Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis.

This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.

Penile traumatic testicular dislocation: a case report.

Traumatic testicular dislocation is rare and usually occurs in patients after a traumatic motor accident. Manual reduction or surgical exploration is the main treatment for this condition. We report a rare case of unilateral traumatic testicular dislocation in a man with an ectopic testis in the middle of the penis after a motorcycle crash injury. On the sixth day of hospitalization, the patient found a lump in the middle of his penis. Doppler ultrasound showed an ectopic testicle in the middle of the penis with good blood flow. After consultation, a manual reduction was successfully performed. A careful physical examination should be performed in patients with multiple injuries from the first medical exam. Early detection and timely reduction are critical to protect testicular function.

A HER2-targeted Antibody-Drug Conjugate, RC48-ADC, Exerted Promising Antitumor Efficacy and Safety with Intravesical Instillation in Preclinical Models of Bladder Cancer.

More than half of non-muscle-invasive bladder cancer (NMIBC) patients eventually relapse even if treated with surgery and BCG without optional bladder-preserving therapy. This study aims to investigate the antitumor activity and safety of a HER2-targeted antibody-drug conjugate, RC48-ADC, intravesical instillation for NMIBC treatment. In this preclinical study, it is revealed that human epidermal growth factor receptor 2 (HER2) expression scores of 1+, 2+, and 3+ are recorded for 16.7%, 56.2%, and 14.6% of NMIBC cases. The antitumor effect of RC48-ADC is positively correlated with HER2 expression in bladder cancer (BCa) cell lines and organoid models. Furthermore, RC48-ADC is revealed to exert its antitumor effect by inducing G2/M arrest and caspase-dependent apoptosis. In an orthotopic BCa model, tumor growth is significantly inhibited by intravesical instillation of RC48-ADC versus disitamab, monomethyl auristatin E, epirubicin, or phosphate-buffered saline control. The potential toxicity of intravesical RC48-ADC is also assessed by dose escalation in normal nude mice and revealed that administration of RC48-ADC by intravesical instillation is safe within the range of effective therapeutic doses. Taken together, RC48-ADC demonstrates promising antitumor effects and safety with intravesical administration in multiple preclinical models. These findings provide a rational for clinical trials of intravesical RC48-ADC in NMIBC patients.

Construction of 3D and 2D contrast-enhanced CT radiomics for prediction of CGB3 expression level and clinical prognosis in bladder cancer.

Objective: The purpose of this study was to construct a 3D and 2D contrast-enhanced computed tomography (CECT) radiomics model to predict CGB3 levels and assess its prognostic abilities in bladder cancer (Bca) patients. Methods: Transcriptome data and CECT images of Bca patients were downloaded from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) database. Clinical data of 43 cases from TCGA and TCIA were used for radiomics model evaluation. The Volume of interest (VOI) (3D) and region of interest (ROI) (2D) radiomics features were extracted. For the construction of predicting radiomics models, least absolute shrinkage and selection operator regression were used, and the filtered radiomics features were fitted using the logistic regression algorithm (LR). The model's effectiveness was measured using 10-fold cross-validation and the area under the receiver operating characteristic curve (AUC of ROC). Result: CGB3 was a differential expressed prognosis-related gene and involved in the immune response process of plasma cells and T cell gamma delta. The high levels of CGB3 are a risk element for overall survival (OS). The AUCs of VOI and ROI radiomics models in the training set were 0.841 and 0.776, while in the validation set were 0.815 and 0.754, respectively. The Delong test revealed that the AUCs of the two models were not statistically different, and both models had good predictive performance. Conclusion: The CGB3 expression level is an important prognosis factor for Bca patients. Both 3D and 2D CECT radiomics are effective in predicting CGB3 expression levels.

Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study.

Corona virus disease 2019 (COVID-19) is prone to induce multiple organ damage. The kidney is one of the target organs of SARS-CoV-2, which is susceptible to inducing acute kidney injury (AKI). Huanglian Jiedu Decoction (HLJDD) is one of the recommended prescriptions for COVID-19 with severe complications. We used network pharmacology and molecular docking to explore the therapeutic and protective effects of HLJDD on COVID-19-associated AKI. Potential targets related to "HLJDD," "COVID-19," and "Acute Kidney Injury/Acute Renal Failure" were identified from several databases. A protein-protein interaction (PPI) network was constructed and screened the core targets according to the degree value. The target genes were then enriched using gene ontology and Kyoto Encyclopedia of Genes and Genomes. The bioactive components were docked with the core targets. A total of 65 active compounds, 85 common targets for diseases and drugs were obtained; PPI network analysis showed that the core protein mainly involved JUN, RELA, and AKT1; functional analysis showed that these target genes were mainly involved in lipid and atherosclerosis signaling pathway and IL-17 signal pathway. The results of molecular docking showed that JUN, RELA, and AKT1 had good binding activity with the effective chemical components of HLJDD. In conclusion, HLJDD can be used as a potential therapeutic drug for COVID-19-associated AKI.

Screening ANLN and ASPM as bladder urothelial carcinoma-related biomarkers based on weighted gene co-expression network analysis.

Introduction: Bladder cancer (BLCA) is one of the most common malignancies in the urinary system with a poor prognosis and high treatment costs. Identifying potential prognostic biomarkers is significant for exploring new therapeutic and predictive targets of BLCA. Methods: In this study, we screened differentially expressed genes using the GSE37815 dataset. We then performed a weighted gene co-expression network analysis (WGCNA) to identify the genes correlated with the histologic grade and T stage of BLCA using the GSE32548 dataset. Subsequently, Kaplan Meier survival analysis and Cox regression were used to further identify prognosis-related hub genes using the datasets GSE13507 and TCGA-BLCA. Moreover, we detected the expression of the hub genes in 35 paired samples, including BLCA and paracancerous tissue, from the Shantou Central Hospital by qRT-polymerase chain reaction. Results: This study showed that Anillin (ANLN) and Abnormal spindle-like microcephaly-associated gene (ASPM) were prognostic biomarkers for BLCA. High expression of ANLN and ASPM was associated with poor overall survival.The qRT-PCR results revealed that ANLN and ASPM genes were upregulated in BLCA, and there was a correlation between the expression of ANLN and ASPM in cancer tissues and paracancerous tissue. Additionally, the increasing multiples in the ANLN gene was obvious in high-grade BLCA. Discussion: In summary, this preliminary exploration indicated a correlation between ANLN and ASPM expression. These two genes, serving as the risk factors for BLCA progression, might be promising targets to improve the occurrence and progression of BLCA.

Predictive model for urosepsis in patients with Upper Urinary Tract Calculi based on ultrasonography and urinalysis using artificial intelligence learning

ABSTRACT Purpose To construct a predicting model for urosepsis risk for patients with upper urinary tract calculi based on ultrasound and urinalysis. Materials and Methods A retrospective study was conducted in patients with upper urinary tract calculi admitted between January 2016 and January 2020. The patients were randomly grouped into the training and validation sets. The training set was used to identify the urosepsis risk factors and construct a risk prediction model based on ultrasound and urinalysis. The validation set was used to test the performance of the artificial neural network (ANN). Results Ultimately, 1716 patients (10.8% cases and 89.2% control) were included. Eight variables were selected for the model: sex, age, body temperature, diabetes history, urine leukocytes, urine nitrite, urine glucose, and degree of hydronephrosis. The area under the receiver operating curve in the validation and training sets was 0.945 (95% CI: 0.903-0.988) and 0.992 (95% CI: 0.988-0.997), respectively. Sensitivity, specificity, and Yuden index of the validation set (training set) were 80.4% (85.9%), 98.2% (99.0%), and 0.786 (0.849), respectively. Conclusions A preliminary screening model for urosepsis based on ultrasound and urinalysis was constructed using ANN. The model could provide risk assessments for urosepsis in patients with upper urinary tract calculi.

Influencing factors for mortality in prostate cancer patients with T1 and T2 stage: a retrospective cohort study.

Background: Few reports have focused on the influencing factors of localized prostate cancer (PCa)-specific mortality so far. This study aimed to develop a competitive risk model for identifying the factors influencing the localized PCa mortality rate based on 135,310 subjects in the Surveillance, Epidemiology, and End Results (SEER) database. Methods: We included 135,310 localized PCa male patients from SEER database 2004-2016 in this cohort study, and collected the baseline information of all patients, including age of diagnosis, race, marital status, socioeconomic status (SES), American Joint Committee on Cancer (AJCC) stage, prostate-specific antigen (PSA) Gleason score, and so on. The outcome was considered as PCa-specific mortality in this study. The end time of follow-up was November 2018. Independent risk factors were examined by multivariate Fine-Gray analysis. The results are shown by hazard ratio (HR) and 95% confidence interval (CI). Results: All patients were divided into three groups: died from localized PCa (n=1,400), died from other causes (n=16,996), and survived (n=116,914). The diagnostic age of 119,899 patients was ≥55 years. The multivariate Fine-Gray analysis indicated that age of diagnosis (55-70 years: HR =1.473, 95% CI: 1.124-1.930; >70 years: HR =2.528, 95% CI: 1.901-3.362), race (American India/Alaska Native, Asian/Pacific Islander: HR =0.653, 95% CI: 0.490-0.870), marital status (divorced: HR =1.433, 95% CI: 1.197-1.717; single: HR =1.463, 95% CI: 1.244-1.719; widowed: HR =1.485, 95% CI: 1.222-1.804), therapeutic method (radiotherapy: HR =1.500; 95% CI: 1.119-2.011), SES (4-10: HR =0.799, 95% CI: 0.664-0.961; ≥11: HR =0.670; 95% CI: 0.534-0.839), AJCC stage (HR =0.820, 95% CI: 0.715-0.940), level of PSA (HR: 1.002, 95% CI: 1.002-1.002) and Gleason score (HR: 2.226, 95% CI: 2.108-2.350) were associated with the risk of localized PCa mortality. Conclusions: The study determined the influencing factors for mortality in patients with localized PCa through a competitive risk model. This finding may provide a reference for localized PCa patients: localized PCa patients who are older, divorced, widowed, single, have a radiotherapy, have a high PSA level, and Gleason score may be at high risk.

Predictive model for urosepsis in patients with Upper Urinary Tract Calculi based on ultrasonography and urinalysis using artificial intelligence learning.

PURPOSE: To construct a predicting model for urosepsis risk for patients with upper urinary tract calculi based on ultrasound and urinalysis. MATERIALS AND METHODS: A retrospective study was conducted in patients with upper urinary tract calculi admitted between January 2016 and January 2020. The patients were randomly grouped into the training and validation sets. The training set was used to identify the urosepsis risk factors and construct a risk prediction model based on ultrasound and urinalysis. The validation set was used to test the performance of the artificial neural network (ANN). RESULTS: Ultimately, 1716 patients (10.8% cases and 89.2% control) were included. Eight variables were selected for the model: sex, age, body temperature, diabetes history, urine leukocytes, urine nitrite, urine glucose, and degree of hydronephrosis. The area under the receiver operating curve in the validation and training sets was 0.945 (95% CI: 0.903-0.988) and 0.992 (95% CI: 0.988-0.997), respectively. Sensitivity, specificity, and Yuden index of the validation set (training set) were 80.4% (85.9%), 98.2% (99.0%), and 0.786 (0.849), respectively. CONCLUSIONS: A preliminary screening model for urosepsis based on ultrasound and urinalysis was constructed using ANN. The model could provide risk assessments for urosepsis in patients with upper urinary tract calculi.

Characteristics of Renal Function in Patients Diagnosed With COVID-19: An Observational Study.

Objective: The aim of the study was to analyze the characteristics of renal function in patients diagnosed with COVID-19. Methods: In this retrospective, single-center study, we included all confirmed cases of COVID-19 in a tertiary hospital in Guangdong, China from January 20, 2020 to March 20, 2020. Blood and urine laboratory findings related to renal function were summarized, and the estimated glomerular filtration rate (eGFR) and endogenous creatinine clearance (Ccr) were also calculated to assess the renal function. Results: A total of 12 admitted hospital patients were diagnosed with COVID-19, included 3 severe cases, and 9 common cases. Serum creatinine (Scr) was not abnormally elevated in all of the patients, and blood urea nitrogen (BUN) was abnormally elevated in only 25.0% of the patients. However, compared with the recovery period, the patient's Scr and BUN increased significantly in peak of disease (p-scr = 0.002 & p-bun < 0.001). By observing the fluctuations in Scr and BUN from admission to recovery, it was found that the peak of Scr and BUN appeared within the first 14 day of the course of the disease. Urinary microprotein detection indicated that the abnormally elevated rates of urine microalbumin (UMA), α1-microglobulin (A1M), urine immunoglobulin-G (IGU), and urine transferring (TRU) standardized by urinary creatinine in peak of disease were 41.7, 41.7, 50.0, and 16.7%, respectively. The abnormal rates of the calculated eGFR and Ccr were 66.7 and 41.7%. Conclusion: Scr and BUN were generally increased during the course of COVID-19. Detection of urinary microproteins and application of multiple indicators assessment could be helpful for discovering abnormal renal function in patients with COVID-19. However, the evidence is limited due to the small sample size and observational nature. Additional studies, especially large prospective cohort studies, are required to confirm these findings.

Comparison of meatal-based flap (Mathieu) and tubularized incised-plate (TIP) urethroplasties for primary distal hypospadias: A systematic review and meta-analysis.

PURPOSE: We conducted this meta-analysis to compare postoperative outcomes between meatal-based flap (Mathieu) and tubularized incised plate (TIP) techniques for distal hypospadias. METHODS: A comprehensive literature search of PUBMED, Web of Science, EMBASE, and Cochrane Library was conducted. Outcomes evaluated in this review were fistula, meatal stenosis, wound dehiscence and flap necrosis. We calculated odds ratio (OR) with 95% confidential interval (CI) to compare postoperative outcomes between Mathieu and TIP after data extraction and literature identification. All data were analyzed using Review Manager 5.2. In order to find potential affective factors, meta-regression and subgroup analyses were applied. RESULTS: 16 studies, 1386 patients, including 762 patients receiving Mathieu and 624 individuals subjected to TIP met the inclusion criteria. The synthetic data suggested that Mathieu and TIP were comparable in terms of fistula (OR = 0.93; 95% CI: 0.65 to 1.33; P = 0.70, I2 = 14%), wound dehiscence (OR = 0.89; 95% CI: 0.33 to 2.39; P = 0.81, I2 = 11%), and flap necrosis (OR = 1.9; 95% CI: 0.51 to 7.09; P = 0.20, I2 = 38%) without significant heterogeneity for each comparison group. Pooled estimates showed a significantly lower rate of meatal stenosis with Mathieu than with TIP (OR = 0.41; 95% CI: 0.24 to 0.73; P = 0.002, I2 = 4%). Subgroup analyses showed that the difference between Mathieu and TIP was more obvious in the studies published before 2013 in meatal stenosis. The modified Mathieu technique and a running suture for urethroplasty might be relevant to a lower rate of meatal stenosis in the data, although no statistical significance in the present effects model overall was found. One-way sensitivity analysis showed that the results were stable. There was no publication bias detected using both funnel plot and Egger's test. CONCLUSION: This meta-analysis suggested that Mathieu and TIP technique were equivalent for primary distal hypospadias in terms of fistula, wound dehiscence, and flap necrosis. Pooled estimates indicated that there was a lower rate of meatal stenosis with Mathieu rather than with TIP significantly. The modified Mathieu technique and a running suture for urethroplasty might be relevant to a lower rate of meatal stenosis. TYPE OF STUDY: Meta-analysis. LEVEL OF EVIDENCE: IV.

The Effect of Daily Fluid Management and Beverages Consumption on the Risk of Bladder Cancer: A Meta-analysis of Observational Study.

Epidemiological studies have evaluated the risk of bladder cancer (BCa) in relation to total fluid intake, as well as specific type of beverages consumption, with controversial results. The aim of this study was to further explore the potential relationship by conducting a meta-analysis. Fifty-four articles involving more than 43,000 BCa patients were included in this meta-analysis. A positive, though not statistically significant, association was found between total fluid intake and risk of BCa comparing the highest with lowest intake (SRRE: 1.16, 95%CI: 1.00-1.36). By conducting dose-response meta-analysis, we found that each 500 ml/day increase in total fluid intake was associated with 3.3% increased risk of BCa (RR: 1.03, 95%CI: 1.00-1.07). Pronounced increase in risk of BCa was detected when total fluid intake was more than 3000 ml/day. Meta-analyses of specific type of beverages showed increasing intake of coffee (RR: 1.03, 95%CI: 1.02-1.05) were risk factors for BCa. On the contrary, increasing intake of milk appeared to be a potential protective factor for BCa (RR: 0.90, 95%CI: 0.83-0.98). The risk of BCa was not significantly related to intake of water (RR: 1.01, 95%CI: 0.98-1.03), alcohol (RR: 1.01, 95%CI: 0.97-1.05), tea (RR: 1.01, 95%CI: 0.97-1.05) and soft drinks (RR: 1.04, 95%CI: 0.96-1.11).

Effect of histone deacetylase on prostate carcinoma.

Commonly occurred in aged males, the incidence of prostate carcinoma is increasing by years. Histone deacetylase (HDACs) as one key enzyme in regulating gene transcription has been found to be related with cancer occurrence. Trichostatin A (TSA) is one HDAC inhibitor for suppressing tumor growth. This study thus treated prostate carcinoma cell line PC3 with TSA, to analyze the effect of HDAC on the occurrence and progression of HDAC. PC3 cells were treated with gradient concentrations of TSA. MTT assay was employed to detect the proliferation of PC3 cells, while flow cytometry was used to detect the cell apoptosis and cell cycle. Apoptotic proteins including caspase-3, caspase-9 and bcl-2 were further quantified by Western blotting. MTT assays showed a dose- and time-dependent manner of TSA in inhibiting PC3 cell proliferation. Most of PC3 cells were arrested at G1 phase after treating with TSA. The apoptotic ratio of cells was also elevated by higher concentrations of drugs. Apoptotic proteins including caspase-3, caspase-9 and bcl-2 were all up-regulated by TSA. HDAC inhibitor can effectively suppress the proliferation of prostate carcinoma cells, which can be arrested at G1 phase. The elevated apoptotic ratio was caused by up-regulation of apoptosis-related proteins caspase-3, caspase-9 and bcl-2, in both dose- and time-dependent manners.