北京大学学报（医学版）最新文献

Objective: To analyze the proportion of nonobstructive azoospermia (NOA) patients opting for sperm bank donation under different sperm retrieval methods [percutaneous testicular sperm aspiration (TESA), microdissection testicular sperm extraction (mTESE)] and its influencing factors.

Methods: Retrospective data from assisted reproductive technology (ART) cycles at the Center for Reproductive Medical, Peking University Third Hospital (from January 2019 to December 2023) were collected. Data-complete ART cycles involving NOA patients and their partners (using the last treatment cycle as the endpoint) were selected. Sperm donation utilization rates were compared across retrieval methods (fresh mTESE, fresh TESA, thawed mTESE, thawed TESA). Log-linear models were used to analyze the relationship between sperm retrieval method and sperm source.

Results: Among the 1 730 couples, the overall sperm donation utilization rate was 12.66%. The highest rate occurred in the fresh mTESE group (23.42%), followed by the thawed mTESE group (5.87%). The rates for the fresh TESA and thawed TESA groups were 5.22% and 0%, respectively. Log-linear analysis demonstrated that sperm retrieval method was significantly associated with sperm source (mTESE: Estimate=4.499; TESA: Estimate=2.780; P < 0.001).

Conclusion: The low overall sperm donation utilization rate in ART cycles may reflect the efficacy of synchronous sperm retrieval ART. The proportion of NOA patients opting for sperm donation was influenced by the retrieval method. Compared with patients undergoing TESA, those undergoing mTESE were more inclined to utilize donor sperm after retrieval failure.

Objective: To evaluate the long-term oncological outcomes of partial nephrectomy (PN) in patients with renal cell carcinoma (RCC) who were clinically staged as clinical T1 (cT1) preoperatively but upstaged to pathological T3a (pT3a) after surgery.

Methods: A total of 427 RCC patients postoperatively diagnosed as pT3aN0M0 at Peking University Third Hospital from February 2013 to December 2022 were retrospectively reviewed. Among them, 33 cT1 patients upstaged to pT3a RCC received PN (PN group), while 394 non-upstaged pT3a RCC patients underwent radical nephrectomy (RN, RN group). Propensity score matching was performed at a 1 ∶ 1 ratio based on baseline characteristics. The Kaplan-Meier method was used to assess overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS), with Log-rank tests and Cox regression models for multivariate analysis.

Results: Before matching, the PN group (n = 33) had significantly higher rates of perirenal fat invasion (PFI, 45.5% vs. 15.2%) and segmental renal vein involvement (42.4% vs. 20.8%), but lower rates of renal sinus invasion (RSI, 21.2% vs. 73.6%) and renal vein tumor thrombus (0% vs. 15.2%) compared with the RN group (n = 394, all P < 0.05). After matching, baseline characteristics were comparable between the PN group (n = 33) and RN group (n = 33). No significant differences were observed in operative time, blood loss, mean hospital stay, complication rate, positive margin rate, or conversion to open surgery between the two groups (P > 0.05). However, the PN group showed significantly higher estimated glomerular filtration rate (eGFR) postoperatively [76.9 (55.4, 87.3) mL/(min·1.73 m²) vs. 61.7 (56.8, 73.5) mL/(min·1.73 m²), P < 0.05], indicating better renal function preservation. No significant differences were found in OS, CSS, or DFS between the groups (P > 0.05). Multivariate ana-lysis identified renal vein invasion (RVI), higher Fuhrman grades (Ⅲ-Ⅳ), and sarcomatoid differentiation as independent risk factors for DFS and CSS in the pT3a RCC patients (P < 0.05).

Conclusion: For cT1 RCC patients upstaged to pT3a, PN preserves renal function more effectively while achieving com-parable oncological outcomes to RN. RVI, higher Fuhrmann grade, and sarcomatoid differentiation are independent risk factors for pT3N0M0 RCC patients.

Objective: To retrospectively evaluate the clinical efficacy and safety of total 3D laparoscopic ileal ureters replacement for bilateral ureters combined with bladder augmentation in patients with post-radiotherapy long-segment bilateral ureteral strictures and contracted bladder.

Methods: Clinical data of two patients (aged 72 and 54 years) with radiation-induced long-segment bilateral ureteral strictures and reduced bladder capacity, treated at the Sixth Affiliated Hospital of Jinan University from October 2023 to June 2024, were analyzed. Both presented with bilateral flank pain, recurrent chills/fever, urinary frequency, and urgency. Preoperative ureteral stricture lengths were measured as follows: left 10.4 cm and right 8.7 cm in the first case; left 10.6 cm and right 11.7 cm in the second case. Bladder capacity assessed by nephrostomy-assisted antegrade urography was 90 mL and 130 mL respectively. Both underwent single-position, one-stage totally 3D laparoscopic bilateral ileal ureteral replacement and bladder augmentation based on membrane anatomy principles, with regular postoperative follow-up.

Results: Procedures were completed by the same experienced urologist. Operative times were 420 min and 355 min, with intraoperative blood loss of 50 mL (no transfusion required). Postoperative bowel function resumed at the end of 4.5 and 3 days. No major perioperative complications occurred. Ureteral stents were removed at 2 months postoperatively, with imaging showing improved hydronephrosis, unobstructed ureteral drainage, symmetrical bladder morphology, and smooth walls. Postoperative bladder capacities were 230 mL and 250 mL. Follow-up durations were 10 and 8 months. Both patients experienced significant relief of flank pain and lower urinary tract symptoms. No complications (enteric fistula, urinary fistula, or metabolic acidosis) were observed. At the final follow-up, one patient had mildly elevated serum creatinine, while the other showed reduced levels compared with preoperative values; both remained stable.

Conclusion: Membrane anatomy-based dissection facilitates safe mobilization of fibrotic ureters with minimal bleeding and collateral damage. Total intracorporeal 3D laparoscopic ileal ureters replacement for bilateral ureters combined with bladder augmentation effectively addresses long-segment ureteral obstruction and improves bladder capacity. This approach is technically safe and feasible, though further validation with larger clinical cohorts is warranted.

Objective: To investigate whether escin (ESC) and dextromethorphan (DEX) have the protective effects on the progression and symptoms of Alzheimer disease (AD).

Methods: The AD model of Caenorhabditis elegans (C. elegans) was established by transgenic amyloid β-protein (Aβ protein). Different concentrations of ESC or DEX or 50 μmol/L memantine (MEM) were used to treat the AD model worms, and their lifespan was detected. The movement ability of AD model C. elegans was evaluated by body bending frequency and head swinging frequency. The changes in cognitive functions of AD model C. elegans before and after treatment were detected by chemotaxis experiments. The changes in Aβ protein and reactive oxygen species (ROS) content in C. elegans were detected. The changes in gene pathways related to oxidative stress were detected by Real-time quantitative polymerase chain reaction (RT-qPCR).

Results: At high dose 1 000 μmol/L, ESC or DEX treatment showed no significant effects on the activity of C. elegans. Compared with untreated worms, the survival time of AD model C. elegans in the 20 μmol/L ESC and 60 μmol/L DEX intervention groups was significantly extended. In the middle stage of AD progression, the body bending frequency and head swinging frequency of AD model worms after ESC or DEX treatment was significantly increased compared with the untreated control group with DEX being more effective in the recovery of head swinging frequency. For the early cognitive function tests, the chemotaxis index of ESC or DEX treated worms was significantly higher than that of the untreated worms, which correlated with marked reductions in the Aβ protein levels. The reactive oxygen species content in the drug intervention group was also lower than that in the control group. RT-qPCR results showed that ESC could inhibit oxidative stress in the AD model C. elegans by a 2-fold upregulation of skn1 expression.

Conclusion: ESC and DEX could improve the reductions of movement ability and cognitive function in the AD model worms and delay the aggravation of AD-related symptoms. ESC delays the progression of AD possibly by activating the SKN-1/Nrf2 pathway to protect against oxidative injury in the AD model.

Objective: The greater tuberosity angle (GTA) and critical shoulder angle (CSA) are commonly referred to as radiographic markers which were used to described morphology of the greater tuberosity and acromion respectively. At present, most international studies focus on the correlation between the above two parameters and rotator cuff tears (RCTs), and their diagnostic value and risk assessment. This study attempts to find out the trend of GTA and CSA changes and risk threshold of RCTs, as well as the protective factors and risk factors.

Methods: In this study, 130 individuals from May 2019 to December 2020 were recruited. According to Southern California Orthopedic Institute (SCOI) classification, the individuals were divided into four groups retrospectively: Group A, negative control group; Group B, partial tears (articular side); Group C, partial tears (bursal side); Group D, full-thickness tears. GTA and CSA were measured respectively on true anteroposterior position X-ray of shoulder with arm in neutral rotation and performed by the same trained technician team in single-blind. The correlations between RCTs and relevant factors were analyzed.

Results: According to the area under the receiver operating characteristic curve (AUC), GTA and CSA of RCTs (Groups B, C and D) were 0.736 and 0.673 with 95% confidence interval (CI), the cut-off value of GTA and CSA of RCTs were 70.5° and 39.5° respectively. Comparing with the control group, RCTs groups had significant statistical differences in age and body mass index (BMI) (P < 0.05), especially the full-thickness RCTs (Group D), which was older than Groups A, B and C (P < 0.05, cut-off value: 56.5 years old) and shorter than Groups A and B (P < 0.05, cut-off value: 1.58 m). Analyzed from scatter plot and regression analysis, there was no linear correlation between GTA and CSA. There were no significant differences in gender, dominant shoulders and smoking between the RCTs groups and the control group (P>0.05).

Conclusion: Larger GTA (>70.5°) and CSA (>39.5°) would be highly predictive in diagnosing RCTs without linear correlation, and GTA has a higher diagnostic value in contrast. Subacromial impingement and shoulder degeneration occurred before RCTs. Patients with age >56.5 years and height < 1.58 m were more likely to develop disease of full-thickness RCTs and no statistic differences in weight and BMI. Gender, dominant shoulder and smoking were neither risk factors nor protective factors.

Objective: To compare the changes of maximun flow rate and residual urine volume after tension-free vaginal tape (TVT) and trans-obturator tape (TOT) in the treatment of stress urinary incontinence in women.

Methods: The clinical data of female patients with stress urinary incontinence who underwent transvaginal midsection tension-free urethral suspension in Peking University People' s Hospital from January 2022 to January 2024 were retrospectively analyzed. All the patients were followed up 1 month, 6 months and 12 months after surgery. Urodynamics were performed to evaluate urethral sphincter function before surgery. At the same time, B-ultrasonography was improved to determine the residual urinary volume of the bladder, and urgent incontinence, detrusor weakness and bladder outlet obstruction were excluded, and the diagnosis was clearly stress incontinence. Maximum flow rate and residual urinary volume were measured during follow-up, and combined with the urinary incontinence questionnaire of the International Urinary Incontinence Advisory Committee, the surgical effect was judged to be cured, improved or ineffective according to the degree of improvement of urinary leakage symptoms after surgery.

Results: A total of 150 female patients with stress urinary incontinence were included in the study, the average age of the patients was (55.12±10.23) years old, and the follow-up time was 12 months. All patients completed postoperative follow-up, of whom 60 underwent TVT and 90 underwent TOT. The overall effective rates (cure + improvement) 1, 6, and 12 months after surgery in the TVT group were 93.3% (56/60), 91.7% (55/60), and 91.7% (55/60), and those in the TOT group were 92.2% (83/90), 90.0% (81/90), 90.0% (81/90), respectively, and there was no statistical difference between the two groups. The average maximum urinary flow rates 1, 6, and 12 months after surgery in the TVT group were (17.21±4.22) mL/s, (18.05±5.33) mL/s, and (18.37±4.92) mL/s, and those in the TOT group were (18.21±5.32) mL/s, (19.05±4.33) mL/s, and (19.27±4.92) mL/s, respectively, and there was no statistical difference between the two groups. The mean residual urine volume 1, 6, and 12 months after surgery in the TVT group was (13.21±5.22) mL, (18.25±5.33) mL, and (16.37±7.92) mL, and those in the TOT group was (11.21±6.32) mL, (13.05±5.33) mL, and (11.27±5.92)mL, respectively, and there was no statistical difference between the two groups. Compared with preoperative levels, there were no significant differences in the average maximum flow rate and the residual urine volume in both group at 1, 6, and 12 months after surgery.

Conclusion: Both TVT and TOT are effective in the treatment of stress incontinence, and have no effect on postoperative maximum flow rate and residual urine volume.

Objective: To compare the clinicopathological characteristics and prognostic outcomes between patients with clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC) accompanied by venous tumor thrombus.

Methods: A retrospective analysis was conducted on clinical and pathological data from patients with RCC and venous tumor thrombus treated in the Department of Urology at Peking University Third Hospital between January 2014 and February 2024. Patients were stratified into two groups based on pathological type: ccRCC and nccRCC. Comparisons of baseline characteristics, intraoperative situation, and prognosis between the two groups were performed using t-tests, Mann-Whitney U tests, chi-square tests, and Log-rank tests. Survival curves were generated using the Kaplan-Meier method.

Results: A total of 437 patients were included, with a median age of 58 years, including 317 males and 120 females. The cohort comprised 366 cases of ccRCC and 71 cases of nccRCC. The non-clear cell group included 38 cases (53.5%) of papillary renal cell carcinoma, 2 cases (2.8%) of chromophobe renal cell carcinoma, 11 cases (15.5%) of unclassified renal cell carcinoma, 19 cases (26.8%) of molecularly defined renal cell carcinoma, and 1 case (1.4%) of collecting duct carcinoma. Compared with the clear cell renal carcinoma group, patients in the non-clear cell carcinoma group demonstrated a younger age at diagnosis (59 years vs. 55 years, P=0.010), larger tumor size (8.4 cm vs. 9.5 cm, P=0.025), higher rates of lymph node metastasis (56.8% vs. 70.6%, P=0.034), more advanced tumor thrombus (P < 0.001) and pathological grading (P=0.010), longer surgical duration (272 minutes vs. 289 minutes, P=0.023), and shorter overall survival (80 months vs. 35 months, P < 0.001). Multivariate Cox analysis indicated that histologic type, distant metastasis, tumor thrombus grading, and sarcomatoid/rhabdoid differentiation were prognostic factors in the renal cell carcinoma patients with venous tumor thrombus. No significant differences were observed between the two groups in terms of gender, body mass index, tumor laterality, distant metastasis, sarcomatoid or rhabdoid differentiation, American Society of Anesthesiologists (ASA) score, surgical approach, conversion to open surgery, blood loss, or transfusion of red blood cells and plasma.

Conclusion: Compared with patients with clear cell renal carcinoma and venous tumor thrombus, those with non-clear cell carcinoma and venous tumor thrombus exhibit earlier onset, more aggressive disease progression, and poorer prognosis.

Objective: To identify genetic etiology of ischemic stroke (IS) based on pleiotropy of obesity related genes.

Methods: A discordant sib-pair study was designed based on the Fangshan family cohort in Beijing. Body mass index (BMI) polygenic risk score (PRS) was first constructed under different P values. Using the polygenic transmission disequilibrium test (pTDT), we then compared the actual BMI genetic risk of siblings with IS to their expected risk, to analyze whether higher BMI was over-transmitted to siblings with IS. The single nucleotide polymorphism (SNP) that comprised the PRS over-transmitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS. This set was then utilized as a candidate set to identify and verify risk SNPs asso-ciated IS by transmission disequilibrium test. Finally, we identified independent genomic risk loci and mapped to genes, we then explored the biological function of the identified risk loci and genes by functional annotation and pathway enrichment.

Results: A total of 541 participants were enrolled, with an average age of (58.4±8.1) years, including 326 discordant sib pairs of ischemic stroke. Compared with non-IS participants, IS participants with males, education level below junior high school, hypertension and hyperlipidemia accounted for a higher proportion (P < 0.05). For all the BMI PRS, we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation, suggesting that genetic risk associated with high BMI was over-transmitted with IS. Compared with other SNP sets, the set (P < 5×10^-4) corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS. Within this set, there were 45 SNPs having linkage and association with IS, which were located in 43 independent genomic risk loci and mapped to 40 genes. These genes were significantly enriched in the lipid metabolism pathway. The rs2232852 corrected by multiple tests was mapped to CYB5R1 and ADIPOR1, which were related to lipid metabolism and the ferroptosis pathway.

Conclusion: Pleiotropy between BMI-related genes and IS was observed. Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes, which were functionally enriched in lipid metabolic pathways. The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1, which were related to lipid metabolism and the ferroptosis pathway, suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective: This study conducts a text analysis of the policy documents related to Medical Consortium issued at the national level, identify the structural characteristics and utilization of Chinese Medical Consortium policy instruments, evaluate their alignment with policy objectives, uncover the structural contradictions in policy design, and provide a basis for optimizing the Medical Consortium system.

Methods: This study systematically searched national-level Medical Consortium policy documents from the PKU Law Database, CNKI Government Document Database using keyword like Medical Consortium. A two-dimensional "policy instrument-policy objective" analytical framework was constructed based on policy instrument theory to quantitatively analyze the frequency, distribution characteristics, and interactive relationships between policy instruments and objectives.

Results: A total of 50 national-level Me-dical Consortium policy documents from 2009 to 2024 were included, with 56% issued solely by single departments. The policy text analysis results showed that the government could use diverse policy instruments to achieve objectives, but the structural imbalances existed, environmental policy instruments accounted for the highest proportion (46.48%), mainly focusing on institutional safeguards (27.27%) and organizational governance (22.73%), with minimal focus on public awareness guidance (6.82%). Supply-side policy instruments (38.38%) overly relied on IT infrastructure development (24.77%) and rational allocation of medical resources (24.77%), with insufficient attention to workforce capacity building (9.17%) and financial input (4.59%). Demand-side policy instruments constituted only 15.14%, dominated by health insurance payment (37.21%) and pilot program promotion (32.56%), while market-oriented instruments such as service outsourcing (9.30%) were rarely used. Interaction analysis revealed that policy instruments were concentrated on enhancing primary care service capacity but provided inadequate support for optimizing allocation of medical resources, which indicated a misalignment between policy instruments and policy objective.

Conclusion: Chinese Medical Consortium policies exhibit weak interdepartmental coordination and structural imbalances, characterized by excessive reliance on environmental and supply-side instruments, underuse of demand-side tools, and internal misalignment within instrument categories. And policy instruments and objectives are not well matched. To address these issues, future policy formulation should strengthen cross-departmental collaboration, diversify policy instruments, optimize their internal structures, and improve the alignment between instruments and objectives.