Objectives: Coronavirus disease 2019 (COVID-19) poses a significant threat to kidney transplant recipients (KTRs) due to chronic immunosuppression. While Azvudine has demonstrated antiviral efficacy, its long-term impact on allograft function in KTRs remains unknown. This single-arm retrospective study provides a comprehensive evaluation of the outcomes. Methods: This single-center, retrospective study consecutively enrolled 20 KTRs diagnosed with COVID-19 during the Omicron surge (December 2022-January 2023), all treated with an Azvudine-centered regimen. Clinical data, treatment responses, and serial renal function parameters were analyzed. Long-term follow-up extended to a median of 39 months. Results: The median time to COVID-19 nucleic acid negativity was 13.22 days. Renal function improved significantly during treatment: estimated glomerular filtration rate increased by a mean of 27.29 mL/min/1.73 m2, and serum creatinine decreased by 57.72 µmol/L (both p < 0.01). Common complications included electrolyte imbalances and co-infections (50% of patients). Crucially, at a median follow-up of 39 months, 75% (15/20) of patients maintained normal allograft function. No Azvudine-related adverse events or drug interactions with immunosuppressants were observed. Conclusions: While acknowledging the inherent limitations of a non-comparative design, this study provides preliminary evidence suggesting that an Azvudine-centered regimen may be associated with promising efficacy, a favorable safety profile without interference with immunosuppressive therapy, and-most importantly-durable renal allograft survival in KTRs with COVID-19. Our data suggest that this regimen could contribute to mitigating the long-term risk of allograft dysfunction, potentially bringing outcomes closer to the expected baseline for stable recipients. Coupled with its low risk of drug-drug interactions, potential immunomodulatory benefits, and superior cost-effectiveness, Azvudine could be considered a valuable therapeutic option for this high-risk population in the post-pandemic era, although these findings warrant cautious interpretation. Controlled trials are ultimately needed to confirm these observations.

We present a case of collapsing glomerulopathy (CG) and thrombotic microangiopathy (TMA) associated with COVID-19 in an Asian kidney transplant recipient who does not have the APOL1 gene variant, and we conduct a literature review. The patient presented with progressive renal function decline following a negative COVID-19 nucleic acid test, accompanied by TMA manifestations such as thrombocytopenia and peripheral blood schistocytes. The renal biopsy conducted after plasma exchange revealed collapsing focal segmental glomerulosclerosis, along with acute tubulointerstitial nephritis and minor microangiopathic changes. The patient underwent cyclic eculizumab therapy and ultimately died of acute pulmonary embolism. Our findings indicate that kidney transplant recipients still may experience severe renal impairment even after testing negative for COVID-19 nucleic acid. COVID-19 can not only directly damage transplanted kidneys, but also indirectly harm transplanted kidneys by causing the release of cytokines and inflammation. COVID-19-related TMA and CG may be a continuous pathological process, and prolonged TMA may lead to the development of CG with a worse prognosis. It is also possible that CG and TMA coexist when patients present with acute kidney injury (AKI). Therefore, even a mild COVID-19 infection can have serious consequences for kidney transplant recipients. Vigilance for TMA and CG should be maintained in the presence of AKI of unknown cause.

Purpose Coronavirus disease 2019 (COVID-19) remains a serious challenge for kidney transplant recipients due to their immunocompromised status. Azvudine may be effective in treating COVID-19 in these patients, but its overall efficacy remains unclear. Methods Twenty kidney transplant COVID-19 patients at Peking University First Hospital received Azvudine-centered treatment from December 2022 to January 2023. Patients were diagnosed via COVID-19 nucleic acid testing. Demographics and treatment outcomes were collected. Results The median duration of Azvudine therapy was 9.6 days (7–14 days), and the median conversion time from positive to negative was 13.22 days (5–33 days). Transplanted renal function improved significantly (estimated glomerular filtration rate increased by 27.29 ml/min/1.73m2, t = 9.755, p < 0.0001; serum creatinine decreased by 57.72 µmol/L, t = 10.45 p < 0.0001). All patients experienced internal environment imbalance during treatment. Half had co-infections, with Mycoplasma pneumonia being the most common (7/20, 35%). The average cost of Azvudine was 220.44 RMB (94.56-342.78 RMB). After a 1-year follow-up, 70% (14/20) of patients maintained normal transplanted kidney function. No Azvudine-related complications were observed, indicating the therapy's initial safety. Conclusion This single-center study suggests that Azvudine-centered therapy may be effective and safe for COVID-19 in kidney transplant recipients. Azvudine could be a cost-effective alternative for those with poor access to first-line anti-COVID-19 agents.

Benign prostatic hyperplasia (BPH) is the most common and progressive urological disease in elderly men worldwide. Epidemiological studies have suggested that the speed of disease progression varies among individuals, while the pathophysiological mechanisms of accelerated clinical progression in some BPH patients remain to be elucidated. In this study, we defined patients with BPH as belonging to the accelerated progressive group (transurethral resection of the prostate [TURP] surgery at ≤50 years old), normal-speed progressive group (TURP surgery at ≥70 years old), or non-progressive group (age ≤50 years old without BPH-related surgery). We enrolled prostate specimens from the three groups of patients and compared these tissues to determine the histopathological characteristics and molecular mechanisms underlying BPH patients with accelerated progression. We found that the main histopathological characteristics of accelerated progressive BPH tissues were increased stromal components and prostatic fibrosis, which were accompanied by higher myofibroblast accumulation and collagen deposition. Mechanism dissection demonstrated that these accelerated progressive BPH tissues have higher expression of the CYP19 and G protein-coupled estrogen receptor (GPER) with higher estrogen biosynthesis. Estrogen functions via GPER/Gαi signaling to modulate the EGFR/ERK and HIF-1α/TGF-β1 signaling to increase prostatic stromal cell proliferation and prostatic stromal fibrosis. The increased stromal components and prostatic fibrosis may accelerate the clinical progression of BPH. Targeting this newly identified CYP19/estrogen/GPER/Gαi signaling axis may facilitate the development of novel personalized therapeutics to better suppress the progression of BPH.

Background After radical prostatectomy, the optimal length of postoperative catheterization time remains to be determined. This study investigates the impact of catheter removal time on urinary continence and overactive bladder (OAB) symptoms after robot-assisted radical prostatectomy (RARP). Methods Four hundred and thirty-two consecutive patients underwent RARP by a single surgeon between Nov 2020 and Oct 2021. Time to catheter removal was categorized into 7, 10, and ≥14 days. Continence was defined as no more than 1 pad used or no more than 20 g of urine leakage per 24 hours. The patients’ continence rates and overactive bladder symptom score (OABSS) were assessed at 48 hours, 1 week, 4, 12, and 24 weeks after catheter removal. Results Overall, continence rates were 37.3% 48 hours after catheter removal, 54.4% 1 week, 77.5% 4 weeks, 92.1% 12 weeks, and 97.9% 24 weeks after catheter removal. The median time to regain continence was 1 week. At 4 weeks after catheter removal, the continence rate in the ≥14 days group (70.5%) was significantly lower than the 7 days group (86.3%) and 10 days group (83.0%) (P=0.001). In a univariate Cox regression analysis, the presence of diabetes, higher pre-operative OABSS, and a catheterization time of 10 days were associated with worse continence recovery. The mean OABSS of patients in the continent group were significantly lower than the incontinent group at 48 hours, 4, 12 and 24 weeks after catheter removal. At 24 weeks after catheter removal, the mean OABSS in the 7 days group was significantly lower than in other groups. Conclusions Early catheter removal (7 days) was associated with better continence results and lower OABSS at 4 and 24 weeks after catheter removal respectively.

Abstract Background After radical prostatectomy, the optimal length of postoperative catheterization time remains to be determined. This study investigates the impact of catheter removal time on urinary continence and overactive bladder symptoms after robot-assisted radical prostatectomy (RARP).Methods Two hundred and fifty consecutive patients underwent RARP by a single surgeon between November 2020 and May 2021. Time to catheter removal was categorized into 7, 10, and ≥ 14 days. Continence was defined as no more than 1 pad used or no more than 20 grams of urine leakage per 24 hours. The patients' continence rates and overactive bladder symptom score (OABSS) were assessed at 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal.Results Overall, continence rates were 36% 48 hours after catheter removal, 55.6% 1 week, 74.8% 4 weeks, 98.4% 12 weeks, and 100% 24 weeks after catheter removal. The median time to regain continence was 1 week. After stratification according to catheterization time, no significant difference in continence rates was found between different groups at each time point after catheter removal. Longer catheterization was not an independent predictor of continence recovery (10 days: OR 0.985, 95% CI 0.689-1.409, p = 0.936; ≥14 days: OR 1.194, 95% CI 0.869-1.642, p = 0.274). The presence of diabetes was associated with worse continence outcomes (OR 1.535, 95% CI 1.105-2.132, p = 0.011). The mean OABSS of patients in the continent group were significantly lower than the incontinent group at 48 hours, 1 week, and 4 weeks after catheter removal. No significant difference in OABSS was found between different catheterization time groups at each time point after catheter removal.Conclusions Our results demonstrated that different catheterization time (7 days, 10 days, ≥14 days) is not associated with short-, intermediate-, long-term continence outcomes or overactive bladder symptoms.

OBJECTIVETo evaluate urinary continence recovery time and risk factors of urinary continence recovery after robot-assisted laparoscopic radical prostatectomy (RARP).METHODSFrom January 2019 to January 2021, a consecutive series of patients with localized prostate cancer (cT1-T3, cN0, cM0) were prospectively collected. RARP with total anatomical reconstruction was performed in all the cases by an experienced surgeon. Lymph node dissection was performed if the patient was in high-risk group according to the D'Amico risk classification. The primary endpoint was urinary continence recovery time after catheter removal. Postoperative and pathological variables were analyzed. Continence was rigo-rously analyzed 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks after catheter removal. Continence was evaluated by recording diaper pads used per day, and all the patients were instructed to perform the 24-hour pad weight test until full recovery of urinary continence. The patient was defined as continent if no more than one safety pad were needed per day, or no more than 20-gram urine leakage on the 24-hour pad weight test. Time from catheter removal to full recovery of urinary continence was recorded, and risk factors influencing continence recovery time evaluated.RESULTSIn total, 166 patients were analyzed. The mean age of the enrolled patients was 66.2 years, and the median prostate specific antigen (PSA) was 8.51 μg/L. A total of 59 patients (35.5%) had bilateral lymphatic dissection, and 28 (16.9%) underwent neurovascular bundle (NVB) preservation surgery. Postoperative pathology results showed that stage pT1 in 1 case (0.6%), stage pT2 in 77 cases (46.4%), stage pT3 in 86 cases (51.8%), and positive margins in 28 patients (16.9%). Among patients who underwent lymph node dissection, lymph node metastasis was found in 7 cases (11.9%). Median continence recovery time was one week. The number of the continent patients at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 65 (39.2%), 32 (19.3%), 34 (20.5%), 24 (14.5%), and 9 (5.4%). Two patients remained incontinent 24 weeks after catheter removal. The continence rates after catheter removal at the end of 48 hours, 1 week, 4 weeks, 12 weeks, and 24 weeks were 39.2%, 58.4%, 78.9%, 93.4%, and 98.8%, respectively. Univariate COX analysis revealed that diabetes appeared to influence continence recovery time (OR=1.589, 95%CI: 1.025-2.462, P=0.038). At the end of 48 hours, 4 weeks, 12 weeks, and 24 weeks after catheter removal, the mean OABSS score of the continent group was significantly lower than that of the incontinent group.CONCLUSIONRARP showed promising results in the recovery of urinary continence. Diabetes was a risk factor influencing continence recovery time. Bladder overactive symptoms play an important role in the recovery of continence after RARP.

BACKGROUND:There are few studies describing the prevalence and immune features of people with subclinical mesangial immunoglobulin A (IgA) deposition in the Chinese population. We sought to investigate the prevalence of mesangial IgA deposition among kidney donors and the immune characteristics of donors with mesangial IgA deposition. METHODS:Fifty blood-related living donors with zero-hour allograft biopsies obtained at Peking University First Hospital were enrolled. Galactose-deficient IgA1 (Gd-IgA1) in glomerular deposits was examined by double immunofluorescent staining using the specific monoclonal antibody KM55. Plasma IgA, IgA1, Gd-IgA1 and antibodies directed against Gd-IgA1 were measured using enzyme-linked immunosorbent assay. RESULTS:Thirteen of 50 (26%) donors had mesangial IgA deposition, which was confirmed by both immunofluorescence and electron microscopy. The levels of plasma IgA, IgA1 and Gd-IgA1 were all increased in donors with IgA deposition compared with those without IgA deposition (mean ± SD, 3.54 ± 0.505 versus 2.356 ± 0.265 mg/ml, p = 0.049; 3.003 ± 0.4048 versus 2.356 ± 0.265 mg/ml, p = 0.057; and 4.719 ± 0.4357 versus 3.356 ± 0.4707 ug/ml, p = 0.0440, respectively). Colocalized IgA1 and Gd-IgA1 indicated that there were galactose-deficient IgA1 deposits in the glomerular mesangium. While donors with IgA deposition showed lower levels of IgG anti-glycan antibodies than patients with IgA nephropathy (37.71 ± 8.886 versus 78.86 ± 5.155 units/ml, p = 0.001). CONCLUSIONS:The immune features of donors with IgA deposition, including IgA1 and Gd-IgA1 deposition, were similar to those of patients with IgA nephropathy, but donors with IgA deposition had lower levels of antiglycan antibodies, which may explain the subclinical status of IgA deposition in donors. Mesangial IgA deposition was common in the Chinese blood related donors cohort, further large study with both living and cadaveric donor kidneys was still needed to confirm these findings.

目的:研究经皮肾镜取石术(PCNL)后发生发热及全身炎症反应综合征(SIRS)的原因及诊治经验,并指导临床早期发现,及时干预,提高围手术期安全.方法:回顾性分析北京大学第一医院泌尿外科2015年11月～2016年10月行PCNL的187例患者的临床资料,采用x2检验和多因素Logistic回归分析的统计学方法,研究术后出现发热和SIRS与患者的年龄、性别、是否合并糖尿病、是否为鹿角形结石、是否患肾积水、术前是否合并尿路感染、术前麻醉ASA分级、手术时间、术后有无残石的关系.结果:187例患者,术后发热25例(13.4％),术后SIRS 19例(10.2％).研究发现,女性和术前无肾积水与术后发热相关(P＜0.05);术前尿路感染、术前无肾积水与术后SIRS相关(P＜0.05);多因素Logistic回归分析提示,女性和术前无肾积水是术后发热的危险因素(P＜0.05),术前无肾积水是术后SIRS的危险因素(P＜0.05).结论:发热和SIRS都是PCNL术后常见的并发症,术前无肾积水的患者术后发生发热和SIRS的风险增加,而女性患者更易在术后出现发热反应.

目的探讨DDD肾肿瘤评分系统对于肾肿瘤手术的指导意义。方法选择北京大学第一医院泌尿外科2013年1月至2017年9月收治2977例病理诊断为肾细胞癌的患者进行病例回顾,筛选病例资料包含泌尿系增强CT的患者561例,收集患者的年龄、性别、手术方式等数据,对其术前CT或磁共振进行回顾分析并进行RENAL及DDD（D1为位于肾内的肿瘤的最长径;D2为肿瘤边界距离肾髓质或肾窦和集合系统的最短距离;D3肿瘤距离肾动静脉主干的距离）系统评分。将各径线D1、D2、D3评分与手术方式进行Mann-Whitney秩和检验,进一步使用Mann-Whitney秩和检验方法,比较不同DDD系统评分与RENAL评分对手术方式的决策影响。结果 RENAL及DDD系统评分均可分为3组:低度、中度、高度。对于肾部分切除（PN）与肾根治性切除（RN）的比较分析,RENAL及DDD系统评分差异具有统计学意义（P ＜0.001）,评分越低,行肾部分切除术的比率越高。对于腹腔镜肾部分切除术（LPN）与腹腔镜肾根治性切除术（LRN）,RENAL及DDD系统评分差异具有统计学意义（P ＜0.001）,评分越低,行腹腔镜部分肾切除的比率越高。对于LRN及开放肾根治切除术（ORN）的比较分析显示,低分组及中分组在使用RENAL及DDD系统评分差异均无统计学意义（P值分别为0.135和0.602）,但是低分组与高分组比较时两评分系统差异均具有统计学意义（P值分别为0.025和＜0.018）,评分越高,行开放肾根治性切除术的比率越高。结论 DDD肾肿瘤评分系统评分是一种直观简便的描述肾肿瘤解剖特征的综合评估体系,具有良好的稳定性,可以反映肾肿瘤手术的难度,协助临床医师进行肾肿瘤的手术决策。

Objective To summarize the characteristics of clinical manifestation of bone flare after the treatment with new endocrine therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) in order to evaluate the curative effect of patients properly and determine the reasonable treatment strategy.Methods We retrospectively analyzed the clinical data of two patients with mCRPC performed "bone flare" defined as PSA decline and bone metastases progression in the initial treatment with new endocrine therapy in Urology Department of Peking University First Hospital,and analyzed the clinical characteristics and treatment methods with the relative literature.Case 1,a 79-year-old man,presented with frequent urination and prostate-specific antigen (PSA) was 115.900 ng/ml,was diagnosed as prostate cancer (cT3N0M1) with bone metastasis.After androgen deprivation therapy of 24 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of enzalutamide.Case 2,a 62-year-old man,complained about emaciation and frequent urination,was diagnosed with prostate cancer(cT4N1M1)with bone and lymph metastases.After androgen deprivation therapy of 22 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of abiraterone.Results Case 1 was treated with enzalutamide and 2 months later PSA decreased from 133.400 ng/ml to 5.530 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions kept stable,and part of lesions presented metabolism decrease.8 months later,the number of metastatic lesions began to decrease.1 year later,the patient started to receive chemical therapy because of the progression of the disease.After 5 cycles of chemotherapy,PSA progression occurred and chemotherapy was stopped.Liver failure and disseminated intravascular coagulation caused death in June 2016.Case 2 was treated with abiraterone and 2 months later PSA decreased from 54.820 ng/ml to 3.580 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions began to decline.10 months later,the number of metastatic lesions kept stable.The treatment of abiraterone was continued so far and the patient was in a stable condition.Conclusions Enzalutamide and abiraterone,two new endocrine therapy,are determined as preferred methods for the treatment of mCRPC.The bone scanning is required to evaluate the possibility of "bone flare" which is defined as PSA decline and bone metastases progression in the initial treatment.These patients should be evaluated to make appropriate clinical decision.

Benign prostatic hyperplasia (BPH) is the most common urological disease in elderly men, but the underlying pathophysiological mechanisms are complex and not fully understood. Phosphodiesterase type 5 inhibitors (PDE5‐Is) used to treat BPH could upregulate the cyclic guanosine monophosphate (cGMP)‐dependent protein kinase G (PKG) signaling, which was shown to blunt inflammation in the prostate. Our previous findings indicate that CD8+ T cells promote the proliferation of BPH epithelial cells (BECs) in low androgen conditions through secretion of CCL5; however, the role of the cGMP/PKG pathway in the process is unclear.

Objective To present a DDD scoring system to access the surgical complexity of renal tumors to assist in the surgical decision-making process. Methods We retrospectively evaluated 561 patients who were histopathologically diagnosed with renal cell carcinoma with available imaging data between January 2013 and September 2017. The surgical approaches, as well as RENAL and DDD scores, were compared. We performed a review of the available English literature published in the last decade and relating to the surgical anatomy pertinent to renal mass excision, and established a solid single renal mass scoring system, the DDD nephrometry score, based on the three most reproducible and pertinent features that characterize the critical anatomical attributes of renal tumors. Each feature in our nephrometry score was designated by an English letter, forming the acronym DDD: (D1)iameter (scores tumor size as the maximal diameter inside the kidney), (D2)epth of the deepest portion of the tumor with the medulla and collecting system or sinus, and (D3) istance (shortest from the mass to the main renal vessels). The points of D1, D2, and D3 were summed as DDD score and tumors were stratified into three complexity levels. The relationships between each D variate and the operation method options were tested by the Mann-Whitney rank sum test. The further Mann-Whitney rank sum test was used to compare the different effects of DDD nephrometry score and RENAL score on surgery method choice. Results In this cohort, 383 (68.3%) patients were men and 178 (31.7%) were women. The mean age was (57.3±11.9) years, and mean BMI was (25.1±3.5) kg/m2. Mean D1 was (4.3±2.0) cm. D2 was 1 pt in 50 (8.9%) patients, 2 pts in 110 (19.6%), and 3 pts in 401 (71.5%). D3 was 1 pt in 357 (63.6%) patients, 2 pts in 33 (5.9%), and 3 pts in 171 (30.5%). There were 36 (6.4%), 186 (33.2%), and 339 (60.4%) patients in the low, moderate, and high DDD score groups, and 140 (25.0%), 289 (51.5%), and 132 (23.5%) in the low, moderate, and high RENAL score groups, respectively. Regarding surgical procedures, 329 (58.6%) patients′ tumors were removed by radical nephrectomy (RN), in which 47 (8.4%) were removed by open radical nephrectomy (ORN) and 282 (50.2%) by laparoscopic radical nephrectomy (LRN); 232 (41.4%) patients′ tumors were removed by partial nephrectomy (PN), in which 32 (5.7%) were removed by open partial nephrectomy (OPN) and 200 (35.7%) by laparoscopic partial nephrectomy (LPN). For partial nephrectomy (PN) rate, significant differences were observed between any two RENAL or DDD score groups (P<0.001 for all), and there was a higher PN rate with the lower score group. Likewise, the same results were observed in the laparoscopic group, and the laparoscopic partial nephrectomy (LPN) rate was higher with the lower score group (P<0.001 for all). As for laparoscopic nephrectomy (LRN) or open nephrectomy (ORN), differences were not significant between low and moderate RENAL or DDD score groups (P=0.135 and P=0.602, respectively), but significant between the low and high groups (P=0.025, <0.018). High DDD score and RENAL groups had significant more patients undergoing ORN than low and moderate groups, respectively. Conclusions DDD score is based on only three variants and all of them are intuitive and pellucid. Even junior urologists and radiologists could easily master this system and it can be measured easily on preoperative CT images. The DDD score could be used to reflect the surgical complexity and assist to make treatment decisions for patients with renal tumors. Key words: Renal cell carcinoma; Surgical procedures; DDD score; RENAL score

Background Metabolic syndrome (MetS) has been found to be prevalent in cancer and have implications in cancer outcomes. In this study, we attempted to evaluate the prognostic value of MetS in localized clear cell renal cell carcinoma (ccRCC) patients. Methods We retrospectively collected clinicopathological data and pre-treatment laboratory test results of 480 patients with localized (T1-2N0M0) ccRCC undergoing radical or partial nephrectomy in Peking University First Hospital. MetS was diagnosed by criteria of the 2004 Chinese Medical Association Diabetes Society. Univariate and multivariate analyses were conducted to analyze the association between clinicopathological characteristics, MetS, and disease outcomes. Results In our cohort, 136 patients (28.3%) were diagnosed with MetS. Among them, 113 (83.1%) were men, suggesting that men were more likely to have MetS. This syndrome was also associated with increased pre-treatment creatinine levels. Median follow-up time was 70 months (range, 1-118 months) and 5-year overall survival (OS) rate was 92%. MetS was an independent favorable factor of cancer-specific survival (CSS) (P=0.017), and similar results were observed in Fuhrman nuclear grade 1-2 ccRCC patients by further analysis. Neither of the four components of the MetS (hypertension, diabetes mellitus, overweight/obesity and dyslipidemia) was an independent predictor of CSS. Patients who met more than 3 of the 4 criteria for MetS had higher CSS than those who met fewer than 2 criteria. Conclusions MetS is an independent prognostic factor for better CSS in localized ccRCC patients.

The present study evaluated programmed cell death-ligand 1 (PD-L1) expression in tumor cells and in the tumor microenvironment (TME) and its association with clinical data in primary testicular diffuse large B cell lymphoma (DLBCL). PD-L1 was determined by immunohistochemistry in 30 patients with primary testicular DLBCL and assessed for associations with clinical characteristics, progression-free survival (PFS) and overall survival (OS). The mean patient age was 62.2 years. Overall, 10 (33.3%) patients had advanced-stage (stage III/IV) disease and 14 (46.7%) patients had an International Prognostic Index (IPI) of ≥3. The median follow-up time following orchiectomy was 23.5 months. During this time, 10 (33.3%) patients experienced disease progression and 11 (36.7%) patients succumbed. PD-L1 expression in tumor cells and in the TME was detected in 20 (66.7%) and 13 (43.3%) patients, respectively. PD-L1 expression on tumor cells and in the TME was higher in those at an early stage compared with patients with an advanced stage of disease (P=0.045 and 0.017, respectively). In addition, PD-L1 expression in tumor cells was higher in patients with a low IPI compared with those with a high IPI (P=0.019). A Kaplan-Meier analysis identified no association of PD-L1 expression on tumor cells with PFS (P=0.763) or OS (P=0.531), or of PD-L1 expression in the TME with PFS (P=0.572) or OS (P=0.934). The present study demonstrated that PD-L1 expression in tumor cells and in the TME was higher in patients at an early stage of disease compared with those at an advanced stage, and that PD-L1 expression on tumor cells was higher in patients with a low IPI than in those with a high IPI. Furthermore, PD-L1 expression in tumor cells and in the TME was not associated with PFS or OS.

BACKGROUND:The magnitude effects of human leukocyte antigen (HLA) mismatching on post-transplant outcomes of kidney transplantation remain controversial. We aim to quantitatively assess the associations of HLA mismatching with graft survival and mortality in adult kidney transplantation.METHODS:We searched PubMed, EMBASE and the Cochrane Library from their inception to December, 2016. Priori clinical outcomes were overall graft failure, death-censored graft failure and all-cause mortality.RESULTS:A total of 23 cohort studies covering 486,608 recipients were selected. HLA per mismatch was significant associated with increased risks of overall graft failure (hazard ratio (HR), 1.06; 95% confidence interval (CI), 1.05-1.07), death-censored graft failure (HR: 1.09; 95% CI 1.06-1.12) and all-cause mortality (HR: 1.04; 95% CI: 1.02-1.07). Besides, HLA-DR mismatches were significant associated with worse overall graft survival (HR: 1.12, 95% CI: 1.05-1.21). For HLA-A locus, the association was insignificant (HR: 1.06; 95% CI: 0.98-1.14). We observed no significant association between HLA-B locus and overall graft failure (HR: 1.01; 95% CI: 0.90-1.15). In subgroup analyses, we found recipient sample size and ethnicity maybe the potential sources of heterogeneity.CONCLUSIONS:HLA mismatching was still a critical prognostic factor that affects graft and recipient survival. HLA-DR mismatching has a substantial impact on recipient's graft survival. HLA-A mismatching has minor but insignificant impact on graft survival outcomes.

Benign prostatic hyperplasia (BPH) is a progressive disease in elderly men, but potential factors accelerating its progression remain largely unknown. The aim of this study was to elucidate the factors affecting BPH progression by understanding the complex mechanisms causing early- progressed BPH, which progresses rapidly and requires surgical intervention before the age of 50. Three groups of human prostate tissue samples, from patients with early-progressed BPH, age-matched prostate and elderly BPH tissues, were collected (n = 25 each). We compared these tissues to determine the histologic features and molecular mechanisms underlying BPH progression. We found that early-progressed BPH samples were characterised by aberrant stromal hyper-proliferation, collagen deposition and increased M2 macrophage infiltration, compared to those from age-matched prostate and elderly BPH tissues. The M2 macrophage–fibroblast co-culture system demonstrated that the myofibroblast phenotypes were strongly induced only in fibroblasts from the early-progressed BPH samples, while the co-cultured M2 macrophages expressed high levels of pro-fibrotic cytokines, such as IL4 and TGFβ1. M2 macrophage-derived IL4, but not TGFβ1, selectively induced the myofibroblast phenotype through the JAK/STAT6, PI3K/AKT and MAPK/ERK signalling pathways in the early-progressed BPH prostate fibroblasts. Taken together, our results indicate that induction of the myofibroblast phenotype may lead to BPH progression through M2 macrophage-mediated IL4 signalling, and that IL4 may represent a potential therapeutic target, allowing the prevention of M2 macrophage activation and fibroblast-to-myofibroblast differentiation.

Background Kidney transplantation is regarded as the optimal treatment for pediatric patients with end-stage renal disease. Here, we address a controversial topic in pediatric kidney transplantation by performing a quantitative evaluation of the effect of human leukocyte antigen (HLA) mismatching on the outcomes of pediatric kidney transplantation. Methods We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 31 December 2016 for cohort studies assessing the risk ratio (RR) of HLA mismatching on pediatric kidney transplantation. Outcome measures included graft failure, rejection and all-cause mortality. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Results Eighteen studies comprising a total of 26 018 pediatric recipients were included in the evaluation. Compared with 0-1 HLA-DR mismatch, 2 mismatches significantly increased the risk of graft failure at 1 year (RR: 1.41, 95% CI: 1.11-1.80), 3 years (RR: 1.28, 95% CI: 1.08-1.52), 5 years (RR: 1.21, 95% CI: 1.04-1.41) and 10 years (RR: 1.30, 95% CI: 1.02-1.67). For HLA-A + B, the 5-year graft failure risk was higher for 2-4 mismatches compared with 0-1 mismatch (RR: 3.17, 95% CI: 1.20-8.36), but not for 3-4 compared with 0-2 mismatches (RR: 1.49, 95% CI: 0.79-2.80). Conclusions Based on pooled analysis, HLA-DR and HLA-A + B are important factors affecting post-transplant outcomes, especially graft failure, in pediatric recipients. Additional randomized controlled trials with higher quality evidence are needed for further investigation.

OBJECTIVE:Contrast enhanced ultrasound (CEUS) is an innovative technique that employs microbubble contrast agents to demonstrate parenchymal perfusion. Ultrasound contrast agent was reported to be directly used in human internal lumen to improve the observation capacity of ultrasound. However, CEUS has never been reported to be used in the guidance of percutaneous renal access in percutaneous nephrolithotomy (PCNL). This study aimed to assess the efficacy of CEUS-guided renal access in PCNL.METHODS:In this retrospective study, percutaneous renal access was performed under real-time monitoring of CEUS during PCNL in a cohort of 20 patients with renal stones at Peking University First Hospital. Data regarding patients' demographic and clinical characteristics, therapeutic regimens, and postoperative information were collected from a comprehensive database containing comprehensive medical records of the patients undergoing PCNL. Briefly, the procedure was as follows. With the patient under general anesthesia, renal access was established by the guidance of CEUS. Afterwords, holmium laser, pneumatic or ultrasonic lithotripsy was used by the same urologist. The patient demographics, stone characteristics and procedure details were noted. Finally, appropriate statistical analyses were performed to evaluate the effectiveness and safety of the CEUS-guided percutaneous renal access in PCNL.RESULTS:All the 20 patients underwent PCNL successfully with the help of CEUS guidance for tract creation. The collecting system was successfully accessed in all the patients, and only one patient underwent re-puncture. All the patients approached through a middle-pole percutaneous access. The median puncture time was 3.9 (2.9-4.6) min, and the median operating time was 112 (98.5-134.5) min. The preliminary stone-free rate of PCNL was 95.0% (19/20) as shown by the kidney, ureter, and bladder (KUB) radiographs 48 h postoperation, and the median decline in hemoglobin level was 10 (5.5-14.5) g/L. Two patients had transient postoperative fever and responded well to antibiotics. In addition, no other major complications were observed.CONCLUSION:CEUS is a safe and effective alternative way of guidance for percuta-neous renal access for PCNL beginners. It makes this procedure more visualized and simpler, and produces clearer images than common ultrasonic ones. PCNL beginners might benefit from this method to shorten the learning curve of PCNL, while it warrants further comparative studies to clarify.