiltrates and the purity of the tumor. Upregulation of GSDMB is significantly related to immune infiltrates and poor survival in ccRCC. The results of this study indicate that GSDMB could be regarded as a biomarker for the detection of poor prognosis and potential target of immune treatment in ccRCC.
Journal Article
Comparison of efficacy and safety of mirabegron and vibegron in the treatment of Overactive Bladder (OAB) in older women: A systematic review and meta-analysis
by
Zhao, Junjie
,
Zhang, Jiankun
,
Lou, Keyuan
in
Acetanilides - adverse effects
,
Acetanilides - therapeutic use
,
Adrenergic beta-3 Receptor Agonists - adverse effects
2025
After the introduction of anticholinergic drugs for the treatment of overactive bladder (OAB), the discovery of β-adrenergic agonists has helped reduce the side effects associated with the former. Currently, the two available medications, mirabegron and vibegron, are β-adrenergic agonists. However, clinical practitioners are still faced with the dilemma of which drug to choose.
To analyze and compare the efficacy and adverse effects of the two medications.
A literature search was conducted to identify randomized controlled trials using mirabegron and vibegron for the treatment of OAB. Databases such as PubMed, Web of Science, Cochrane Library, and Embase were searched. The search cutoff date was July 25 2024. Data extraction and quality assessment were performed using standardized methods. A meta-analysis was then conducted using RevMan software and a random-effects model, with studies weighted according to sample size and variance. Heterogeneity was assessed using the I² statistic. All statistical analyses were performed using RevMan, and results were presented as effect sizes (e.g., mean difference or risk ratio).
Three randomized controlled trials compared the safety and efficacy of mirabegron and vibegron head-to-head, involving 368 patients. The trials, each lasting 8 or 12 weeks. The trials compared the changes in various indices of the OABSS (Overactive Bladder Symptom Score) between the two drugs. The statistical methods used in the analysis included Mean Difference (MD), 95% Confidence Interval (CI), p-value, and I² statistic. For OABSS: MD = 0.38, 95% CI = - 0.19 to 0.95, p = 0.28, I² = 21%; for Q1: MD = 0.08, 95% CI = - 0.01 to 0.26, p = 0.31, I² = 4%; for Q2: MD = 0.08, 95% CI = - 0.21 to 0.37, p = 0.67, I² = 0%; for Q3: MD = 0.05, 95% CI = - 0.45 to 0.56, p = 0.90, I² = 0%; for Q4: MD = - 0.21, 95% CI = - 0.68 to 0.27, p = 0.35, I² = 0%. The relative risk (RR) of adverse effects between the two drugs was: RR = 0.87, 95% CI = 0.57 to 1.34, p = 0.27, I² = 25%; for constipation: RR = 0.73, 95% CI = 0.37 to 1.43, p = 0.27, I² = 25%; and for dry mouth: RR = 0.98, 95% CI = 0.42 to 2.30, p = 0.78, I² = 0%.
There appears to be no statistically significant difference in efficacy and safety between mirabegron and vibegron for OAB patients. Further high-quality prospective studies are needed to confirm these results.
Journal Article
The Efficacy and Safety of Daily Use of Tadalafil in Treatment of Premature Ejaculation: A Systematic Review and Meta-Analysis
by
Zhang, Jiankun
,
Yan, Huilei
,
Zhao, Shikai
in
Male Sexual and Reproductive Health
,
Meta-analysis
,
Systematic review
2025
The purpose of this meta-analysis was to evaluate the efficacy and safety of the once-daily use of 5 mg tadalafil in the treatment of patients with premature ejaculation. The databases MEDLINE/PubMed, EMBASE, and Cochrane Library from January 1980 until December 2024 were searched to identify randomized controlled trials (RCTs) that referred to the use of tadalafil for the treatment of premature ejaculation. A systematic review and meta-analysis was conducted. Five publications involving 397 patients were included in the meta-analysis. No statistically significant difference was identified between tadalafil and placebo for intravaginal ejaculatory latency time (IELT; mean difference [MD] = 68.43; 95% confidence interval [CI] = [−12.59 to 149.45]; p = .10) and Arabic index of premature ejaculation (AIPE; MD = 11.44; 95% CI = [−11.79, 34.66]; p = .33). Tadalafil appeared to improve the score of the premature ejaculation diagnostic tool (PEDT; MD = −0.30; 95% CI = [−0.57, −0.03]; p = .03). In terms of adverse events, the tadalafil group was significantly higher than the placebo group for headache (odds ratio [OR] = 16.06, 95% CI = [3.80, 67.94], p = .0002), back pain and myalgia (OR = 21.76, 95% CI = [4.17, 113.53], p = .0003), flushing (OR = 6.05, 95% CI = [1.05, 34.92], p = .04), and dyspepsia (OR = 10.27, 95% CI = [1.90, 55.96], p < .007). Our meta-analysis indicates that the once-daily use of 5 mg tadalafil had no statistically significant effect in the treatment of premature ejaculation. Meanwhile, the tadalafil therapy showed a higher risk of complications.
Journal Article
Evaluating the safety and effectiveness of α-blockers versus mirabegron for medical expulsive therapy in ureteral calculi: A Systematic review and meta-analysis
by
Zheng, Xiaobo
,
Li, Xiaoni
,
Cheng, Yan
in
Acetanilides - adverse effects
,
Acetanilides - therapeutic use
,
Adrenergic alpha-Antagonists - adverse effects
2024
The main categories of drugs employed for medical expulsive therapy in patients with ureteral calculi (UC) are alpha-blockers (α-B) and beta-adrenoceptor agonists. This meta-analysis evaluated the safety and effectiveness of α-B versus mirabegron (MIR) in treating UC.
From January 1980 to October 2024, we extensively searched the Pubmed, Web of science, Cochrane and EMBASE databases to identify randomized controlled trials (RCTs) that compared the effectiveness of α-B and MIR in managing UC. Furthermore, a systematic review and meta-analysis were carried out.
The meta-analysis included six publications with 592 patients, comparing α-B with MIR. The stone expulsion rate (SER) was found to be significantly greater in the α-B group than in the MIR group, as indicated by an odds ratio (OR) of 1.51 (95% confidence interval [CI]: 1.05 to 2.16, P = 0.03) in the meta-analysis. However, no significant differences were found between the α-B group and the MIR group for stone expulsion time (SET) (mean difference [MD]: 1.20; 95% CI, -2.71 to 5.10; P = 0.55), pain episodes (PE) (MD: 0.36; 95% CI, -0.04 to 0.76; P = 0.07), or analgesic requirements (MD: 0.79; 95% CI, -0.37 to 1.94; P = 0.18). The α-B group exhibited a significantly higher incidence of adverse events compared to the MIR group for orthostatic hypotension (OR 12.16, 95% CI 3.36 to 43.95, P = 0.0001), headache (OR 3.46, 95% CI 1.41 to 8.49, P = 0.007), and retrograde ejaculation (OR 16.30, 95% CI 5.87 to 45.31, P < 0.00001). While in the dizziness (OR 1.65, 95% CI 0.67 to 4.09, p = 0.28), it made no difference.
Our meta-analysis identified a substantial enhancement in the SER among patients with UC who received α-B therapy instead of those who were administered MIR therapy. Nonetheless, α-B therapy was connected to an increased risk of adverse events.
PROSPERO, ID CRD42024595934.
Journal Article
Comparison of the efficacy and complications of tolterodine and α-adrenergic receptor blockers in improving ureteral stent-related symptoms: A systematic review and meta-analysis
by
Liu, Shangjing
,
Liu, Ming
,
Mao, Qiancheng
in
Adrenergic alpha-Antagonists - therapeutic use
,
Adrenergic receptors
,
Bias
2024
We conducted a systematic evaluation of the therapeutic efficacy and complications of tolterodine and α-adrenergic receptor blockers in alleviating ureteral stent-related symptoms.
Until August 2023, we conducted a comprehensive literature search on PubMed, Embase, Web of Science, and Cochrane Library to identify randomized controlled trials evaluating the efficacy and complications of tolterodine and α-adrenergic receptor blockers in treating ureteral stent-related symptoms. Two reviewers independently screened studies and extracted data. The scores from various domains of the Ureteral Stent Symptom Questionnaire (USSQ) were summarized and compared, and statistical analysis was performed using RevMan 5.4.0 software.
A total of 8 studies met the inclusion criteria for our analysis. These studies were conducted at different centers. All studies were randomized controlled trials, involving a total of 487 patients, with 244 patients receiving α-adrenergic receptor blockers and 243 patients receiving tolterodine. The results showed that tolterodine demonstrated significantly better improvement in body pain (MD, 1.56; 95% CI [0.46, 2.66]; p = 0.005) (MD, 0.46; 95% CI [0.12, 0.80]; p = 0.008) (MD, 3.21; 95% CI [1.89, 4.52]; p = 0.00001) among patients after ureteral stent placement compared to α-adrenergic receptor blockers at different time points. Additionally, at 4 weeks, tolterodine showed superior improvement in general health (MD, 0.15; 95% CI [0.03, 0.27]; p = 0.01) and urinary symptoms (MD, 1.62; 95% CI [0.59, 2.66]; p = 0.002) compared to α-adrenergic receptor blockers, while at 6 weeks, tolterodine showed better improvement in work performance (MD, -1.60; 95% CI [-2.73, -0.48]; p = 0.005) compared to α-adrenergic receptor blockers. Additionally, the incidence of dry mouth (RR, 4.21; 95% CI [1.38, 12.87]; p = 0.01) is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, there were no significant statistical differences between the two drugs in other outcomes.
This meta-analysis suggests that tolterodine is superior to α-adrenergic receptor blockers in improving physical pain symptoms after ureteral stent placement, while α-adrenergic receptor blockers are more effective than tolterodine in enhancing work performance. Additionally, the incidence of dry mouth is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, higher-quality randomized controlled trials are needed to further investigate this issue.
Journal Article
A new predictive factor VGF based on IHC experiments, gene pathways and molecular functional groups for tumor immune microenvironment and prognosis of adrenocortical carcinoma
by
Zhang, Jiankun
,
Lou, Keyuan
,
Chi, Junpeng
in
Adrenal Cortex Neoplasms - genetics
,
Adrenal Cortex Neoplasms - immunology
,
Adrenal Cortex Neoplasms - metabolism
2025
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis, and its clinical management remains a significant challenge due to the high recurrence rates and limited treatment options. Despite advances in understanding the molecular mechanisms underlying ACC, no reliable biomarkers have been validated for routine clinical use.
We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) database (n=79) and Genotype Tissue Expression (GTEx) database (n=128) to investigate the expression of VGF in ACC and normal adrenal tissues. Gene expression levels of VGF were quantified and correlated with clinicopathological features and survival outcomes. Statistical methods included Cox proportional hazards models and Kaplan-Meier analysis, while Gene Set Enrichment Analysis (GSEA) was utilized to identify relevant biological pathways associated with VGF expression. Clinical data from 7 ACC patients from YANTAI YUHUANGDING Hospital were also analyzed. The expression of VGF in ACC and normal adrenal gland tissue was further validated through IHC experiments.
Our results demonstrate that VGF expression is elevated in ACC tissues compared to normal adrenal tissues and is significantly associated with advanced disease stages, lymph node involvement, metastasis and poor overall survival. VGF levels also correlate with immune cell infiltration, including Th2 cells, T helper cells, and Neutrophils. Importantly, our study establishes VGF as a potential prognostic biomarker for ACC and highlights its role in tumor progression and immune modulation. Additionally, GSEA analysis suggests that VGF is involved in cytokine receptor interaction and the P13K-Akt signaling pathway, possibly relating to tumor immunity.
VGF could serve as a valuable marker for patient stratification, monitoring disease progression, and predicting responses to immunotherapies. Future studies should focus on investigating circulating VGF levels as a non-invasive biomarker for ACC to improve clinical management and treatment outcomes.
Journal Article
Mirabegron and antimuscarinics for treating ureteral stent-related symptoms: a systematic review and meta-analysis of RCTs
2023
Objective: We conducted a meta-analysis to assess the efficacy and safety of mirabegron (50 mg/day) and antimuscarinics in treating ureteral stent-related symptoms (SRSs). Methods: All randomized controlled trials (RCTs) were identified by searching PubMed, Embase, Web of Science, and Cochrane Library. The RevMan version 5.3.0 software was used for statistical analysis. Results: This meta-analysis included five RCTs involving 317 patients. A fixed effects model revealed that mirabegron was superior to antimuscarinics in treating urinary symptoms (MD −1.39, 95% CI −2.63 to −0.15, p = 0.03) and general health (MD −1.65, 95% CI −2.60 to −0.69, p = 0.0007) 1 week after treatment initiation. We observed no significant differences in body pain (MD 0.05, 95% CI −1.06 to 1.15, p = 0.94), work performance (MD −0.86, 95% CI −1.77 to 0.06, p = 0.07), and sexual matters (MD 0.03, 95% CI −0.77 to 0.83, p = 0.94). Two weeks after treatment initiation, the ureteral stent symptom questionnaire (USSQ) revealed no significant differences between the two groups. The mirabegron group demonstrated a significant improvement in the quality of life (QoL) (MD −0.18, 95% CI −0.34 to −0.01, p = 0.03), while the International Prostate Symptom Score did not reveal a significant difference between the two groups (MD −0.74, 95% CI −1.79 to 0.32, p = 0.17). Regarding safety, a pooled data analysis presented that the incidence of constipation was lower in the mirabegron group (OR 0.10, 95% CI 0.01 to 0.77, p = 0.03). The mirabegron and antimuscarinics groups did not differ significantly concerning the risk of dry mouth (OR 0.15, 95% CI 0.02 to 1.27, p = 0.08). Conclusion: Mirabegron is superior to antimuscarinics in alleviating ureteral SRSs and improving QoL. Additionally, mirabegron 50 mg/day presented safety with a lower incidence of constipation.
Journal Article
Uncovering the prognostic implications and immunological roles of transmembrane protein 208 in bladder cancer by multi omics analysis and experimental verification
2025
In this study, we explored the role of transmembrane protein 208 (TMEM208), a transmembrane protein predominantly located in the endoplasmic reticulum, in bladder cancer (BLCA), where its absence is associated with developmental defects and cellular polarity disorders. Utilizing data from the TCGA database and 15 GEO datasets, we correlated TMEM208 expression with clinical features and employed the ComPPI website and Gene Set Enrichment Analysis (GSEA) to dissect its protein interactions and functional roles. Our analysis revealed that TMEM208 is significantly upregulated in BLCA, positively correlating with clinical severity and poor survival. GSEA indicated associations with oxidative phosphorylation, epithelial-mesenchymal transition, and stemness pathways. Immunoinfiltration analysis showed a predominantly positive correlation with immune cells, except for central memory T cells (Tcm) and T helper cells. Spatial transcriptomics and single-cell sequencing demonstrated TMEM208’s predominant expression in tumor cells and fibroblasts, aligning with tumor cell counts, and highlighting its crucial function within the tumor microenvironment. Cellular assays confirmed TMEM208’s ability to enhance BLCA cell proliferation, migration, and invasion. In conclusion, TMEM208’s overexpression in BLCA suggests its potential as an oncogenic factor, a prognostic indicator of poor outcomes, and a potential therapeutic target.
Journal Article