Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

An increasing number of studies suggested that the tumor microenvironment exerts a substantial influence on the pathophysiology of pancreatic cancer. As a crucial component of the tumor microenvironment,the tumor stroma plays a pivotal role in the occurrence,development,and chemotherapy resistance of pancreatic cancer. By serving as a proxy for the interaction between tumor cells and the microenvironment,the tumor stroma ratio(TSR) has emerged as a focal point of investigation in recent years. At present,numerous studies show that a low TSR is a protective factor for the prognosis of resectable pancreatic cancer. Additionally, patients with a low TSR are more suitable for the gemcitabine and albumin-bound paclitaxel chemotherapy regimen. But these researches are not conclusive, and there is still a gap between guiding precision treatment. Further research and exploration are required. Integration of artificial intelligence deep learning models into traditional pathological and imaging assessments facilitates precise evaluation of the TSR. It can also enable stratification and precision treatment of pancreatic cancer patients based on this index.

An increasing number of studies suggested that the tumor microenvironment exerts a substantial influence on the pathophysiology of pancreatic cancer. As a crucial component of the tumor microenvironment,the tumor stroma plays a pivotal role in the occurrence,development,and chemotherapy resistance of pancreatic cancer. By serving as a proxy for the interaction between tumor cells and the microenvironment,the tumor stroma ratio(TSR) has emerged as a focal point of investigation in recent years. At present,numerous studies show that a low TSR is a protective factor for the prognosis of resectable pancreatic cancer. Additionally, patients with a low TSR are more suitable for the gemcitabine and albumin-bound paclitaxel chemotherapy regimen. But these researches are not conclusive, and there is still a gap between guiding precision treatment. Further research and exploration are required. Integration of artificial intelligence deep learning models into traditional pathological and imaging assessments facilitates precise evaluation of the TSR. It can also enable stratification and precision treatment of pancreatic cancer patients based on this index.

【Objective】 To investigate the efficacy and surgical technique of total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion, so as to provide reference for the selection of surgery for patients with bladder cancer. 【Methods】 Clinical data of 48 patients with bladder cancer who underwent laparoscopic radical cystectomy during Mar.2017 and Aug.2022 in our hospital were retrospectively analyzed, including 23 cases who received traditional laparoscopic radical cystectomy combined with extracorporeal ileal conduit, and 25 who received total laparoscopic radical cystectomy with intracorporeal ileal conduit.The operation time, blood loss, postoperative intestinal function recovery time, drainage tube removal time and hospital stay were compared between the two groups. 【Results】 All procedures were successfully performed, and no Clavien-Dindo>grade 3 complications were observed.The operation time, and amount of estimated blood loss of the traditional group and total laparoscopic radical group were (227.0±46.4) min vs. (253.6±58.9) min, and (131.7±79.8) mL vs. (154.0±93.0) mL, respectively.There were no differences in postoperative intestinal function recovery time and drainage tube removal time (P>0.05).The hospital stay was shorter in the total laparoscopic radical group than in the traditional group (P=0.035). 【Conclusion】 Total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion is safe and feasible.which is comparable to the traditional laparoscopic surgery, while the hospital stay in the total laparoscopic group is shorter, which is conducive to rapid postoperative recovery.

Objective:We aim to investigate the clinical characteristics and prognosis of upper tract urothelial carcinoma (UTUC) in patients with non-muscle invasive bladder cancer (NMIBC) after renal transplantation.Methods:We retrospectively analyzed the clinical and follow-up information of 13 kidney recipients with NMIBC admitted to our hospital from January 2014 to June 2022 who subsequently underwent complete transperitoneal laparoscopic nephroureterectomy. There were 8 males and 5 females, aged (56.1±11.5), 3 cases with history of smoking and 10 cases without history of smoking, 4 cases with history of Aristolochic acids and 9 cases with no history of Aristolochic acids. Six and seven cases were treated with transurethral resection of bladder tumor for hematuria and bladder tumors detected by ultrasound or imaging respectively. Single and multiple bladder tumors were 9 and 4 cases; bladder tumor size ≤ 3 cm, >3 cm were 9 and 4 cases respectively; low-and high-grade bladder tumors were 3 and 10 cases separately, with; T a and T 1 of 3 and 10 cases respectively; recurrent bladder cancer and non-recurrent bladder cancer were 5 and 8 cases respectively. Follow-up after transurethral resection of bladder tumor showed that 6 cases with imaging evidence of UTUC for 6-52 months after transurethral resection of bladder tumor were treated with ipsilateral laparoscopic nephroureterectomy, including 2 cases of hydronephrosis, 1 case of renal pelvis mass, and 3 cases of ureteral mass, and 7 cases without imaging evidence of UTUC were performed with bilaterally prophylactic laparoscopic nephroureterectomy. The Kaplan-Meier curve and log-rank test were used for survival analysis to evaluate the prognostic effect of UTUC in kidney recipients with NMIBC. Results:Six of 13 patients named UTUC group were diagnosed with UTUC and 7 of 13 patients named no-UTUC group were not detected with UTUC. There was no statistical difference between these two groups in terms of clinical characteristics, including age( P=0.10), sex( P=0.10), smoking( P=0.19), history of Aristolochic acids( P=0.99), number( P=0.56), grade( P=0.19), stage ( P=0.19)and recurrence of bladder tumor number( P=0.10), and radiological findings of UTUC ( P=0.29). However, patients with larger-sized bladder tumors (larger than 3cm) had a higher rate of UTUC compared to patients with equal or smaller than 3 cm ( P=0.29). In addition, two patients with negative radiological findings developed UTUC following the detection of a large bladder tumor size (larger than 3 cm). The median survival of overall survival time and cancer specific survival time after laparoscopic nephroureterectomy were 42(17, 65) months. Two patients died from any cause during follow-up in patients with UTUC, whereas no significant difference between UTUC group and non-UTUC group in overall survival time and cancer specific survival time, as evaluated by the Kaplan-Meier curves and log-rank tests. ( P=0.29). Conclusions:After kidney transplantation, the diameter of the bladder tumor in NMIBC patients with UTUC was significantly larger than that in patients without UTUC, and no significant difference was observed in the remaining clinical features. Considering the non-functioning kidney after kidney transplantation, prophylactic laparoscopic nephroureterectomy can be considered for NMIBC patients with bladder tumor size >3 cm. Survival analysis showed no significant difference between UTUC group and non-UTUC group.