Analysis on the risk factors and establishment of a prediction model for primary non-response to the treatment of anti-tumor necrosis factor-α monoclonal antibody in Crohn′s disease patients / 中华消化杂志

Objective:To investigate the risk factors and establish a prediction model of primary non-response (PNR) to anti-tumor necrosis factor-α(TNF-α) monoclonal antibody in Crohn′s disease (CD) patients.Methods:From December 1, 2018 to July 31, 2022, 103 patients with CD treated with the anti-TNF-α monoclonal antibody in Renmin Hospital of Wuhan University were enrolled (modeling group), and at the same time, 109 patients with CD treated with anti-TNF-α monoclonal antibody in Zhongnan Hospital of Wuhan University were selected (validation group). The baseline clinical data of all the patients before the first treatment of anti-TNF-α monoclonal antibody were collected, which included C-reactive protein (CRP), the simplified Crohn′s disease activity index (CDAI), and modified multiplier simple endoscopic score for Crohn′s disease (MM-SES-CD), etc. Multivariate logistic regression was used to screen the independent risk factors of PNR in patients with CD treated with the anti-TNF-α monoclonal antibody, and to establish the nomograms prediction model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC), the net reclassification index (NRI), integrated discrimination improvement index (IDI), and decision curve analysis (DCA) were used to evaluate the predictive efficacy and clinical application value of the prediction model. DeLong test was used for statistical analysis.Results:The results of multivariate logistic regression analysis showed that high level of CRP ( OR=1.030, 95% confidence interval (95% CI) 1.002 to 1.059), simplified CDAI ( OR=1.399, 95% CI 1.023 to 1.913), and MM-SES-CD ( OR=1.100, 95% CI 1.025 to 1.181) in baseline were independent risk factors of PNR in patients with CD treated with the anti-TNF-α monoclonal antibody ( P=0.033, 0.036 and 0.008). The results of ROC analysis showed that the AUCs of CRP, simplified CDAI, MM-SES-CD, and the prediction model in the modeling group and the validation group were 0.697(95% CI 0.573 to 0.821), 0.772(95% CI 0.666 to 0.879), 0.819(95% CI 0.725 to 0.912), 0.869 (95% CI 0.786 to 0.951) and 0.856 (95% CI 0.756 to 0.955), respectively. The AUC of the prediction model in the modeling group was greater than those of CRP and simplified CDAI, and the differences were statistically significant ( Z=3.00 and 2.75, P=0.003 and 0.006), while compared with MM-SES-CD and the validation group, the differences were not statistically significant (both P>0.05). However, compared with MM-SES-CD, the NRI and IDI of the prediction model in the modeling group were 0.205(95% CI 0.002 to 0.409, P=0.048) and 0.098(95% CI 0.022 to 0.174, P=0.011), respectively, suggesting that the predictive ability of the prediction model was better than that of MM-SES-CD. The results of DCA indicated that the prediction model had significant clinical benefits in both the modeling group and the validation group. Conclusions:A prediction model was successfully constructed based on the independent risk factors for PNR in patients with CD treated with the anti-TNF-α monoclonal antibody. After verification, the prediction model has good prediction performance and significant clinical benefits.

Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study / 中华内科杂志

Objective:To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD).Methods:A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results:A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion:The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

A multicenter survey on the psychological status and quality of life of patients with inflammatory bowel disease in China / 中华消化杂志

Objective:To investigate the psychology status and quality of life in patients with inflammatory bowel disease(IBD) in China, and to analyze the influencing factors.Methods:From September 2021 to May 2022, 42 hospitals in 22 provinces(autonomous regions and municipalities directly under the central government) in China, the clinical data of 2 478 IBD patients were collected, which included age, gender, weight, first visit or not, disease activity, disease course, main clinical manifestations(diarrhea, abdominal pain, hematochezia, extraintestinal manifestations), complications, treatment medication(5-aminosalicylic acid, glucocorticoids, immunosuppressive agents, and biological agents), and whether to have surgery. Anxiety, depression, sleep quality and quality of life of IBD patients were evaluated by generalized anxiety disorder-7 items, patient health questionnaire-9 items, Pittsburgh sleep quality index and inflammatory bowel disease questionnaire, and the related influencing factors were analyzed. Univariate analysis and multiple linear regression analysis were used for statistical analysis.Results:The average age of 2 478 IBD patients was 37.96 years old, and male counted for 62.43%(1 547/2 478). There were 61.82%(1 532/2 478) of the IBD patients in the active stage of disease, mostly mild or moderate(588 and 734 cases). There were 60.61%(1 502/2 478) of the IBD patients with different degrees of anxiety, 58.35%(1 446/2 478) of the IBD patients with different degrees of depression, and 48.87%(1 211/2 478) of the IBD patients had different degrees of sleep problems. The results of multiple linear regression analysis indicated that female, higher level of disease activity and longer disease course were independent risk factors of anxiety, depression and sleep quality in the IBD patients(unstandardized regression coefficient(95% confidence interval) 1.08(0.65 to 1.50), 0.45(0.23 to 0.68), 0.19(0.02 to 0.36), 0.83(0.33 to 1.32), 0.62(0.36 to 0.88), 0.28(0.08 to 0.47), 0.47(0.16 to 0.77), 0.39(0.23 to 0.55), 0.14(0.02 to 0.26); P<0.001, <0.001, =0.025 , =0.001, <0.001, =0.005, =0.003, <0.001, =0.027). The usage of biological agents was an independent protective factor of anxiety(unstandardized regression coefficient(95% confidence interval) -0.67(-1.17 to -0.17), P=0.008), and older age was an independent risk factor of sleep quality(unstandardized regression coefficient(95% confidence interval) 0.35(0.09 to 0.61), P=0.008). Higher level of disease activity, symptoms of diarrhea, abdominal pain, presence of extraintestinal manifestations, usage of 5-aminosalicylic acid and glucocorticoid, and with surgical treatment were independent risk factors of quality of life(unstandardized regression coefficient(95% confidence interval) -11.00(-12.24 to -9.76), -2.90(-5.26 to -0.55), -3.93(-6.25 to -1.61), -5.79(-9.87 to -1.71), -4.78(-7.79 to -1.76), -7.71(-11.07 to -4.35), -4.37(-8.00 to -0.73); P<0.001, =0.016, =0.001, =0.005 , =0.002, <0.001, =0.019), while the usage of biological agents was an independent protective factor of quality of life (unstandardized regression coefficient(95% confidence interval) 4.72(1.97 to 7.48), P=0.001). Conclusion:IBD patients generally have different degrees of anxiety, depression and sleep problems, which affect the quality of life of patients. Gender, disease activity and disease course are the influencing factors of mental disorders in IBD patients.

The mechanism of microRNA-124-3p in regulating proliferation and invasion of gastric cancer cell by aryl hydrocarbon receptor-activated β-catenin pathway / 中华消化杂志

Objective:To explore the value of microRNA(miR)-124-3p and its target gene aryl hydrocarbon receptor (AHR) in the diagnosis and prognostic evaluation of gastric cancer, and the related molecular mechanisms in regulating proliferation and invasion of gastric cancer cell.Methods:The clinical and prognostic characteristics of patients with gastric adenocarcinoma expressing miR-124-3p were obtained from The Cancer Genome Atlas database and Genotype-Tissue Expression database. The correlation between miR-124-3p expression level and pathological stage, TNM stage, overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in patients with gastric adenocarcinoma were studied by bioinformatics analysis. The interaction sites between miR-124-3p and AHR mRNA were predicted by Target Scan 7.1 online tool. The target binding sites of miR-124-3p in AHR mRNA were verified by subcutaneous tumorigenesis experiment in mice, immunohistochemistry, dual luciferase assay, quantitative real time-polymerase chain reaction (RT-qPCR) and Western blotting. Nine male Balb/c nude mice, aged 4 to 6 weeks with weight of (18.43±0.29) g were injected with miR-124-3p simulant (miR-124-3p group), negative control simulant (negative control group) and 0.9% sodium chloride solution (sodium chloride control group) through the tail vein. Gastric cancer cell lines (MKN-45, AGS) were transfected with RNA simulants (including miR-124-3p simulant, negative control simulant and 0.9% sodium chloride solution). The expression of AHR and Catenin β 1 gene ( CTNNB1) at mRNA level, the expression of AHR and β-catenin at protein level in 3 mice groups and the effects of miR-124-3p transfection on the proliferation and invasion of transfected gastric cancer cells were analyzed. Pearson correlation analysis and Holm-Sidak corrected multiple t test were used for statistical analysis. Results:Low expression of miR-124-3p was positively correlated with severe pathological stages and TNM stages in patients with gastric adenocarcinoma ( R2=0.83 and 0.86, P=0.031 and 0.023). High expression of miR-124-3p was positively correlated with OS, DSS and PFI ( R2=1.00, 0.99 and 0.99, P=0.029, 0.044 and 0.049). The results of subcutaneous tumorigenesis experiment in mice demonstrated that the number of apoptotic cells in the tumor of miR-124-3p group was more than that of negative control group and sodium chloride control group ((43.33±1.86)/high power field (HPF) vs. (20.00±1.73)/HPF and (18.67±1.76)/HPF), and the differences were statistically significant ( t=8.55 and 8.33, P=0.013 and 0.014). The results of immunohistochemistry showed that the optical density of AHR protein in mice tumor tissue of miR-124-3p group was lower than that of negative control group and sodium chloride control group (0.081±0.008 vs. 0.276±0.019 and 0.273±0.018), and the differences were statistically significant ( t=9.06 and 7.51, P=0.012 and 0.017). The results of dual luciferase assay indicated that the fluorescence intensity in wild-type AHR MKN-45 cells transfected with miR-124-3p simulant was lower than that of negative control group (0.293±0.020 vs. 1.000±0.032), and the difference was statistically significant ( t=18.56, P<0.001). The results of RT-qPCR demonstrated that the mRNA levels of AHR and CTNNB1 in MKN-45 cells transfected with miR-124-3p simulant were both lower than those in untreated MKN-45 cells (0.51±0.09 vs. 1.02±0.02, 0.46±0.03 vs. 1.03±0.01), and the differences were statistically significant ( t=4.51 and 16.60, P=0.046 and 0.004). The results of Western blotting experiments showed that the relative protein expression levels of AHR and β-catenin of MKN-45 cells transfected with miR-124-3p simulant were lower than those of transfected with 0.9% sodium chloride solution and negative control simulant (3 332.94±81.25 vs. 9 041.60±439.79 and 8 276.54±562.52, 2 725.79±167.57 vs. 9 701.94±410.02 and 8 081.66±275.84), and the differences were statistically significant ( t=15.49, 7.91, 17.35 and 19.42, P=0.004, 0.016, 0.003 and 0.003). Conclusions:MiR-124-3p is correlated with diagnosis and prognosis of gastric cancer. MiR-124-3p induces apoptosis of gastric cancer cells in vitro and vivo by negatively regulating AHR expression at mRNA and protein level, thereby down-regulating the expression of CTNNB1 mRNA and β-catenin pathway-related protein. Therefore, miR-124-3p may become a potential diagnostic and prognostic marker of gastric cancer.

Application of the Glissonean pedicle approach based on the triangular area among the right anterior pedicle, the right posterior pedicle and the right hepatic vein in laparoscopic anatomical resection of right hepatic segments / 中华肝胆外科杂志

Objective:To study the use of the Glissonean pedicle approach based on the triangular area among the right anterior pedicle, the right posterior pedicle and the right hepatic vein ( "APR triangle" ), followed by indocyanine green fluorescence negative staining in laparoscopic anatomical resection of right hepatic segments.Methods:The clinical data of 34 patients with liver tumors who underwent laparoscopic anatomical right hepatic segmentectomy at the Chinese Academy of Medical Sciences and Peking Union Medical College from September 2020 to September 2021 were analyzed retrospectively. Of the 34 patients, there were 24 males and 10 females, aged (58.3±10.3) years old. Data on completion of operation, operation time, intraoperative blood loss, intraoperative blood transfusion, postoperative complications and postoperative hospital stay were collected.Results:All the 34 patients had malignant liver tumors, and they were successfully operated using total laparoscopic surgery. There was no conversion to open surgery. Three patients underwent segment V resection, 3 patients segment VI resection, 5 patients segment VII resection, 2 patients segment V + segment VI resection, 9 patients segment VI + segment VII resection, 3 patients segment V + segment VII resection, 5 patients segment V dorsal segment + segment VI + segment VII resection, 3 patients right posterior section resection + anterior dorsal segment resection and 1 patient anterior dorsal section resection. The operation time was (275.58±82.28) min, the amount of intraoperative blood loss was 100(100, 300) ml, and there were no patients requiring blood transfusion during the operation. Liquid food was started on the first day after operation, and out-of bed activities were carried out on the second to third days after operation. The Clavien Dindo classification of postoperative complications was grade I in 32 patients and grade III in 2 patients. The postoperative hospital stay was (7.23±3.10) d. All tumor margins were negative for malignancy. All the 34 patients were followed-up for (8.94±2.94) months. By the end of follow-up, 34 patients had survived without tumor recurrence.Conclusion:The right Glisson pedicle approach based on the "APR triangle" and the anatomical resection of right hepatic segments with fluorescence negative staining were safe and feasible.

Risk factors in predicting lymph node metastases in intrahepatic cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the risk factors of lymph node metastases in patients with intrahepatic cholangiocarcinoma (ICC) and to establish a risk prediction model of lymph node metastases in ICC.Methods:The clinicopathological data of 587 ICC patients who underwent radical hepatectomy and lymph node dissection at Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) from January 2007 to December 2011 were retrospectively analyzed. There were 395 males and 192 females with ages which ranged from 20 to 82 (54.7±10.8) years. Independent risk factors of lymph node metastases were studied using univariate and multivariate logistic regression analysis, and a risk prediction model was established. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of this model.Results:Of 587 patients, 158 (26.9%) had lymph node metastases. Multivariate logistic regression analysis showed that platelet count >300×10 9/L ( OR=1.985, 95% CI: 1.030-3.824, P=0.041), carbohydrate antigen 19-9 >37 U/ml ( OR=2.978, 95% CI: 1.994-4.448, P<0.001), tumor situated in left hemiliver ( OR=1.579, 95% CI: 1.065-2.341, P=0.023), multiple tumors ( OR=1.846, 95% CI: 1.225-2.783, P=0.003), and absence of cirrhosis ( OR=2.125, 95% CI: 1.192-3.783, P=0.011) were independent risk factors for lymph node metastases in ICC. The area under the ROC curve was 0.714, with a cutoff value of 0.215, and the sensitivity and specificity being 75.9% and 58.3%, respectively. Conclusions:The risk prediction model of ICC lymph node metastases was established using readily available clinical data obtained before operation. This model has good predictive values and can provide a reference for treatment decision on patients with ICC.

Influence of different options of preoperative biliary drainage on perioperative complications of patients with periampullary carcinoma undergoing pancreaticoduodenectomy / 中华肝胆外科杂志

Objective:To evaluate the effect of different options of preoperative biliary drainage (PBD) on perioperative complications of patients undergoing pancreaticoduodenectomy (PD).Methods:The clinical data of patients undergoing PD for periampullary carcinoma from January 2016 to November 2021 at Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) were retrospectively analyzed. The 303 patients including 199 males and 104 females, aged (64.2±8.8) years. According to PBD, the patients were divided into two groups: percutaneous transhepatic biliary drainage (PTBD) group ( n=228) and endoscopic retrograde cholangiopancreatography (ERCP) group ( n=75). PBD operation-related complications (including bleeding, biliary leakage, etc.), postoperative complications of PD (including pancreatic fistula, biliary leakage, surgical site infection, etc.) and perioperative complications (PBD operation-related complications + postoperative complications of PD) were compared between the two groups. Univariate and multivariate logistic regression analysis were used to analyze factors influencing perioperative complications of PD. Results:The incidence of PBD operation-related complications in PTBD group was 10.1% (23/228), lower than that in ERCP group 25.3%(19/228), and the difference was statistically significant (χ 2=10.99, P=0.001). The incidence of postoperative complications of PD in PTBD group was 38.2%(87/228), lower than that in ERCP group 69.3%(52/75), the difference was statistically significant (χ 2=22.09, P<0.001). The incidence of total perioperative complications in PTBD group was 44.3% (101/228), lower than that in ERCP group 73.3%(55/75), the difference was statistically significant (χ 2=19.05, P<0.001). Multivariate logistic regression analysis showed that patients with periampullary carcinoma undergoing ERCP biliary drainage and PD had increased risk of surgical site infection ( OR=2.86, 95% CI: 1.59-5.16, P<0.001) and pancreatic fistula ( OR=3.06, 95% CI: 1.21-7.74, P=0.018). Conclusion:ERCP biliary drainage is a risk factor for postoperative pancreatic fistula and surgical site infection in patients with periampullary carcinoma undergoing PD. PTBD should be recommended as the first choice for the patients underwent PD.

Clinical characteristics of 70 patients with coronavirus disease 2019 accompanied with diarrhea / 中华消化杂志

Objective:To retrospectively analyze the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) accompanied with diarrhea.Methods:From January 11 to February 6 in 2020, the clinical data of 663 patients diagnosed with COVID-19 admitted to Renmin Hospital of Wuhan University were collected and divided into diarrhea group and non-diarrhea group according to whether they had diarrhea or not. The differences in baseline characteristics, basic disease history, clinical manifestations, chest computed tomography (CT), laboratory findings, disease severity and mortality between the two groups were compared. Chi-square test and Fisher exact test were used for statistical analysis.Results:Among 663 COVID-19 patients, 70 (10.6%) patients accompanied with diarrhea. The proportion of fatigue and increased lactate dehydrogenase (LDH) levels of diarrhea group were higher than those of non-diarrhea group (58.6%, 41/70 vs. 28.2%, 167/593; and 64.2%, 43/67 vs. 50.4%, 277/550), and the differences were statistically significant ( χ2=26.891 and 4.566, both P<0.05). There was no statistically significant difference in the proportion of pneumonia in chest CT between diarrhea group and non-diarrhea group (100.0%, 62/62 vs. 99.4%, 529/532) ( P>0.05). There were no statistically significant differences in the proportions of mild and normal type, severe type and critical type between diarrhea group and non-diarrhea group (35.7%, 25/70 vs. 38.6%, 229/593; 50.0%, 35/70 vs. 47.2%, 280/593; and 14.3%, 10/70 vs. 14.2%, 84/593, respectively) (all P>0.05). There were no statistically significant differences in the mortality of mild and normal type, severe type and critical type between diarrhea group and non-diarrhea group (0 vs. 0.5%, 3/593; 0 vs. 0 and 1.4%, 1/70 vs. 3.5%, 21/593) (all P>0.05). Conclusions:Patients with COVID-19 accompanied with diarrhea are more likely to have fatigue and increased LDH level. Diarrhea is not significantly correlated with the disease severity of patients with COVID-19.

Analysis of clinical characteristics of asymptomatic carriers with 2019 novel coronavirus / 中华传染病杂志

Objective:To investigate the clinical characteristics of asymptomatic carriers with 2019 novel coronavirus (2019-nCoV), and to provide clinical guidance for the management of asymptomatic infection with 2019-nCoV.Methods:The clinical data of 663 patients with confirmed coronavirus disease 2019 (COVID-19) admitted to Renmin Hospital of Wuhan University from January 11 to February 6, 2020 were collected. Patients were divided into asymptomatic group (21 cases) and symptomatic group (642 cases) according to the diagnostic criteria. General conditions, clinical classification, death, chest computed tomograph (CT) and laboratory results of patients were retrospectively collected. Mann-Whitney U test, chi-square test and Fisher exact test were used for statistical analysis. Results:All 663 patients were positive for 2019-nCoV nucleic acid tests. The age of patients in the asymptomatic group were significantly younger than those in symptomatic group (35.0 (31.5, 58.0) years old vs 58.5 (45.0, 69.0) years old, U=4 234.500, P=0.002). The proportion of patients <30 years old in the two groups was significantly different (19.0%(4/21) vs 6.1%(39/642), Fisher exact test, P=0.047). There were 15 women (71.4%) in the asymptomatic group and 327 women (50.9%) in the symptomatic group, while the difference of gender distributions was not statistically significant ( χ2=3.420, P=0.064). In addition, among patients with asymptomatic infection, the proportions of mild/ordinary, severe and critical patients were 10 cases (47.6%), 10 cases (47.6%), and one case (4.8%), respectively, which were not significantly different from those in symptomatic group (244 cases (38.0%), 305 cases (47.5%) and 93 cases (14.5%), respectively, χ2=1.847, P=0.397). As of February 9, one(4.8%) mild/ordinary patient in the asymptomatic group died who had malignant tumor. Twenty-four (3.7%) patients in the symptomatic group died including two mild/ordinary and 22 critical patients. There was no significant difference in mortality between the two groups(Fisher exact test, P=0.560). CT examination was performed on 594 patients, and 591 cases (99.5%) showed unilateral or bilateral pneumonia, and three cases (0.5%) showed normal. Conclusions:Patients with asymptomatic infection with 2019-nCoV are younger than symptomatic patients, and there are more patients under 30 years old in the asymptomatic group. The absence of clinical symptoms is not significantly associated with clinical classifications and mortality in COVID-19 patients.

Effects of diagnostic delay on early disease course of Crohn's disease / 中华消化杂志

Objective To explore the effects of diagnostic delay on early disease course of Crohn's disease (CD ), and to analyze the risk factors related with the progress of early disease course. Methods From December 2014 to July 2017,a total of 56 patients in Renmin Hospital of Wuhan University initially diagnosed as CD were selected.The clinical manifestation,previous history,imaging examination, endoscopic examination and pathological results of the patients were collected after initial diagnosis of CD. CD-related surgery,CD-related rehospitalization and use of immunomodulators were followed.According to time interval between initial symptom onset and initial diagnosis,the patients were divided into diagnostic delay group (diagnostic delay time＞two years,14 cases)and non-diagnostic delay group (diagnostic delay time≤two years,42 cases).The clinical characteristics at initial diagnosis and early prognosis were compared between the two groups.The risk factors affecting early prognosis of CD patients were analyzed. Kaplan-Meier was used for prognosis analysis.Log-rank test and Cox proportional hazards model were performed to analyze factors affecting early prognosis.Results The results of imaging examination indicated that the proportion of intestinal injury of diagnostic delay group was significantly higher than that of non- diagnostic delay group (χ2＝ 4.49,P ＝ 0.03 ).During follow-up,the proportion of CD-related rehospitalization of diagnostic delay group was higher than that of non-diagnostic delay group,and the difference was statistically significant (χ2＝7.34,P＝0.01).During follow-up,the nine patients received surgery.The one-year and three-year cumulative incidence of surgery was 10.7% and 22.7%,respectively;one-year cumulative incidence of surgery in diagnostic delay group and non-diagnostic delay group was 38 .6%and 9 .6%,respectively.The results of Cox univariable and multivariable analyses both indicated that intestinal injury in imaging examination at diagnosis was the risk factor of surgery (both hazard ratio (HR)＝2.313,both P＜0.01).A total of 21 patients had CD-related rehospitalization during follow-up.And one-year and 31-month cumulative incidence of hospitalization was 27 .8% and 5 6 .3%,respectively;one-year cumulative incidence of CD-related rehospitalization in diagnostic delay group and non-diagnostic delay group was 43 .7% and 2 1 .6%,respectively;and the difference was statistically significant (χ2＝5 .88 ,P＝0.02).The results of Cox univariable analysis indicated that having systematic manifestation,intestinal inj ury in imaging examination and diagnostic delay were the risk factors of CD-related rehospitalization (HR＝2.972,2.313 and 1.403,all P＜0.05).The results of multivariable analysis indicated that having systematic manifestation and intestinal injury in imaging examination were independent risk factors of CD-related rehospitalization (HR＝3.891 and 2.541, P ＜ 0.01,respectively).Conclusions The proportion of intestinal injury of patients with diagnostic delay is high and the early prognosis is poor. Intestinal injury in imaging examination at initial diagnosis is independently risk factor of CD-related surgery and rehospitalization during follow-up.

Effects of siRNA inhibit HMGA1 gene expression on LX-2 cell biological functions / 重庆医学

Objective To investigate the effects of siRNA mediated HMGA 1 silence on proliferation and the gene expression of HMGA1 ,α-SMA and E-cadherin in activated hepatic stellate cells and its mechanisms .Methods Synthetic HMGA1 siRNA was transfected into LX-2 cells to silence the HMGA1 gene .The expression level of HMGA1 ,α-SMA and E-cadherin was determined by RT-PCR and Western blot experiments .LX-2 cell proliferation was assessed by M TT assay .Results The best inhibited effect was HMGA1-siRNA-1 .Compared with control group ,the cell proliferation and the mRNA and protein expression of HMGA 1 ,α-SMA in TGF-β1 group and TGF-β1 + NC-siRNA group were significantly increased (P 0 .05) ,while the expression of E-cadherin in TGF-β1 group and TGF-β1 + NC-siRNA group were significantly decreased compared with control group (P< 0 .05) .Meanwhile ,the cells in TGF-β1 + HMGA1 siRNA group showed significantly decreased proliferation level ,down-regulated mRNA and protein expression of HMGA 1 ,α-SMA but up-regulated expression of E-cadherin compared with TGF-β1 group and TGF-β1 + NC-siRNA group(P< 0 .05) .Conclusion HMGA1 interference could signifi-cantly down-regulate the expression of HMGA1 in LX-2 cells cultured with TGF-β1 ,thus inhibiting the proliferation and activation of the cells .

Research progress on RLRs in the treatment of multiple sclerosis / 天津医药

At present, the etiology and pathogenesis of multiple sclerosis are unclear. RIG-Ⅰ-like receptors are a new-ly discovered pattern recognition receptors (RLRs), which are located in cytoplasm. They can recognize the helicase of viral dsRNAs, and interact with interferon beta promoter stimulator (IPS)-1 through their caspase activation recruitment domain (CARD), then form IPS-1 signalsome and induce the expression of interferon typeⅠ(Ⅰ-IFN), thereby initiate innate im-mune response and induce antiviral response. Recent studies have found that mice lacking IPS-1 would develop exacerbated disease and accompanied by markedly higher inflammation, increasing axonal damage and demyelination. Furthermore, initi-ating the RIG-Ⅰ-like helicase receptor on the immune cells can alleviate inflammation and myelin fracture in multiple scle-rosis of mouse model, thus limit the incidence of paralysis. This paper is a review about the research progress on RLRs in the treatment of multiple sclerosis.

Research progress of miR-224 and tumor / 天津医药

miR-224 is a small noncoding RNA that usually binds to response element of target mRNA through the seed sequences,leading to the suppression of translation or mRNA degradation. Recent researches indicate that miR-224 not on?ly aberrantly expresses in multiple tumors(hepatocellular carcinoma,gastric carcinoma, diffuse large B-cell lymphoma, prostatecancer,colorectal cancer, etc),playing an important role in tumor suppressor or oncognen,but also has an effect on the chemosensitivity of tumor.In this article,we review recent studies about the mechanism of miR-224 in the tumor develop?ment ,progression and chemosensitivity.

Effects of xeroderma pigmentosum group D and p53 on replication of HBV / 中国病理生理杂志

AIM:To investigate the effects of xeroderma pigmentosum D ( XPD) and p53 on the replication of hepatitis B virus ( HBV) .METHODS:Recombinant plasmid pEGFP-N2/XPD and vacant vector plasmid pEGFP-N2 were transfected into HepG2.2.15 cells by liposome.On the next day, these cells were incubated with pifithrin-α, a p53 inhibi-tor, at a concentration of 20 μmol/L for 24 h.The cells were divided into 5 groups: blank control group, pEGFP-N2 group, pEGFP-N2/XPD group, pEGFP-N2/XPD+pifithrin-αgroup and pifithrin-αgroup.The mRNA expression of XPD, hepatitis B surface antigen ( HBsAg) , hepatitis B e antigen ( HBeAg) and hepatitis B virus X protein ( HBx) was detected by RT-PCR.The content of HBsAg and HBeAg in the supernatants of culture medium was measured by ELISA.The con-tent of HBV-DNA in the supernatants of culture medium was examined by fluorescence quantitative PCR.Using the method of bDNA, the content of HBV-DNA in the core particles was assessed.RESULTS:The expression of XPD mRNA was ele-vated by the transfection of recombinant plasmid pEGFP-N2/XPD.The increase in XPD expression significantly down-regu-lated the mRNA expression of HBsAg, HBeAg and HBx.The content of HBsAg and HBeAg in the supernatants of culture medium was significantly decreased by the increase in XPD expression.The results of fluorescence quantitative PCR showed that the content of HBV-DNA in the supernatants of culture medium was significantly down-regulated by the increase in XPD expression.bDNA results showed that the content of HBV-DNA in the core particles was significantly decreased by the increase in XPD expression.Pifithrin-αabolished the above-mentioned effects of XPD (all P<0.01).CONCLUSION:XPD inhibits the replication of HBV through p53 pathway.Therefore, XPD and p53 may be the targets for antiviral therapy of hepatitis B.

The Effects of Autophagy Inhibitor on Activation of Alcohol induced Hepatic Stellate Cells / 天津医药

Objective To observe the effect of autophagy inhibitor on the activation of alcohol induced hepatic stel-late cells, and the mechanisms thereof. Methods HSC-T6 cells were cultured in vitro and divided into four groups, includ-ing blank control group, alcohol group, 5 mmol/L 3-MA+alcohol group (low alcohol group) and 10 mmol/L 3-MA+alcohol group (high alcohol group). RT-PCR was used to detect the expression levels ofα-smooth muscle actin (α-SMA) and typeⅠcollagen. The levels of LC3Ⅱ,α-SMA and typeⅠcollagen were detected by Western blot assay. The cell viability of HSC-T6 was detected by MTT assay. Results The mRNA expressions ofα-SMA, typeⅠcollagen and the protein of expressionsα-SMA, typeⅠcollagen and LC3Ⅱwere significantly up-regulated in alcohol group compared with those of control group (P<0.05), while the expressions of those parameters were significantly down-regulated in 10 mmol/L 3-MA+alcohol group (P<0.01). The mRNA and protein levels ofα-SMA and typeⅠcollagen were significantly decreased in two 3-MA-treated groups compared with those in alcohol group (P<0.05). Meanwhile, compared with the 5 mmol/L 3-MA+alcohol group,the protein expressions ofα-SMA, typeⅠcollagen and LC3Ⅱwere significantly decreased in10 mmol/L 3-MA+alcohol group (P < 0.05 ). Compared with the alcohol group,there was significantly lower proliferation activity in all two 3-MA-treated groups (P<0.05). Conclusion 3-MA can inhibit the protein expression of LC3Ⅱ,α-SMA and typeⅠcollagen induced by alcohol in HSC-T6 cells, and inhibit the proliferation of HSC cells.

Reaserch progress of complement receptors involved in animal models of disease / 医学研究生学报

Complement receptor of the immunoglobulin superfamily ( CRIg) can regulate immune reactions via T cells and cy-tokines and is involved in various diseases .The effect of CRIg on the pathogenesis of immunological liver injury , intestinal ischemia-reperfusion injury , type Ⅰdiabetes mellitus , experimental autoimmune uveoretinitis , and rheumatoid arthritis etc .in animal models of disease are reviewed in this article .

Cyclooxygenase-2 Polymorphisms and Susceptibility to Colorectal Cancer: A Meta-Analysis

PURPOSE: Four polymorphisms, -765G>C, -1195G>A, 8473T>C, and Val511Ala, in the cyclooxygenase-2 (COX-2) gene were identified to be associated with colorectal cancer (CRC) risk. However, the results are inconsistent. The objective of this meta-analysis was to evaluate the association between these four polymorphisms and the risk of CRC. MATERIALS AND METHODS: All eligible case-control studies published up to December 2012 on the association between the four polymorphisms of COX-2 and CRC risk were identified by searching PubMed and Web of Science. The CRC risk associated with the four polymorphisms of the COX-2 gene was estimated for each study by odds ratio (OR) together with its 95 % confidence interval (CI), respectively. RESULTS: A total of 15 case-control studies were included. Overall, no evidence has indicated that the -1195A allele, -765C allele, 8473C allele, and 511Ala allele are associated with susceptibility to CRC (-1195G>A: OR=1.11, 95 % CI: 0.82-1.51, p=0.78; -765G>C: OR=1.08, 95 % CI: 0.96-1.21, p=0.07; 8473T>C: OR=1.03, 95 % CI: 0.89-1.18, p=0.91; Val511Ala: OR=0.71, 95 % CI: 0.46-1.09, p=0.94). However, stratified analysis with ethnicity indicated that individuals with -765GC or GC/CC genotypes had an increased risk of CRC among Asian populations (GC vs. GG: OR=1.05, 95 % CI: 0.87-1.28, p=0.03; GC+CC vs. GG: OR=1.08, 95 % CI: 0.96-1.21, p=0.07). CONCLUSION: This meta-analysis indicated that -765G>C polymorphism was significantly associated with susceptibility to CRC in Asian populations.

Bile duct injuries associated with vascular injuries in laparoscopic cholecystectomy / 中华肝胆外科杂志

Vascular injury is a severe complication when combined with biliary injuries in laparoscopic cholecystectomy. The most frequent injury is damage to the right branch of the hepatic artery. The incidence ranges between 6. 7% and 61.1%. When bile duct transection is combined with vascular injury, the clinical course is complicated by liver ischaemia or necrosis, biliary stricture, and liver lobar atrophy which sometimes necessitating liver resection or even transplantation. Reconstruction of vascular injury is helpful when the injury is identified early.

Clinical analysis of 61 cases of imported malaria / 中华全科医师杂志

Clinical data of 61 cases of imported malaria were analyzed retrospectively.Patients with malaria were divided into three groups,asymptomatic tertian (vivax) malaria,symptomatic tertian malaria and pernicious (falciparum) malaria.Only mild hepatic damage occurred in some patients with asymptomatic tertian malaria,compared with other groups Symptomatic tertian malaria and pernicious malaria were misdiagnosed in 6 of 20 and three of six,respectively before hospitalization,and 16 of 20 and four of six patients complicated with thrombocytopenia,respectively,and both of them had increased serum level of C-reactive protein (CRP).Platelet count negatively correlated with their serum level of CRP significantly in patients with symptomatic tertian malaria (r =-0.555,P ＜ 0.05).Routine anti-malaria therapy was used in imported malaria,blackwater fever occurred in two patients and acute renal failure occurred in one with falciparum malaria.It is suggested plasmodium exam ination in peripheral blood should be performed in all persons returned from countries prevalent with malaria,thrombocytopenia is an indicator of acute malaria,and more severe complications usually tend to occur in falciparum malaria.

The Growth Inhibition Induced by SUMO-1 siRNA in Hepatocellular Carcinoma Cell Line SMMC-7721 / 天津医药

Objective: To study the efficiency of silencing small ubiquitin-like modifier-1(SUMO-1) induced by siRNA in hepatocellular carcinoma cell line SMMC-7721 and the growth inhibition of SMMC-7721 thereof. Methods: The SUMO-1 siRNA was transfected into SMMC-7721 by means of lipofectamine~(TM) 2000. The silencing efficiency of SUMO-1 was examined by RT-PCR and western blot. The cell growth and cell cycle were examined by MTT and flow cytometry(FCM). The cell apoptosis was detected by DeadEnd~(TM) Colorimetric TUNEL System. Results: The siRNA could significantly silence the expression of SUMO-1 in SMMC-7721.The maximal silencing rate was utmost 73.43% at 48 hours after being transfected SUMO-1 siRNA. MTT assay revealed that the cell line grew more slowly. FCM result showed that the number of G_2 stage cells was increased significantly. But apoptosis cells were not found by TUNNEL assay. Conclusion: SiRNA is a good manner to silence the expression of SUMO-1 in SMMC-7721 in vitro. Owing to the growth inhibition induced by SUMO-1 siRNA, SUMO-1 plays an important role in development of SMMC-7721.