BACKGROUND:Accurate detection of lymph node metastasis is crucial for precise tumour staging and treatment planning. Conventional pathological examination can overlook lymph node micrometastasis, resulting in underdiagnosis and suboptimal clinical outcomes. This study aimed to develop a pan-cancer artificial intelligence diagnostic model (PanCAM) for detecting lymph node metastasis across cancer types. METHODS:In this multicentre diagnostic study, patients who had undergone tumour resection and lymph node dissection from 17 hospitals in China were included. The entire dataset included nine common and 24 rare cancers. Histological slides of resected lymph nodes were collected and scanned to generate whole slide images (WSIs). PanCAM was developed by use of supervised learning and incremental learning strategies and trained and internally validated retrospectively on WSIs from nine common cancers at Sun Yat-sen Memorial Hospital of Sun Yat-sen University (Guangzhou, China). Its generalisability was retrospectively validated by use of WSIs from 15 external hospitals in China and the publicly available CAMELYON16 dataset from the Netherlands, representing both common and rare cancers. Prospective validation was done in a multicentre study (NCT06517979) across nine hospitals in China. The primary outcome was diagnostic sensitivity for detecting lymph node metastasis. In a secondary analysis, we compared performance between PanCAM and pathologists. FINDINGS:Between Jan 1, 2013, and Nov 30, 2024, 9256 patients from 17 hospitals in China were included in the study (4735 [51·2%] men; 4521 [48·8%] women; median age 60 years [IQR 50-69]; 3486 [37·7%] with lymph node metastasis). The dataset comprised 1303 patients in the training set, 558 in the internal validation set, 6006 in the external validation sets, and 1389 in the prospective validation sets, totalling 69 502 images and 153 985 lymph nodes. The CAMELYON16 dataset consisted of 399 images. In the retrospective validation, the diagnostic sensitivity of PanCAM for detecting lymph node metastasis ranged from 0·97 (95% CI 0·92-0·99) to 1·00 (0·98-1·00) across 16 hospitals, and was 0·96 (0·92-0·99) on the CAMELYON16 dataset. In the prospective validation, PanCAM exhibited sensitivity ranging from 0·93 (0·78-0·99) to 1·00 (0·98-1·00) across nine hospitals. Despite being trained solely on images from common cancers, PanCAM achieved a sensitivity of 0·98 (0·95-1·00) for rare cancers in both retrospective and prospective validations. At the patient level, PanCAM identified 120 additional patients with lymph node metastasis who were missed by pathologists in the retrospective validation and 21 additional cases in the prospective validation. INTERPRETATION:PanCAM provided a generalisable solution for detecting lymph node metastasis across cancer types. With high sensitivity and robust performance, the model could assist pathologists in diagnosing lymph node metastasis, improving diagnostic accuracy, supporting treatment decision making, and ultimately enhancing patient outcomes. FUNDING:National Natural Science Foundation of China, National Science and Technology Major Project, Science and Technology Projects in Guangzhou, Guangdong Provincial Clinical Research Centre for Urological Diseases, and Science and Technology Planning Project of Guangdong Province.

Intratumoral microbiota-related metabolites are emerging regulators of tumor immunity, yet their therapeutic potential remains largely unexplored. Here, indole-3-pyruvic acid (I3P), a Lactobacillus-associated tryptophan metabolite, is identified as a molecule associated with immunotherapy response in bladder cancer. Mechanistically, I3P suppresses macrophages ferroptosis and sustains CD8+ T cell activity through an AHR-NF-κB-SLC7A11 signaling axis that maintains macrophages redox homeostasis. Disruption of AHR or NF-κB signaling abolishes these effects. Notably, liposomal delivery of I3P facilitates efficient targeting of tumor-associated macrophages and enhances immunotherapy response without apparent toxicity. Together, these findings identify I3P as an immunoregulatory metabolite that potentiates anti-tumor immunity and support nanoparticle-mediated delivery as a promising strategy for immunotherapy sensitization in bladder cancer.

The advent of chimeric antigen receptor (CAR) T cell therapy has yielded transformative efficacy in hematological malignancies, yet its application in solid tumors remains constrained by the immunosuppressive tumor microenvironment (TME). Characterized by hypoxia, acidosis, and nutrient deprivation, the TME critically compromises CAR-T cell infiltration, persistence, and effector functions. Hypoxia-inducible factor 1α (HIF-1α), a central regulator of cellular adaptation to hypoxia within the TME, modulates T cell metabolism and functionality—presenting a strategic framework for enhancing CAR-T cell efficacy in solid malignancies. This review characterizes the role of HIF-1α in reprogramming the tumor-immune microenvironment, with specific emphasis on its metabolic regulation of T cells and translational implications for CAR-T therapy. Under hypoxic stress, HIF-1α orchestrates a metabolic shift toward glycolysis in effector T cells by suppressing oxidative phosphorylation (OXPHOS) while upregulating key glycolytic enzymes (e.g. GLUT1, HK2, LDHA). This adaptation sustains ATP production while attenuating mitochondrial reactive oxygen species (ROS) accumulation, thereby mitigating T cell exhaustion and augmenting cytotoxic persistence. This HIF-1α-mediated metabolic reprogramming provides critical insights for overcoming barriers to CAR-T cell efficacy in solid tumors.

The clinical benefits of neoadjuvant chemoimmunotherapy (NACI) are demonstrated in patients with bladder cancer (BCa); however, more than half fail to achieve a pathological complete response (pCR). This study utilizes multi-center cohorts of 2322 patients with pathologically diagnosed BCa, collected between January 1, 2014, and December 31, 2023, to explore the correlation between tumor budding (TB) status and NACI response and disease prognosis. A deep learning model is developed to noninvasively evaluate TB status based on CT images. The deep learning model accurately predicts the TB status, with area under the curve values of 0.932 (95% confidence interval: 0.898-0.965) in the training cohort, 0.944 (0.897-0.991) in the internal validation cohort, 0.882 (0.832-0.933) in external validation cohort 1, 0.944 (0.908-0.981) in the external validation cohort 2, and 0.854 (0.739-0.970) in the NACI validation cohort. Patients predicted to have a high TB status exhibit a worse prognosis (p < 0.05) and a lower pCR rate of 25.9% (7/20) than those predicted to have a low TB status (pCR rate: 73.9% [17/23]; p < 0.001). Hence, this model may be a reliable, noninvasive tool for predicting TB status, aiding clinicians in prognosis assessment and NACI strategy formulation.

Resistance to immune checkpoint inhibitors remains a significant challenge in the treatment of cancer. Emerging evidence suggests that metabolic reprogramming plays a crucial role in tumor metabolism and progression. Our study strived to investigate the role and underlying mechanisms of the glutamate transporter SLC1A6 in resistance to immunotherapy of cancer. Single-cell RNA sequencing was performed on bladder cancer patients receiving neoadjuvant immunotherapy to identify the expression of SLC1A6 in treatment-resistant cases. The clinical prognostic value of SLC1A6 in cancer was validated using publicly available lung cancer single-cell datasets, as well as transcriptomic data from both bladder and lung cancer cohorts. Flow cytometry was employed to assess the impact of SLC1A6 knockdown on the effector function of CD8⁺ T cell. In vivo tumor models were used to evaluate the role of SLC1A6 in immunotherapy resistance, with immunofluorescence staining performed to examine GZMB⁺ CD8⁺ T cell infiltration. SLC1A6 was highly expressed in bladder cancer patients resistant to neoadjuvant immunotherapy, and its expression was associated with disease progression, poor prognosis, and low immune infiltration. Knockdown of SLC1A6 in tumor cells enhanced CD8⁺ T cell effector function. SLC1A6 knockdown also improved the efficacy of immunotherapy and increased the infiltration of GZMB⁺ CD8⁺ T cells within the tumor microenvironment. SLC1A6 plays a critical role in resistance to immunotherapy in cancer. Targeting SLC1A6 may provide a promising therapeutic strategy for improving responses to neoadjuvant immunotherapy and advancing combination treatment approaches.

Background Many urothelial bladder carcinoma (UBC) patients don’t respond to immune checkpoint blockade (ICB) therapy, possibly due to tumor-associated neutrophils (TANs) suppressing lymphocyte immune response. Methods We conducted a meta-analysis on the predictive value of neutrophil-lymphocyte ratio (NLR) in ICB response and investigated TANs’ role in UBC. We used RNA-sequencing, HALO spatial analysis, single-cell RNA-sequencing, and flow cytometry to study the impacts of TANs and prostaglandin E2 (PGE2) on IDO1 expression. Animal experiments evaluated celecoxib’s efficacy in targeting PGE2 synthesis. Results Our analysis showed that higher TAN infiltration predicted worse outcomes in UBC patients receiving ICB therapy. Our research revealed that TANs promote IDO1 expression in cancer cells, resulting in immunosuppression. We also found that PGE2 synthesized by COX-2 in neutrophils played a key role in upregulating IDO1 in cancer cells. Animal experiments showed that targeting PGE2 synthesis in neutrophils with celecoxib enhanced the efficacy of ICB treatment. Conclusions TAN-secreted PGE2 upregulates IDO1, dampening T cell function in UBC. Celecoxib targeting of PGE2 synthesis represents a promising approach to enhance ICB efficacy in UBC.

Additional file 10: (A) BLCA with lymphovascular invasion expressed more FAP and VCAN than without lymphovascular invasion. In OS (B) and DSS (C) events, FAP, VCAN, N-cadherin, and Vimentin expression in the deceased group is higher than in the alive group. (D) In PFI events, VCAN and N-cadherin are more highly expressed in the deceased group. Immunohistochemistry (E) and dot blot (F) shows that the expression of TGF-β1, FAP, VCAN, N-cadherin, and Vimentin in BLCA tissues is significantly higher than in adjacent normal tissues, while the expression of E-cadherin in BLCA tissues is lower than in adjacent normal tissues. (G) TGF-β1 dominates stromal fibroblast-mediated EMT of bladder cancer cells via the FAP/VCAN axis to promote the invasion and metastasis of BLCA.

Background Bladder cancer is one of the most common malignant tumors of the urinary system and is associated with a poor prognosis once invasion and distant metastases occur. Epithelial-mesenchymal transition (EMT) drives metastasis and invasion in bladder cancer. Transforming growth factor β1 (TGF-β1) and stromal fibroblasts, especially cancer-associated fibroblasts (CAFs), are positive regulators of EMT in bladder cancer. However, it remains unclear how TGF-β1 mediates crosstalk between bladder cancer cells and CAFs and how it induces stromal fibroblast-mediated EMT in bladder cancer. We aimed to investigate the mechanism of TGF-β1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells. Methods Primary CAFs with high expression of fibroblast activation protein (FAP) were isolated from bladder cancer tissue samples. Subsequently, different conditioned media were used to stimulate the bladder cancer cell line T24 in a co-culture system. Gene set enrichment analysis, a human cytokine antibody array, and cytological assays were performed to investigate the mechanism of TGF-β1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells. Results Among the TGF-β family, TGF-β1 was the most highly expressed factor in bladder cancer tissue and primary stromal fibroblast supernatant. In the tumor microenvironment, TGF-β1 was mainly derived from stromal fibroblasts, especially CAFs. In stimulated bladder cells, stromal fibroblast-derived TGF-β1 promoted bladder cancer cell migration, invasion, and EMT. Furthermore, TGF-β1 promoted the activation of stromal fibroblasts, inducing CAF-like features, by upregulating FAP in primary normal fibroblasts and a normal fibroblast cell line. Stromal fibroblast-mediated EMT was induced in bladder cancer cells by TGF-β1/FAP. Versican (VCAN), a downstream molecule of FAP, plays an essential role in TGF-β1/FAP axis-induced EMT in bladder cancer cells. VCAN may also function through the PI3K/AKT1 signaling pathway. Conclusions TGF-β1 is a critical mediator of crosstalk between stromal fibroblasts and bladder cancer cells. We revealed a new mechanism whereby TGF-β1 dominated stromal fibroblast-mediated EMT of bladder cancer cells via the FAP/VCAN axis and identified potential biomarkers (FAP, VCAN, N-cadherin, and Vimentin) of bladder cancer. These results enhance our understanding of bladder cancer invasion and metastasis and provide potential strategies for diagnosis, treatment, and prognosis.

The limited response rate of immunotherapy in upper tract urothelial carcinoma (UTUC) might be attributed to additional immunosuppressive mechanisms in vivo. As a promising immune checkpoint target, the expression and prognostic role of indoleamine 2,3-dioxygenase 1 (IDO1) in UTUC remains unknown. In this study, the expression and prognostic value of IDO1 was analyzed in 251 patients from 3 independent cohorts. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to construct an IDO1-based immune classifier and external validation was performed to further validate the classifier. RNA sequencing and immunofluorescence were used to explore the immune contexture of different risk groups stratified by classifier. We found that high IDO1 expression on tumor cells (TC) indicated a poorer overall survival and disease-free survival in all cohorts. Patients with high expression of IDO1 TC possessed increased infiltration of CD4+ , CD8+ and Foxp3+ T cells. An immune classifier based on intratumoral CD8+ lymphocytes, IDO1 TC, and stromal PD-L1 expression status was developed, with its area under the curves (AUCs) values for overall survival at 5 y being 0.79 (95% confidence interval [CI] 0.65-0.93) in the discovery cohort, 0.75 (95% CI 0.58-0.92) and 0.78 (95% CI 0.65-0.92) in the internal and external validation cohorts, respectively. The high-risk group stratified by the immune classifier was associated with immunosuppressive contexture, accompanied by enhanced CD8+ T cells exhaustion patterns. Our IDO1-based immune classifier can provide a superior accuracy for survival prediction and lead to individual stratification of UTUC immune subtypes.

BACKGROUND:Substantial evidence indicate that long non-coding RNA (lncRNA) and microRNA (miRNA) act as key role in bladder cancer. Differentiation antagonistic ncRNA (DANCR) could be used as a biomarker in the occurrence and development of cancer. This study aims to explore the mechanism of DANCR/miR-335/VEGF-C axis affecting lymphatic metastasis of bladder cancer.METHODS:qRT-PCR detects the expression of DANCR in bladder cancer cell lines (SW780, 5637, T24, UM-UC-3) and normal bladder cell lines (SV-HUC-1), and selects T24 cell lines for subsequent experiments. The expression levels of DANCR, miR-335 and VEGF were measured by qRT-PCR, and the dual luciferase reporter gene verified the targeted regulation of DANCR on miR-335 and miR-335 on VEGF. CCK-8, Transwell and Wound healing assay detect the proliferation, invasion and migration ability of bladder cancer cells, Endothelial cell adhesion assay and Western blot further prove the lymphatic metastasis of bladder cancer.RESULTS:In this study, DANCR was highly expressed in bladder cancer cell lines. Transfection of si-DANCR significantly inhibits the proliferation, migration, invasion and lymphatic metastasis of bladder cancer cells. Dual luciferase assay confirmed that DANCR targets miR-335/VEGF-C. Transfection of miR-335 mimic promotes the proliferation, migration, invasion and lymphatic metastasis of bladder cancer cells, overexpression of DANCR eliminates the promotion of miR-335 mimic on bladder cancer cells. Further experiments proved that inhibition of miR-335 and overexpression of VEGF-C can reverse the inhibitory effect of silencing DANCR on bladder cancer cells.CONCLUSIONS:In bladder cancer, DARCR plays an important role, which regulates the proliferation, migration, invasion and lymphatic metastasis of bladder cancer cells through the miR-335/VEGF-C molecular axis.

Tumors are one of the main causes of death in humans. The development of safe and effective methods for early diagnosis and treatment of tumors is a difficult problem that needs to be solved urgently. It is well established that the occurrence of tumors involves complex biological mechanisms, and the tumor microenvironment (TME) plays an important role in regulating the biological behavior of tumors. Cancer-associated fibroblasts (CAFs) are a group of activated fibroblasts with significant heterogeneity and plasticity in the tumor microenvironment. They secrete a variety of active factors to regulate tumor occurrence, development, metastasis, and therapeutic resistance. Although most studies suggest that CAFs have significant tumor-promoting functions, some evidence indicates that they may have certain tumor-suppressive functions in the early stage of tumors. Current research on CAFs continues to face many challenges, and the heterogeneity of their origin, phenotype, and function is a major difficulty and hot spot. To provide new perspectives for the research on CAFs and tumor diagnosis and treatment, this review summarizes the definition, origin, biomarkers, generation mechanism, functions, heterogeneity, plasticity, subpopulations, pre-metastasis niches (PMN), immune microenvironment, and targeted therapy of CAFs, describes the research progress and challenges, and proposes possible future research directions based on existing reports.

Objective To compare the clinical effect of 3D and 2D retroperitoneal laparoscopic nephrectomy, and summarize the surgical experience of retroperitoneal laparoscopic nephrectomy. Methods The clinical data of 69 cases with nonfunctioning kidney who were treated in our department from February 2015 to February 2018 were analyzed retrospectively. 29 cases in group A used laparoscopic 3D system, and 40 cases in group B used 2D laparoscopic system. The operative time, intraoperative blood loss, postoperative intestinal exhaust time, postoperative drainage time, hospital time, transit open surgery and complications were compared between the two groups. Results 69 cases were performed by the same surgeon. 61 cases (88.4%) were treated by retroperitoneal laparoscopic nephrectomy successfully. 8 cases were transferred to open surgery due to severe adhesion (or massive bleeding). The operation time in group A was significantly shorter than that in group B[(118±21) min vs (134±19) min,t=-3.3003,P=0.0008]. There was no significant difference in intraoperative blood loss, postoperative intestinal exhaust time, postoperative drainage time, hospital time and operative complications between the two groups (P>0.05). Conclusion Retroperitoneal laparoscopic nephrectomy is a safe and effective nephrectomy method. Compared with 2D laparoscopic system, 3D laparoscopic systems can effectively shorten the operation time after being skilled, it is worthy of clinical application. Key words: 3D, laparoscopy; 2D laparoscopy; Nephrectomy

Objective To explore the feasibility and safety of flexible ureteroscope with tubeless in the treatment of middle or upper calyx renal calculi.Methods The clinical data of 107 patients with renal calculi treated from January 2015 to October 2018 were analyzed retrospectively.Age ranged from 18 to 55 years,with mean of (32.1 ± 5.2) years.Calculi was single,locating in the middle or upper calyx,with the diameter less than 2.0 cm,the CT value ≤ 800 HU,and mild renal hydronephrosis.All patients were routinely indwelling double-J tube using cystoscopy 2 weeks preoperatively,and ureteroscopic lithotripsy was performed.Fifty patients in group A were received tubeless treatment,and 57 patients in group B were given routinely indwelling double-J tube.The 50 patients in group A were (30.4 ± 5.9) years of age,including 33 males and 17 females,28 cases on the left and 22 cases on the right,24 cases locating in the upper calyx and 26 cases locating in the middle calyx,and calculi diameter of (1.3 ± 0.5) cm.The 57 patients in group B were (31.3 ± 5.4) years of age,including 35 males and 22 females,26 cases on the left and 31 cases on the right,27 cases locating in the upper calyx and 30 cases locating in the middle calyx,and diameter of (1.4 ± 0.4) cm.There were no significant difference in the demographics between the two groups (P ＞ 0.05).Results There were no obvious ureteral malformations,stenosis,polyps or tumors in the 107 cases intraoperatively,and the flexible ureteroscope sheath was placed smoothly.The operation time in group A [(48.2 ± 9.7) min] was significantly lower than that in group B [(51.7 ± 7.8) min,P ＜ 0.05].There was no significant difference in the calculi clearance rate between the two groups on the first day [92.0％ (46/50) vs.91.2％ (52/57)] and two weeks[96.0％ (48/50) vs.98.2％ (56/57)] after operation(P ＞ 0.05),and the calculi clearance rate reached 100％ at 1 month after operation.The incidence of hematuria in group A [24.0％ (12/50)] was significantly lower than that in group B [54.4％ (31/57),P =0.001].The incidence of bladder irritative symptoms in group A [14.0％ (7/50)] was significantly lower than that in group B [36.8％ (21/57),P =0.007].The incidence of lumbar and abdominal pain at 1 week,2 weeks and 1 month after operation was significantly lower in group A [32.0％ (16/50),8.0％ (4/50),2.0％ (1/50)] than that in group B [57.9％ (33/57),49.1％ (28/57),33.3％ (19/57),P ＜ 0.05].There was no significant difference between the two groups about the incidence of lumbar and abdominal pain at first day after operation [86.0％ (43/50) vs.84.2％ (48/57),P ＞ 0.05].Conclusions It was feasibility and safety to perform flexible ureteroscope with tubeless for the patients with renal primary and single calculi,ideal ureteral conditions (no malformations,stenosis,polyps or tumors),mild renal hydronephrosis,calculi,diameter ＜ 2.0 cm,CT value ≤ 800 HU,locating in the middle or upper calyx,and no history of urinary calculi.This procedure had not only similar calculi clearance rate compared with routinely indwelling double-J tube,but also has a lower incidence of complications (hematuria,bladder irritative symptoms,lumbar or abdominal pain).

目的:研究快速康复外科(ERAS)在经尿道等离子前列腺剜除术(PKEP)中的临床作用.方法:回顾性分析2017年1月-2018年1月收治125例BPH患者的临床资料,所有患者均接受PKEP治疗,根据是否采取ERAS干预,分为ERAS组(72例)和对照组(53例),对比两组患者的手术时间、术中出血量、切除腺体重量、术后肛门首次排气时间、术后进饮时间、术后进食时间、术后24 h补液量、术后首次下床活动时间、术后首次提肛训练时间、留置尿管时间、住院时间、住院费用、手术并发症、术后3个月尿失禁情况等指标.结果:125例患者手术均顺利完成,术后均无膀胱冲洗.两组患者在手术时间、切除腺体重量、术中出血量方面均差异无统计学意义(P>0.05).ERAS组术后进食时间、进饮时间、首次排气时间、术后24 h补液量、首次下床活动时间、首次提肛训练时间、总住院时间、术前住院时间、术后住院时间、拔除尿管时间、住院费用显著低于对照组(P<0.05).ERAS组拔除尿管后第1天尿失禁发生率显著高于对照组(P<0.05).ERAS组术后1周、2周、1个月、2个月尿失禁的发生率和对照组差异无统计学意义(P>0.05);随访至术后3个月,所有患者尿失禁症状消失.两组患者均无其余并发症发生.结论:将ERAS理念引入PKEP的围手术期管理中,具有术后恢复快、住院时间短、住院费用低等优点,值得临床推广应用.

Objective To evaluate the clinical efficacy of laparoscopic radical nephrectomy combined with sunitinib for the treatment of locally advanced renal cell carcinoma.Methods The clinical data of 47 cases of locally advanced renal cell carcinoma treated in our institute from January 2012 to January 2014 were analyzed retrospectively.All patients were treated by laparoscopic radical nephrectomy in the first place,in which 27 cases of patients treated by sunitinib and 20 cases of patients treated by IL-2 were divided into group A and group B.The operation time,blood loss,postoperative drainage time,postoperative gastrointestinal function recovery time,hospital time and pathological data were observed in all patients.Follow-up 13-46 months,the complete remission rate,progression-free survival (PFS) and other indicators of drug efficacy and adverse drug reactions were compared between the two groups.Results All the operations were completed uneventfully without conversions to open surgery and no severe complications occurred,of which 12 cases were performed concurrent ipsilateral adrenal gland resection.The operation time was (150.3 ± 25.4) min,blood loss was (280.6 ± 30.4) mL,postoperative drainage time was (7.2 ± 1.4) d,postoperative gastrointestinal function recovery time was (1.5 ± 0.4) d,hospital stay was (11.8 ± 1.7) d.No statistical differences were detected between the two groups in complete remission rate (81.5％ vs.75.0％,P ＞ 0.05).The PFS in group A were significantly longer than in group B[(16.7 ± 5.1)months vs.(14.2 ± 4.6) months] (P ＜ 0.05).The incidence of grade Ⅰ adverse reactions in group A were significantly higher than in group B (66.7％ vs.25.0％,P ＜0.05).However,the incidence of grade Ⅱ adverse reactions in group A were significantly lower than group B (25.9％ vs.65.0％,P ＜ 0.05).Conclusions The laparoscopic radical nephrectomy combined with sunitinib for the treatment of locally advanced renal cell carcinoma is safe and effective,which can effectively improve the prognosis of patients with locally advanced renal cell carcinoma,it is worthy of clinical application.

Objective To investigate the clinical efficacy of dorsal mosaic surgery with penis free flap for the treatment of anterior urethral stricture after TURP.Methods We analyzed the clinical data of the patients with anterior urethral stricture after TURP from January 2010 to December 2017 in Yan'an hospital affiliated to Kunming medical university retrospectively.The patients' age ranged from 58 to 75 years,with an average of 64.3 years.The time from TURP to the diagnosis of anterior urethral stricture was 1-12 month,with an average of 3.5 months.5 cases were urethral stricture at penis segment,11 cases were urethral stricture at the junction of penis and scrotum,and the length of the narrow urethra was 2-5 cm,with an average of 3.4cm.The average maximum uroflowmetry in preoperative was (5.3 ± 2.7) ml/s.11 cases were treated with regular urethral dilatation and the treatment durable time was more than 6 months,5 cases were treated with intraurethral incision combined with urethral dilatation (1 or 2 times).16 cases were not effective after receiving the above treatment,so that all cases were treated with dorsal mosaic surgery with penis free flap.Subarachnoid anesthesia combined with epidural anesthesia,the patient took the supine position.The distal end of urethral stricture was defined by urethral dilator.Incision from the ventral side of the urethra.The length of the incision was extended 0.5 cm based on the length of urethral stricture in urethral angiography.Anatomize the left and right sides of the urethral stricture and longitudinally incision the ventral side of the urethral cavernous body.The length of the incision was extended 0.5 cm to the normal urethral mucosa.The traction line retracts the ventral urethral edge along both sides.The corresponding medial line of the dorsal urethra was incised to the tunica albuginea,and the urethral edge of the dorsal side was separated from the tunica albuginea to form an elliptical region on the tunica albuginea.According to the size of the ellipse,the full thickness of the penis flap was taken,and the size of the flap was beyond the edge of the elliptical area about 0.3 cm.The free flap was covered with the 6-0 absorbable suture on the elliptical area (the skin surface was on the inner side of the urethra),the edge of the free flap was intermittently sutured with the urethral edge of the dorsal side,Multi-needle intermittent sutured flap surface on the corpus cavernosum bed.Using a silicone catheter as the stent tube of the new urethra,the 6-0 absorbable suture closes the ventral side of the incisional urethral sponge.The multi-layered meat film was sutured to prevent leakage of urine,and the fascia and skin were sutured layer by layer.The 5-0 absorbable thread sutures the wound after the foreskin was taken.Results The operations were successfully completed.The operation time was 90-120 min,with an average of 102.3 min.The intraoperative blood loss was 10-30 ml.The symptoms of dysuria were relieved in all patients after removal of the catheter at 3 weeks postoperative.4 weeks after surgery,no signs of urethral stricture were observed in urethrography.And the maximum flow rate was ＞ 15 ml/s in 13 cases,while 3 cases was 10-15 ml/s.The mean maximum flow rate in postoperative was [(20.4 ± 7.3) ml/s],which was significantly higher than that in preoperative (t =7.7602,P ＜ 0.05).B-ultrasound showed 13 cases without residual urine and 3 cases of residual urine volume ＜ 30 ml.All patients had no serious complications such as urinary fistula,urethral diverticulum and extravasation of urine.After 1 year of follow-up,1 patient was lost to follow up,and none of the remaining15 cases had urethral obstruction due to re-stricture.Conclusion Dorsal mosaic surgery with penis free flap could be an effective method and had no obvious complications for the treatment of anterior urethral stricture after TURP.

Hypoxia plays a critical role in cancer biology. It induces genomic instability, which in turn helps cancer cells respond adaptively to meet the needs of carcinogenesis, cancer progression and relapse. Circular RNA has not been reported among the variety of downstream factors in this adaptive response. Although a few studies have demonstrated the important role of circular RNAs in driving human bladder cancer progression, their carcinogenic roles are still under investigated. Here, we identified a hypoxia-elevated circular RNA, circELP3, that contributes to bladder cancer progression and cisplatin resistance. Decreasing the level of circELP3 via siRNA clearly reduced the in vitro proliferation and cisplatin resistance of bladder cancer cells and promoted apoptosis. Interfering with circELP3 suppressed tumor xenograft growth in nude mice in vivo. In addition, lower circELP3-expressing bladder cancer cells displayed poorer self-renewal capacity, as demonstrated by lower levels of sphere formation and stem cell marker expression. Furthermore, in human bladder cancer patients, strong correlations between a high circELP3 level and advanced tumor grade and lymph node metastasis were observed. In summary, we provide the first direct evidence that circular RNA participates in the adaptive response to hypoxia and may play a role in the progression and drug resistance of bladder cancer.

盐酸坦索罗辛缓释胶囊(α1-受体阻滞剂)对输尿管中下段结石有明显促进排出作用,推荐为输尿管排石一线用药[1].作为α1-受体阻滞剂,作用于输尿管中下段及尿道(α1-受体分布密集),具有明显扩张输尿管,助结石排出[1].统计2013年1月-2014年12月云南省昆明市延安医院门诊及住院部,口服盐酸坦洛新缓释胶囊药物保守治疗7d后,结石未排出的68例患者,按照患者自主选择,继续药物保守治疗、要求体外冲击波碎石及输尿管镜取石患者分组,资料汇总,具体报告如下.

Studies have proven that IL-2 and IL-15 showed contrasting roles during CIK cells preparation. By employing microarray, we analyzed miRNA expression profiles of PBMC, CIK IL-2 and CIK IL-15 . Advanced bioinformatic analyses were performed to explore the key miRNAs which may regulate cell proliferation and anti-tumor activity of CIK. We identified 261 differentially expressed miRNAs (DEMs) between PBMC and CIK IL-2 and 249 DEMs between PBMC and CIK IL-15 . MiR-143-3p/miR-145-5p was miRNA cluster which may positively regulate cell proliferation. In contrast, miR-340-5p/miR-340-3p cluster may negatively regulate cell proliferation via induction apoptosis, which may cause decreased cell proliferation capacity of CIK IL-2. MiRNA-target interaction analysis indicated that 10 co-downregulated miRNAs may synergistically turn on the expression of a pool of tumor cytotoxic genes in CIK cells. The DEMs between CIK IL-2 and CIK IL-15 may contribute to enhanced tumor cytotoxic capacity of CIK IL-2 . Importantly, we found that repressed miR-193a-5p may regulate the expressions of inhibitory receptor KLRD1. The results of the validation assay have shown that KLRD1 were upregulated in CIK cells. Our findings have provided new insights into mechanisms of CIK cells production and tumor cytotoxic function and shed light on their safety for clinical trial.