Objective To systematically identify key risk biomolecules associated with the diagnosis of prostate cancer using multi-omics analysis methods, and to explore potential drug intervention targets. Methods Based on prostate cancer genome-wide association study data, GTEx v8 expression quantitative trait locus data, and The Cancer Genome Atlas database, this study screened for differentially expressed genes associated with prostate cancer pathogenesis through transcriptome imputation, summary data-based Mendelian randomization (SMR) analysis, colocalization analysis, and differential expression analysis.The identified differentially expressed genes were subjected to gene ontology analysis, single-cell RNA sequencing analysis, and correlation analysis with immune cell infiltration levels.Mendelian randomization (MR) was employed to investigate immune pathways and circulating metabolites associated with prostate cancer diagnosis.Potential drug targets for prostate cancer were screened using SMR analysis. Results Four differentially expressed genes associated with prostate cancer were identified, among which BHLHA15 (OR=1.08) was found to be associated with prostate cancer risk for the first time. MR analysis revealed that immune cell surface molecules and the inflammatory cytokine interleukin-17A (IL-17A) (OR=1.25) were risk factors for prostate cancer.MR analysis also indicated that higher levels of sebacate (OR=1.05) and cystine disulfide (OR=1.11) were associated with an increased risk of prostate cancer.Drug target analysis screened 14 potential target genes, among which high expression of OPRL1 was significantly correlated with poorer disease-free survival in prostate cancer patients (HR=2.00, P=0.024). Conclusion This study identified biomolecules associated with prostate cancer pathogenesis through multi-omics analysis, which may help deepen the clinical understanding of the pathogenic mechanisms underlying prostate cancer and reveal potential drug targets.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Urolithiasis represents a prevalent clinical challenge marked by high recurrence rates and morbidity，with existing preventive strategies struggling to effectively curb its epidemic trajectory，thereby posing a significant threat to public health. The etiology of this condition is intricate，involving a complex network of interactions spanning classical supersaturation-crystallization theory，Randall’s plaque theory，and multifactorial elements such as cellular injury，inflammatory responses，metabolic derangements，the gut-kidney axis，immune dysregulation，and genetic predisposition. However，the critical mechanisms initiating stone formation and the early pathophysiological processes remain incompletely elucidated，constituting the core impasse in current preventive strategies. This review systematically synthesizes classical theories and cutting-edge advancements in urolithiasis etiology research，emphasizing the urgent need to integrate emerging technologies，including high-dimensional omics，advanced imaging modalities，and artificial intelligence，to dissect pivotal pathological nodes in early stone formation. Such interdisciplinary efforts are essential to overcome cognitive bottlenecks and ultimately achieve personalized，precision-based prevention strategies.

Objective To investigate the perspectives and consensus among high-level medical professionals in China regarding critical thinking skills,identify key factors influencing the cultivation of critical thinking skills among medical students,propose optimization strategies,and provide both theoretical and practical guidance for standardizing mechanisms of critical thinking training within the medical education system.Methods A mixed-methods approach was employed.Semi-structured in-depth interviews were conducted with 22 core personnel involved in critical thinking training from multiple medical universities,hospitals,and clinical research teams across China between March 2023 and June 2023.Grounded theory was applied to explore the influencing factors,and the decision-making trial and evaluation laboratory(DEMATEL)method was applied to construct a structural model of the influencing factors.Centrality and causality analyses were conducted to examine the interrelationships among factors.Results The grounded theory analysis revealed a shared conceptual understanding of critical thinking skills among the participants,who emphasized that the development of critical thinking skills was influenced by multiple factors,including individual traits,teaching methods,and institutional environments.According to the DEMATEL analysis,13 core factors influencing the development of critical thinking skills in high-level medical professionals were identified.Among these,knowledge foundation was the most important influencing factor,exhibiting the highest centrality(22.35).Curriculum design was the second most important influencing factor.Conclusion The cultivation of critical thinking skills in medical education exhibits a multi-level interactive structure that encompasses individual,organizational,and institutional dimensions.Future efforts should focus on reinforcing the cognitive scaffolding role of knowledge construction and interdisciplinary curriculum design.

Urolithiasis represents a prevalent clinical challenge marked by high recurrence rates and morbidity，with existing preventive strategies struggling to effectively curb its epidemic trajectory，thereby posing a significant threat to public health. The etiology of this condition is intricate，involving a complex network of interactions spanning classical supersaturation-crystallization theory，Randall’s plaque theory，and multifactorial elements such as cellular injury，inflammatory responses，metabolic derangements，the gut-kidney axis，immune dysregulation，and genetic predisposition. However，the critical mechanisms initiating stone formation and the early pathophysiological processes remain incompletely elucidated，constituting the core impasse in current preventive strategies. This review systematically synthesizes classical theories and cutting-edge advancements in urolithiasis etiology research，emphasizing the urgent need to integrate emerging technologies，including high-dimensional omics，advanced imaging modalities，and artificial intelligence，to dissect pivotal pathological nodes in early stone formation. Such interdisciplinary efforts are essential to overcome cognitive bottlenecks and ultimately achieve personalized，precision-based prevention strategies.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Objective To investigate whether E.coli infection increases surgical site infection and postoperative fever in comparison with other pathogens.Methods A retrospective cohort study was conducted on 506 patients who underwent urethral segment resection and end anastomosis for the bulb or posterior urethral stenosis in our department during 2011 and 2019.According to occurrence of postoperative surgical site infection(SSI)or postoperative fever(POF),they were divided into SSI group(n=19)and non-SSI group(n=487),as well as POF group(n=61)and non-POF group(n=445 patients)respectively.Multivariate logistic regression analysis and LASSO algorithm were used to screen the potential risk factors.According to the results of positive preoperative urine culture in 302 patients,they were subsequently divided into E.coli infection group(n=80)and other pathogen infection group(n=222),and after reducing potential bias with propensity score matching,finally 48 patients were assigned into E.coli infection group,and 192 into other pathogen infection groups.The differences in occurrences of SSI and POF were compared between the above 2 groups of patients.Results Multivariate logistic regression analysis and LASSO algorithm revealed that positive preoperative urine culture was an independent risk factor for predicting SSI(P=0.012)and POF(P＜0.01).Among the 302 patients with positive results in preoperative urine culture,E.coli infections was in the first rank,accounting for 26.5％.After propensity score matched treatment,the incidence of SSI in the E.coli group and other pathogen groups was 29.2％and 2.1％,respectively(P＜0.01).The incidence of POF was also higher in the E.coli infection group than the other pathogen infection group(27.1％vs 13.5％,P=0.02).Conclusion Preoperative E.coli infection may increase the risk of SSI and POF after urethroplasty when compared with other pathogen infections.

Objective:To explore the risk factors for urethral stricture after transperineal anastomotic urethroplasty (TAU) by retrospectively analyzing patient data and to develop a nomogram to predict the risk of recurrence before the surgery.Methods:Clinical data of patients who underwent TAU because of post-traumatic urethral stricture from January 2016 to December 2017 in West China Hospital, Sichuan University were reviewd. A total of 78 patients were included in the retrospective analysis, with 13 of them having recurrence. The patients in the recurrence group had a median age of 49.8 and 76.9% (10/13) of them had membranous urethral stricture. The proximal urethra end was located above the superior margin of the pubic ramus (higher stricture site) in 53.8%(7/13)of patients in the recurrence group and the length of the stricture measured in the operation was (2.19±0.22) cm. In the non-recurrence group, the median age was (44.8±13.6) years old, 58.5% (38/65) of them had membranous urethral stricture, 21.5% (14/65) had higher stricture site, and the length of the stricture was (2.03±0.11) cm. Both univariate and multivariate logistics analyses were performed to evaluate the risk factors of recurrence of urethral stricture 5 years after surgery. The nomogram was built based on the multivariate logistics analysis. The Concordance Index (C-index), Receiver Operating Characteristic(ROC) curve and Calibration curve were used to evaluate the nomogram.Results:Univariate logistics analysis showed that higher stricture site, history of urethral dilation, smoking, diabetes and total serum protein may be associated with recurrence after surgery. Multivariate logistics analysis further confirmed that higher stricture site ( OR=34.64, 95% CI 3.71-754.53), history of urethral dilation( OR=13.15, 95% CI 1.27-210.00), smoking ( OR=13.75, 95% CI 2.15-166.05) and diabetes ( OR=64.98, 95% CI 3.80-1957.60) were independent risk factors for recurrent urethral stricture while higher total serum protein before surgery was related to lower recurrence risk ( OR=0.78, 95% CI 0.62-0.93). A nomogram was built based on the results. The C-index of the nomogram was 0.923(95% CI 0.908-0.938), the area under curve (AUC) was 0.923 (95% CI 0.855-0.991), and the Brier Score was 0.079. Conclusion:Higher stricture site, history of urethral dilation before surgery, smoking, diabetes and lower total serum protein before surgery are associated with higher recurrence TAU of post-traumatic urethral stricture patients. With the nomogram developed, prediction of the risk of recurrence could be achieved prior surgery.

Rats ; Animals ; Urinary Bladder Neck Obstruction/pathology* ; Survivin/genetics* ; Urinary Bladder/pathology* ; Fibrosis

Objective:To investigate the efficacy and safety of bladder neck resection combined with multipoint injection of triamcinolone acetonide in the treatment of bladder neck contractures (BNC) after transurethral resection prostate (TURP).Methods:The data of 25 patients with BNC after TUPR who underwent transurethral surgery in West China Hospital of Sichuan University from July 2019 to November 2021 were retrospectively analyzed, and the patients were divided into 2 groups according to the treatment method. There were 15 cases in the steroid injection group, with an average age of (67.5±8.8) years, 1 case of diabetes, and 2 cases of hypertension. And the average postoperative time after TURP was (21.9±29.1) months, the preoperative International Prostate Symptom Score (IPSS) was (30.0±3.5) points, quality of life (QOL) score was (5.7±0.5) points. There were 10 cases in the non-steroid injection group, with an average age of (65.2±10.5) years, 1 case of diabetes, and 2 cases of hypertension. And the average postoperative time of TURP was (29.3±33.5) months, and the preoperative IPSS was (30.4±2.6) points, QOL score was (5.8±0.4) points. There was no significant difference between the two groups ( P>0.05). In the steroid injection group, bladder neck resection combined with multipoint injection of triamcinolone acetonide was performed. The patients were in the lithotomy position, and a scope was placed through the urethra into the distal end of the narrow urethra under direct vision for observation, and a supersmooth guide wire was placed. The narrow section is then incised at 6 o'clock. After replacing the resectoscope, the urethral stricture scar was excised until the normal tissue of the bladder neck was exposed. Hemostasis by electrocoagulation resulted in no active bleeding from the urethra after resection. After the bladder injection needle was inserted, 80 mg (12 ml) of triamcinolone acetonide injection was injected in 6 equally spaced needles at the direction of the bladder neck from 3 to 9 o'clock. A supersmooth guide wire was placed, and a three-channel silicone urinary catheter was indwelled along the guide wire. The non-steroid injection group underwent simple bladder neck resection. Re-examination of urethroscopy at 3 and 6 months after operation showed that the patient had obvious dysuria and the microscopic examination showed that the recurrence of bladder neck stenosis was defined as the recurrence of stenosis. The efficacy, complications, and recurrence-free survival rates of the two groups were compared. Predictors of postoperative BNC recurrence were analyzed. Results:The operations in both groups were successfully completed. The operation time of the steroid injection group and the non-steroid injection group were (36.0±17.8) min and (48.5±57.9) min respectively ( P=0.438), and the intraoperative blood loss was (1.9±3.0) ml and (12.0±31.1) ml ( P=0.221)respectively. The length of hospital stay was (5.8±1.2) d and (4.4±2.5) d, respectively ( P=0.070). There was 1 case of transient hematuria and 1 case of epididymitis in the steroid injection group, and 1 case of transient hematuria and 1 case of transient dysuria in the non-steroid injection group ( P>0.05), all of which were relieved after symptomatic treatment. The IPSS of steroid injection group and non-steroid injection group were (11.0±5.6) points and (12.4±3.9) points at 3 months after operation, and (10.1±4.9) points and (14.7±7.7) points at 6 months after operation, respectively. QOL at 3 months after operation was (1.7±1.2) points and (2.1±1.5) points, respectively, and at 6 months after operation, it was (1.5±1.3) points and (3.0±2.0) points, respectively. There was statistical significance ( P<0.05). There were 1 case and 2 cases of recurrence in the steroid injection group and non-steroid injection group at 3 months after operation ( P=0.543), and 1 case and 5 cases at 6 months after operation ( P=0.023). The difference in survival curve between the two groups was statistically significant ( P=0.013). Combined steroid therapy ( OR=14.000, 95% CI1.299-150.889, P=0.030), time after scar resection ( OR=1.138, 95% CI1.017-1.273, P=0.025), postoperative IPSS( OR=1.302, 95% CI1.018-1.666, P=0.036), postoperative QOL score ( OR=4.280, 95% CI1.523-12.030, P=0.006) were the predictors of stenosis recurrence 6 months after surgery. Conclusion:Bladder neck scar resection combined with steroid injection could be safe and effective in the treatment of BNC after TURP, and local steroid injection may help reduce the recurrence rate of postoperative stenosis.