尿液外泌体lncRNA PCAT-1评估非浸润性膀胱癌患者复发的价值

目的探究尿液外泌体长链非编码RNA前列腺癌相关转录本1（lncRNA PCAT-1）评估非浸润性膀胱癌患者复发的价值。方法随机选取2015年1月—2016年3月进行治疗的非浸润性膀胱癌患者50例作为非浸润性膀胱癌组，选取同期在进行健康体检的健康受检者50例作为对照组。测定两组尿液外泌体中lncRNA PCAT-1表达情况。分析尿液外泌体lncRNA PCAT-1表达与临床病理参数的相关性、尿液外泌体lncRNA PCAT-1与尿液脱落细胞学对非浸润性膀胱癌的诊断价值、影响非浸润性膀胱癌患者复发的相关因素，评估非浸润性膀胱癌复发的价值及尿液外泌体lncRNA PCAT-1表达与非浸润性膀胱癌患者预后的关系。结果与对照组比较，非浸润性膀胱癌组患者尿液外泌体lncRNA PCAT-1表达水平明显升高（P<0.01）。尿液外泌体lncRNA PCAT-1表达与病理分期具有明显相关性（P<0.01）。尿液外泌体lncRNA PCAT-1诊断非浸润性膀胱癌的曲线下面积明显高于尿液脱落细胞学。采用Cox比例风险因素回归模型分析，病理分期及lncRNA PCAT-1均为影响非浸润性膀胱癌患者复发的独立危险因素。以尿液外泌体lncRNA PCAT-1相对表达量5.14±1.04分为高表达组（23例）与低表达组（27例），Kaplan-Meier生存曲线分析结果显示，lncRNA PCAT-1低表达量组生存期明显高于lncRNA PCAT-1高表达组。结论外泌体lncRNA PCAT-1在非浸润性膀胱癌患者尿液中的表达水平较健康受检者明显升高，且其表达水平与患者病理分期明显相关。尿液外泌体lncRNA PCAT-1对评估非浸润性膀胱癌患者的复发具有重要作用。     

Long-term prevention of bladder cancer progression by alpha1-oleate alone or in combination with chemotherapy

Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.     

Immunotherapy for urothelial carcinoma: Metastatic disease and beyond

For advanced and metastatic urothelial carcinomas (UCs), platinum (preferably cisplatin)‐based chemotherapy has been the standard treatment for many years. However, many patients are ineligible for cisplatin‐based chemotherapy because of poor performance status and/or other age‐related conditions. At the other end of the spectrum, patients with localized non‐muscle–invasive bladder cancer who are unresponsive to intravesical Bacillus Calmette‐Guérin (BCG) treatment often face radical cystectomy as the only option. In recent years, the application of immunotherapy in the form of immune‐checkpoint inhibitors has provided viable alternatives in the second‐line postplatinum and first‐line cisplatin‐ineligible settings. Recent and ongoing clinical trials are also assessing the safety and efficacy of immunotherapy for neoadjuvant and adjuvant uses before/after cystectomy, for BCG‐unresponsive cases, and for combination treatments that include the newer indoleamine 2,3‐dioxygenase‐1 inhibitors and/or BCG. This review summarizes recent developments in immunotherapy for UCs.     

基于TCGA数据库分析肿瘤突变负荷在肌层浸润性膀胱癌预后评估中的价值

目的：探讨肿瘤突变负荷（TMB）在肌层浸润性膀胱癌（MIBC）预后评估中的价值。方法：从TCGA数据库下载MIBC测序数据，结合临床数据分析TMB在MIBC中的临床意义，从TMB分组中识别出差异表达的免疫相关基因进行预后分析；另外采用非负矩阵分解CIBERSORT算法确定免疫细胞与TMB亚型之间的相关性。结果：纳入的375例MIBC患者样品中单核苷酸多态性（SNP）和C > T是最常见的错义突变；TP53、TTN、KMT2D、MUC16、ARID1A基因的突变率较高；与低TMB组MIBC患者相比，高TMB组的患者预后较好（P < 0.01）；以KIR2DL4、IL1RL1、SSTR5构建的COX回归模型中低风险组MIBC患者较高风险组预后更佳，曲线下面积（ROC）为0.71；与正常膀胱组织相比，高TMB组的CD8⁺ T细胞、活化的CD4⁺ T细胞、嗜酸性粒细胞表达较高，而在低TMB组中记忆B细胞及未活化的肥大细胞表达比例较高（P < 0.05）。结论：TMB较高的MIBC患者可能在免疫治疗中获得较好的预后，TMB具有预测肿瘤免疫治疗疗效的潜在应用价值；还发现了不同组分的免疫细胞在TMB分组的MIBC肿瘤微环境中存在表达差异。     

针刺足运感区结合局部电针围刺治疗中风后尿失禁的临床观察

[目的]观察针刺足运感区结合局部电针围刺与常规针刺、常规针刺联合足运感区治疗中风后尿失禁的临床疗效差异。[方法]将90例患者随机分为治疗组、对照1组和对照2组,每组30例,治疗组予针刺足运感区结合膀胱体表相应投影区域电针围刺;对照1组参照全国高等中医药院校"十三五"规划教材《针灸治疗学》中有关"尿失禁"的治疗选穴;对照2组在对照1组的基础上联合足运感区针刺,每日上午行神经内科常规治疗,每日下午行中风后尿失禁的临床治疗,每次30 min,每周连续治疗6次,6次为1个疗程,疗程间休息1 d,共2个疗程。观察3组治疗前后尿失禁程度、尿失禁临床症状评分及日常生活活动能力量表(ADL)评分,并比较3组患者的临床疗效。[结果] 3组患者治疗后尿失禁程度、尿失禁临床症状评分及ADL评分均较前改善(均P0.05),治疗组对尿失禁程度及尿失禁临床症状评分的改善较其他两组更明显(P0.05),且治疗组和对照2组的ADL评分明显优于对照1组(P0.05)。治疗组总有效率为93.3%(30/28),优于对照1组76.7%(30/23)和对照2组83.3%(30/25,P0.05)。[结论]针刺足运感区结合局部电针围刺治疗中风后尿失禁疗效显著。     

SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7

Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5’s interaction with SOX18 on MMP7‐mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR‐133a‐3p. Ectopic expression of SLC12A5 partly abolished miR‐133a‐3p‐mediated suppression of cell migration. SLC12A5‐SOX18 complex‐mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR‐133a‐3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma.     

电针结合膀胱康复对脊髓损伤者神经源性膀胱的疗效观察

目的 观察电针结合膀胱康复对脊髓损伤者神经源性膀胱的疗效。方法 选择2018年1～9月我院收治的62例脊髓损伤的神经源性膀胱患者,随机分为治疗组和对照组各31例,两组均给予膀胱功能训练及间歇导尿术,治疗组针刺时间为15:00～17:00的任一时刻,按子午流注法选取每日开穴,并选取膀胱经相关治疗穴位,连接电针进行治疗;对照组针刺时间为8:00～12:00的任一时刻,选取膀胱经相关治疗穴位,常规留针。针刺时间每次30 min,每天1次,治疗30 d后评定疗效。于治疗前后对患者膀胱容量、残余尿量及膀胱功能积分进行比较评定,并参照《实用理疗手册》中的疗效标准评价疗效。结果 治疗30 d后,两组患者的膀胱容量、残余尿量及膀胱功能积分较治疗前均有不同程度的改善(P0.05),治疗组治疗后的改善优于对照组,差异均有统计学意义(P0.05)。根据疗效标准评价,治疗组有效率为90.32%,对照组有效率为80.64%(P0.05)。结论 在膀胱功能训练及间歇导尿术的基础上给予特定时段电针法比普通针刺法可更有效地改善脊髓损伤患者的膀胱功能,使患者尽早实现自主排尿,提高生存质量。