Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn³⁺SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn²⁺SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn²⁺SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn²⁺SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn²⁺ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O₂^• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O₂^• into the inner sphere, and avoid O₂^•/Mn²⁺ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH^-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

Objective:To analyze the efficacy and feasibility of performing a new surgical procedure, tunnel esophagogastrostomy, to perform proximal gastrectomy.Methods:The study cohort comprised 10 consecutive patients who had undergone esophagogastrostomy by the tunnel technique in Jiangsu Cancer Hospital between October 2019 and July 2022. All patients were male. Their average age was (64.2±8.1) years and body mass index (25.5±3.2) kg/m2. Nine had upper gastric body adenocarcinoma, the remaining one having signet ring cell carcinoma. TNM staging of the tumors showed that seven were Stage IA, one Stage IB, one Stage IIA, and one Stage IIIA. Briefly, tunnel esophagogastrostomy is performed as follows: After performing a proximal gastrectomy, a rectangular seromuscular flap (3.0 cm × 3.5 cm) is created. The posterior esophageal wall is sutured to the gastric wall at the orad end of the seromuscular flap 5 cm from the stump with three to four stitches. Next, the stump of the esophagus is opened, the posterior esophageal wall is sutured to the gastric mucosa and submucosa, and the anterior esophageal wall is sutured to the full layer of the stomach. Finally, the caudad end of the seromuscular flap is closed. Data on surgical safety, postoperative morbidity, and postoperative reflux esophagitis were analyzed. All enrolled patients completed endoscopic follow-up 1 year and 2 years after surgery.Results:All procedures were completed. They comprised four cases of laparoscopic assisted surgery, four of DaVinci robotic surgery, and two of open surgery. The mean operation time was 212.7±33.2 mins, mean anastomosis time (51.6±5.3) minutes, mean tunnel preparation time (20.0±3.5) minutes, and mean operative blood loss (90.0±51.6) mL. The time to first postoperative passage of flatus was (64.8±11.5) hours. The mean hospital stay after surgery was (9.2±1.7) days. There were no postoperative complications above Clavien-Dindo Grade II. The mean preoperative Reflux Disease Questionnaire score was (3.3± 0.4) before the surgery, (3.8±1.0) 1 month postoperatively, and (3.3±0.4) 12 months postoperatively. All patients underwent endoscopic follow-up; no anastomotic stenoses were found. However, one patient had Grade A reflux esophagitis 1 year after surgery and another Grade B reflux esophagitis 2 years after surgery.Conclusion:Esophagogastrostomy by the tunnel technique is a safe and feasible means of performing proximal gastrectomy.

Ubiquitin-specific protease 1 (USP1) is one of the deubiquitinating enzymes which has received increasing attention in cancer research. USP1 is overexpressed in many types of cancer cells, and has been found to control tumorigenesis and progression by regulating various proteins associated with tumors, such as SIK2, GSK-3β, and Bcl-2. Knockdown or pharmacological inhibition of USP1 can effectively suppress tumors and is also expected to address the issues of cisplatin and poly ADP-ribose polymerase (PARP) inhibitor resistance. This review describes the structure and function of USP1 and the relationship between USP1 targets and tumors and systematically summarizes the structure-activity relationships of small molecule USP1 inhibitors disclosed from 2013 to 2023. Finally, this review discusses the challenges and opportunities in developing small molecule USP1 inhibitors.

Objective:To analyze plaque characteristics of non-culprit coronary lesions with cholesterol crystals in patients with acute myocardial infarction(AMI) by using optical coherence tomography(OCT). We also investigated the potential association between cholesterol crystals with plaque rupture and healed plaque at non-culprit segment.Methods:This study was a retrospective cohort study. Between January 2017 and December 2017, patients with AMI who underwent 3-vessel OCT imaging were included in this study. Patients were divided into two groups according to the presence or absence of cholesterol crystals at the non-culprit lesions. All patients underwent coronary angiography and OCT examination, and non-culprit plaque characteristics were compared between the two groups. The generalized estimating equation log-binomial multirariate regression model was used to assess the relationship between non-culprit lesions with cholesterol crystals and plaque rupture and plaque healing. The follow-up data collection ended in October 2023. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the cumulative incidence of major adverse cardiovascular events between the two groups.Results:A total of 173 AMI patients were included (aged (56.8±11.6) years; 124 men (71.7%)). Among 710 non-culprit lesions identified by OCT, there were 102 (14.4%) in cholesterol crystals group and 608 (85.6%) in non-cholesterol crystals group. Compared with non-culprit lesions without cholesterol crystals, those with cholesterol crystals had smaller minimum lumen diameter, severer diameter stenosis, and longer lesion length (all P<0.01). The prevalence of plaque rupture (17.6% (18/102) vs. 4.9% (30/608), P=0.001) and thin-cap fibroatheroma (31.4% (32/102) vs. 11.5% (70/608), P<0.01) was higher in the cholesterol crystals groups than in the non-cholesterol crystals group. In addition, vulnerable plaque characteristics such as (44.1% (45/102) vs. 25.8% (157/608), P<0.01), macrophages were more frequently observed in non-culprit lesions with cholesterol crystals. The generalized estimating equation log-binomial multivariate regression analyses showed that non-culprit cholesterol crystals were positively correlated with healed plaque ( OR=1.583, 95% CI: 1.004-2.495, P=0.048). Conversely, cholesterol crystals were not associated with plaque rupture ( OR=1.632, 95% CI: 0.745-3.576, P=0.221). The follow-up time was 2 142 (1 880, 2 198) days. Non-culprit cholesterol crystals were not related to the major adverse cardiovascular events in patients with AMI (log-rank P=0.558). Conclusions:Among AMI patients, non-culprit lesions with cholesterol crystals presented with severer luminal stenosis and increased plaque vulnerability. The presence of non-culprit cholesterol crystals was associated with rather than plaque rupture.

Objective:To analyze the efficacy and feasibility of performing a new surgical procedure, tunnel esophagogastrostomy, to perform proximal gastrectomy.Methods:The study cohort comprised 10 consecutive patients who had undergone esophagogastrostomy by the tunnel technique in Jiangsu Cancer Hospital between October 2019 and July 2022. All patients were male. Their average age was (64.2±8.1) years and body mass index (25.5±3.2) kg/m2. Nine had upper gastric body adenocarcinoma, the remaining one having signet ring cell carcinoma. TNM staging of the tumors showed that seven were Stage IA, one Stage IB, one Stage IIA, and one Stage IIIA. Briefly, tunnel esophagogastrostomy is performed as follows: After performing a proximal gastrectomy, a rectangular seromuscular flap (3.0 cm × 3.5 cm) is created. The posterior esophageal wall is sutured to the gastric wall at the orad end of the seromuscular flap 5 cm from the stump with three to four stitches. Next, the stump of the esophagus is opened, the posterior esophageal wall is sutured to the gastric mucosa and submucosa, and the anterior esophageal wall is sutured to the full layer of the stomach. Finally, the caudad end of the seromuscular flap is closed. Data on surgical safety, postoperative morbidity, and postoperative reflux esophagitis were analyzed. All enrolled patients completed endoscopic follow-up 1 year and 2 years after surgery.Results:All procedures were completed. They comprised four cases of laparoscopic assisted surgery, four of DaVinci robotic surgery, and two of open surgery. The mean operation time was 212.7±33.2 mins, mean anastomosis time (51.6±5.3) minutes, mean tunnel preparation time (20.0±3.5) minutes, and mean operative blood loss (90.0±51.6) mL. The time to first postoperative passage of flatus was (64.8±11.5) hours. The mean hospital stay after surgery was (9.2±1.7) days. There were no postoperative complications above Clavien-Dindo Grade II. The mean preoperative Reflux Disease Questionnaire score was (3.3± 0.4) before the surgery, (3.8±1.0) 1 month postoperatively, and (3.3±0.4) 12 months postoperatively. All patients underwent endoscopic follow-up; no anastomotic stenoses were found. However, one patient had Grade A reflux esophagitis 1 year after surgery and another Grade B reflux esophagitis 2 years after surgery.Conclusion:Esophagogastrostomy by the tunnel technique is a safe and feasible means of performing proximal gastrectomy.

Objective To construct an artificial intelligence assisted diagnosis model based on deep learning for dynamically recognizing gastric lesions and their locations under gastroscopy in real time,and to evaluate its ability to detect and recognize gastric lesions and their locations.Methods The gastroscopy videos of 104 patients in our hospital was retrospectively analyzed,and the video frames were manually annotated.The annotated picture frames of lesion category were divided into the training set and the validation set according to the ratio of 8∶2,and the annotated picture frames of location category were divided into the training set and the validation set according to the patient sources at the ratio of 8∶2.These sets were utilized for training and validating the respective models.YoloV4 model was used for the training of lesion recognition,and ResNet152 model was used for the training of location recognition.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value and location recognition accuracy of the auxiliary diagnostic model were evaluated.Results A total of 68 351 image frames were annotated,with 54 872 frames used as the training set,including 41 692 frames for lesion categories and 13 180 frames for location categories.The validation set consisted of 13 479 frames,comprising 10 422 frames for lesion categories and 3 057 frames for location categories.The lesion recognition model achieved an overall accuracy of 98.8%,with a sensitivity of 96.6%,specificity of 99.3%,positive predictive value of 96.3%,and negative predictive value of 99.3% in validation set.Meanwhile,the location recognition model demonstrated an top-5 accuracy of 87.1% .Conclusion The artificial intelligence assisted diagnosis model based on deep learning for real-time dynamic recognition of gastric lesions and their locations under gastroscopy has good ability in lesion detection and location recognition,and has great clinical application prospects.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.