Background::Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods::We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results::We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1, X 2, and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions::ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC.Registration::Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Gastrointestinal cancers are the common malignant tumors of the digestive system, and their morbidity and mortality are in the forefront of malignant tumors. Currently, cancer immunotherapy is the hottest topic in cancer research field. Although cancer immunotherapy has achieved some results in the fundamental research and clinical application of gastrointestinal tumors, there are still a series of problems that need to be resolved. In this article, we review the fundamental and clinical research progress of several common methods of cancer immunotherapy in the field of gastrointestinal tumors.

To evaluate the psychological symptoms of patients with Crohn disease (CD), and to explore the risk factors affecting quality of life (QOL) in CD patients, 50 adult patients with CD, and 50 healthy controls were enrolled. Psychological questionnaires including self-rating anxiety scale (SAS), self-rating depression scale (SDS), the inflammatory bowel disease questionnaire (IBDQ) and the short form-36 health survey (SF-36) were completed. The results showed both the SAS (40.3±8.5 VS 37.6±7.0) and the SDS (47.1±11.1 VS 41.8±9.6) in CD patients were significantly higher than those in the healthy controls ( t=5.4, P<0.05; t=10.6, P<0.05). The IBDQ scores revealed the physical symptoms scores were 49.50±7.62, systemic symptoms scores 23.92±5.07, emotional functions scores 57.13±15.62, and social function scores 22.15±9.08 in CD active phase. However, the above scores were 60.12±4.01, 26.24±3.97, 67.34±15.17, and 25.44±2.03 respectively in the remission phase. Four subscale items of IBDQ in CD active phase were significant lower than those in the remission phase (all P<0.05). The subscale items of SF-36 scores (PF, RP, BP, GH, VT, SF, RE, MH) in CD patients were significant lower than those in healthy controls (all P<0.05). The SF-36 items scores of PF,RP and MH in the remission phase were significant higher than those in the active phase (all P<0.05). The SF-36 items scores of GH and VT in patients with malnutrition were significant lower than those with nutrition (both P<0.05). Multivariate regression analysis showed that disease status and nutritional risk ( P<0.05) significantly affected the patients' IBDQ scores. Factors including sex, age, marital status, education background, medical insurance, use of biologicals, surgery treatment had little influence on the total score of IBDQ ( P>0.05). Psychological conseling and treatment in the active phase may improve QOL of CD patients.

Objective:To explore the detection rate of non-caseating granuloma under endoscopy in patients with Crohn′s disease and its influencing factors, in order to improve the pathological diagnosis rate of Crohn′s disease.Methods:From July 2016 to April 2021, at the First Affiliated Hospital of Soochow University, 199 patients who met the clinical diagnostic criteria for Crohn′s disease and underwent endoscopic biopsy were collected. The detection rates of non-caseating granulomas in all patients with Crohn′s disease, in different types (primary and recurrent) and whether the biopsy site included the colon were analyzed. According to whether non-caseating granulomas were detected by endoscopic biopsy, the patients were divided into the detected group and the undetected group. The clinical data of the two groups of patients were compared, which included gender, age, course of disease, body mass index, smoking status, clinical manifestations (abdominal pain, diarrhea, gastrointestinal bleeding, perianal lesions, weight loss, fever, intestinal obstruction), therapeutic medication (5-aminosalicylic acid, immunosuppressants, glucocorticoid, biological agents, exclusive enteral nutrition), history of bowel surgery, laboratory examination results (hemoglobin, platelet count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate, albumin), endoscopic manifestation (ulcer, fistula, stricture), simplified Crohn′s disease activity index (CDAI), total number of biopsy samples, and site of biopsy. Chi-square test, continuity correction chi-square test, Mann-Whitney U test and Fisher exact test were used for statistical analysis, and logistic regression analysis was used to analyzed the influencing factors of detection of non-caseating granulomas under endoscopy. Results:Among the 199 patients with Crohn′s disease, 67 cases were detected with non-caseating granuloma (detected group), and the overall detection rate was 33.7% (67/199); 132 cases were not detected with non-caseating granuloma (undetected group). The detection rate of non-caseating granulomas in patients with primary Crohn′s disease was higher than that of recurrent patients (39.9%, 59/148 vs. 15.7%, 8/51), and the detection rate of non-caseating granulomas in patients with Crohn′s disease whose biopsy site included the colon was higher than that of patients whose biopsy site did not include colon (64.1%, 25/39 vs. 26.3%, 42/160), and the differences were statistically significant ( χ2=9.93 and 20.12 , P=0.002 and <0.001). The age of patients in the detected group was younger than that of the undetected group; the course of disease of the detected group was shorter than that of the undetected group; the proportions of patients with abdominal pain and history of biological treatment in the detected group were lower than those of the undetected group; the simplified CDAI score of the detected group was higher than that of the undetected group; and the total number of biopsy samples of the detected group was more than that of the undetected group (30.0 years old (25.0 years old, 37.00 years old) vs. 32.0 years old (28.0 years old, 41.0 years old); 1.0 year (0.0 year, 3.0 years) vs. 2.0 years (0.0 year, 5.0 years), 61.2%, 41/67 vs. 75.8%, 100/132; 0, 0/67 vs. 10.6%, 14/132; 5.00 (2.00, 7.00) vs. 4.00 (2.00, 6.00); 10 (8, 12) vs. 6 (3, 9)), and the differences were statistically significant ( Z=-2.29, -1.99, χ2=4.56, corrected χ2=6.11, Z=-2.05, -5.64, all P<0.05). The case number of biopsy location in terminal ileum, colon, ileocolon, upper gastrointestinal tract, terminal ileum+ upper gastrointestinal tract, ileocolon+ upper gastrointestinal tract in the detected group was 36, 4, 18, 1, 5 and 3, respectively, compared with those of undetected group (94, 4, 8, 11, 13 and 2), the difference was statistically significant (Fisher′s exact test, P<0.001). The results of multivariate logistic regression analysis suggested that the total number of biopsy samples, whether the biopsy site included the colon and disease type were independent influencing factors for the detection of non-caseating granulomas under endoscopy in patients with Crohn′s disease (regression coefficients=0.157, 0.979 and -0.960, OR=1.171, 2.662 and 0.383; 95% confidence interval 1.067 to 1.284, 1.140 to 6.214, 0.158 to 0.929; P=0.001, 0.024 and 0.034). Conclusions:For endoscopic examination in patients with suspected Crohn′s disease, the total number of biopsy samles should be increased as much as possible, and biopsy should be performed at the colonic lesions, in order to improve the detection rate of non-caseating granulomas under endoscopy thereby providing more pathological evidence for the diagnosis of Crohn′s disease.

Background: Gastric cancer is one of the common gastrointestinal malignancies. Early diagnosis can reduce the mortality rate significantly. In the Chinese consensus published in 2017, the New Gastric Cancer Screening Scoring System was recommended to be used for risk stratification of gastric cancer. Aims: To preliminarily explore the value of the New Gastric Cancer Screening Scoring System in early gastric cancer screening in asymptomatic community population. Methods: At several communities in Suzhou City Xiangcheng District, a questionnaire survey was conducted in asymptomatic community residents willing to accept voluntary serum tests to collect information on high risk factors of gastric cancer. Serum pepsinogen (PG), PGⅡ, gastrin 17 (G-17) and Helicobacter pylori (Hp) IgG were tested simultaneously. Risk stratification of gastric cancer was carried out in accordance with the New Gastric Cancer Screening Scoring System. Gastroscopy was recommended for moderate to high risk individuals. Results: A total of 540 asymptomatic individuals completed the study, of which 11 were categorized as high risk (2.0%), 168 as moderate risk (31.1%), and 361 as low risk (66.9%). Sixty-four moderate to high risk individuals completed the gastroscopy with a response rate of 35.8%. Four precancerous lesions were detected (6.2%), including 3 gastric low-grade intraepithelial neoplasia and 1 duodenal adenoma. No gastric cancer was detected. Conclusions: The New Gastric Cancer Screening Scoring System is useful for risk stratification of gastric cancer in asymptomatic population and may provide a basis for further endoscopic examination. However, the value of this scoring system in low risk areas of gastric cancer needs to be further verified.

Background:The incidence of inflammatory bowel disease(IBD)is increasing recently. However,the pathogenesis has not been fully clarified. Aims:To investigate the expressions and significance of interleukin-22( IL-22),matrix metalloproteinase-9(MMP-9)and macrophage migration inhibitory factor(MIF)in peripheral blood of patients with IBD. Methods:A total of 80 patients with IBD admitted from May 2011 to Nov. 2014 at the First Affiliated Hospital of Soochow University were enrolled,in which 43 cases were Crohn’s disease(CD),37 cases were ulcerative colitis(UC). Forty healthy subjects were served as normal controls. Peripheral levels of IL-22,MMP-9 and MIF were detected by ELISA. Multivariate Logistic regression model was used to analyze IL-22,MMP-9 and MIF in active CD and UC and ROC curve was used to evaluate the diagnostic performance of these markers for screening of active CD and UC. Results:Compared with normal control group,peripheral levels of IL-22,MMP-9 and MIF increased significantly in CD and UC groups(P <0. 05),while no significant difference was found between CD and UC groups(P > 0. 05). Peripheral levels of IL-22, MMP-9 and MIF in active CD and UC were significantly higher than those in remission stage(P < 0. 05). For screening of active IBD,the area under ROC curve(AUC)of combined detection of IL-22 and MMP-9(0. 853 for CD,0. 867 for UC) was superior to that of IL-22,MMP-9 or MIF only(0. 747,0. 770 and 0. 699 for CD,0. 774,0. 815 and 0. 761 for UC). Conclusions:Peripheral levels of IL-22,MMP-9 and MIF increase markedly in IBD patients,which are correlated closely with the activity of IBD. Combined detection of IL-22 and MMP-9 might greatly increase the accuracy for screening of active IBD.

Objective To investigate neurological function, volume of cerebral infarction, changes of lipid peroxidation, and the intervention effect of compound angelica injection (CAI) on rats with focal cerebral ischemia injury. Methods Models of rat with cerebral ischemia were reproduced by middle cerebral artery occlusion (MCAO). All animals were randomly divided into sham-operation group, model group, CAI group, and edaravone group. 1 hour after the models were established, rats in the sham-operation group and model group received intraperitoneal injection with normal saline, while rats in CAI group and edaravone group received intraperitoneal injection with relevant medicine for continuing 7 days. Volume of cerebral infarction was detected by Tetrazole staining method, neurologic function were detected by neuroethology, and concentration of MDA in brain tissue was also detected. Results After 7-day cerebral ischemia, compared with the model group, volume of cerebral infarction in CAI group was significantly reduced (P<0.05), and the concentration of MDA was a little lower. Conclusion CAI has significant protective effects which can significantly improve neurological function, reduce volume of cerebral infarction, and alleviate the effects of lipid peroxidation of rats with focal cerebral ischemia injury.

Background:Matrix metalloproteinase-9(MMP-9)is known to play a key role in tumor invasion and metastasis by mediating the degradation of extracellular matrix. It has been revealed that neutrophil gelatinase-associated lipocalin ( NGAL)is capable of protecting MMP-9 from degradation and thereby preserving its enzymatic activity. Aims:To explore the MMP-9 and NGAL levels in peripheral blood of gastric cancer patients and their clinical significance. Methods:Serum levels of MMP-9 and NGAL were determined by ELISA in 76 gastric cancer patients and 50 healthy controls. Correlations of serum MMP-9 and NGAL levels with clinicopathological features of gastric cancer were analyzed,and their diagnostic performance for screening gastric cancer was evaluated by ROC curve. Results:Serum levels of MMP-9 and NGAL in patients with gastric cancer were significantly higher than those in healthy controls(P<0. 01),and either of them was positively correlated with the TNM stage of gastric cancer. Furthermore,MMP-9 was correlated with lymph node metastasis and serosal invasion,while NGAL was correlated with distant metastasis. However,tumor differentiation was not correlated with either MMP-9 or NGAL. By ROC curve,608. 19 ng/mL and 14. 71 ng/mL were identified as the cutoff value of serum MMP-9 and NGAL,respectively,for screening gastric cancer. Sensitivity and specificity of MMP-9 were 64. 5% and 90. 0%,and those of NGAL were 85. 5% and 90. 0%,respectively. When parallel test was taken,the sensitivity would be increased to 94. 7% and specificity being 82. 0%. Conclusions:Serum levels of MMP-9 and NGAL are elevated and associated with tumor progression in patients with gastric cancer. Both of them might be used as potential markers for screening,disease assessment and prognosis prediction of gastric cancer.

Objective To investigate the protective effects of thalidomide on rats with acute necrotizing pancreatitis (ANP) and its mechanism. Methods Fifty four SD rats were randomly divided into the three groups; ANP group, thalidomide group and control group with 18 rats in each group. The model of ANP was induced by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct. Rats in thalidomide group received thalidomide 200 mg/kg body weight gastric lavage 1 h after ANP induction. The rats were sacrificed 3 h, 6 h, and 12 h after ANP induction, and the amount of intraperitoneal ascites was quantified. The serum levels of TNF-α, IL-6, IL-18 were measured by EUSA. The proportion of CD4 + T cell, CD8 + T cell in peripheral blood was determined by flow cytometry. The expression of TNF-α mRNA in pancreatic tissue were measured by RT-PCR. The expression of ICAM-1 protein in pancreatic tissue was measured by immunohistochemistry. Pancreatic tissue underwent pathologic examination. Results Six hours after surgery, the amount of ascite, serum levels of TNF-α, IL-6, IL-18, CD4 + T cell, CD,+ T cell, pancreatic TNF-α mRNA and ICAM-1 protein expression, pathologic score in control group was (1.03 ±0.31)ml,(57.17±11.29)pg/ml, (24.45 ±4.14)pg/ml, (64.23 ±21.85)pg/ml, (47.58 ±9.21)% , (40.88 ± 2.96)%, 0.07 ±0.02, 0.57 ±0.30, 0.67 ±0.81, respectively, and the corresponding values were (3.63 ± 0.38)ml, (107.54 ±33.05) pg/ml, (47.30 ± 11.40) pg/ml, (367.76 ± 108.43 ) pg/ml, (54.90 ± 7.15)%, (17.17 ±3.12)%, 0.65 ±0.26, 3.20 ±0.57, 11.50 ±1.87 in ANP group; and (1.45 ±0.53)ml, (80.60 ±20.48) pg/ml, (26.61 ±10.85) pg/ml, (321.82 ±85.20) pg/ml, (29.80 ±2.19)% , (15.52± 1.96)%, 0.35 ±0.23, 2.37 ±0.67, 8.00 ±3.03. Besides the value of CD8 + T cell was significantly decreased, all other values were significantly increased when compared with control group (P <0.05). Conclusions Thalidomide can decrease the release of inflammatory mediator, and reduce the pathological damage of pancreas of ANP rats by inhibiting TNF-α mRNA expression.

Objective To investigate the microRNAs expression profile in human colorectal cancer with or without liver metastasis and try to screen miRNA associated with liver metastasis in colorectal cancer. Methods Twenty five surgical resected colorectal cancer specimens were collected and frozen in liquid nitrogen. Three without liver metastasis and three with liver metastasis were selected, from which total RNAs were isolated. The expressions of miRNAs in these two types of specimens were detected by illumine microRNA microarray, and the difference of miRNA expression was screened. The biochip results were verified with real-time RT-PCR in all colorectal caner specimens. Results The miRNA expression was significantly different in colorectal cancer with liver metastasis and without liver metastasis. Compared with colorectal cancer without liver metastasis, 28 miRNA expressions was different in colorectal cancer with liver metastasis, 4 up regulated and 24 down regulated. The quantity of miR-139-3p expression in colorectal cancer with liver metastasis was 1.75±0.40, up regulated compared with that incolorectal cancer without liver metastasis(0. 69 ±0.58,P＜0.05). The quantity of miR-19a expression in liver metastasis was 0. 39±0. 20, downregulated compare with no liver metastasis( 1.38 ± 0.98, P＜0. 05). The result of miRNA biochip was consistent with that of RT-PCR. Conclusion The difference of miRNA expression might relate to liver metastasis of colorectal cancer. The specific miRNAs expression profile might provide new target for diagnosis and treatment of colorectal cancer with liver metastasis.