Blockage of TIM-3 relieves lupus nephritis by expanding Treg cells and promoting their suppressive capacity in MRL/lpr mice.

T Cell Immunoglobulin and Mucin Containing Protein-3 (TIM-3) is an important immune checkpoint protein that is expressed in Tregs and affects their function. However, the expression and role of TIM-3 in modulating regulatory T cells (Tregs) in lupus nephritis (LN) are still unknown. In this study, we found that the percentage of TIM-3+ cells among spleen lymphocytes, CD4+ T cells and Tregs was higher in MRL/lpr mice than in MpJ mice. TIM-3high CD4+ T cells and TIM-3high Tregs were mainly responsible for the increase. The percentage of Tregs in TIM-3high CD4+ T cells was lower than that in TIM-3low CD4+ T cells, and the expression of CTLA-4 and IL-10 was lower in TIM-3high Tregs than in the TIM-3low Tregs in MRL/lpr mice. Blockade of TIM-3 in vivo significantly increased the Treg population and the expression of CTLA-4 and IL-10 in Tregs, thus relieving the LN symptoms and pathology in MRL/lpr mice. Additionally, bioinformatics analysis indicated that TIM-3 regulates Treg cells in LN mainly through cytokine-cytokine receptor interactions, the PI3K-Akt signaling pathway, the T cell receptor signaling pathway, Th17 cell differentiation and the FoxO signaling pathway. Together, our study has demonstrated that TIM-3 regulates Tregs in LN and that overexpression of TIM-3 in CD4+ T cells and Tregs leads to Treg quantity and quality deficiency in MRL/lpr mice. Blockade of TIM-3 protects against LN by expanding Tregs and enhancing their suppressive capacity. Finally, TIM-3 might be a potential therapeutic target for the treatment of LN.

Current knowledge of primary prostatic extra-gastrointestinal stromal tumor: a case report and review of the literature.

The patient was a 62-year-old man diagnosed as having prostatic extra-gastrointestinal stromal tumor (EGIST) who was treated with imatinib. No recurrence or metastasis was found after a 6-month follow-up. We identified 14 cases of prostatic primary EGIST in PubMed and summarized these cases with our case. The patients' ages ranged from 31 to 78 years (average: 53.6 years), and most patients' prostate-specific antigen (PSA) concentrations were within normal limits (92.9%, 13/14). All patients underwent imaging examinations; prostatic masses measured 6 to 14.2 cm (mean: 9.43 cm), and imaging excluded secondary prostatic masses from the intestinal tract. By immunohistochemical staining, the tumors were positive for cluster of differentiation (CD)117 (71.4%, 10/14), DOG1 (100%, 7/7), and CD34 (100%, 14/14), and negative for smooth muscle actin (SMA) (71.4%, 10/14), desmin (100%, 11/11), and S100 (100%, 12/12). Treatment depended on the results of the gene mutation detection as well as the risk estimation according to tumor size and microscopic mitotic rates (>5 per 50 high-power fields: 60%, 6/10). Among the 12 patients with reported outcomes, nine achieved good results (no recurrence or metastasis), one achieved reduced mass volume, one experienced recurrence, and one died.

Robotic-assisted Laparoscopic Nephrectomy with Vein Thrombectomy: Initial Experience and Outcomes from a Single Surgeon.

This study was designed to explore the safety and feasibility of robotic-assisted laparoscopic nephrectomy with vein thrombectomy (RAL-NVT) for the treatment of renal cell carcinoma (RCC) with venous tumor thrombus (VTT). Clinical data of 6 patients treated with RAL-NVT between July 2016 and November 2017 in our hospital were retrospectively collected and analyzed. There were 5 males and 1 female with their age ranging from 48 years to 68 years. Five renal tumors were right-sided and one left-sided. Three cases fell in level 0 VTT, one in level I and two in level II. Preoperative imaging revealed lymph node involvement in 1 case and distant metastasis in 2 cases. For RCC with level 0 VTT, the renal vein of the affected side was adequately and carefully dissected around the thrombus to the proximity of inferior vena cava (IVC) and was ligated with Hem-o-loks without cross-clamping the IVC. For level I and II VTT, the IVC was crossclamped cephalically and caudally around the tumor thrombus and all tributaries were sequentially blocked to ensure the safe retrieval of VTT. All operations were successfully completed without conversion to open operation. The mean operative time was 150 (115-230) min. Cross-clamping of the IVC happened in 3 cases, and the blocking time was 14, 19 and 20 min, respectively. The mean estimated blood loss during the operation was 400 (200-580) mL. The peritoneal drainage tube was removed 5 to 9 days after the operation, and all patients were postoperatively discharged at 6 to 11 days. Postoperative pathological analysis confirmed that the RCCs were comprised of 4 clear cell RCCs, 1 papillary cell RCC, and 1 medullary cell RCC; 2 cases were Fuhrman grade II, 3 cases grade III, and 1 case undefined grade. No recurrence or progression was observed during the follow-up of 4.2 (3-6) months. We concluded that RAL-NVT is highly challenging but safe and feasible for the treatment of RCC with VTT.