Huachansu (HCS), a class of toxic steroids extracted from toad venom, which has been shown to be a valuable anticancer drug in many kinds of cancers. However, the effect of HCS on bladder cancer has not been elucidated. In this study, we focused on the antitumor activities and related mechanisms of HCS on bladder cancer in vitro and in vivo. Cell viability of T24, EJ, RT-4, SV-HUC-1 cells after HCS treatment was measured by MTS, whereas the changes of cell morphology were observed by transmission electron microscopy. The early apoptosis induced by HCS was evaluated by flow cytometry, and the expression level of apoptosis-related molecules (Bax, Bcl-2, XIAP, PARP, cleaved-Caspases 3, 8, 9) was detected using Western blot. We then evaluated the impact of HCS on the expression of Fas/Fasl, TNF- alpha/TNFR1, and the activation of NF-Kappa B pathway, and furthermore the effect of these pathways in HCS induced-apoptosis were also detected. At last, xenograft tumor in nude mice was used to further investigate the antitumor effect of HCS in vivo. Our results showed that HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cell lines. The expression of Fas, Fasl, TNF- alpha were all elevated at both mRNA and protein level after HCS treatment. Furthermore, down regulation of TNF- alpha, TNFR1, Fas or inhibition of Fas/Fasl interaction decreased the relative number of death cells induced by HCS. In vivo, HCS treatment significantly suppressed tumor growth and induced apoptosis in xenografts tumor in nude mice. HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cells in vitro and in vivo, which is largely mediated by Fas/Fasl and TNF- alpha/TNFR1 pathway.

Kidney renal clear cell carcinoma (KIRC) has high morbidity and gradually increased in recent years, and the rate of progression once relapsed is high. At present, owing to lack of effective prognosis predicted markers and post-recurrence drug selection guidelines, the prognosis of KIRC patients is greatly affected. Necroptosis is a regulated form of cell necrosis in a way that is independent of caspase. Induced necroptosis is considered an effective strategy in chemotherapy and targeted drugs, and it can also be used to improve the efficacy of immunotherapy. Herein, we quantified the necroptosis landscape of KIRC patients from The Cancer Genome Atlas (TCGA) database and divided them into two distinct necroptosis-related patterns (C1 and C2) through the non-negative matrix factorization (NMF) algorithm. Multi-analysis revealed the differences in clinicopathological characteristics and tumor immune microenvironment (TIME). Then, we constructed the NRG prognosis signature (NRGscore), which contained 10 NRGs (PLK1, APP, TNFRSF21, CXCL8, MYCN, TNFRSF1A, TRAF2, HSP90AA1, STUB1, and FLT3). We confirmed that NRGscore could be used as an independent prognostic marker for KIRC patients and performed excellent stability and accuracy. A nomogram model was also established to provide a more beneficial prognostic indicator for the clinic. We found that NRGscore was significantly correlated with clinicopathological characteristics, TIME, and tumor mutation burden (TMB) of KIRC patients. Moreover, NRGscore had effective guiding significance for immunotherapy, chemotherapy, and targeted drugs.

Laparoscopic radical cystectomy (LRC) has been shown to have less estimated blood loss (EBL), transfusion rate, narcotic analgesic requirement, earlier return of bowel function, and shorter hospital stay. The aim of this study was to investigate the feasibility, peri-operative and oncologic outcomes of laparoscopic radical cystectomy (LRC) in patients with previous abdominal surgery (PAS). We retrospectively reviewed 243 patients undergoing open radical cystectomy (ORC) or LRC with bilateral pelvic lymph node dissection and urinary diversion or cutaneous ureterostomy at a single center from January 2010 to December 2015. Demographic parameters, intra-operative variables, peri-operative records, pathologic outcomes, and complication rate were reviewed to assess the impact of PAS on peri-operative and oncologic outcomes. Patients in both ORC and LRC subgroups were homogeneous in terms of demography characteristics including age, gender, BMI, ASA score, and comorbidity. Estimated blood loss (EBL) was higher in patients with PAS undergoing ORC compared to those with no PAS (P = 0.008). However, there was no significant difference of EBL among patients undergoing LRC with or without PAS (P = 0.896). There was no statistical difference in peri-operative parameters and pathological outcomes. Patients with PAS undergoing ORC and ileal conduit had a higher vascular injury rate (P = 0.017). Comparing patients with PAS performed by LRC and ORC, the number of patients with the vascular injury was higher in ORC groups regardless of the type of diversion (ileal conduit, P = 0.001, cutaneous ureterostomy, P = 0.025). There is no significant difference in other complications. The presence of adhesions from PAS is not a contraindication to LRC. Patients with PAS may benefit from LRC with lower estimated blood loss, fewer transfusion rates, and vascular injuries. Furthermore, the overall oncologic outcomes and complication rate are similar between LRC and ORC patients with PAS.

Diabetes mellitus (DM) is a chronic metabolic disease that often leads to vascular endothelial injury and peripheral neuropathy. Erectile dysfunction (ED), a common condition in andrology, is frequently associated with DM. The incidence of diabetes mellitus-induced ED (DMED) is second only to the cardiovascular complications of diabetes. Compared to other types of ED, DMED presents with more severe symptoms, rapid progression, and notable resistance to phosphodiesterase type 5 inhibitors (PDE5is). Various forms of programmed cell death (PCD)—including apoptosis, autophagy, pyroptosis, and ferroptosis—play pivotal roles in the pathogenesis of DMED. An exacerbation of DMED is linked to critical irritants like advanced glycation end-products (AGEs) and reactive oxygen species (ROS) in the corpus cavernosum tissue. These irritants can spark anomalous activations of diverse PCDs, which damage primary corpus cavernosum cells like cavernous nerve cells, endothelial cells, and myocytes, leading to ED. Hence, we reviewed current knowledge on the mechanisms and therapeutic potential of targeting PCDs in DMED, aiming to advance strategies for enhancing erectile function.

Kidney renal clear cell carcinoma (KIRC) is a heterogeneous malignant tumor with high incidence, metastasis, and mortality. The imbalance of copper homeostasis can produce cytotoxicity and cause cell damage. At the same time, copper can also induce tumor cell death and inhibit tumor transformation. The latest research found that this copper-induced cell death is different from the known cell death pathway, so it is defined as cuproptosis. We included 539 KIRC samples and 72 normal tissues from the Cancer Genome Atlas (TCGA) in our study. After identifying long non-coding RNAs (lncRNAs) significantly associated with cuproptosis, we clustered 526 KIRC samples based on the prognostic lncRNAs and obtained two different patterns (Cuproptosis.C1 and C2). C1 indicated an obviously worse prognostic outcome and possessed a higher immune score and immune cell infiltration level. Moreover, a prognosis signature (CRGscore) was constructed to effectively and accurately evaluate the overall survival (OS) of KIRC patients. There were significant differences in tumor immune microenvironment (TIME) and tumor mutation burden (TMB) between CRGscore-defined groups. CRGscore also has the potential to predict medicine efficacy.

Background: Cisplatin-based neoadjuvant chemotherapy combined with radical cystectomy (RC) plus pelvic lymph node dissection (PLND) is the preferred treatment option for muscle-invasive bladder cancer (MIBC). However, some patients are unable to tolerate RC or may have postoperative complications after RC. And most patients have a strong desire for bladder-preserving treatment. There are no reports on the efficacy of maximal transurethral resection of the bladder tumor (TURBT) in combination with chemotherapy plus tislelizumab for bladder-preserving in recurrent MIBC patients.Case presentation: We report two cases diagnosed with recurrent MIBC who achieved pathological complete response (pCR) and bladder-preserving after maximal TURBT combined with chemotherapy plus tislelizumab.Conclusion: Postoperative immunotherapy should be considered for all patients with recurrent MIBC who are eligible for immunotherapy. In addition, high programmed death ligand-1 (PD-L1) expression, high tumor mutation burden (TMB), and TP53 mutation level can be combined to predict tislelizumab efficacy.