Utilizing network pharmacology, molecular docking, and cellular experimental validation, this study delved into the therapeutic efficacy and underlying mechanisms of matrine in combating senescence. Databases were utilized to predict targets related to the anti-senescence effects of matrine, resulting in the identification of 81 intersecting targets for matrine in the treatment of senescence. A protein-protein interaction(PPI) network was constructed, and key targets were screened based on degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on the key targets to elucidate the critical pathways involved in the anti-senescence effects of matrine. Molecular docking was conducted between matrine and key targets. A senescence model was established using human umbilical vein endothelial cells(HUVECs) induced with hydrogen peroxide(H_2O_2). Following treatment with varying concentrations of matrine(0.5, 1, and 2 mmol·L~(-1)), cell viability was assessed by using the CCK-8. SA-β-galactosidase staining was employed to observe the positive rate of senescent cells. Flow cytometry was utilized to measure the apoptosis rate. Real-time quantitative PCR(RT-PCR) was utilized to measure the mRNA expression of apoptosis-related cysteine peptidase 3(CASP3), albumin(ALB), glycogen synthase kinase 3β(GSK3B), CD44 molecule(CD44), and tumor necrosis factor-α(TNF-α). Western blot was performed to detect the protein expression of tumor protein p53(p53), cyclin-dependent kinase inhibitor 1A(p21), cyclin-dependent kinase inhibitor 2A(p16), and retinoblastoma tumor suppressor protein(pRb) in the senescence signaling pathway, p38 protein kinase(p38), c-Jun N-terminal kinase(JNK), and extracellular regulated protein kinases(ERK) in the mitogen-activated protein kinase(MAPK) pathway, and phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in the PI3K/Akt signaling pathway. The experimental results revealed that matrine significantly increased the viability of HUVECs(P<0.05), decreased the positive rate of senescent cells and the apoptosis rate(P<0.05), and reduced the mRNA expression levels of CASP3, ALB, GSK3B, CD44, and TNF-α(P<0.05). It also inhibited the protein expression of p53, p21, p16 and pRb in the senescence signaling pathway(P<0.05), upregulated the protein expression of p-PI3K/PI3K and p-Akt/Akt(P<0.05), and downregulated the protein expression of p-p38/p38, p-JNK/JNK, and p-ERK/ERK(P<0.05). Collectively, these findings suggest that matrine exerts an inhibitory effect on HUVECs senescence, and its mechanism involves the modulation of the senescence signaling pathway, MAPK pathway, and PI3K/Akt signaling pathway to suppress cell apoptosis and inflammation.
Humans ; Matrines ; Quinolizines/chemistry* ; Alkaloids/chemistry* ; Human Umbilical Vein Endothelial Cells/cytology* ; Cellular Senescence/drug effects* ; Network Pharmacology ; Molecular Docking Simulation ; Signal Transduction/drug effects* ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology*

Pancreatic ductal adenocarcinoma(PDAC)is one of the leading causes of cancer-related mortality worldwide,but current clinical methods lack effective screening and treatment options.Despite the widespread use of gemcitabine as a first-line chemotherapeutic agent in the treatment of PDAC over the past decade,its efficacy is limited by the development of drug resistance,which significantly shortens patient survival.This review systematically elucidates the critical role of the tumor microenvironment in the development of gemcitabine resistance of PDAC cells,highlighting the contributions of the extracellular matrix barrier,hypoxia-induced adaptive changes in cancer cells,and the formation of an immunosuppressive microenvironment as key factors in gemcitabine resistance.Additionally,we also introduce novel strategies for reversing chemoresistance,including advanced drug delivery systems,and provide a comprehensive overview of the current opportunities and challenges.

Objective To evaluate the effects of anterior cruciate ligament (ACL) reconstruction timing on the motor performance and proprioception by clinical evaluation as well as proprioception and motor performance tests on the patients more than 2 years after ACL reconstruction. Methods The patients who underwent ACL reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from January 2015 to January 2021 and met the inclusion criteria were followed up,and the postoperative data were collected retrospectively.Fifty-six patients who met the inclusion criteria were included in this study and categorized into two groups:early surgery (n=28,who underwent ACL reconstruction ≤3 weeks after injury) and delayed surgery (n=28,who underwent ACL reconstruction >3 weeks after injury).The basic information,clinical evaluation results,proprioception,and motor performance were compared between the two groups. Results The ACL return to sport after injury scale (ACL-RSI) score in the early surgery group was higher than that in the delayed surgery group [(68.68±22.04)scores vs. (55.82±24.87)scores,P=0.045].There was no difference in the range of motion of the knee joint,the positive rate of pivot shift test,or the scores of Tegner,Marx,Lysholm,knee injury and osteoarthritis outcome score (KOOS),and international knee documentation committee (IKDC) between the two groups (all P>0.05).Although there was no significant difference in range of motion of the knee joint between the two groups,the proportion of knee flexion and extension affected in the early surgery group was smaller than that in the delayed surgery group.Neither motor performance (isokinetic strength test,Y-balance test,and single-leg jump test) nor proprioception had difference between the two groups (all P>0.05). Conclusions Early ACL reconstruction outperformed delayed ACL reconstruction in improving the psychological health,emotions,and confidence in returning to sport,accelerating functional recovery of the patients.The timing of ACL reconstruction has no significant effect on the short-term postoperative knee stability,knee function,motor performance,or proprioceptive recovery of the patients.Early ACL reconstruction is recommended for improving the clinical outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Proprioception/physiology* ; Retrospective Studies ; Male ; Female ; Range of Motion, Articular ; Anterior Cruciate Ligament Injuries/physiopathology* ; Adult ; Postoperative Period ; Time Factors ; Return to Sport ; Recovery of Function ; Knee Joint/physiopathology* ; Young Adult

Objective To evaluate the effects of knee flexor and extensor strength on the subjective function and motor performance of knees after anterior cruciate ligament reconstruction. Methods A total of 53 patients who underwent anterior cruciate ligament reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from June 2015 to June 2021 and met the inclusion criteria were enrolled in this study.The patients were followed up time for at least 2 years.An isometric muscle strength test system was used to measure the strength of bilateral quadriceps and hamstring muscles.The patients were grouped according to whether the limb symmetry index (LSI) of peak torque of quadriceps and hamstring muscle reached 85% at an angular velocity of 60°/s.Specifically,26 patients were classified into group A (LSI≥85%) and 27 patients were classified into group B (LSI<85%).The subjective function and motor performance of knees were compared between the two groups. Results In terms of subjective function of knees,the international knee documentation committee (IKDC) score (88.76±9.93 vs. 81.08±12.57,P=0.017) and knee injury and osteoarthritis outcome score (KOOS) (86.27±8.96 vs. 80.22±11.31,P=0.036) were different between groups A and B.There was no significant difference in Lysholm score [95.0 (79.8,100.00) vs. 86.00 (66.00,100.00),P=0.238],ACL return to sports after injury scale score (66.08±22.25 vs. 61.12±23.53,P=0.434),Marx score [6.00 (4.75,7.00) vs. 6.00 (4.00,7.00),P=0.805] or Tegner activity score [8.00 (4.00,12.00) vs. 4.00 (2.00,12.00),P=0.566] between the two groups.In terms of motor performance,the single-leg triple hop LSI (0.92±0.13 vs. 0.81±0.18,P=0.016) and single-leg crossover hop LSI (0.96±0.12 vs. 0.84±0.22,P=0.021) showed significant differences between groups A and B,while there was no significant difference in single-leg hop LSI (0.90±0.18 vs. 0.79±0.25,P=0.116) between the two groups.In addition,there was no statistical significance in proprioception [30°:8.83±4.66 vs. 10.73±4.63,P=0.143;45°:6.94±3.82 vs. 7.66±3.93,P=0.504;60°:4.10 (3.20,4.72) vs. 3.90 (2.30,5.20),P=0.493] or Y-balance test results [anterior LSI:0.98 (0.84,1.02) vs. 0.94 (0.86,0.98),P=0.328;posterolateral LSI:1.00±0.08 vs. 0.97±0.07,P=0.249;posteromedial LSI:1.00 (0.97,1.03) vs. 0.96 (0.93,1.03),P=0.179] between groups A and B. Conclusion The patients with good symmetry of quadriceps and hamstring muscle strength after anterior cruciate ligament reconstruction had better subjective function and movement performance of knees than the patients with poor symmetry,which was mainly reflected in the IKDC score,KOOS,single-leg triple hop,and single-leg crossover hop.
Humans ; Anterior Cruciate Ligament Reconstruction ; Muscle Strength/physiology* ; Male ; Quadriceps Muscle/physiology* ; Female ; Adult ; Anterior Cruciate Ligament Injuries/physiopathology* ; Hamstring Muscles/physiopathology* ; Knee Joint/physiopathology* ; Anterior Cruciate Ligament/physiopathology* ; Torque ; Knee/physiopathology*

ObjectiveTo investigate the mRNA expression levels of various aquaporins （AQPs） in luteinized granulosa cells from follicles of different diameters. MethodsFrom March 25， 2022 to September 23， 2022 in our reproductive medicine center， 48 women undergoing in-vitro fertilization （IVF） were enrolled and divided into the antagonist group and the agonist group according to the ovarian stimulation protocol. Follicular fluid samples were collected on the day of oocyte pick-up and granulosa cells were extracted from follicles of different diameters： small （<13 mm）， medium （13~18 mm） and large （≥18 mm）. After RNA quantification， 22 cases （66 samples） were included for analysis and mRNA expression levels of AQPs were compared among the three follicle groups. ResultsThe mRNA expression of aquaporin 2 （AQP2） in luteinized granulosa cells increased with the increase of follicle diameter （linear trend P = 0.004） and the difference was statistically significant between two groups of large and small follicles （P = 0.017）. Statistical difference was found in the antagonist group （P = 0.049 6）， but not in the agonist group （P = 0.108）. ConclusionThe mRNA level of AQP2 in luteinized granulosa cells increases with the increase of follicle diameter and its expression is related to the ovarian stimulation protocol， suggesting that AQP2 may play a role in follicle growth and follicular fluid formation， and its mRNA expression level may be regulated by follicle stimulating hormone （FSH） and luteinizing hormone （LH）.

ObjectiveThe fractional flow reserve （FFR） computed from coronary computed tomographic （CT） angiograms makes it possible to noninvasively assess coronary artery disease， but the impact of plaque on FFR derived from computed tomography angiography （CTA） is still unknown. The study used invasive FFR as the reference standard to analyze the impact of plaque on coronary computed tomography angiography （CCTA）-based quantitative flow ratio （CT-QFR）. MethodsThe retrospective study included 108 patients with suspected coronary heart disease （CHD） who underwent both CCTA and FFR within 60 days. CCTA images were analyzed by the software. We obtained the CT-QFR of target vessels， perfomed the quantitative and qualitative analyses on target vascular plaques， including total plaque volume （TPV）， plaque burden， calcified plaque volume （CPV）， fibrous plaque volume （FPV）， lipid plaque volume （LPV）， and the presence or absence of high-risk plaque. ResultsAccording to the difference between CT-QFR and FFR at blood vessel level， 137 target vessels of 108 patients were divided into the overestimated group （difference＞0.03， n＝29）， reference group （-0.03≤difference≤0.03， n＝88） and underestimated group （difference＜-0.03， n＝20）. The underestimated group （14.81mm³） presented higher LPV than overestimated group （1.97mm³， P < 0.05）. There was a negative correlation between LPV and the difference （P＜0.05）. ConclusionsWhen CT-QFR is used to estimate hemodynamics of coronary artery stenosis， the presence of lipid plaque may underestimate the virtual FFR.

ObjectiveTo investigate the perioperative safety and complications of radical cystectomy （RC）. MethodsThe clinicopathological indexes， postoperative complications and prognosis of patients who underwent RC at Sun Yat-sen University Cancer Centre from January 2001 to August 2020 were retrospectively collected and analyzed. Among them， patients from 2011 to 2020 were further analyzed and compared according to the open surgery group （ORC）， laparoscopic group （LRC） and robot-assisted laparoscopic group （RARC）. Independent sample t test， Chi-square test， K-M survival curve and other statistical methods were used to describe the complications and prognosis of patients， and Logistic regression was used to analyze the influencing factors of complications of RC. ResultsAmong the 1041 patients who underwent RC surgery from 2001 to 2020， the median age was 63 （55-69） years. In terms of the gender ratio， men were the majority at 86 percent. Compared with that of the first 10 years， the complication rate of the second 10 years decreased significantly （37.4% vs. 26.7%）. Complications of 667 patients who underwent RC surgery were analyzed from 2010 to 2020， with a median follow-up of 34 months. A total of 415 patients were enrolled in the ORC group， 161 in the LRC group， and 91 in the RARC group. Ileal conduit （659 cases， 63.3%） accounted for the highest proportion of all urinary diversion methods， while orthotopic neobladder accounted for the second （343 cases， 32.9%）. The incidence of all grade complications was 30.5%， and the most common complication was urinary complications. The incidence of total complications and grade ≥3 complications in the ORC group was higher than that in the LRC and RARC groups （Total complications： ORC， 30.8%； LRC，21.1%， RARC，24.2%； P=0.047； Grade ≥3 complications： ORC， 14.7%； LRC，9.3%； RARC，6.6%； P=0.043）. ConclusionsWith the improvement of surgical techniques and experience， the incidence of recent postoperative complications after radical resection of bladder cancer in our center has decreased. Compared with open surgery， minimally invasive surgery has some advantages in reducing the complication rate.

Objective: To Summarize the safety, clinical outcome and technical evolution of laparoscopic gastric cancer surgery. Methods: A retrospective cohort study was carried out. Clinical data of 3012 patients who underwent laparoscopic radical gastrectomy for gastric cancer from January 2010 to March 2022 at Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University were retrospectively collected and analyzed. Case inclusion criteria were gastric malignancies confirmed by pathology, without distant metastasis by examination before operation and exploration during operation, patients undergoing laparoscopic radical gastrectomy, intact function of important organs and with complete data. Exclusion criteria were patients who underwent emergency gastric cancer resection due to gastric bleeding, perforation or obstruction, etc., tumor found to invade adjacent organs such as pancreas or transverse colon during the operation, conversion to open surgery during the operation, those who had other malignant tumors (except thyroid cancer) within 5 years, and those had severe cardiopulmonary, liver, or kidney insufficiency before surgery. Outcomes included: (1) baseline information of patients; (2) trend of the quantity of laparoscopic radical gastrectomy year by year; (3) evolution of the mode of digestive tract reconstruction; (4) periopertive outcome short-term complication was defined as complication occurring within 30 days after operation and classified accordiny to the clavien-Dindo criteria; and (5) 5-year overall survival. SPSS software was used for statistical analysis. Continuous variables that obeyed the normal distribution were expressed in the form of Mean±SD. Days of hospital stay that did not follow a normal distribution were expressed as median (Q₁,Q₃), and the Mann-Whiney U test was used for comparison. Discrete variables were expressed as cases (%), and chi-square test or rank sum test was used for comparison between groups. Linear regression analysis was used to analyze the relationship between the amount of surgery and the year of surgery. Kaplan-Meier method and log-rank test were used for survival analysis. Two-tailed P<0.05 was considered as statistically significant. Results: Among the 3012 cases, 2114 were male and 898 were female. The patients' average age at surgery was (61.1±10.7) years old. According to the number of cumulative cases, the patients were divided into three groups: early, intermediate and late, with 1004 patients in each group. The early group consisted of patients undergoing operation from January 2010 to October 2018, the intermediate group consisted of patients undergoing operation from October 2018 to January 2021, and the late group consisted of patients undergoing operation from January 2021 to March 2022. (1) General information: There were 691 (68.8%), 699 (69.6%) and 724 (72.1%) male patients in early, intermediate and late groups respectively; the average age increased from 56.6 years in 2010 to 62.8 years in March 2022. As for the tumor stage T1, T2, T3, T4, there were 49.0%, 14.4%, 23.9% and 12.6% in the early group; 47.5%, 12.9%, 26.9% and 12.6% in the intermediate group; 39.7%, 14.6%, 30.0%, and 15.6% in the late group, respectively. Patients with N0, N1, N2, N3a, N3b stage were 56.8%, 13.7%, 13.4%, 11.0%, and 5.0% in the early group; 55.7%, 12.9%, 12.8%, 11.6%, and 6.9% in the intermediate group; 51.0%, 16.1%, 12.8%, 12.5%, and 7.5% in the late group, respectively. (2) Year-by-year change in the number of gastric cancer operations: From 19 cases per year in 2010 to 786 per year in 2021, the annual number of gastric cancer operations was proportional to the year of operation (y=47.505x, R²=0.67). The proportion of patients with stage I disease showed a fluctuating downward trend over time, while the proportion of patients with stage III disease increased slightly, accounting for 34% until March 2022. (3) Evolution of digestive tract reconstruction methods: Except in 2010, the digestive tract reconstruction method of distal gastrectomy focused on Billroth-II+Braun anastomosis among patients undergoing laparoscopic gastric cancer surgery in other years, whose proportion had gradually increased from less than 20% in 2016 to about 70% after 2021; the gastrointestinal reconstruction methods after total gastrectomy had gradually increased in π anastomosis and overlap anastomosis since 2016, of which π anastomosis reached about 65% in 2019, and overlap anastomosis reached almost 30% in 2020; the anastomosis methods after proximal gastrectomy had been mainly double-channel anastomosis (54%) and esophagogastric anastomosis (30%) since 2016, and double-channel anastomosis accounted for up to 70% in 2019. (4) Operation time: The operation time of early, intermediate and late group was (193.3±49.8) min, (186.9±44.3) min and (206.7±51.4) min respectively. Intermediate group was significantly shorter than early group (t=3.005, P=0.003), while late group was significantly longer than early group (t=5.875, P<0.001) and intermediate group (t=9.180, P<0.001). (5) Postoperative hospital stay: The median length of hospital stay for gastric cancer patients in early, intermediate and late groups was 9 (8, 11) d, 8 (7, 10) d, and 8 (7.5, 10) d respectively. The postoperative hospital stay of intermediate group and late group was significantly shorter than that of early group (Z=-12.467, Z=-5.981, both P<0.001), but there was no significant difference between intermediate group and late group (Z=0.415,P=0.678). (6) Postoperative complication: The morbidity of short-term complication in early, intermediate and late group was 20.4% (205/1004), 16.2% (163/1004), and 16.2% (162/1004) respectively, and above morbidity of intermediate group and late group was significantly lower than that of early group (χ²=5.869, P=0.015; χ²=6.165, P=0.013), while there was no significant difference between intermediate group and late group (χ²=0.004,P=0.952). The morbidity of short-term complication of grade IIIor higher was 8.0% (80/1004), 7.6% (76/1004), and 4.9% (49/1004) in early, intermediate and late group respectively, and above morbidity of late group was significantly lower than that of early and intermediate group (χ²=7.965, P=0.005; χ²=6.219,P=0.013), while there was no significant difference between intermediate group and early group (χ²=0.111,P=0.739). (7) Survival analysis: The follow-up deadline for survival data was December 31, 2021, and the median follow-up time was 29.5 months. The overall 5-year survival rate of all the patients was 74.7%. The 5-year survival rates of stage I, II and III patients were 92.0%, 77.2%, and 40.3% respectively and 5-year survival rates of patients with stage IA, IB, IIA, IIB, IIIA, IIIB and IIIC were 93.2%, 87.8%, 81.1%, 72.7%, 46.2%, 37.1%, and 34.0% respectively. Conclusions: The number of laparoscopic gastric cancer operation in our center is increasing year by year. With the maturity of laparoscopic technology, the morbidity of complication in laparoscopic gastric cancer surgery is decreasing.
Aged ; Data Analysis ; Female ; Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome

Objective: To explore the efficacy and feasibility of transanal hand-sewn reinforcement of low stapled anastomosis in preventing anastomotic leak after transanal total mesorectal excision (taTME). Methods: A descriptive cohort study was conducted. Clinical data of 51 patients with rectal cancer who underwent taTME with transanal hand-sewn reinforcement of low stapled anastomosis at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2020 were retrospectively collected. Inclusion criteria: (1) age >18 years old; (2) rectal cancer confirmed by preoperative pathology; (3) distance from tumor to anal verge ≤ 8 cm according to pelvic MR; (4) the lesion was evaluated to be resectable before operation; (5) with or without neoadjuvant chemotherapy and radiotherapy; (6) taTME, end-to-end stapled anastomosis, and reinforcement in the anastomosis with absorbable thread intermittently were performed, and the distance between anastomosis and anal verge was ≤ 5 cm. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) emergency surgery due to intestinal obstruction, bleeding or perforation; (3) patients with local recurrence or distant metastasis; (4) the period of postoperative follow-up less than 3 months. The procedure of transanal hand-sewn reinforcement was as follows: firstly, no sign of bleeding was confirmed after checking the anastomosis. Then, the anastomosis was reinforced by suturing the muscle layer of rectum intermittently in a figure-of-eight manner using 3-0 single Vicryl. The entry site of the next suture was close next to the exit site of the last one. Any weak point of the anastomosis could also be reinforced according to the specimen from the circular stapler. The primary outcome were the incidence of anastomotic leak, methods of the secondary operation, anastomotic infection, anastomotic stricture, and conditions of Intraoperative and postoperative. Results: All the 51 enrolled patients completed surgery successfully without any conversion to open surgery. The median operative time was 169 (109-337) minutes, and the median intraoperative blood loss was 50 (10-600) ml. The median postoperative hospital stay was 8 (5-16) days. The mssorectum was complete and distal resection margin was negative in all patients. Postive circumferential resection margin was observed in 1 patients (2.0%). Twelve (23.5%) patients underwent prophylactic ileostomy. One patient developed anastomosis stricture which was cured by digital dilatation of the anastomosis. ISREC grade C anastomotic leak was observed in 3 (5.9%) male patients, of whom 2 cases did not received prophylactic ileostomy during the operation, and were cured by a second operation with the ileostomy and anastomotic repair. The other one healed by transanal repair of the anastomosis and anti-infection therapy. One (2.0%) patient suffered from perianal infection and healed by sitz bath and anti-infection therapy. No death was reported within 30 days after operation. Conclusion: Transanal hand-sewn reinforcement in low rectal stapled anastomosis in preventing anastomotic leak after taTME is safe and feasible.
Adolescent ; Anal Canal/surgery* ; Anastomosis, Surgical ; Anastomotic Leak/prevention & control* ; Cohort Studies ; Humans ; Laparoscopy ; Male ; Postoperative Complications/prevention & control* ; Rectal Neoplasms/surgery* ; Rectum/surgery* ; Retrospective Studies ; Treatment Outcome