Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective:To explore the predictive value of preoperative pelvic floor electromyography(EMG)parameters for the risk of urinary incontinence after prostate cancer surgery.Methods:This study retrospectively analyzed the medical records of 271 patients who underwent radical prostatectomy in the urology department of Peking University First Hospital from January 2020 to October 2022.The data included patient age,body mass index(BMI),international prostate symptom score(IPSS),prostate-specific antigen(PSA)levels,Gleason score,type of surgery,urethral reconstruction,lymph node dis-section,nerve preservation,catheterization duration,D'Amico risk classification,American Society of Anesthesiologists(ASA)score,Charlson comorbidity index,postoperative duration,prostate volume,and pelvic floor EMG parameters(pre-resting mean,fast muscle mean,and slow muscle mean scores).Independent risk factors affecting early postoperative urinary incontinence were identified through multiva-riate Logistic regression analysis.The predictive efficacy of pelvic floor EMG results was evaluated by cal-culating the area under the receiver operating characteristic(ROC)curve,and the optimal threshold for early postoperative urinary incontinence was determined based on the Youden index and clinical signifi-cance.Results:The study included 271 prostate cancer patients,with an 81.9％rate of voluntary urinary control post-surgery.The median score for fast pelvic floor muscles was 23.5(18.2,31.6),and for slow muscles,it was 12.5(9.6,17.3).Among the patients,179(66.1％)did not preserve nerves,and 110(40.6％)underwent urethral reconstruction.Advanced age and low fast muscle scores were identified as independent risk factors for urinary incontinence.Patients aged ≤60 had 5.482 times the voluntary urinary control rate compared with those aged ≥70(95％CI:1.532-19.617,P＜0.05).There was a significant correlation between fast muscle scores and urinary incontinence recovery(OR=1.209,95％CI:1.132-1.291,P＜0.05).When the optimal threshold for preoperative fast muscle score was set at 18.5,the ROC sensitivity and specificity were 80.6％and 61.2％,respectively.Con-clusion:Preoperative pelvic floor EMG parameters show good predictive accuracy and clinical applicabili-ty for the risk of urinary incontinence after prostate cancer surgery.These parameters can be used for ear-ly identification of urinary incontinence risk,with age and fast muscle scores being important predictors.

Objective:To describe the characteristics, etiology and patterns of outpatients and inpatients patients with moderate or severe valvular heart disease (VHD).Methods:This is a cross-sectional study. Outpatients and inpatients with moderate or severe VHD who underwent transthoracic echocardiography for first examination from 1 st January 2001 to 1 st January 2020 in Southwest Hospital, Army Medical University were enrolled. Data were collected from medical records and big data platform of Southwest Hospital. Characteristics of age and gender, etiology and types of VHD were descriptively analysed. Results:A total of 68 354 patients with moderate or severe VHD were enrolled. The age was 63 (50, 72) years. And 35 706 (52.24%) patients were female. (1) Age characteristics: There was similar age trend between male and female patients with moderate or severe VHD. The number of patients increased firstly and then decreased and reached its peak in the age group of 65-69 years old. The peak age of mitral stenosis patients was 45-49 years, which was earlier than that of whole patients with moderate or severe VHD. The median age of patients with bicuspid aortic valve was 42 years. (2) Gender characteristics: The proportion of tricuspid regurgitation, pulmonary regurgitation, mitral regurgitation, mitral stenosis and valve surgery in female patients with moderate or severe VHD were higher than those in male patients. The proportion of aortic regurgitation, aortic stenosis and bicuspid aortic valve in male patients with moderate or severe VHD were significantly higher than those in female patients (all P<0.05). (3) Etiology: The proportion of rheumatic VHD was 13.07% (8 934/68 354), which was higher than that of degenerative VHD (0.67% (458/68 354)). (4) Types of VHD: Tricuspid regurgitation made contribution to the largest proportion with 60.72% (41 503/68 354), followed by mitral regurgitation, aortic regurgitation, mitral stenosis, pulmonary regurgitation and aortic stenosis. Conclusions:There are certain regional characteristics in the prevalence of moderate or severe VHD in southwest China, suggesting different attention should be paid on the whole process of refined management of moderate or severe VHD.

Objective To investigate the prognostic value of prognostic nutritional index (PNI) and modified Glasgow prognostic score (mGPS) in patients with cervical cancer. Methods A total of 120 patients with cervical cancer were selected as the study subjects. Patients' data were collected and analyzed, with follow-up conducted until June 30, 2023. Kaplan-Meier method was used to plot survival curves. Log-rank test and Cox regression analysis were employed to identify prognostic factors. Results The median follow-up time for patients in this study was 61 months, with a median survival time of 52 months. During the follow-up period, 41 patients (34.17%) died. The 3-year and 5-year survival rates were 82.50% and 66.67%, respectively. Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUC) for PNI, mGPS, albumin (ALB), lymphocytes (LYM), C-reactive protein (CRP), and neutrophils (NEU) in predicting patient prognosis were 0.90, 0.81, 0.84, 0.86, 0.82, and 0.71, respectively. The optimal cutoff values were determined to be 41.80 for PNI, 0.50 points for mGPS, 34.25 g/L for ALB, 1.44×10⁹/L for LYM, 5.45×10⁹/L for CRP and 7.25 mg/L for NEU. Cox regression analysis indicated that PNI (HR=4.18, 95%CI=2.83 to 9.21, P=0.015), mGPS [HR=1.95, 95%CI=1.37 to 3.59, P < 0.001 (mGPS=1 point); HR=3.07, 95%CI=2.38 to 5.36, P < 0.001(mGPS=2 points)] and International Federation of Gynecology and Obstetrics (FIGO) staging [HR=2.03, 95%CI=1.34 to 3.85, P=0.030(FIGO stage=stage Ⅲ); HR=3.46, 95%CI=2.15 to 6.62, P=0.003 (FIGO stage=stage Ⅳ)]were significant risk factors affecting the prognosis of cervical cancer patients. Conclusion PNI, mGPS and FIGO staging are important predictors of prognosis in cervical cancer patients. Attention to PNI and mGPS before treatment may help improve clinical outcomes.

Objective:To explore the influencing factors of the poor sustainability of the evidence-based practice project for irritant dermatitis around urostomy.Methods:This is a qualitative study. From April to May 2020, 12 nurses working in the Urology Surgery of Peking University First Hospital were selected by purposive sampling for the semi-structured interview. The integrated-Promoting Action on Research Implementation in Health Services framework (i-PARIHS framework) was applied to analyze and extract the obtained data.Results:The interview results found that, in terms of transform (evidence) , the localization and continuity of evidence for the evidence-based practice project of irritant dermatitis around urostomy needed to be improved, including the high matching between evidence and practice environment, and the insufficient continuity of evidence application. In terms of transform recipients, the leadership of project practitioner needed to be improved, including the conflict between the roles of practitioners and researchers, the lack of knowledge reserves of practitioners, and the conflict among the values of practitioners. In terms of organizational environment, the leadership of managers and the imformatization degree of project needed to be improved, including insufficient support from leaders and insufficient facilities.Conclusions:At the initial stage of formulating the nursing evidence-based practice project, the project implementer should fully incorporate the opinions of stakeholders for localization debugging, and consider the sustainability of the project. In addition, the leadership of managers, nurses and interns should be increased, the use and training of urostomy talents should be strengthened, the training of urostomy knowledge should be continued, the information-based follow-up system should be improved, and the intervention strategy should be continuously adjusted to ensure the project is carried out.

Objective:This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) .Methods:A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model.Results:The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions:PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

Objective:To learn about the iodine nutritional status of pregnant women in Suqian City, Jiangsu Province, and to provide evidence for scientific supplementation of iodine of pregnant women.Methods:From May 2016 to July 2020, five sampling districts were divided in each county (district) of Suqian City according to the oriation of east, west, south, north and center each year. One township (street) was selected from each district, and 20 pregnant women who lived in the local area for more than half a year were selected from each township (street). The 30 g of household salt samples of pregnant women and 5 ml of urine samples at random once were collected to test the salt iodine and urinary iodine content.Results:A total of 2 483 household salt samples of pregnant women were tested, and the median salt iodine was 23.9 mg/kg; among them, 2 454 were iodized salt, and the coverage rate of iodized salt was 98.8%; the qualified iodized salt was 2 383, the qualified rate of iodized salt was 97.1%, and the consumption rate of qualified iodized salt was 96.0%. There were statistically significant differences in coverage rate of iodized salt, qualified rate of iodized salt and consumption rate of qualified iodized salt between different years (χ 2 = 10.55, 13.23, 11.37, P < 0.05). A total of 2 483 urine samples of pregnant women were tested, and the median urinary iodine was 167.6 μg/L, which was at the appropriate iodine level. However, the median urinary iodine of pregnant women in 2020 was 146.7 μg/L, lower than the WHO/UNICEF/ICCIDD recommendation standard (150 μg/L). The differences of median urinary iodine of pregnant women in different years, pregnancy periods and regions were statistically significant ( H = 26.08, 8.17, 19.87, P < 0.05). Conclusions:The coverage rate of iodized salt, qualified rate of iodized salt and consumption rate of qualified iodized salt in Suqian City , meet the national standard for eliminating iodine deficiency disorders. Iodine nutrition of pregnant women in Suqian City is at an appropriate iodine level, but some pregnant women may have iodine deficiency.

Bronchial asthma and obesity are two chronic diseases that do harm to children′s health.The incidence of the two diseases is increasing, and they promote each other appearing to be causal.This paper reviews the clinical characteristics, atopy, potential biomarkers of obese asthma in children, as well as obesity-mediated metabolic abnormalities and immune responses, including inflammatory factors in fat and the role of adipokines in obese asthma.

Objective:To explore the effects of the LEARNS model in health education of urinary incontinence for patients undergoing laparoscopic radical prostatectomy.Methods:From September 2019 to August 2020, totally 60 patients who underwent laparoscopic radical prostatectomy in the Department of Urinary Surgery, Peking University First Hospital were selected by convenience sampling and divided into a control group and an intervention group according to the time of admission, with 30 cases in each group. Patients in the control group underwent conventional health education, while patients in the intervention group received nursing using the LEARNS model, with specific steps including listen (L), establish (E), adopt (A), reinforce (R), name (N), and strengthen (S). The mastery of knowledge about pelvic floor muscle before discharge was compared between the two groups, and the urinary continence of the two groups at 1 and 3 months after discharge was observed.Results:The knowledge level and correctness of pelvic floor muscle in the intervention group were higher than those in the control group, and the differences were statistically significant ( P<0.01). At 3 months after surgery, the urinary incontinence score of the intervention group was lower than that of the control group; the number of urine pads used was less than that of the control group; the rate of continence was higher than that of the control group, with statistically significant differences ( P<0.01) . Conclusions:The LEARNS mode can effectively improve the mastery of knowledge about pelvic floor muscle in patients undergoing laparoscopic radical prostatectomy, and improve their postoperative urinary continence.