1.Effects of cyclooxygenase-2 on immunologic function of rats with sepsis
Bin LI ; Yumin LI ; Bin SHI ; Xun LI ; Wence ZHOU ; Xiaoliang ZHU ; Mingyan HE
Chinese Journal of Digestive Surgery 2008;7(2):126-129
Objective To study the expression of cyclooxygenase-2(COX-2)in hepatic inflammatory reaction and the effects of COX-2 on immunologic function of rats with sepsis.Methods Fifty-four Wistar rats were divided into sham group(n=6),sepsis group(n=24),and NS-398 intervention group(n=24).All rats were subjected to cecal ligation and puncture or sham operation.The expression of COX-2 mRNA in rat hepatic tissue was determined by RT-PCR,serum levels of IL-6,IL-10 and TNF-α were detected by ELISA,and percentage changes of CD4+,CD8+ cells by flow eytometry.The pathological changes of liver were observed at the same time.Results (1)Severe pathologic injuries of liver were observed in sepsis group,while not in NS-398 intervention group.(2)The expression of COX-2 mRNA was up-regulated in sepsis group and NS-398 intervention group,and the expression value was higher in sepsis group than that in NS-398 intervention group.The expression of COX-2 mRNA was the lowest in sham group.(3)The level of IL-6 was higher in sepsis group than that in sham group and NS-398 intervention group(F=125.582,134.712,54.760,121.441,P<0.05).(4)The level of IL-10 was higher in NS-398 intervention group than that in sham group and sepsis group(F=39.064,34.382,51.115,8.174,P<0.05).(5)The levels of TNF-α in sepsis group and NS-398 intervention group were increased,and the difference between the 2 groups had no statistical significance(x2=5.600,6.162,7.136,7.200,P>0.05).(6)The ratio of CD4+to CD8+ was higher in NS-398 group than that in sepsis group(F=17.448,15.055,30.068,64.210,P<0.05).Conclusions COX-2 plays an important role in the development of sepsis by changing the dynamic equilibrium between pro-inflammatory and anti-inflammatory cytokine and that between CD4+and CD8+.
2.Polymorphisms Val762Ala in PARP-1 and gastric cancer
Quanbao ZHANG ; Yumin LI ; Xun LI ; Wence ZHOU ; Bin SHI ; Hao CHEN ; Wenzhen YUAN
Chinese Journal of General Surgery 2008;23(9):706-709
Objective To investigate the frequency distribution of Val762Ala(T2444C)polymorphism among Han Chinese population in Gansu province,and to explore its relation to the suseeptibihty to gastric cancer. Methods A hospital-based,case-control study was performed involving 138 patients with gastric cancer and 110 healthy controls by PCR-RFLP method.Logistic regression and Chisquare analyses were used to assess OR and 95% CI. Results PARP-1762Ala allele was overexpressed in gastric cancer cases(11.5%)compared with controls(4.5%)(OR=3.012,95%CI 1.054-8.603,P=0.033).Statistic analysis showed increaged risk for gastric cancer patients with the 762Ala allele.Conclusion PARP-1 Val762Ala(T2444C)is related to the risk of gastric cancer,PARP-1762Ala allele could be used as a susceptibility marker for the development of gastric cancer.
3.Effects of cyclooxygenase-2 in ischemia reperfusion injury in liver transplantation in rat
Yumin LI ; Xiaoliang ZHU ; Xun LI ; Wence ZHOU ; Bin LI ; Bin SHI
Chinese Journal of Digestive Surgery 2009;8(1):43-46
Objective To investigate the expression and role of cyclooxygenase-2(COX-2)in the ischemia reperfusion in"ury in liver transplantation in rat.Methods Fifty-four male Wistar rats were divided into control group(n=6),liver transplantation group(n=24)and NS398 treated group(n=24)according to random number table.The expression of COX-2 mRNA was detected by RT-PCR,the distribution of COX-2 positive cells by immunohistochemistry.and the content of serum TNF-αand IL-10 by enzyme-linked immunosorbent assay.All the data were processed by one-way ANOVA.Results The serum indexes and changes of TNF-α.expression were in accordance with the histological injury of liver graft.The expression of COX-2 mRNA was essential to the ischemia reperfusion injury of the liver graft.Inhibition of the expression of COX-2 mRNA would aggravate the isehemia reperfusion injury of the liver graft.Conclusions COX-2 plays an important role in the ischemia reperfusion injury in liver transplantation.COX-2 may decrease the isehemia repertusion injury of liver graft.
4.Study of the characteristics of gastric carcinoma in Wuwei City of Gansu province
Yumin LI ; Bin SHI ; Xun LI ; Wence ZHOU ; Hu LIU ; Denghai MI
Chinese Journal of General Surgery 2001;0(09):-
Objective To study the pathological features and developmental tendency of gastric carcinoma(GC) in Wuwei City. Methods The clinical data of 7346 cases of GC found in 85427 cases undergoing endoscopy in Wuwei City from 1977 to 2000 were retrospectively analysed. Results The detectation rate of GC by endoscopy in Wuwei City was 8.7%. GC developed to a peak at 40~70 years of age(92.0%).In the GC cases, the Hp infection rate was 64.6%, which is higher than that in the area of low incidence of GC and the general population. Hp infection rate in poorly differentiated adenocarcinoma was higher than that in well differenciated type.Most GC(43.8%) were located in the proximal portion of the stomach. Poorly differentiated adenocarcinoma appeared to be the most common pathological type. Conclusions GC in Wuwei City is related to Hp infection. GC location has shifted from the distal to the proximal portion of the stomach in the last 23 years.
5.Clinical application value of difficulty score systems before laparoscopic liver resection
Zhilong SHI ; Hao XU ; Changpeng CHAI ; Sijie YANG ; Wence ZHOU
Journal of Clinical Hepatology 2021;37(8):1888-1893.
ObjectiveTo investigate the accuracy of three laparoscopic liver resection (LLR) difficulty score systems (DSSs) in evaluating surgical difficulty and predicting short-term postoperative outcome. MethodsThe retrospective cohort study was conducted for 142 patients who underwent LLR in The First Hospital of Lanzhou University from June 2015 to May 2020, and their preoperative, intraoperative, and postoperative clinical data were collected. According to preoperative clinical data, DSS-B score, Hasegawa score, and Halls score were used to determine the difficulty score of surgery for each patient, and then the patients were divided into low, medium, and high difficulty groups. Intraoperative data were compared between the three groups to verify the accuracy of the three DSSs, and postoperative clinical data were used to evaluate the ability of DSSs to predict short-term postoperative outcome. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple or two groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups, and the Bonferroni method was used for correction of P values between two groups. The receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated to evaluate the efficiency of each DSS in predicting postoperative complications. ResultsAmong the 142 patients, there were 37 patients in the low difficulty group, 56 in the medium difficulty group, and 49 in the high difficulty group based on DSS-B score; there were 70 patients in the low difficulty group, 47 in the medium difficulty group, and 25 in the high difficulty group based on Hasegawa score; there were 46 patients in the low difficulty group, 62 in the medium difficulty group, and 34 in the high difficulty group based on Halls score. For the low, medium, and high difficulty groups based on DSS-B score, Hasegawa score, or Halls score, time of operation, intraoperative blood loss, and rate of hepatic portal occlusion increased with the increase in difficulty score (all P<0.001); there was a significant difference in intraoperative blood transfusion rate between the medium and high difficulty groups based on DSS-B score (P<0.017), between the low and high difficulty groups based on Halls score (P<0.017), and between the low, medium, and high difficulty groups based on Hasegawa score (P<0.017). There was a significant difference in the rate of conversion to laparotomy between the medium and high difficulty groups based on DSS-B score (P<0.017), and Hasegawa score and Halls score identified the difference between the low and high difficulty groups (P<0.017). For the length of postoperative hospital stay, DSS-B score and Halls score only identified the difference between the low and high difficulty groups (P<0.05), while Hasegawa score identified the difference between the low difficulty group and the medium/high difficulty groups (P<0.05); for the incidence rate of postoperative complications, only Hasegawa score effectively identified the difference between the high difficulty group and the low/medium difficulty groups (P<0.017). DSS-B score, Halls score, and Hasegawa score had an AUC of 0.636 (95% confidence interval [CI]: 0.515-0.758), 0.557 (95% CI: 0.442-0.673), and 0.760 (95% CI: 0.654-0.866), respectively, in predicting postoperative complications, among which Hasegawa score had the highest predictive efficiency. ConclusionDSS-B score and Hasegawa score can better assess the difficulty of LLR, and Hasegawa score has an advantage in predicting short-term postoperative outcome.
6.Frontier and Future of Immunotherapy for Pancreatic Cancer
Wence ZHOU ; Hui ZHANG ; Xin LI ; Shi DONG
Cancer Research on Prevention and Treatment 2023;50(4):338-344
Pancreatic cancer remains as one of the most lethal malignancies. Resistance to conventional therapies has led to little improvement in the survival of pancreatic cancer patients over the past few decades. Immune-based treatment strategies for pancreatic cancer, such as immune-checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies show promise. Many immunotherapies have been explored in clinical trials, but they have yet to show significant therapeutic effects. Nevertheless, immunotherapy is inevitably the future of pancreatic cancer cure. This article introduces the current research progress and bottlenecks of immunotherapy for pancreatic cancer and puts forward further optimization directions and solutions. We hope to provide a reference for the future use of immunotherapy for pancreatic cancer.
7.Risk factors for common bile duct calculi recurrence and application value of its prediction model after endoscopic retrograde cholangiopancreatography
Wen XU ; Zhengfeng WANG ; Haiping WANG ; Long MIAO ; Zhilong SHI ; Wence ZHOU
Chinese Journal of Digestive Surgery 2021;20(8):890-897
Objective:To investigate the risk factors for common bile duct calculi recurrence and application value of its prediction model after endoscopic retrograde cholangiopancreato-graphy (ERCP) .Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 506 patients with common bile duct calculi who were admitted to the First Hospital of Lanzhou University from January 2015 to December 2017 for ERCP routine treatment were collected. There were 251 males and 255 females, aged (59±15)years. Patients received ERCP for common bile duct calculi. Observation indicators: (1) clinicopathological data of patients with common bile duct calculi; (2) risk factors for common bile duct calculi recurrence after ERCP; (3) establishment of prediction model for common bile duct calculi recurrence after ERCP. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate and multivariate analysis were conducted using the COX proportional hazard model. The prediction model for the recurrence of common bile duct stones after ERCP was established according to the coefficient of regression equation. The receiver operating characteristic curve(ROC) was drawed for efficiency evaluation with area under curve (AUC). Results:(1) Clinicopathological data of patients with common bile duct calculi: 104 of 506 patients with common bile duct calculi had recurrence and 402 had no recurrence. There were significant differences in the age, hyperlipidemia, common bile duct diameter, distal bile duct stricture, the number of calculi, gallbladder status, history of biliary tract surgery, endoscopic spinecterotomy, postoperative drainage mode between patients with and without recurrence ( Z=?2.844, χ2=6.243, Z=?2.897, χ2=11.631, 4.617, 16.589, 18.679, 2.070, 50.274, P<0.05). (2) Risk factors for common bile duct calculi recurrence after ERCP: Results of univariate analysis showed that age, time of first attack, hyperlipidemia, common bile duct diameter, distal bile duct stricture, the number of calculi, the maximum calculi diameter, gallbladder status, history of biliary tract surgery and postoperative biliary drainage mode were related factors for common bile duct calculi recurrence after ERCP ( hazard ratio=1.656, 2.179, 1.712, 1.657, 2.497, 1.509, 1.971, 2.635, 3.649,95% confidence interval as 1.113?2.463, 1.135?4.184, 1.122?2.644, 1.030?2.663, 1.501?4.154, 1.025?2.220, 1.122?3.464, 1.645?4.221, 1.575?8.456, P<0.05). Results of multivariate analysis showed that time of first attack <30 days, hyperlipidemia, distal bile duct stricture, history of biliary tract surgery and postoperative biliary drainage mode as cholangiopancreatic stent were independent risk factors for common bile duct calculi recurrence after ERCP ( hazard ratio=2.332, 1.676, 2.088, 2.566, 3.712, 95% confidence interval as 1.089?4.998, 1.060?2.649, 1.189?3.668, 1.456?4.521, 1.296?10.635, P<0.05). (3) Establishment of prediction model for common bile duct calculi recurrence after ERCP: based on multivariate analysis, indicators including time of first attack <30 days, hyperlipidemia, distal bile duct stricture, history of biliary tract surgery and postoperative biliary drainage mode as cholangiopancreatic stent were included into the coefficient of regression equation, and the prediction model for common bile duct calculi recurrence after ERCP was established: ln[(λ(t))/(λ 0(t))]=0.847×time of first attack+0.516×hyperlipidemia+0.736×distal bile duct stricture+0.942×history of biliary tract surgery+1.312×cholangiopancreatic stent. The perfor-mance evaluation showed that the AUC of ROC of prediction model was 0.757 (95% confidence interval as 0.713?0.811, P<0.05), and the optimal cut-off value was 1.41, the sensitivity and specificity were 69.2% and 72.9% respectively. Conclusions:The time of first attack <30 days, hyperlipidemia, distal bile duct stricture, history of biliary tract surgery and postoperative biliary drainage mode as cholangiopancreatic stent are independent risk factors for common bile duct calculi recurrence after ERCP. Patients with evaluation score >1.41 in prediction model were at high risk for common bile duct calculi recurrence after ERCP.
8.Tumor-associated macrophages in the pancreatic cancer microenvironment: potential therapeutic targets
Shi DONG ; Xin LI ; Yan DU ; Wence ZHOU
Chinese Journal of Hepatobiliary Surgery 2023;29(12):955-960
Pancreatic cancer is one of the deadliest gastrointestinal malignancies in the world. Although the standard of treatment has been improved, it is not enough to effectively improve the prognosis of patients. As a major component of tumor microenvironment, tumor-associated macrophage (TAM) plays an important role in the field of tumor development, invasion and metastasis, angiogenesis, chemotherapy resistance and immune escape, and are closely related to poor prognosis of patients. Therefore, in-depth exploration of the complex mechanism of TAM in pancreatic cancer immunotherapy may provide new insights into the regulation of pancreatic cancer microenvironment. This article comprehensively introduces the role and mechanism of TAM in the progression of pancreatic cancer, summarizes the pancreatic cancer treatment strategies for TAM and proposes further optimization schemes, hoping to provide a new direction and reference for TAM-based pancreatic cancer immunotherapy.
9.Effects of different treatment strategies on clinical outcomes in coronary heart disease patients aged over 75 years with coronary fractional flow reserve in the grey zone
Haiyan QIAN ; Ji HUANG ; Wenjian MA ; Wence SHI ; Zhiyao WEI ; Mengyue YU
Chinese Journal of Geriatrics 2020;39(3):273-276
Objective:To study the effects of conservative treatment versus percutaneous interventional treatment(PCI)on symptoms and prognosis of chronic coronary syndrome patients aged over 75 years with fractional flow reserve(FFR)in the grey zone(0.75≤FFR≤0.80).Methods:A total of 96 coronary heart disease(CHD)patients aged over 75 years undergone FFR examination in our hospital from January 2011 to December 2017 were retrospectively selected.All patients showed stenosis of 50%-90% in at least one main coronary artery and had FFR values within the range of 0.75-0.80(0.75≤FFR≤0.80). According to the treatment, patients were divided into the optimized medication group(OMT group, n=35)and the PCI group(n=61). The degree of angina alleviation assessed by the Seattle Angina Questionnaire(SAQ)and the incidence of major adverse cardiovascular endpoints(death, myocardial infarction, stroke, and repeated revascularization)were recorded during the one-year follow-up after treatment.Results:There was no significant difference in baseline data including age, gender and comorbidities between the OMT and PCI groups( P>0.05). The incidence of previous myocardial infarction, and the basal level of low-density lipoprotein cholesterol(LDL-C)were higher in the PCI group than in the OMT group( P<0.05). One-year follow-up showed that there was no significant difference between the OMT and PCI groups in the score of SAQ(77.6 ± 19.5 vs. 83.1 ± 22.8, P>0.05)and the incidence of composite MACEs(11.4% or 4 / 35 vs. 9.8% or 6/61, P>0.05). However, the incidence of repeated target vessel revascularization was lower in the PCI group than in the OMT group(1.6% or 1 case vs. 5.8% or 2 cases, P<0.05). Conclusions:In elderly CHD patients aged over 75 years with FFR values between 0.75-0.8 in the grey zone, optimal medication treatment has similar effects as the PCI on symptom alleviation, and no significant increase in composite MACEs is found at one-year follow-up.
10.The effect of SUMOylated peroxisome proliferator-activated receptor γ in the regulation of diabetes mellitus accelerated atherosclerosis
Dewei WU ; Wence SHI ; Fei SONG ; Jinggang XIA ; Chunlin YIN ; Mengyue YU
Chinese Journal of Postgraduates of Medicine 2022;45(3):263-270
Objective:To explore the role of SUMOylaiton of peroxisome proliferator-activated receptor γ (PPARγ) in diabetes mellitus prompted inflammation and atherosclerosis in vascular and endothelial cells.Methods:From September 2014 to January 2017, 32 Sprague-Dawley rats in 14 weeks-old were divided into sham operated group, artery injured without diabetes group, artery injured with diabetes group and ubiquitin-conjugating enzyme 9 (UBC9) transfection group (Group D) by random digits table method with 8 rats each. Model of type 1 diabetes mellitus (T1DM) and rat carotid artery balloon injury was made in the assigned group. One rat was excluded because of model failure in each group. Systolic and diastolic common carotid artery diameter and intimal thickness of injured and healthy common carotid artery were evaluated by vascular ultrasound, and the standardized common carotid artery diastolic diameter (sCADD) was calculated. Histological tests and immunohistochemical staining were performed to evaluate intimal hyperplasia, and the ratio of intimal area to media area was calculated when the media area was equal. Human umbilical vein endothelial cells (HUVEC) were cultured 24 h in high glucose medium with different duration and concentration, and the expression levels of interleukin (IL)-8 and IL-1β mRNA were determined by real time reverse transcription polymerase chain reaction (RT-PCR), the expression level of UBC9 was determined by Western blot method, SUMOylation assay kit was used to evaluate SUMOylation of PPARγ. HUVEC was cultured in vitro and PPAR was stimulated by high glucose at different concentrations and different times PPARγ SUMOylation level. UBC9 was overexpressed by lentivirus in vivo and in vitro, and the PPARγ SUMOylation level was detected.Results:The intimal thickness, intimal area and ratio of intimal area to media area 8 weeks after carotid artery injuring in sham operated group, artery injured without diabetes group and artery injured with diabetes group were increased respectively: (0.026 ± 0.018), (0.084 ± 0.007) and (0.264 ± 0.022) mm; (0.18 ± 0.09) × 10 6, (0.32 ± 0.06) × 10 6 and (1.64 ± 0.22)×10 6 μm 2; 0.345 ± 0.073, 0.570 ± 0.080 and 2.710 ± 0.220, the sCADD was decreased respectively: 0.903 ± 0.084, 0.800 ± 0.071 and 0.330 ± 0.036, and there were statistical differences ( F = 10.40, 9.40, 8.20 and 8.60; P<0.05). After HUVEC was cultured in high glucose for 24 h, the IL-8 mRNA at sugar concentrations of 10, 20 and 40 mmol/L was 1.00 ± 0.11, 3.57 ± 0.22 and 4.07 ± 0.40, the IL-1β mRNA was 1.00 ± 0.07, 3.32 ± 0.29 and 5.13 ± 0.19, and there were statistical differences ( F = 73.05 and 205.80, P<0.05). The level of PPARγ SUMOylation and UBC9 in artery injured with diabetes group were significantly lower than those in artery injured without diabetes group (0.46 ± 0.25 vs. 1.00 ± 0.21 and 0.45 ± 0.02 vs. 1.00 ± 0.07), and there were statistical differences ( P<0.05); there was no statistical difference in PPARγ between 2 groups (0.94 ± 0.07 vs. 1.00 ± 0.04, P>0.05). The UBC9 and PPARγ SUMOylation at sugar concentrations of 0, 10, 20 and 40 mmol/L were decreased respectively (0.99 ± 0.05, 0.80 ± 0.06 and 0.62 ± 0.05; 1.00 ± 0.05, 0.57 ± 0.13 and 0.55 ± 0.08), and there were statistical differences ( F = 21.02 and 14.31, P<0.05); there was no statistical difference in PPARγ (1.00 ± 0.03, 0.90 ± 0.04 and 0.91 ± 0.05; F = 3.11, P>0.05). In HUVEC cultured in high glucose medium (20 mmol/L) for 6, 12, 24 and 48 h, the UBC9 and PPARγ SUMOylation were downregulated progressively (1.00 ± 0.09, 0.75 ± 0.05, 0.70 ± 0.08, 0.38 ± 0.04 and 0.35 ± 0.03; 1.00 ± 0.03, 0.86 ± 0.01, 0.59 ± 0.01, 0.51 ± 0.11 and 0.35 ± 0.08), and there were statistical differences ( F = 36.06 and 33.13, P<0.05); but there was no statistical difference in PPARγ (1.00 ± 0.03, 1.14 ± 0.02, 1.18 ± 0.17, 0.98 ± 0.01 and 1.04 ± 0.05; F = 1.90, P>0.05). After overexpression of UBC9 in rats with diabetes, histological analysis showed that UBC9 in artery injured without diabetes group, artery injured with diabetes group and UBC9 transfection group was 1.53 ± 0.18, 1.00 ± 0.22 and 3.62 ± 0.35, there was statistical difference ( F = 5.64, P<0.05). Ultrasonic test results show that in artery injured without diabetes group, artery injured with diabetes group and UBC9 transfection group intimal thickness was increased respectively: (0.077 ± 0.015), (0.216 ± 0.007) and (0.125 ± 0.014) mm, and there was statistical difference ( F = 27.18, P<0.05). Histological analysis showed that intimal area in artery injured without diabetes group, artery injured with diabetes group and UBC9 transfection group was (0.335 ± 0.066) ×10 6, (1.053 ± 0.103) ×10 6 and (0.544 ± 0.040) ×10 6 μm 2, the ratio of intimal area to media area was 0.63 ± 0.063, 2.03 ± 0.052 and 0.93 ± 0.100, there were statistical differences ( F = 13.58 and 53.96, P<0.05). Conclusions:Diabetes mellitus could inhibit the PPARγ SUMOylaiton and prompt inflammation and atherosclerosis in vascular and endothelial cells. Upregulation of PPARγ SUMOylaiton though UBC9 overexpressioncould play a protecting role in diabetes mellitus prompted atherosclerosis.