Glioblastoma(GBM)originates from glial cells,and complete surgical resection followed by radiotherapy and chemotherapy is the current standard treatment.However,gliomas are subjected to not only accelerated cell death after radiotherapy and chemotherapy but also cellular senescence.Senescent cells produce a senescence-associated secretory phenotype(SASP),which has a dual effect on the tumor microenvironment.The"one-two punch"strategy of specifically eliminating senescent cells and inhibiting SASP-derived secretions provides a new direction for tumor therapy.In this article,we review the mechanisms that mediate tumor cellular senescence and SASP,the elimina-tion of senescent cells by senolytics for SASP inhibition,and the current situation of the"one-two punch"strategy for the treatment of glioma.

Objective:Analysis of the characteristics of influenza epidemic in Anhui Province and quantification of the impact of different factors on influenza occurrence, providing scientific basis for better influenza prevention and control.Methods:Descriptive analysis and factor analysis were conducted on influenza-like illness (ILI) cases and RT-PCR results in Anhui Province from 2013 to 2021 using data from China's Influenza Monitoring Information System.Results:The percentage of influenza-like illness (ILI%) of sentinel hospitals in Anhui Province from April 1, 2013 to March 31, 2021 was 3.80% (1 209 142/31 779 987), showing an overall increasing trend, with a relatively high proportion in 2017-2018 at 4.30% (191 148/4 448 211). The proportion of ILI cases in infants and young children aged 0-4 years was a relatively high at 54.14% (654 676/1 209 142), and the highest ILI% was observed in Fuyang City, Anhui Province (6.25%, 236 863/3 788 863). Laboratory monitoring results showed that the positive rate of ILI cases in sentinel hospitals in 8 influenza monitoring years was 16.38% (34 868/212 912), showing an increasing trend year by year, with a relatively proportion in 2017-2018 at 26.19% (6 936/26 488). The detection rate of school-age children aged 5-14 years was a relativelyhigh at 28.81% (13 869/48 144), and the positive rate was a relatively high in Wuhu City among the 16 cities, reaching 22.01% (2 693/122 237). Influenza activity showed a single peak in winter-spring and alternating double peaks in winter-spring and summer, with different subtypes alternating, and A (H3N2) was the dominant subtype in summer. The results of a multiple logistic regression model showed that the positive rate was higher in 2017-2018, among children aged 5-14 years, in winter, and in southern Anhui.Conclusions:Influenza epidemic in Anhui Province has a clear seasonal pattern, and the ILI% and detection rate have shown an upward trend from 2013 to 2021. Therefore, it is suggested to ensure vaccine supply before the winter-spring influenza season arrives, and to strengthen vaccine uptake and health education to avoid the risk of infection during the peak period of influenza.

Objective:To investigate the application value of three-dimensional visualization technology in management of middle hepatic vein (MHV) processing in associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).Methods:The retrospective and descriptive study was conducted. The clinical data of 40 patients with right massive liver cancer or multiple right liver lesions who underwent ALPPS in the First Affiliated Hospital of Guangxi Medical University from November 2017 to August 2019 were collected. There were 34 males and 6 females, aged (44±9)years, with a range from 26 to 64 years. All patients underwent multi-slice computed tomography (CT) plain and enhanced scan of superior abdominal region before operation, and the data were transmitted to the liver visualization analysis software IQQA system with 1.5 mm thin-layer images to complete the three-dimensional reconstruction of the liver and its blood vessels. Patients were performed ALPPS based on results of three-dimensional reconstruction and intraoperative findings. Observation indicators: (1) results of preoperative three-dimensional reconstruction; (2) surgical situations; (3) follow-up. Follow-up was conducted using outpatient examinations and telephone interview to detect postopeartive survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were described as M (range). Count data were represented as absolute numbers. Results:(1) Results of preoperative three-dimensional reconstruction: 40 patients underwent three-dimensional reconstruction successfully, of which 37 clearly showed MHV, tumor location and relationship between them, 3 patients showed unclearly MHV and were classified based on two-dimensional images. Of the 40 patients, 12 had MHV classified as type A, 13 as type B, 9 as type C, and 6 as type D. Three-dimensional reconstruction of vessels showed 22 with umbilical veins and 9 with anterior veins. Of the 40 patients, 35 were predicted to preserve MHV, and 5 were predicted to resect MHV. Total estimated liver volume, tumor volume, and reserved liver volume were (1 012±119)cm 3, 600 cm 3(8-2 055 cm 3), (346±80)cm 3. The ratio of future liver remnant to standard liver volume was 34%±8%. (2) Surgical situations : 40 patients underwent the first-stage ALPPS, including 35 with preservation of MHV and 5 with resection of MHV, which was accorded with preoperative prediction. Thirty-four patients underwent the second-stage ALPPS, and 6 patients had failure to receive the second-stage ALPPS due to undificiency future liver remnant. The operation time and volume of intraoperative blood loss for 40 patients undergoing first-stage ALPPS were (350±79)minutes and 300 mL(range, 100-2 600 mL). Three patients received blood transfusion and no perioperative death occurred. There were 24 patients with grade A heptic insufficiency according to criteria of International StudyGroup of Liver Surgery (ISGLS) and 16 patients with grade B heptic insufficiency after the first-stage ALPPS. Twenty-eight patients had grade Ⅰ complications of Clavien-Dindo classification, including 17 with a small pleural effusion, 10 with a small pleural and abdominal effusion, 1 with hypoproteinemia; 8 patients had grade Ⅱ complications of Clavien-Dindo classification, including 5 with pneumonia, 1 with pneumonia combined with pleural and abdominal effusion, 1 with coagulation disorders, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 2 with pneumothorax and pneumonia, 1 with pneumothorax, pneumonia and coagulation disorders; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as systemic inflammatory response syndrome. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. For the 34 patients undergoing the second-stage ALPPS, the operation time and volume of intraoperative blood loss were (320±83)minutes and 500 mL(range, 200-6 000 mL). Twelve patients received blood transfusion. There were 12 patients with grade A heptic insufficiency according to criteria of ISGLS and 22 with grade B heptic insufficiency after the second-stage ALPPS. Eighteen patients had grade Ⅰ complications of Clavien-Dindo classification, including 11 with a small pleural effusion, 7 with a small pleural and abdominal effusion; 12 patients had grade Ⅱ complications of Clavien-Dindo classification, including 4 with pneumonia, 4 with coagulation disorders, 3 with massive abdominal effusion, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 1 with pneumothorax and pneumonia, 1 with massive pleural effusion, 1 with obstructive jaundice; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as pneumonia and anemia. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. (3) Follow-up: 40 patients were followed up for 2-35 months, with a median follow-up time of 17 months. The 6-month, 1-, and 2-year survival cases were 35, 26, 21 cases. Conclusion:Three-dimensional visualization technology can clearly show the MHV classification and its relationship with tumor location, which has an important guiding significance in the decision-making of MHV management in ALPPS.

Objective:To investigate the application value of barbed suture in reinforcing anastomosis during laparoscopic radical resection of rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 215 patients with rectal cancer who underwent laparoscopic radical resection in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March 2016 to December 2018 were collected. There were 122 males and 93 females, aged (62.3±0.7)years, with a range from 20 to 75 years. Of 215 patients, 86 patients undergoing laparoscopic radical resection of rectal cancer with barbed suture for anastomosis were allocated into barbed suture group, and 129 patients undergoing laparoscopic radical resection of rectal cancer without reinforced anastomosis were allocated into traditional group, respectively. Observation indicators: (1) intraoperative situations; (2) postoperative situations; (3) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect postoperative complications, anastomotic healing and patency of patients up to May 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Ordinal data were analyzed using the Friedman non-parametric test. Results:(1) Intraoperative situations: patients in the two groups underwent laparoscopic radical resection of rectal cancer successfully, without conversion to open laparotomy. The volume of intraoperative blood loss, operation time, distance between the anastomosis and dentate line, length of auxiliary incision of the barbed suture group were (127±9)mL, (160.2±3.8)minutes, (3.56±0.15)cm, (4.12±0.11)cm, respectively, versus (114±6)mL, (128.9±2.4)minutes, (3.67±0.12)cm, (4.25±0.09)cm of the traditional group. There was a significant difference in the operation time between the two groups ( t=7.33, P<0.05), but no significant difference in the other indicators between the two groups ( t=1.32, 0.61, 0.94, P>0.05). (2) Postoperative situations: the time to first flatus after surgery and duration of postoperative hospital stay of the barbed suture group were (72.5±2.2)hours and (8.1±0.5)days, respectively, versus (76.2±1.7)hours and (8.0±0.5)days of the traditional group, showing no significant difference between the two groups ( t=1.33, 0.87, P>0.05). (3) Follow-up: 215 patients were followed up for 6-12 months, with a median follow-up time of 8 months. In the barbed suture group, 2 patients had postoperative anastomotic leakage, 5 had urinary retention, 6 had incision infection, 4 had intestinal obstruction, 3 had bowel dysfunction in 6 months after operation. In the traditional group, 13 patients had postoperative anastomotic leakage, 15 had urinary retention, 11 had incision infection, 8 had intestinal obstruction, 9 had bowel dysfunction in 6 months after operation. There was a significant difference in the anastomotic leakage between the two groups ( t=4.77, P<0.05), but no significant difference in the urinary retention, incision infection, intestinal obstruction, bowel dysfunction in 6 months after operation between the two groups ( t=2.07, 0.17, 0.22, 1.26, P>0.05). Patients in the two groups showed unobstructed intestinal tract on enteroscopy. Conclusion:The barbed suture for reinforcing anastomosis in radical resection of rectal cancer is safe and feasible, which can reduce the incidence of anastomotic leakage.

Objective:To compared the short-term surgical outcomes of the vertical supraumbilical incision with the left lower oblique incision for specimen retrieval in laparoscopic resection for rectal cancer.Methods:A retrospective cohort study was performed. Inclusion criteria: (1) rectal cancer confirmed by colonoscopy and pathological examination; (2) undergoing the operation for the first time; (3) laparoscopic rectal surgery performed by the same surgeon team; (4) age of > 18 years and < 76 years old. According to above criteria, clinical data of 178 consecutive patients scheduled for laparoscopic surgery for rectal cancer at Department of Gastrointestinal Surgery of Renji Hospital between March 2015 and December 2017 were collected. Based on incision site of the mini-laparotomy, patients were classified to the vertical supraumbilical incision group (n=75) and the left lower oblique incision group ( n=103). There were no significant differences in baseline data, such as age, gender, body mass index (BMI), tumor diameter, preoperative carcinoembryonic antigen (CEA) level, score of American Society of Anesthesiologists, TNM stage, between the two groups (all P>0.05). Perioperative variables and follow-up data were compared between two groups. Results:Between the vertical supraumbilical incision group and the left lower oblique incision group, the operation time [(131.7±3.7) minutes vs. (138.5±3.5) minutes], operative bleeding volume [(138.9±11.5) ml vs. (154.3±10.3) ml], length of auxiliary incision [(4.0±0.1) cm vs. (4.0±0.1) cm], and distance from anastomosis to dentate line [(3.8±0.1) cm vs. (4.2±0.1) cm] were not significantly different (all P>0.05). As compared to the left lower oblique incision group, patients in vertical supraumbilical incision group had earlier flatus [(62.7±2.3) hours vs. (69.2±1.7) hours, t=2.282, P=0.023], earlier ambulation [(41.9±1.8) hours vs. (46.78±1.42) hours, t=2.131, P=0.032], lower pain VAS scores at postoperative 24 hours (2.0±0.1 vs. 2.4±0.1, t=2.172, P=0.032) and 48 hours (2.7±0.1 vs. 3.0±0.1, P<0.05), and lower incidence of postoperative incisional hernia [6.7% (5/75) vs. 9.7% (10/103), χ 2=3.942, P=0.042]. However, the postoperative fluids intake time, hospitalization days, pain VAS scores at postoperative 12 hours and postoperative complications (wound infection, anastomotic leakage, urinary retention, intestinal obstruction) were not significantly different between the two groups (all P>0.05). Conclusion:The vertical supraumbilical incision in laparoscopic resection for rectal cancer can reduce the degree of postoperative pain, facilitate early recovery of intestinal function and decrease the incidence of incisional hernia.

Objective:To compared the short-term surgical outcomes of the vertical supraumbilical incision with the left lower oblique incision for specimen retrieval in laparoscopic resection for rectal cancer.Methods:A retrospective cohort study was performed. Inclusion criteria: (1) rectal cancer confirmed by colonoscopy and pathological examination; (2) undergoing the operation for the first time; (3) laparoscopic rectal surgery performed by the same surgeon team; (4) age of > 18 years and < 76 years old. According to above criteria, clinical data of 178 consecutive patients scheduled for laparoscopic surgery for rectal cancer at Department of Gastrointestinal Surgery of Renji Hospital between March 2015 and December 2017 were collected. Based on incision site of the mini-laparotomy, patients were classified to the vertical supraumbilical incision group (n=75) and the left lower oblique incision group ( n=103). There were no significant differences in baseline data, such as age, gender, body mass index (BMI), tumor diameter, preoperative carcinoembryonic antigen (CEA) level, score of American Society of Anesthesiologists, TNM stage, between the two groups (all P>0.05). Perioperative variables and follow-up data were compared between two groups. Results:Between the vertical supraumbilical incision group and the left lower oblique incision group, the operation time [(131.7±3.7) minutes vs. (138.5±3.5) minutes], operative bleeding volume [(138.9±11.5) ml vs. (154.3±10.3) ml], length of auxiliary incision [(4.0±0.1) cm vs. (4.0±0.1) cm], and distance from anastomosis to dentate line [(3.8±0.1) cm vs. (4.2±0.1) cm] were not significantly different (all P>0.05). As compared to the left lower oblique incision group, patients in vertical supraumbilical incision group had earlier flatus [(62.7±2.3) hours vs. (69.2±1.7) hours, t=2.282, P=0.023], earlier ambulation [(41.9±1.8) hours vs. (46.78±1.42) hours, t=2.131, P=0.032], lower pain VAS scores at postoperative 24 hours (2.0±0.1 vs. 2.4±0.1, t=2.172, P=0.032) and 48 hours (2.7±0.1 vs. 3.0±0.1, P<0.05), and lower incidence of postoperative incisional hernia [6.7% (5/75) vs. 9.7% (10/103), χ 2=3.942, P=0.042]. However, the postoperative fluids intake time, hospitalization days, pain VAS scores at postoperative 12 hours and postoperative complications (wound infection, anastomotic leakage, urinary retention, intestinal obstruction) were not significantly different between the two groups (all P>0.05). Conclusion:The vertical supraumbilical incision in laparoscopic resection for rectal cancer can reduce the degree of postoperative pain, facilitate early recovery of intestinal function and decrease the incidence of incisional hernia.

Crohn's disease(CD)is a chronic non-specific intestinal inflammatory disease,and the incidence of perianal fistulizing CD(PFCD)is 17%-43%. Non-cutting setons is the first choice for surgical treatment of PFCD. Some new surgical methods are effective for specific types of PFCD,however,the efficacy of most new methods remains to be confirmed by further studies. The multidisciplinary team(MDT)mode has become a new direction of PFCD surgery. This article reviewed the advances in surgical treatment of PFCD.

Objective To compare the short-term and long-term outcomes between laparoscopic and open total proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC).Methods The retrospective cohort study was conducted.The clinical data of 150 UC patients who underwent total proctocolectomy with IPAA in the Renji Hospital of Shanghai Jiaotong University between January 2003 and December 2016 were collected.Among 150 patients,87 undergoing laparoscopic total proctocolectomy with IPAA and 63 undergoing open total proctocolectomy with IPAA were respectively allocated into the laparoscopy group and open group.Observation indicators:(1) comparisons of intra-and post-operative situations;(2) postoperative complications;(3) follow-up situation.Follow-up using outpatient examination and telephone interview was performed to detect postoperative recovery and complications up to December 2017.Measurement data with normal distribution were represented as x-±s and comparison between groups was analyzed using the t test.Comparison between groups of count data was analyzed using the chi-square test.Results (1) Comparisons of intra-and post-operative situations:operation time,volume of intraoperative blood loss,time of initial intestinal stoma exsufflation and duration of hospital stay were respectively (306±3) minutes,(197± 12) mL,(62.1±1.8) hours,(8.2±0.4) days in the laparoscopy group and (224±4) minutes,(308±24) mL,(75.6±2.0) hours,(10.1±0.6) days in the open group,with statistically significant difference between groups (t =16.23,4.33,5.03,2.61,P＜ 0.05).All patients discharged successfully from hospital.All the 150 patients underwent stoma reversion of ileum at 3-12 months postoperatively,and the average time in the laparoscopy group and open group was respectively (6.0±5.6) months and (6.0±4.6)months,with no statistically significant difference between groups (t =0.01,P＞ 0.05).(2) Postoperative complications:cases with postoperative wound infection,retention of urine and frequency of defecation ＞ 4 times / day were respectively 2,8,21 in the laparoscopy group and 8,15,29 in the open group,with statistically significant differences between groups (x2 =5.25,4.37,0.96,P＜0.05).The cases with postoperative intestinal obstruction,anastomotic leakage,pelvic infection,pouch infection,pouch-related Crohn's disease and hyperplasia of ileal pouch were respectively 3,10,5,23,2,1 in the laparoscopy group and 8,7,4,24,1,0 in the open group,with no statistically significant differences between groups (x2=3.65,0.11,0.01,0.96,0.17,0.82,P＞0.05).Patients with postoperative complications were improved by acid suppression,fasting,anti-infection and fluid infusion.(3) Follow-up situation:150 patients were followed up for 12-60 months,with a median time of 48 months.There was no abnormality of postoperative anastomotic stoma and intestinal mucosa through comparison of colonoscopy results between pre-operation and 5 year postoperatively.During the follow-up,50 patients had shapeless stool and irregular defecation (times ＞ 4 times / day) at 3 years after stoma reversion of small intestine bypass,including 21 in the laparoscopy group and 29 in the open group,with a statistically significant differences between groups (x2 =4.72,P＜0.05).Eleven and 10 patients in the laparoscopy group and open group had shapeless stool and irregular defecation at 5 years postoperatively,but status were improved compared with the preoperative status,with no statistically significant difference between groups (x2=0.32,P ＞ 0.05).Conclusion The security of laparoscopic total proctocolectomy with IPAA for UC is equivalent to that of open total proctocolectomy,with the better short-term and long-term outcomes.

Equilibrative nucleoside transporters (ENTs), which facilitate cross-membrane transport of nucleosides and nucleoside-derived drugs, play an important role in the salvage pathways of nucleotide synthesis, cancer chemotherapy, and treatment for virus infections. Functional characterization of ENTs at the molecular level remains technically challenging and hence scant. In this study, we report successful purification and biochemical characterization of human equilibrative nucleoside transporter 1 (hENT1) in vitro. The HEK293F-derived, recombinant hENT1 is homogenous and functionally active in proteoliposome-based counter flow assays. hENT1 transports the substrate adenosine with a K of 215 ± 34 µmol/L and a V of 578 ± 23.4 nmol mg min. Adenosine uptake by hENT1 is competitively inhibited by nitrobenzylmercaptopurine ribonucleoside (NBMPR), nucleosides, deoxynucleosides, and nucleoside-derived anti-cancer and anti-viral drugs. Binding of hENT1 to adenosine, deoxyadenosine, and adenine by isothermal titration calorimetry is in general agreement with results of the competitive inhibition assays. These results validate hENT1 as a bona fide target for potential drug target and serve as a useful basis for future biophysical and structural studies.
Adenine Nucleotides ; chemistry ; metabolism ; Equilibrative Nucleoside Transporter 1 ; chemistry ; genetics ; metabolism ; HEK293 Cells ; Humans ; Protein Domains ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Structure-Activity Relationship

Objective To explore the optimal exercise way of improving the risk indicators of electrocardiogram (ECG) during exercise.Methods Twenty-four healthy male subjects aged between 40 and 49 years old were divided randomly into a control group (n=9),a low amount exercise group of 1200 kcal/wk (n=7) and a high amount exercise group of 2000 kcal/wk (n=8).The intensity of the exercise groups was 65％～ 80％VO2max training in the standard 400 m track for 12 weeks.The accelerometer and polar watch were worn to monitor the exercise process.During the exercise,the exercise amount was controlled using the distance and duration while the intensity was controlled using target heart rate.The subjects took part in the graded exercise test before and after the exercise intervention.Twelve lead electrocardiograms were used to measure the indicators of ST segment depression and corrected QT interval dispersion (QTcd) during the exercise.Results The exercise intervention did not result in significant change in ST segment depression,while the QTcd indicator in both the exercise groups decreased significantly after the intervention (P＜0.05).Moreover,the decrease of QTcd indicator in the low amount exercise group was significantly higher than that of the control group (P＜0.05),while the decrease of QTcd indicator in high volume group was higher than that of the control group (P＜0.01).No significant differences were found in the ST segment depression among the 3 different groups.Conclusion The Twelve-weeks exercise interventions with intensity of 65％ ～ 80％ VO2max and exercise amount of 1200 kcal/wk and 2000 kcal/wk have no effect on the ST segment depression during the exercise.However,they can result in significant decrease in the QTcd of ECG during exercise,reducing the risk of exercise-induced myocardial ischemia.