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Purpose Results of previous studies have demonstrated that T-cell receptor cross-linking rapidly generates reactive oxygen species, which play essential signaling roles within mitochondria for the antigen-specific expansion of T-cells. However, oxidative stress also causes damage to cellular organelles. Thus, modulating ROS metabolism using antioxidants during naïve T-cell activation may promote the expansion and generation of functional T-cells. Notably, urothelial cancer is a sex-specific malignancy with high mortality rates worldwide. The present study aimed to evaluate the effects of various antioxidants on γδ T-cell proliferation, and the associated cytotoxicity against urothelial carcinoma cells (UCs). Methods Over a period of cell induction and expansion, peripheral blood mononuclear cells were cultured with or without different antioxidants, including N -acetyl cysteine (NAC), vitamin C and vitamin E. Subsequently, phenotypic characterization of γδ T-cells and their cytolytic effects against UCs were analyzed by flow cytometry and cell viability assays, respectively. Results and Conclusions The results revealed that NAC partially inhibited T-cell expansion in a dose-dependent manner. In addition, CD3 + /Vγ9 + levels and natural killer group 2D receptor expression were mildly reduced following treatment with a high dose of NAC, whereas CD3 + /CD56 + levels and CD314 expression in natural killer-like cells were moderately decreased following treatment with vitamin E. Particularly, the direct co-incubation of bladder cancer cells with γδ T-cells supplemented with antioxidants significantly enhanced bladder cancer cytolysis. Collectively, results of the present study revealed that co-administration of functional antioxidants during γδ T-cell expansion may enhance the quality and efficacy of adoptive T-cell therapies for cancer treatment.

Background and Objectives: The limited literature on the significance and risk factors of intraoperative anastomotic leakage (IAL) following Retzius-sparing robot-assisted radical prostatectomy (Rs-RARP) highlights the need for further investigation. This study aimed to assess the incidence of IAL, identify its associated risk factors, and evaluate its clinical implications. Materials and Methods: Patients with prostate adenocarcinoma who underwent Rs-RARP performed by a single surgeon between February 2015 and August 2023 were included in this study. Positive IAL was defined as the presence of anastomotic leakage identified through a water injection test performed immediately after vesicourethral anastomosis (VUA). Postoperative urinary continence was defined as the use of no pads or only a safety pad. Patients were categorized into two groups: those with positive IAL and those without. Immediate repair was performed in cases of positive IAL, and cystography was conducted approximately 10–14 days postoperatively. Chi-square test, Fisher’s exact test, Mann–Whitney U test, as well as univariable and multivariable logistic regression analyses, were used to evaluate the risk factors associated with IAL. Additionally, we analyzed the continence rate and the time to achieve continence following surgery. Results: A total of 230 patients underwent Rs-RARP for prostate adenocarcinoma performed by a single surgeon at our center during the aforementioned period. A water injection test was performed in all patients immediately after the VUA. IAL was observed in 32 patients (14%) during the water injection test. Postoperative cystography revealed very mild contrast medium leakage in only two patients (0.9%), with no impact on clinical recovery. No major IAL cases were identified on postoperative cystography. Patients with positive IAL required a significantly longer time to achieve continence compared to those without IAL (2.13 vs. 0.46 months, p = 0.008). Univariable analysis showed that a locally advanced T stage (>T2), longer console time, and absence of nerve-sparing were significantly associated with positive IAL. In multivariable analysis, a longer console time and a locally advanced T stage remained significant predictors of IAL. Conclusions: IAL detected by the water injection test was associated with the development of postoperative urinary incontinence and delayed recovery of continence. A tumor stage greater than T2 and longer console time were significant predictors of IAL. Further prospective randomized studies with larger sample sizes are required to validate our findings.

Abstract Background Remission rate is associated with higher dose of Gamma Knife Radiosurgery (GKRS; Gamma Knife: Elekta AB, Stockholm, Sweden) for acromegaly, but the dose ≥25 Gy is not always feasible when the functioning adenoma is close to optic apparatus Objective To evaluate the efficacy and safety of low-dose (<25 Gy) GKRS in the treatment of patients with acromegaly. Methods Single-center retrospective review of acromegaly cases treated with GKRS between June 1994 and December 2016. A total of 76 patients with the diagnosis of acromegaly who were treated with low-dose GKRS were selected for inclusion. Patients were treated with a median margin dose, isodose line, and treatment volume of 15.8 Gy, 57.5%, and 4.8 mL, respectively. Any identifiable portion of the optic apparatus was limited to a radiation dose of 10 Gy. All patients underwent full endocrine, ophthalmological, and imaging evaluation prior to and after GKRS treatments, and results of these were analyzed. Results Biochemical remission was achieved in 33 (43.4%) patients. Actuarial remission rates were 20.3%, 49.9%, and 76.3% at 4, 8, and 12 yr, respectively. Absence of cavernous sinus invasion (P = .042) and lower baseline insulin-like growth factor-1 levels (P = .019) were significant predictors of remission. New hormone deficiencies were found in 9 (11.8%) patients. Actuarial hormone deficiency rates were 3%, 14%, and 22.2% at 4, 8, and 10 yr, respectively. Two (2.6%) patients who achieved initial remission experienced recurrence. No optic complications were encountered. CONCLUSION Reasonable remission and new hormone deficiency rates can be achieved with low-dose GKRS for acromegaly. These rates may be comparable to those with standard GKRS margin doses.

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

Aim： To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca2＋ overload in ventricular myocytes and to explore the underlying mechanisms. Methods： Hydrogen peroxide （H2O2, 200 μmol/L）） was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca2＋ （[Ca2＋]i）. Ca2＋/calmodulin-dependent protein kinases II （CaMKII） activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na＋ and Ca2＋ currents were examined using whole-cell recording in myocytes. Results： H2O2 markedly prolonged Ca2＋ transient duration （CaTD）, and induced early afterdepolarization （EAD）-like and delayed afterdepolarization （DAD）-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol （30 or 50 μmol/L） dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol （50 μmol/L） effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca2＋]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na＋ current （INa,L） and L-type Ca2＋ current （ICa,L） in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. Conclusion： Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2＋ overload through inhibition of INa,L/ICa,L, reduction of ROS generation, and prevention of CaMKII activation.