Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? α‐blocker tamsulosin in medical expusion therapy was determined to be safe and effective for distal ureteric stones with renal colic. This trial further demonstrates that the tamsulosin in MET is more efficative and more safer than nifedipine for distal ureteric stones with renal colic. OBJECTIVE: To determine the comparative efficacy of tamsulosin and nifedipine in medical expulsive therapy (MET) for distal ureteric stones with renal colic. PATIENTS AND METHODS: We evaluated the comparative efficacy of tamsulosin and nifedipine in MET in a prospective randomized trial of 3189 outpatients from 10 centres in China. Eligible patients randomly received tamsulosin or nifedipine. Efficacies of the two agents in MET were compared at 4 weeks. The primary endpoint was overall stone‐expulsion rate. Secondary endpoints were stone‐expulsion time, rate of pain relief therapy, mean analgesic consumption for renal colic recurrence, and side‐effects incidence. RESULTS: Stone‐expulsion rates in the tamsulosin group (group 1) were greater than those in the nifedipine group (group 2; P < 0.01). There was a significant variation in stone‐expulsion rates and times between groups 1 and 2 ( P < 0.01); with improvements in stone‐expulsion rate and time significantly better in group 1 than in group 2. There was a significant variation in the rate of pain relief therapy for renal colic recurrence between groups 1 and 2 ( P < 0.01); patients in group 1 required significantly less analgesics than those in group 2 ( P < 0.01). There were no statistically significant differences in side‐effects incidence between the groups. CONCLUSIONS: Administration of tamsulosin and nifedipine in MET was determined to be safe and effective for distal ureteric stones with renal colic. Tamsulosin was significantly better than nifedipine in relieving renal colic and facilitating ureteric stone expulsion.

Graphical abstract of CMNPs delivering different therapeutic agents for enhancing cancer immunotherapy.

Renal tubular cell injury induced by calcium oxalate (CaOx) is a critical initial stage of kidney stone formation. Theaflavin (TF) has been known for its strong antioxidative capacity; however, the effect and molecular mechanism of TF against oxidative stress and injury caused by CaOx crystal exposure in kidneys remains unknown. To explore the potential function of TF on renal crystal deposition and its underlying mechanisms, experiments were conducted using a CaOx nephrocalcinosis mouse model established by glyoxylate intraperitoneal injection, and HK-2 cells were subjected to calcium oxalate monohydrate (COM) crystals, with or without the treatment of TF. We discovered that TF treatment remarkably protected against CaOx-induced kidney oxidative stress injury and reduced crystal deposition. Additionally, miR-128-3p expression was decreased and negatively correlated with SIRT1 level in mouse CaOx nephrocalcinosis model following TF treatment. Moreover, TF suppressed miR-128-3p expression and further abolished its inhibition on SIRT1 to attenuate oxidative stress in vitro. Mechanistically, TF interacted with miR-128-3p and suppressed its expression. In addition, miR-128-3p inhibited SIRT1 expression by directly binding its 3'-untranslated region (UTR). Furthermore, miR-128-3p activation partially reversed the acceerative effect of TF on SIRT1 expression. Taken together, TF exhibits a strong nephroprotective ability to suppress CaOx-induced kidney damage through the recovery of the antioxidant defense system regulated by miR-128-3p/SIRT1 axis. These findings provide novel insights for the prevention and treatment of renal calculus.

Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in the tumor microenvironment (TME), especially in solid tumors. It has been confirmed that it can not only interact with tumor cells to promote cancer progression and metastasis, but also affect the infiltration and function of immune cells to induce chemotherapy and immunotherapy resistance. So, targeting CAF has been considered an important method in cancer treatment. The rapid development of nanotechnology provides a good perspective to improve the efficiency of targeting CAF. At present, more and more researches have focused on the application of nanoparticles (NPs) in targeting CAF. These studies explored the effects of different types of NPs on CAF and the multifunctional nanomedicines that can eliminate CAF are able to enhance the EPR effect which facilitate the anti-tumor effect of themselves. There also exist amounts of studies focusing on using NPs to inhibit the activation and function of CAF to improve the therapeutic efficacy. The application of NPs targeting CAF needs to be based on an understanding of CAF biology. Therefore, in this review, we first summarized the latest progress of CAF biology, then discussed the types of CAF-targeting NPs and the main strategies in the current. The aim is to elucidate the application of NPs in targeting CAF and provide new insights for engineering nanomedicine to enhance immune response in cancer treatment.