ObjectiveTo investigate the influence of phosphoinositide 3-Kinase-C2-gamma (PI3Kγ)on pancreas acinar cells autophagy in experimental acute pancreatitis in mice and explore its significance.MethodsEighteen C57BL/6 wild type (WT) and eighteen PI3Kγ knockout (KO) mice were randomly divided into control group (n =6) and acute panereatitis (AP) group (n =12),respectively.AP models were induced by intraperitoneal injection of 50 μg cerulein/kg body weight,once the other hour for seven times.The mice were sacrificed 7 hours after model induction.The pathological changes of the pancreas were observed through microscope,LC3 dots were determined by immunofluorescence,the trypsin activity was measured by fluorescence spectrophotometer,and the expression of autophagy related protein beclin1,p62 and LC3- Ⅱ were measured by Western blot.ResultsThe autophagy vacuoles counts in pancreatic tissue of WT mice and KO mice were (5.14 ±0.85),(2.25 ±0.54)/HPF,the LC3 immunofluorescence dots counts were (78.6 ±9.38),( 26.4 ± 4.21 )/HPF,the trypsin activities were ( 0.827 ± 0.126 ),( 0.358 ± 0.098 ) pmol/mg protein,the difference between the two groups was statistically significant ( P ＜ 0.05 ).The p62 protein expression was greatly decreased in WT mice compared with their KO counterpart (0.11 vs 0.92,P ＜ 0.05 ),while the expressions of LC3 Ⅱ,beclin1 were greatly increased in WT mice compared with their KO counterpart ( 1.82 vs 0.93,1.43 vs 1.05,P ＜ 0.05 ).Conclusions PI 3 Kγmay up- regulate autophagy of pancreatic acinar cells during acute pancreatitis in mice,then promote trypsinogen activation and necrosis of acinar cells.

Objective To study the role and mechanism of phosphatidylinositide 3-kinase gamma (P13Kγ) in mediating acinar cell necrosis in rat models with acute pancreatitis.Methods Twelve male C57BL/6 wild-type and twelve male P13Ky knockout mice were randomly divided into saline group and pancreatitis group.The pancreatitis group received an intraperitoneal injection of cerulean (50 μg/kg) to induce acute panreatitis.Pathologic changes in the two groups were observed by measuring the trypsin,cathepsin B,and cathepsin L activity.The protein expressions of cathepsin B and cathepsin L were detected by the Western blot assay.Results Compared with the wild-type mice,the P13Kγγknockout mice had fewer acinar cell necrosis [(2.25± 0.54)/HP vs (5.14±0.85)/HP] and vacuoles [(1.24±0.21)/HP vs (2.36± 0.34)/HP]according to histology.The cathepsin B activity [(1232± 21)pmolAMC/min/mg vs (1891 ±35)pmolAMC/min/mg] and trypsin activity [(0.358± 0.098)pmol/mg vs (0.827± 0.126)pmol/mg] were significantly decreased in the pancreatitis group (P＜0.05) compared to the saline group.However,the cathepsin L activity [ (415 ±11 ) pmolAMC/ min/mg vs (346 ± 6)pmolAMC/min/mg] was significantly higher in P13Kγγ knockout mice than in wild-type mice(P＜0.01).Conclusions P13Kγmay promote cell necrosis in acute pancreatitis by possibly changing the balance between eathepsin B and cathepsin L levels to promote the activation of trypsinogen.

Objective To evaluate the value of endorectal ultrasound(ERUS)combined with real-time elastography in the staging of advanced rectal cancer in elderly patients.Methods A total of 50 patients with advanced rectal cancer underwent endorectal ultrasound and real-time tissue elastography imaging at our hospital from Jun.2014 to Oct.2015.Their staging results were compared with postoperative pathology.Results The accuracy,sensitivity and specificity of ERUS in the staging of advanced rectal cancer(T3)were 90％ (45/50),93.5％ (43/46)and 50％ (2/4),respectively.The accuracy,sensitivity and specificity of real-time elastography in the staging of advanced rectal cancer(T3)were 84％(42/50),89.1％(41/46)and 25％(1/4),respectively.With the combination of the two techniques,the accuracy,sensitivity and specificity in the staging of advanced recta[cancer(T3)were 96％ (48/50),97.8％ (45/46)and 75％ (3/4),respectively.There was no significant difference in accuracy and sensitivity(x2 ＝4.000 and 3.100,P＝0.373 and 0.542)between the three approaches.Kappa values between each of the three approaches and surgical pathology were 0.531,0.252 and 0.728,respectively.Conclusions Real-time tissue elastography in the diagnosis and staging of advanced rectal cancer can be enhanced when used in combination with endorectal ultrasound.

Objective To investigate the comparison of clinical effects between two models of alimentary reconstruction after total gastrectomy in the elderly patients with gastric cancer.Methods 70 patients receiving alimentary tract reconstructions of Orr-type Roux-en-Y reconstruction (Orrtype,40 cases) and modified Brawn Ⅰ (30 cases) from January 2007 to December 2012 were retrospectively analyzed.The operative time,amount of bleeding,early postoperative complications and mortality,food intake,nutritional status and alimentary tract function were compared at 6 months after surgery.Results There were no significant differences between the two methods in the operative time [(198.8±14.0)min vs 233.5±30.7)min,t=-l.697,P＞0.05)],amount of bleeding [(420 ± 43) ml vs (340 ± 25) ml t =-1.956,P ＞ 0.05],and early postoperative complications [(17.5％ vs 16.7％),x2 =0.008,P＞0.05].However,times of liquid diet intake and semi liquid diet intake of the Orr-type reconstruction method was comparatively shorter than that of the modified Brawn Ⅰ [(4.8±2.1) d vs (7.6±2.4) d,and (9.5±3.6) d vs (11.5±3.7) d,t=-5.192,P＜0.05)].Nutritional status (weight,hemoglobin,total serum proteins and serum albumin) at 6 months after operation showed no significant differences between the two methods.But constituent ratio of Visick scores Ⅰ-Ⅱ of Orr-type was bigger than that of modified Brawn Ⅰ (86.7％ vs 62.5％,x2 =5.063,P＞0.05).Conclusions Orr-type Roux-en-Y reconstruction method can avoid reflux esophagitis,and the procedure is more simple than the modified Brawn Ⅰ method.Therefore,Orr-type Roux-en-Y reconstruction should be recommended as an adoptable method of digestive reconstruction after total gastrectomy for gastric cancer in the elderly patients.

Objective:To compare the prediction efficiency of traditional linear regression model and four machine learning models on the learning behavior of clinical medical postgraduates, and to explore the pros and cons and applicability of different prediction models.Methods:A total of 6,922 clinical medical postgraduates were surveyed, their comprehensive learning behavior scores were obtained through the learning behavior scale. In the training set, Lasso linear regression and artificial neural network, decision tree, Bootstrap random forest, and lifting tree were used to build prediction models respectively. The above models were used to predict the validation set data and compare the prediction efficiency.Results:The comprehensive learning behavior score of clinical medical postgraduates was (3.31±0.54) points, and the overall compliance rate was 74.02%. In the linear regression model, the influence of age, school level, degree type, learning interest, pressure and satisfaction on learning behavior were statistically significant. In the prediction of validation set, the sensitivity, specificity, and accuracy of the linear regression model were 0.484, 0.914, and 0.801, respectively. The indexes of the four machine learning models were higher than those of the traditional linear regression model, and the Bootstrap random forest had the highest elevation.Conclusion:The linear regression model has a good prediction effect on learning behavior, and machine learning is superior to linear regression model in terms of accuracy of prediction. However, traditional linear regression models are superior to machine learning models in computational efficiency and interpretability.

Objective:To investigate the characteristics of gene mutations in colorectal cancer(CRC)patients by using next-generation generation sequencing(NGS).Methods:Blood and tissue samples were collected from 90 CRC patients admitted to Beijing Hospital between August 5, 2016 and December 29, 2020.Analysis of driver gene mutations was performed by using a 1021-gene NGS panel.Results:There were 43 tissue samples and 83 blood samples.Also, 36 patients had both tissue and blood samples.The frequency rates of KRAS and BRAF mutations were 51.2%(22/43)and 20.9%(9/43)in tissue samples, and 3 rare concomitant KRAS/ BRAF mutations were detected.The frequency rates of KRAS and BRAF mutations were 26.5%(22/83)and 10.8%(9/83)in blood samples.In patients with tissue and blood samples, the rates of KRAS and BRAF mutations were 52.8%(19/36)and 10.8%(8/36). Conclusions:The rate of KRAS mutations in tissue samples from colorectal cancer patients is similar to rates reported in the literature, but the rate of BRAF mutation and the rate of rare KRAS and BRAF co-mutations are higher than those reported from other countries.

OBJECTIVETo investigate the risk of postoperative complications in elderly colorectal cancer patients over 65 years with comorbid cardiovascular diseases.

METHODSA total of 381 elderly colorectal cancer patients over 65 years were pathologically diagnosed as colorectal adenocarcinoma and underwent the first surgery in Beijing Hospital during January 2013 and December 2014. Patients were divided into comorbid cardiovascular disease group (258 cases) and non-cardiovascular disease group (123 cases) according to the existence of comorbid cardiovascular disease. The morbidity of postoperative complication was compared between two groups.

RESULTSThere was no significant difference in the morbidity of postoperative complication between two groups [27.9%(72/258) vs. 29.3%(36/123), P>0.05]. According to the Clavien-Dindo classification of postoperative complications, the morbidities of complication at all levels between two groups were not significantly different(all P>0.05). But in terms of cardiovascular complications, the morbidity of comorbid cardiovascular disease group was significantly higher than that of non-cardiovascular disease group [7.4%(19/258) vs. 0.8%(1/123), χ=6.678, P=0.010], while no significant differences in pulmonary and abdominal complications were found between two groups(all P>0.05). The morbidities of other complications (deep vein thrombosis, urinary tract infection and renal complications, etc.) of comorbid cardiovascular disease group were lower than those in non-cardiovascular disease group [2.7%(7/258) vs. 8.1%(10/123), χ=5.733, P=0.017]. Different types of cardiovascular diseases, different levels of cardiac risk index and American Society of Anesthesiologists(ASA) rating were not significantly related to the patient's occurrence of postoperative complications(all P>0.05).

CONCLUSIONSSurgery treatment for elderly colorectal cancer patients over 65 years with comorbid cardiovascular diseases is safe. However, strict cardiovascular monitoring should be performed and necessary measures should be carried out in time.

Adenocarcinoma ; complications ; surgery ; Aged ; Aged, 80 and over ; Cardiovascular Diseases ; complications ; Colorectal Neoplasms ; complications ; surgery ; Comorbidity ; Digestive System Surgical Procedures ; adverse effects ; Female ; Humans ; Male ; Postoperative Complications ; epidemiology ; Risk Factors

Objective To evaluate the value of endorectal ultrasonography (ERUS) combined with real-time elastography in the diagnosis of benign and malignant rectal neoplasms in elderly patients.Methods Fifty-six consecutive patients with rectal neoplasms underwent ERUS and realtime tissue elastography at Beijing Hospital from February 2016 to December 2016.The imaging results were compared with results from postoperative or colonoscopic findings.Results Histopathological examinations identified 50 cases of adenocarcinomas,5 cases of adenomas and 1 case of neurilemmoma.The accuracy,sensitivity and specificity of ERUS in the diagnosis of benign and malignant rectal neoplasms were 89.3％ (50/56),92.0％ (46/50),and 66.7％ (4/6),respectively.The accuracy,sensitivity and specificity of real-time elastography in the diagnosis of benign and malignant rectal neoplasms were 80.4％ (45/56),82.0％ (41/50),and 66.7％ (4/6),respectively.However,there was no significant difference in sensitivity and specificity (x2 =3.20 and 0.50,P=0.074 and 0.480) between the two approaches.With the combination of ERUS and real-time elastography in the diagnosis of benign and malignant rectal neoplasms,the sensitivity and specificity were 75.4％ and 98.6％ for the series method and 88.9％ and 44.5％ for the parallel method.Conclusions Although elastography may not improve the accuracy of the diagnosis of benign and malignant rectal neoplasms,the strain information it provides can be used as a basis for subsequent diagnosis and treatment decisions.

OBJECTIVETo investigate the prophylactic and therapeutic effect of oxymatrine on experimental liver fibrosis and to reveal its mechanism.

METHODSBy establishing D-galactosamine-induced rat liver fibrosis model, we observed the effect of oxymatrine on serum and tissue biochemical indexes, content of liver hydroxyline, expression of TGF?1 mRNA and changes of tissue pathology.

RESULTSThere was a decline of liver hydroxyline and serum AST and ALT in oxymatrine group compared to those of the D-GalN group. The hydroxyline content in oxymatrine pretreatment group was (0.50 0.11)mug/mg compared with (0.99 0.14)mug/mg in D-GalN group (t=8.366, P<0.01). The content in oxymatrine treatment group was (0.44 0.04)mug/mg compared with 0.70 0.06 in D-GalN group (t=9.839, P<0.01). The SOD activity was (149.81 15.28) NU/mg in oxymatrine pretreatment group and (95.22 16.33) NU/mg in the model group (t=7.309, P<0.01); (157.68 19.54) NU/mg in the treatment group compared with (119.88 14.94) NU/mg in the model group (t=4.348, P<0.01). MDA in the pretreatment group was (2.06 0.17) nmol/mg, lower than (4.57 0.37) nmol/mg in the model group (t=17.529, P<0.01). In the treatment group, it was (1.76 0.24)nmol/mg, lower than (3.10 0.17) nmol/mg in the model group (t=12.697, P<0.01). TGF?1 mRNA reduced in the pretreatment and treatment groups as compared with that in the model group (0.21 0.01 vs 0.50 0.01, t=48.665, P<0.01; 0.18 0.02 vs 0.38 0.01, t=22.464, P<0.01). Electron microscopy showed that oxymatrine group had milder hepatocyte degeneration and less fibrosis accumulation than did the model group. Microscopy revealed wide septa expansion from the portal area to the central venous, piecemeal and confluent necrosis and pseudo-nodular formation in part of the lobular in the model group. While in oxymatrine group these lesions were much improved.

CONCLUSIONSOxymatrine shows prophylactic and therapeutic effect in D-galactosamine induced rat liver fibrosis. This is partly by protecting hepatocyte and suppressing fibrosis accumulation through anti-lipoperoxidation.

Alkaloids ; therapeutic use ; Animals ; Anti-Arrhythmia Agents ; therapeutic use ; Calcium Hydroxide ; metabolism ; Chemoprevention ; Disease Models, Animal ; Galactosamine ; Liver Cirrhosis ; chemically induced ; drug therapy ; metabolism ; pathology ; prevention & control ; Liver Function Tests ; Male ; Quinolizines ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta ; genetics ; metabolism