The efficacy and safety of Hyperthermia intravesical chemotherapy in the treatment non-muscle invasive bladder cancer:A meta analysis.

Background：The current treatment of non-muscle-invasive bladder cancer is suboptimal. However, in recent years, hyperthermia intravesical chemotherapy has emerged as a more effective alternative to conventional bladder perfusion. This novel treatment approach appears to have a similar therapeutic effect as BCG perfusion. Objective: This study aims to evaluate the safety and effectiveness of hyperthermia intravesical chemotherapy compared to conventional bladder perfusion chemotherapy for non-muscle-invasive bladder cancer. Additionally, it aims to evaluate the safety and effectiveness of hyperthermia intravesical chemotherapy in comparison to BCG perfusion therapy for non-muscle-invasive bladder cancer. Methods：We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases to gather relevant studies on hyperthermia intravesical chemotherapy for non-muscle-invasive bladder cancer. The analysis of the collected data was carried out using RevMan 5.3 software. Results：A total of 8 randomized controlled trials (RCTs) were included in this meta-analysis, involving 1203 patients. Among them, 629 cases received hyperthermia intravesical chemotherapy (HIVEC), 419 cases received conventional bladder perfusion chemotherapy with mitomycin C (MMC), and 155 cases received Bacillus Calmette-Guérin (BCG). The combined analysis revealed that the recurrence rate of bladder hyperthermic perfusion was significantly lower than that of conventional perfusion chemotherapy (RR=0.65, 95%CI 0.52-0.82, P=0.0003). However, there was no significant difference in recurrence rate between hyperthermia intravesical chemotherapy and BCG perfusion (RR=0.78, 95%CI 0.56-1.09, P=0.14). Furthermore, no significant difference was found in the progression rate between the hyperthermia intravesical chemotherapy group and either the conventional bladder chemotherapy group (RR=1.08, 95%CI 0.52-2.26, P=0.83) and the BCG perfusion group (RR=0.48, 95%CI 0.19-1.25, P=0.13). However, Compared with the conventional bladder perfusion chemotherapy group, there was no significant statistical difference in adverse events between the bladder hyperthermia chemotherapy group and the conventional bladder perfusion chemotherapy group (RR1.08, 95% CI 0.80,1.45, p=0.63). No significant difference in the incidence of adverse events was observed between hyperthermia intravesical chemotherapy and BCG perfusion (RR1.03, 95% CI 0.83,1.29, p=0.79).

A difficulty-aware and task-augmentation method based on meta-learning model for few-shot diabetic retinopathy classification.

Background: Accurate classification techniques are essential for the early diagnosis and treatment of patients with diabetic retinopathy (DR). However, the limited amount of annotated DR data poses a challenge for existing deep-learning models. This article proposes a difficulty-aware and task-augmentation method based on meta-learning (DaTa-ML) model for few-shot DR classification with fundus images. Methods: The difficulty-aware (Da) method operates by dynamically modifying the cross-entropy loss function applied to learning tasks. This methodology has the ability to intelligently down-weight simpler tasks, while simultaneously prioritizing more challenging tasks. These adjustments occur automatically and aim to optimize the learning process. Additionally, the task-augmentation (Ta) method is used to enhance the meta-training process by augmenting the number of tasks through image rotation and improving the feature-extraction capability. To implement the expansion of the meta-training tasks, various task instances can be sampled during the meta-training stage. Ultimately, the proposed Ta method was introduced to optimize the initialization parameters and enhance the meta-generalization performance of the model. The DaTa-ML model showed promising results by effectively addressing the challenges associated with few-shot DR classification. Results: The Asia Pacific Tele-Ophthalmology Society (APTOS) 2019 blindness detection data set was used to evaluate the DaTa-ML model. The results showed that with only 1% of the training data (5-way, 20-shot) and a single update step (training time reduced by 90%), the DaTa-ML model had an accuracy rate of 89.6% on the test data, which is a 1.7% improvement over the transfer-learning method [i.e., residual neural network (ResNet)50 pre-trained on ImageNet], and a 16.8% improvement over scratch-built models (i.e., ResNet50 without pre-trained weights), despite having fewer trainable parameters (the parameters used by the DaTa-ML model are only 0.47% of the ResNet50 parameters). Conclusions: The DaTa-ML model provides a more efficient DR classification solution with little annotated data and has significant advantages over state-of-the-art methods. Thus, it could be used to guide and assist ophthalmologists to determine the severity of DR.

The role of the methyltransferase METTL3 in prostate cancer: a potential therapeutic target.

The incidence of prostate cancer (PCa), the most prevalent malignancy, is currently at the forefront. RNA modification is a subfield of the booming field of epigenetics. To date, more than 170 types of RNA modifications have been described, and N6-methyladenosine (m6A) is the most abundant and well-characterized internal modification of mRNAs involved in various aspects of cancer progression. METTL3, the first identified key methyltransferase, regulates human mRNA and non-coding RNA expression in an m6A-dependent manner. This review elucidates the biological function and role of METTL3 in PCa and discusses the implications of METTL3 as a potential therapeutic target for future research directions and clinical applications.

Laparoscopic ureteroneocystostomy with bladder flap for benign ureteral stenosis: our initial experience.

To present our experience with laparoscopic ureteroneocystostomy with bladder flap (LUCBF) for treating benign ureteral stenosis and evaluate its feasibility and efficacy. The clinical data of 27 patients with benign ureteral stenosis who underwent LUCBF were retrospectively analyzed. After identification and excision of the ureteral stenosis segment, the healthy ureteral stump was dissected and incised longitudinally. A U-shaped or spiral bladder flap was harvested from the anterolateral bladder wall for ureteroplasty. All patients underwent LUCBF successfully, including 14 patients were combined with psoas hitch technique, between 90 and 220 min (median, 155 min). The median length of ureteral defect was 6 cm (range, 5-17 cm). The median blood loss was 40 ml (20-150 ml). The median indwelling time of double-J stent was 8 weeks (range, 4-8 weeks). Five patients (10.6%) suffered postoperative complications during the follow-up period (range, 12-48 months), including fever, hematuria, urinary tract infection and recurrent stenosis. The success rate was 96.3% (26/27). Patients with long ureter defects had longer operative time and more blood loss than short ureter defects. LUCBF was a safe and feasible technique for benign ureteral stenosis. Long ureter defect was related to longer operative time and more blood loss.

The role of RNA modification in urological cancers: mechanisms and clinical potential.

RNA modification is a post-transcriptional level of regulation that is widely distributed in all types of RNAs, including mRNA, tRNA, rRNA, miRNA, and lncRNA, where N6-methyladenine (m6A) is the most abundant mRNA methylation modification. Significant evidence has depicted that m6A modifications are closely related to human diseases, especially cancer, and play pivotal roles in RNA transcription, splicing, stabilization, and translation processes. The most common urological cancers include prostate, bladder, kidney, and testicular cancers, accounting for a certain proportion of human cancers, with an ever-increasing incidence and mortality. The recurrence, systemic metastasis, poor prognosis, and drug resistance of urologic tumors have prompted the identification of new therapeutic targets and mechanisms. Research on m6A modifications may provide new solutions to the current puzzles. In this review, we provide a comprehensive overview of the key roles played by RNA modifications, especially m6A modifications, in urologic cancers, as well as recent research advances in diagnostics and molecularly targeted therapies.

Comparison of traditional and novel tip-flexible suctioning ureteral access sheath combined with flexible ureteroscope to treat unilateral renal calculi.

OBJECTIVES: To compare the safety and efficacy of novel tip-flexible suctioning ureteral access sheath (NTFS-UAS) and traditional ureteral access sheath (T-UAS) combined with flexible ureteroscope for treating unilateral renal calculi. MATERIALS AND METHODS: The clinical data of 214 patients with unilateral renal calculi treated by NTFS-UAS (n = 102) and T-UAS (n = 112) combined with flexible ureteroscope from August 2021 to April 2022 were analyzed retrospectively. Demographic characteristics, stone-related parameters, operative time, stone-free rates (SFR), hospitalization time and complication rate (CR) were analyzed. RESULT: No significant difference was observed between the two groups in terms of demographic characteristics, stone-related parameters, intraoperative CR, and hospitalization time. The operative time of NTFS-UAS group was significantly shorter than T-UAS group (55.25 ± 11.42 min vs. 59.36 ± 15.59 min; P = 0.028). The NTFS-UAS group obtained significantly higher SFR on 1 day postoperatively (86.3% vs. 75.0%; P = 0.038), and higher SFR on 30 days postoperatively than T-UAS group (91.2% vs. 81.3%; P = 0.037). The hemoglobin loss of NTFS-UAS group (- 0.54 ± 0.69 g/dl) was significantly lower than T-UAS group (- 0.83 ± 0.66 g/dl; P = 0.002). There was a significantly lower incidence of overall CR (11.8% vs. 22.3%; P = 0.041), and infectious CR (8.8% vs. 18.8%; P = 0.037) in the NTFS-UAS group. CONCLUSION: Compared to T-UAS combined with flexible ureteroscope for treating unilateral renal calculi, NTFS-UAS had superiority in higher SFR on 1 day and 30 days postoperatively. Shorter operation time, lower hemoglobin loss, lower incidences of overall and infectious CR were observed in NTFS-UAS group. REGISTRATION NUMBER AND DATE: ChiCTR2300070210; April 5, 2023.

Therapeutic potential of vasculogenic mimicry in urological tumors.

Angiogenesis is an essential process in the growth and metastasis of cancer cells, which can be hampered by an anti-angiogenesis mechanism, thereby delaying the progression of tumors. However, the benefit of this treatment modality could be restricted, as most patients tend to develop acquired resistance during treatment. Vasculogenic mimicry (VM) is regarded as a critical alternative mechanism of tumor angiogenesis, where studies have demonstrated that patients with tumors supplemented with VM generally have a shorter survival period and a poorer prognosis. Inhibiting VM may be an effective therapeutic strategy to prevent cancer progression, which could prove helpful in impeding the limitations of lone use of anti-angiogenic therapy when performed concurrently with other anti-tumor therapies. This review summarizes the mechanism of VM signaling pathways in urological tumors, i.e., prostate cancer, clear cell renal cell carcinoma, and bladder cancer. Furthermore, it also summarizes the potential of VM as a therapeutic strategy for urological tumors.

Targeting integrin α5ß1 in urological tumors: opportunities and challenges.

Urological tumors, such as prostate cancer, renal cell carcinoma, and bladder cancer, have shown a significant rise in prevalence in recent years and account for a significant proportion of malignant tumors. It has been established that metastasis to distant organs caused by urological tumors is the main cause of death, although the mechanisms underlying metastasis have not been fully elucidated. The fibronectin receptor integrin α5ß1 reportedly plays an important role in distant metastasis and is closely related to tumor development. It is widely thought to be an important cancer mediator by interacting with different ligands, mediating tumor adhesion, invasion, and migration, and leading to immune escape. In this paper, we expound on the relationship and regulatory mechanisms of integrin α5ß1 in these three cancers. In addition, the clinical applications of integrin α5ß1 in these cancers, especially against treatment resistance, are discussed. Last but not least, the possibility of integrin α5ß1 as a potential target for treatment is examined, with new ideas for future research being proposed.

NLG-919 combined with cisplatin to enhance inhibitory effect on cell migration and invasion via IDO1-Kyn-AhR pathway in human nasopharyngeal carcinoma cell.

As a common aggressive head and neck cancer, nasopharyngeal carcinoma (NPC) received cisplatin treatment as a first-line chemotherapy. Platinum-induced resistance is a major limitation of current treatment strategy in the advanced NPC. Increased indoleamine 2,3-dioxygenase (IDO1) activities are found in cisplatin-resistant NPC cells versus cisplatin-sensitive NPC cells. As an IDO1 immunosuppressant, NLG-919 has entered clinical phase I to treat advanced solid tumors. To reverse cisplatin resistance, we investigated the combinatory application of cisplatin and NLG-919 in NPC treatment. In vitro biological studies on cisplatin-resistant and cisplatin-sensitive NPC cells were taken to imply that the combination of NLG-919 and cisplatin got a stronger impact on the induction of cell apoptosis and the inhibition of cell migration, exploring superior effect of antitumor over single drug. We proved that the mechanism of the combined therapy could inhibit the activity of IDO1, blocking amino acid tryptophan conversion to kynurenine through the kynurenine pathway, which further inhibited the aryl hydrocarbon receptor expression. Our study underscored the combination of cisplatin and NLG-919 as a potent therapeutic way for the reversal of cisplatin resistance.

Naphthalene Diimide-Functionalized Half-Sandwich Ru(II) Complexes as Mitochondria-Targeted Anticancer and Antimetastatic Agents.

In this work, four naphthalene diimide (NDI)-functionalized half-sandwich Ru(II) complexes Ru1-Ru4 bearing the general formula [(η6-arene)RuII(N^N)Cl]PF6, where arene = benzene (bn), p-cymene (p-cym), 1,3,5-trimethylbenzene (tmb), and hexamethylbenzene (hmb), have been synthesized and characterized. By introducing the NDI unit into the N,N-chelating ligand of these half-sandwich complexes, the poor luminescent half-sandwich complexes are endowed with excellent emission performance. Besides, modification on the arene ligand of arene-Ru(II) complexes can influence the electron density of the metal center, resulting in great changes in the kinetic properties, catalytic activities in the oxidative conversion of NADH to NAD+, and biological activities of these compounds. Particularly, Ru4 exhibits the highest reactivity and the strongest inhibitory activity against the growth of three tested cancer cell lines. Further study revealed that Ru4 can enter cells quickly in an energy-dependent manner and preferentially accumulate in the mitochondria of MDA-MB-231 cells, inducing cell apoptosis via reactive oxygen species overproduction and mitochondrial dysfunction. Significantly, Ru4 can effectively inhibit the cell migration and invasion. Overall, the complexation with NDI and modification on the arene ligand endowed the half-sandwich Ru(II) complexes with improved spectroscopic properties and anticancer activities, highlighting their potential applications for cancer treatment.

Essential role of bromodomain proteins in renal cell carcinoma (Review).

Histone alterations are a hallmark of kidney cancer. Histone acetylation modification mediated by bromodomain proteins (BRD) has been indicated to be related to a variety of cancer types and several targeted inhibitors have been proven to be promising modalities for cancer adjuvant therapy. As renal cell carcinoma (RCC) is not sensitive to radiotherapy or chemotherapy, the exploration of effective adjuvant therapies remains an important research direction for advanced RCC. At present, studies on bromodomain family proteins in RCC are limited and the roles of bromodomain family proteins in RCC have remained to be fully elucidated. The present review discussed the role of bromodomain family proteins in RCC, aiming to explore possible potential therapeutic targets of BRD­related drugs in this type of cancer.

Preclinical models and evaluation criteria of prostatitis.

Prostatitis is a common urological condition that affects almost half of all men at some point in their life. The prostate gland has a dense nerve supply that contributes to the production of fluid to nourish sperm and the mechanism to switch between urination and ejaculation. Prostatitis can cause frequent urination, pelvic pain, and even infertility. Long-term prostatitis increases the risk of prostate cancer and benign prostate hyperplasia. Chronic non-bacterial prostatitis presents a complex pathogenesis, which has challenged medical research. Experimental studies of prostatitis require appropriate preclinical models. This review aimed to summarize and compare preclinical models of prostatitis based on their methods, success rate, evaluation, and range of application. The objective of this study is to provide a comprehensive understanding of prostatitis and advance basic research.

Case report: Robot-assisted laparoscopic partial nephrectomy for renal cell carcinoma in a patient with situs inversus totalis and abdominal cocoon.

Background: Situs inversus totalis (SIT) is a congenital condition wherein organs in abdominal or thoracic cavity are mirrored from their normal positions. Abdominal cocoon, is a rare disease of unknown aetiology that is characterised by total or partial small intestine encapsulation by a compact fibrocollagenous membrane. Aside from having two extremely rare conditions (SIT and Abdominal cocoon), our patient developed renal cell carcinoma (RCC), which makes this case even more uncommon. Case Presentation: We report the case of a 64-year-old man who was admitted to our hospital with an extremely rare case of localized RCC in the left kidney complicated with SIT and abdominal cocoon. Computer tomography urography (CTU) and angiography (CTA) showed that the patient was confirmed as having SIT, for the space-occupying lesion in the left kidney, clear cell RCC (ccRCC) was considered, the lesion in the right kidney was probably cystic. We diagnosed our patient as having a cT1aN0M0 left RCC, and the RENAL score was 7x. With partial nephrectomy (PN) being the preferred treatment approach, robot-assisted laparoscopic partial nephrectomy (RALPN) was performed after obtaining informed consent. After insertion of the laparoscope, adhesions were observed between the entire colon and the anterior abdominal wall. Then, abdominal cocoon was diagnosed. The surgery was uneventful, and the tumour was resected successfully while preserving the tumour capsule. No intestinal injury or any other complication occurred in the intraoperative or postoperative, and the patient recovered well after the operation. Conclusion: PN is an extremely challenging procedure in patients with SIT and abdominal cocoon. The da Vinci Xi surgical system and thorough preoperative assessment allowed the surgeon to overcome stereotyping, visual inversion, and successfully perform PN in a patient with SIT and abdominal cocoon without increasing the risk of complications and preserving as much renal function as possible. Considering the satisfactory outcomes, this report may hopefully provide a practical reference for the treatment of RCC in patients with other special conditions.