This study focused on various databases and literatures related to drug metabolism, collated and analyzed the information related to bacterial and human drug metabolic enzymes, and compared the similarities and differences between the information included in the database of bacterial and human drug metabolic enzymes. Results found more bacterial drug metabolic enzymes than human drug metabolic enzymes (9 703 vs 964), but much less than the total number of bacterial enzymes in BRENDA database (9 703 vs 20 835 235), indicating that the influence of bacteria on drug metabolism could have been greatly underestimated, and that further systematic research is needed.We summarized the progress and shortcomings of the current research on the influence of intestinal flora on drug metabolism, and proposed a research idea, that is, to predict through artificial intelligence whether intestinal bacterial proteins have the ability to metabolize drugs, to verify their biological functions by in vitro/in vivo experiments and gene editing, and to establish a database of drug metabolic enzymes from intestinal bacteria with complete annotation functions, in an attempt to provide a solid theoretical basis for further exploration of the effects of intestinal flora on drug metabolism.

Objective:To explore the surgical technique and efficacy of pure retroperitoneoscopic extravesical standardized seeable (P.R.E.S.S.) technique for bladder cuff excision (BCE).Methods:Ninety five patients with UTUC from five domestic centers (30 cases from Changzheng Hospital, 21 cases from Peking University First Hospital, 20 cases from Yuhuangding Hospital, 21 cases from Dalian Medical University affiliated No.2 Hospital and 3 cases from General Hospital of Eastern Theater Command)between August 2017 and December 2020 were retrospectively analyzed. There were 57 males and 38 females with a mean age of (67.7±10.0) years and median tumor size of 3.0 cm. All patients underwent pure retroperitoneoscopic radical nephroureterectomy with a single surgical position and four (36 cases) or five (59 cases) trocar layout according to the surgeon’s prefer habit and experience. The demographics of the two groups were the age of [(66.3±11.2)years vs. (68.6±9.1)years], male/female ratio of (25/11 cases vs. 32/27 cases), body mass index of [(25.0± 3.0)kg/m 2 vs. (24.8±3.4)kg/m 2], tumor maximum diameter of [2.8(1.6, 3.5)cm vs. 3.0(2.0, 4.0)cm], left/right side tumor of(19/17 cases vs. 34/25 cases), T 1-2/T 3-4/Tis stage of(25/10/4 cases vs. 49/10/0 cases), and multifocal tumors of(3 cases vs. 2 cases), and the difference was not statistically significant( P>0.05). On the other hand, the differences of hydronephrosis of the operated kidney(13 cases vs. 39 cases, P=0.004), and tumor location (in renal pelvis or calyx or upper/middle/lower ureter being 23/9/4 cases vs. 35/4/20 cases, P=0.005), were statistically significant. The umbilical artery cord was used as anatomical landmark in the process of P. R.E.S.S. bladder cuff excision. The pelvic floor and extraperitoneal space around the ureter were expanded, the bladder wall was opened to form pneumovesicum, and a sufficient bladder cuff resection and exact bladder cuff closure was performed. Perioperative outcomes and follow-up data were analyzed, and the clinical outcomes between the four and five trocars were compared to evaluate the impact of trocar layout on the surgical outcomes. Results:There were 91(95.8%) cases successfully undergoing P. R.E.S.S. BCE technique, with one case converted to open BCE due to bleeding and three cases converted to distal ureter Hem-o-lok clipping because of poor exposure. Median operative time was 180(125, 230)min, and estimated blood loss was 100(50, 100)ml. The overall complication rate was 10.5%(10/95), including 2 cases(2.1%) of intraoperative bleeding, with 1 case treated by transfusion (400 ml), the other case converted to open surgery without transfusion. There were 8 cases of postoperative complications(8.4%), including 7 cases of Clavien-Dindo grade Ⅱ(3 cases of secondary hemorrhage, one case for each of drug allergy, acute renal insufficiency, blood creatinine increased to 490 μmol/L, or lung infection with lymphatic leakage), 1 case of grade Ⅲa(intestinal obstruction treated with insertion of the intestinal obstruction catheter under local anesthesia), and all these patients were discharged smoothly. The difference between the four and five trocars was not statistically significant in the following variables, including the rate of surgical conversion(8.3% vs. 1.7%), estimated intraoperative blood loss(100 ml vs. 60 ml), ratio of intraoperative lymph node dissection (25.0% vs.20.3%), P. R.E.S.S. bladder cuff excision success rate(91.7% vs.98.3%), the incidence of intraoperative and postoperative complications (13.8% vs.8.5%), pT 1-2/pT 3-4/pTis stage(22/11/3 cases vs.37/19/3 cases) and the proportion of recurrence or metastasis(8.3% vs.3.4%)(all P>0.05). However, the differences in the operation time(190 min vs.170 min, P=0.011)and postoperative hospital stay(5 d vs.6 d, P=0.005) were statistically significant. Conclusions:P. R.E.S.S. bladder cuff resection technique is safe and feasible during the procedure of pure retroperitoneoscopic radical nephroureterectomy by a single surgical position and facilitates seeable adequate bladder cuff excision by establishing an enlarged pelvic lateral extraperitoneal space and pneumovesicum. Five-trocar technique is more suitable for patients with lower ureteral tumors but may be associated with a longer postoperative hospital stay compared with the four-trocar technique.