• 文章类型: Journal Article
    背景:联合使用2-巯基乙烷磺酸钠(mesna)和环磷酰胺(CYC)治疗ANCA相关性血管炎(AAV)的实践可能存在一些差异。
    目的:评估CYC治疗的AAV患者处方mesna预防的实践。
    方法:我们邀请了MEDLINE在过去10年中引用的AAV出版物的作者参加匿名在线调查。如果受访者参与了AAV的CYC治疗,他们就有资格。调查询问了受访者的特征以及他们使用CYC和mesna治疗AAV的做法以及基本原理。我们比较了mesna处方者及其对应者之间的18个变量,以确定与mesna使用相关的因素。
    结果:总计,139名符合条件的个人完成了调查。参与者来自34个国家,基本上是医生(98%)。总的来说,68%,19%和13%的受访者系统地处方mesna,从来没有,或者在选择性的基础上。与从不/选择性处方者相比,系统处方者通常≤39岁(P=0.008),更经常使用间歇脉冲治疗作为专有/主要CYC给药方案(P<0.001),在法国/德国/意大利的频率高于英国/美国(P<0.001),并且更经常表明遵守当地标准(P=0.003)或(国际)AAV指南(P<0.001)作为其mesna实践的理由。与以前的实践相比,从未/选择性处方者更常报告其mesna处方模式发生了变化(P<0.001)。
    结论:Mesna的系统共同处方是CYC治疗AAV的普遍做法。这种做法似乎涉及实用性考虑,并且各代人之间有所不同。
    BACKGROUND: There may be some diversity in the practice of co-prescribing 2-mercaptoethane sodium sulfonate (mesna) with cyclophosphamide (CYC) for ANCA-associated vasculitis (AAV).
    OBJECTIVE: To assess the practice of prescribing mesna prophylaxis for CYC-treated patients with AAV.
    METHODS: We invited authors of publications on AAV referenced in MEDLINE over the previous 10 years to participate in an anonymous online survey. Respondents were eligible if they were involved in CYC treatments for AAV. The survey asked about the characteristics of the respondents and their practice in using CYC and mesna to treat AAV and the underlying rationale. We compared 18 variables between mesna prescribers and their counterparts to identify factors associated with mesna use.
    RESULTS: In total, 139 eligible individuals completed the survey. The participants were from 34 countries and were essentially physicians (98%). Overall, 68%, 19% and 13% of respondents prescribed mesna systematically, never, or on a selective basis. As compared with never/selective-prescribers, systematic-prescribers were more often ≤ 39 years old (P = 0.008), more often used intermittent pulse therapy as the exclusive/predominant CYC administration scheme (P < 0.001), were more frequently based in France/Germany/Italy than in England/United States (P < 0.001), and more often indicated adherence to local standards (P = 0.003) or (inter)national guidelines for AAV (P < 0.001) as a rationale for their mesna practice. Never/selective-prescribers more commonly reported that their mesna prescription pattern had changed as compared with their former practice (P < 0.001).
    CONCLUSIONS: Systematic co-prescription of mesna is the prevailing practice for CYC treatments for AAV. The practice seems to involve practicability considerations and differs between generations.
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  • 文章类型: Journal Article
    推断基因调控网络(GRN)是系统生物学的重要挑战之一。和许多优秀的计算方法已经被提出;然而,仍然存在一些挑战,特别是在真实的数据集。在这项研究中,我们提出了基于有向图卷积神经网络的GRN推断方法(DGCGRN)。为了更好地理解和处理GRN的有向图结构数据,进行了有向图卷积神经网络,在保留有向图结构信息的同时,还充分利用了邻居节点特征。图神经网络采用局部增广策略解决了GRN中大量低度节点导致预测精度差的问题。此外,对于像大肠杆菌这样的真实数据,利用Bi-GRU提取隐藏特征,计算基因序列的统计理化特征,得到序列特征。在训练阶段,采用动态更新策略,将得到的边预测分数转换为边权重,指导模型后续的训练过程。在合成基准数据集和真实数据集上的结果表明,DGCGRN的预测性能明显优于现有模型。此外,膀胱尿路上皮癌和肺癌细胞的案例研究也说明了所提出模型的性能。
    Inferring gene regulatory network (GRN) is one of the important challenges in systems biology, and many outstanding computational methods have been proposed; however there remains some challenges especially in real datasets. In this study, we propose Directed Graph Convolutional neural network-based method for GRN inference (DGCGRN). To better understand and process the directed graph structure data of GRN, a directed graph convolutional neural network is conducted which retains the structural information of the directed graph while also making full use of neighbor node features. The local augmentation strategy is adopted in graph neural network to solve the problem of poor prediction accuracy caused by a large number of low-degree nodes in GRN. In addition, for real data such as E.coli, sequence features are obtained by extracting hidden features using Bi-GRU and calculating the statistical physicochemical characteristics of gene sequence. At the training stage, a dynamic update strategy is used to convert the obtained edge prediction scores into edge weights to guide the subsequent training process of the model. The results on synthetic benchmark datasets and real datasets show that the prediction performance of DGCGRN is significantly better than existing models. Furthermore, the case studies on bladder uroepithelial carcinoma and lung cancer cells also illustrate the performance of the proposed model.
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  • 文章类型: Journal Article
    目的:本研究的目的是通过经腹超声检查比较膀胱过度活动症女孩和健康女孩膀胱颈角度的差异。
    方法:本研究包括28名患有膀胱过度活动症的女孩(I组)和40名健康女孩(II组)。膀胱前后壁角(APVA),尿道膀胱后壁角(UPVA),尿道前膀胱壁角(UAVA),膀胱粘膜厚度,尿道口距离,使用经腹超声在仰卧位测量输尿管和尿道口之间的距离。比较两组的结果。
    结果:I组的UAVA高于II组(135.2±12.2mmvs.117.4±14.0mm;p=0.009)。第一组的UPVA比第二组小(114.6±19.5mmvs.135.3±16.5mm;p=0.014)。第一组输尿管口之间的距离为31.8±8.5mm,第二组为17.0±4.1mm(p<0.001)。两组之间在APVA方面无统计学差异,膀胱粘膜厚度,输尿管和尿道口之间的距离(p>0.05)。
    结论:由于UPVA的差异,膀胱颈部动力学可能在膀胱过度活动症的病理生理学中起重要作用,无人机,以及该患者人群中输尿管口的位置。
    OBJECTIVE: The aim of this study was to compare the differences between angles of bladder neck in girls with overactive bladder and those in healthy ones using transabdominal ultrasonography.
    METHODS: This study consists of 28 girls complicated with overactive bladder (Group I) and 40 healthy girls (Group II). The anteroposterior vesical wall angle (APVA), urethroposterior vesical wall angle (UPVA), urethroanterior vesical wall angle (UAVA), thickness of bladder mucosa, distance of urethral orifices, and distance between ureter and urethra orifice were measured in supine position using transabdominal ultrasonography. The results were compared between the two groups.
    RESULTS: UAVA in Group I was higher than Group II (135.2 ± 12.2 mm vs. 117.4 ± 14.0 mm; p = 0.009). UPVA was smaller in Group I than Group II (114.6 ± 19.5 mm vs. 135.3 ± 16.5 mm; p = 0.014). The distance between the ureteral orifices was 31.8 ± 8.5 mm in Group I and 17.0 ± 4.1 mm in Group II (p < 0.001). There was no statistically significant difference between groups in terms of APVA, bladder mucosa thickness, and distance between ureter and urethra orifice (p > 0.05).
    CONCLUSIONS: Bladder neck dynamics may play an important role in overactive bladder pathophysiology due to differences in UPVA, UAV, and location of ureteral orifices in this patient population.
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  • 文章类型: Case Reports
    乳腺癌(BrC)是女性最常见的恶性肿瘤,大多数与BrC相关的死亡是由于转移。BrC经常转移到淋巴结,肝脏,肺,骨骼和大脑,而膀胱被认为是乳腺转移的不寻常部位。我们报告了一例膀胱转移病例,该病例是在一名有BRC病史的患者中发现的,表现为血尿,下尿路症状,和肾积水.
    Breast cancer (BrC) is the most frequently diagnosed malignancy in woman and most BrC related deaths are due to metastasis. BrC frequently metastasizes to the lymph nodes, liver, lung, bone and brain while the urinary bladder is considered as an unusual site for breast metastasis. We report a case of bladder metastasis identified in a patient with past BrC history, presenting with hematuria, low urinary tract symptoms, and hydronephrosis.
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  • 文章类型: Journal Article
    2024ASCO泌尿生殖系统癌症研讨会,今年庆祝20周年,探讨了尿路上皮癌(UC)和前列腺癌(PC)的关键进展。对于UC,从pembrolizumab辅助治疗肌肉浸润性尿路上皮癌,和EV-302研究中enfortumabvedotin+pembrolizumab在转移环境中的疗效。在PC中,探索了大剂量放疗方案加长期ADT的辅助治疗。在转移性去势抗性PC中,重点包括用于不良预后患者的新型组合(卡博替尼+阿特珠单抗);证实ARSI+PARPi在BRCA突变患者中的获益;以及ARSI治疗的安全性考虑.研讨会继续发挥其作为塑造专门肿瘤护理不可或缺的平台的作用。
    The 2024 ASCO Genitourinary Cancer Symposium, this year celebrating the 20th anniversary, delved into key advancements in urothelial carcinoma (UC) and prostate cancer (PC). For UC, insights emerged from adjuvant pembrolizumab for muscle-invasive urothelial carcinoma, and from the efficacy of the EV-302 study of enfortumab vedotin +pembrolizumab in the metastatic setting. In PC, adjuvant therapy with high-dose radiotherapy schedules plus long-t erm ADT was explored. In metastatic castration-resistant PC, highlights included a novel combo (cabozantinib+atezolizumab) for poor prognosis patients; confirmed benefits of ARSI+PARPi in BRCA-mutated patients; and safety considerations for ARSI treatments. The symposium continued its role as an indispensable platform for shaping specialized oncological care.
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  • 文章类型: Journal Article
    由于当前运动跟踪技术的局限性以及对用于MRI系统内部和外部运动跟踪的替代传感器的兴趣日益增加,在这项研究中,我们分享了我们的初步经验,三个替代传感器利用不同的技术和与组织的相互作用来监测身体表面的运动,主要器官的呼吸相关运动,和深层器官的非呼吸运动。这些包括(1)一个Pilot-ToneRF发射器与深度学习算法相结合,用于跟踪肝脏运动,(2)采用深度学习的单通道超声换能器监测膀胱运动,和(3)用于观察前躯干表面的运动的3D飞行时间相机。此外,我们展示了这些传感器同时捕获MRI环境之外的运动数据的能力,这与放射治疗等程序特别相关,其中运动状态可能与先前表征的周期性解剖数据有关。我们的发现表明,超声传感器可以跟踪深层器官(膀胱)的运动以及与呼吸有关的运动。飞行时间相机易于解释,并在检测表面运动(呼吸)方面表现出色。Pilot-Tone展示了跟踪大量呼吸运动和主要器官(肝脏)运动的功效。同时使用所有三个传感器可以在MRI孔外提供互补的运动信息,在诸如放射治疗的位置敏感治疗期间为运动跟踪提供潜在价值。
    Due to limitations in current motion tracking technologies and increasing interest in alternative sensors for motion tracking both inside and outside the MRI system, in this study we share our preliminary experience with three alternative sensors utilizing diverse technologies and interactions with tissue to monitor motion of the body surface, respiratory-related motion of major organs, and non-respiratory motion of deep-seated organs. These consist of (1) a Pilot-Tone RF transmitter combined with deep learning algorithms for tracking liver motion, (2) a single-channel ultrasound transducer with deep learning for monitoring bladder motion, and (3) a 3D Time-of-Flight camera for observing the motion of the anterior torso surface. Additionally, we demonstrate the capability of these sensors to simultaneously capture motion data outside the MRI environment, which is particularly relevant for procedures like radiation therapy, where motion status could be related to previously characterized cyclical anatomical data. Our findings indicate that the ultrasound sensor can track motion in deep-seated organs (bladder) as well as respiratory-related motion. The Time-of-Flight camera offers ease of interpretation and performs well in detecting surface motion (respiration). The Pilot-Tone demonstrates efficacy in tracking bulk respiratory motion and motion of major organs (liver). Simultaneous use of all three sensors could provide complementary motion information outside the MRI bore, providing potential value for motion tracking during position-sensitive treatments such as radiation therapy.
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  • 文章类型: Journal Article
    这项研究使用预定义的指标分析了饮食的整体质量,包括健康饮食指数-2015(HEI-2015),替代健康饮食指数-2010(AHEI-2010),替代地中海饮食(AMED)评分,停止高血压的饮食方法(DASH)评分,和膳食炎症指数(DII®),在多种族队列研究中探讨它们与膀胱癌风险的关系。数据来自186,979名非洲裔美国人,日裔美国人,拉丁裔,夏威夷原住民,45-75岁的非西班牙裔白人参与者,在平均19.2±6.6年的随访期间,发生了1152例浸润性膀胱癌。Cox模型用于计算风险比(HR)和95%置信区间(CI),并对吸烟进行综合调整。比较最高的与最低的饮食质量得分五分之一,HEI-2015男性的HR(95%CI)为1.08(0.86-1.36),AHEI-2010为1.05(0.84-1.30),aMED为1.01(0.80-1.27),1.13(0.90-1.41)对于DASH,DII®为0.96(0.76-1.21),而女性的相应HR为0.75(0.53-1.07),0.64(0.45-0.92),0.60(0.40-0.88),0.66(0.46-0.95),和0.63(0.43-0.90),所有p值趋势<0.05。在女性中发现的反向关联并不因吸烟状况或种族和种族而异。我们的发现表明,采用高质量的饮食可以降低多种族人群中女性患浸润性膀胱癌的风险。
    This study analyzed the overall quality of the diet using predefined indices, including the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED) score, the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII®), to explore their association with the risk of bladder cancer in the Multiethnic Cohort Study. Data were taken from 186,979 African American, Japanese American, Latino, Native Hawaiian, and non-Hispanic White participants aged 45-75 years, with 1152 incident cases of invasive bladder cancer during a mean follow-up period of 19.2 ± 6.6 years. Cox models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) with comprehensive adjustment for smoking. Comparing the highest vs. lowest diet quality score quintile, HRs (95% CIs) in men was 1.08 (0.86-1.36) for HEI-2015, 1.05 (0.84-1.30) for AHEI-2010, 1.01 (0.80-1.27) for aMED, 1.13 (0.90-1.41) for DASH, and 0.96 (0.76-1.21) for DII®, whereas the corresponding HRs for women were 0.75 (0.53-1.07), 0.64 (0.45-0.92), 0.60 (0.40-0.88), 0.66 (0.46-0.95), and 0.63 (0.43-0.90) with all p values for trend <0.05. The inverse association found in women did not vary by smoking status or race and ethnicity. Our findings suggest that adopting high-quality diets may reduce the risk of invasive bladder cancer among women in a multiethnic population.
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  • 文章类型: Journal Article
    卤化环硼氧烷K2[B3O3F4OH](HB),硼酸环酐的无机衍生物,作为含硼化合物获得专利,具有治疗良性和恶性皮肤变化的潜力。HB有效地抑制了几种癌细胞系的生长。由于对自噬诱导作为膀胱癌(BC)的治疗方法的兴趣与日俱增,我们旨在评估HB对5637例人膀胱癌细胞(BC)代谢表型和自噬水平的影响。使用Alamar蓝测定法评估细胞毒性,并通过显微镜测定自噬的程度。同时测量线粒体呼吸和糖酵解。通过实时PCR测定自噬相关基因BECN1、P62、BCL-2和DRAM1的相对表达量。HB影响细胞生长,与未处理的阴性对照中的基础自噬水平相比,饥饿显着增加了阳性对照中的自噬水平。在HB处理的培养物中,自噬程度高于基础水平,代谢表型改变;HB在0.2和0.4mg/mL时,糖酵解和氧化磷酸化(OXPHOS)均降低。基因表达随着自噬诱导和扩增而去调节。总之,HB破坏了生物能量代谢并降低了BC细胞的细胞内存活潜力。需要进一步的分子研究来证实这些发现并研究其应用潜力。
    Halogenated boroxine K2[B3O3F4OH] (HB), an inorganic derivative of cyclic anhydride of boronic acid, is patented as a boron-containing compound with potential for the treatment of both benign and malignant skin changes. HB has effectively inhibited the growth of several carcinoma cell lines. Because of the growing interest in autophagy induction as a therapeutic approach in bladder carcinoma (BC), we aimed to assess the effects of HB on metabolic phenotype and autophagy levels in 5637 human bladder carcinoma cells (BC). Cytotoxicity was evaluated using the alamar blue assay, and the degree of autophagy was determined microscopically. Mitochondrial respiration and glycolysis were measured simultaneously. The relative expression of autophagy-related genes BECN1, P62, BCL-2, and DRAM1 was determined by real-time PCR. HB affected cell growth, while starvation significantly increased the level of autophagy in the positive control compared to the basal level of autophagy in the untreated negative control. In HB-treated cultures, the degree of autophagy was higher compared to the basal level, and metabolic phenotypes were altered; both glycolysis and oxidative phosphorylation (OXPHOS) were decreased by HB at 0.2 and 0.4 mg/mL. Gene expression was deregulated towards autophagy induction and expansion. In conclusion, HB disrupted the bioenergetic metabolism and reduced the intracellular survival potential of BC cells. Further molecular studies are needed to confirm these findings and investigate their applicative potential.
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  • 文章类型: Journal Article
    尿路上皮癌的治疗随着腹腔镜或机器人手术等微创技术的引入而发展。挑战传统的开放手术方法,并导致非典型复发(AR)。AR包括端口部位转移和腹膜癌,然而,作者之间在精确分类方面仍然存在差异.AR的发病率在不同的研究中差异很大,在肌肉浸润性膀胱癌(MIBC)和上尿路上皮肿瘤(UTUC)中,范围从不到1%到超过10%。腹膜转移是MIBC患者中最常见的AR,而由于不同的手术方法,腹膜后转移在UTUC患者中普遍存在。AR表现的时间和生存结果与传统复发的时间密切相关,他们经常与之联系在一起。气腹逐渐被认为是ARs的病因,而与手术相关的危险因素越来越突出。目前与手术相关的主要原因包括手术期间肿瘤溢出和尿路侵犯,避免使用endo袋进行标本提取,和低手术经验。肿瘤分期等因素,组织学变异,和淋巴血管侵犯与ARs的风险相关,表明与肿瘤生物学密切相关。需要进一步的研究来更好地了解发病率,危险因素,特点,和AR的结果。
    The management of urothelial carcinoma has evolved with the introduction of minimally invasive techniques such as laparoscopic or robotic procedures, challenging the traditional approach of open surgery, and giving rise to atypical recurrences (ARs). ARs include port-site metastasis and peritoneal carcinomatosis, yet discrepancies persist among authors regarding their precise classification. Incidence rates of ARs vary widely across studies, ranging from less than 1% to over 10% in both muscle-invasive bladder cancer (MIBC) and upper tract urothelial tumor (UTUC). Peritoneal metastases predominate as the most common ARs in patients with MIBC, while retroperitoneal metastases are prevalent in those with UTUC due to differing surgical approaches. The timing of AR presentation and survival outcomes closely mirror those of conventional recurrences, with which they are frequently associated. Pneumoperitoneum has progressively been regarded less as the cause of ARs, while surgical-related risk factors have gained prominence. Current major surgical-related causes include tumor spillage and urinary tract violation during surgery, avoidance of endo bag use for specimen extraction, and low surgical experience. Factors such as tumor stage, histological variants, and lympho-vascular invasion correlate with the risk of ARs, suggesting a close association with tumor biology. Further studies are required to better understand the incidence, risk factors, characteristics, and outcomes of ARs.
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  • 文章类型: Journal Article
    晚期膀胱癌的治疗涉及多学科方法,但许多患者的预后仍然较差。免疫系统在这种疾病中起着至关重要的作用,影响肿瘤的发展和对治疗的反应,利用免疫系统对抗肿瘤可能是破坏肿瘤细胞的有价值的策略。这是卡介苗(BCG)使用的生物学原理,最近,免疫检查点抑制剂(ICIs),如PD-1(程序性死亡-1)/PD-L1(程序性死亡-配体1)抑制剂。事实上,研究最好的免疫检查点之一是由PD-1/PD-L1轴代表,这是肿瘤膀胱细胞采用的众所周知的免疫逃逸系统。PD-L1表达与较高的病理分期相关,并在膀胱癌中显示出预后价值。有趣的是,高级别膀胱癌倾向于表达更高水平的PD-1和PD-L1,提示此类轴在介导疾病进展中的潜在作用.因此,PD-1和PD-L1抑制剂的免疫治疗已成为一种有价值的治疗选择,并已在晚期膀胱癌患者中显示出疗效。PD-L1高表达水平与更好的治疗反应相关。我们的综述旨在全面概述PD-L1在晚期膀胱癌中的作用。重点关注其对治疗决策和治疗反应预测的影响。总的来说,我们的工作旨在有助于理解PD-L1作为一种预测性生物标志物,并强调其在形成晚期膀胱癌治疗方法中的作用.
    The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the tumor can be a valuable strategy to destroy neoplastic cells. This is the biological principle underlying Bacillus Calmette-Guérin (BCG) use and, more recently, immune checkpoint inhibitors (ICIs), like PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) inhibitors. In fact, one of the best studied immune checkpoints is represented by the PD-1/PD-L1 axis, which is a well-known immune escape system adopted by neoplastic bladder cells. PD-L1 expression has been associated with a higher pathologic stage and has shown prognostic value in bladder carcinoma. Interestingly, high-grade bladder cancers tend to express higher levels of PD-1 and PD-L1, suggesting a potential role of such an axis in mediating disease progression. Immunotherapy with PD-1 and PD-L1 inhibitors has therefore emerged as a valuable treatment option and has shown efficacy in advanced bladder cancer patients, with high PD-L1 expression levels associated with better treatment responses. Our review aims to provide a comprehensive overview of the role of PD-L1 in advanced bladder cancer, focusing on its implications for treatment decisions and the prediction of treatment response. Overall, our work aims to contribute to the understanding of PD-L1 as a predictive biomarker and highlight its role in shaping therapeutic approaches for advanced bladder cancer.
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