Advances in the study of brain function changes in inflammatory bowel disease / 医学研究生学报

Inflammatory bowel disease(IBD) is a chronic non-specific inflammatory disorder that commonly affects gastrointestinal tract. The cause is not clear. Previous studies have shown that IBD patients often suffer from anxiety and depression, which may be associated with impaired brain structure and function and changes in gut microbiome. Based on these findings, many researches indicate brain-gut-microbiome axis may play an important role in the occurrence and development of IBD. Blood oxygenation level dependent functional magnetic resonance (BOLD-fMRI) can detect brain function area with special response accurately and objectively, which helps to investigate the changes of brain function and its pathogenesis in IBD patients. This article reviews the current status and future prospects in IBD brain function changes based on the brain-gut-microbiome axis.

Role of protease and self-digestion in the pathogenesis of inflammatory bowel disease / 医学研究生学报

Inflammatory bowel diseases (IBD) are non-specific inflammatory diseases of unknown cause, mainly including ulcerative colitis and Crohn’s disease. IBDs have some similarities to peptic ulcer diseases (PUD) in clinical manifestations, histopathological changes and treatment strategies, and therefore pepsin might have a similar effect on both PUD and IBD. Recent studies show that “self-digestion” induced by digestive enzymes, especially trypsin, may play an important role in the development and progression of IBD. This article focuses on the role of mucosal barrier injury induced by trypsin and self-digestion in the formation of digestive ulcer in IBD.

Mechanisms of deoxycholic acid to promote the initiation and progression of colorectal cancer / 医学研究生学报

Colorectal cancer is a malignant disease of digestive system, with increasing morbidity. As a risk factor of colorectal cancer, high fat diet changes the secretory form of hepatic bile acids and stimulates its secretion. As a result, it increases the concentration of bile acids in the large intestine. Deoxycholic acid promotes the initiation and progression of colorectal cancer through affecting various intracellular signals, modulating expression of multiple genes and influencing the balance of the gut microbiota. The article reviewes the mechanisms of deoxycholic acid to promote the initiation and progression of colorectal cancer.

The value of fecal calprotectin in predicting endoscopic activity and severity of ulcerative colitis / 医学研究生学报

Objective The invasive colonoscopy is an important method for evaluating the severity of intestine and the muco-sal healing in ulcerative colitis(UC)patients. The aim of this study was to investigate the advantage of fecal calprotectin(FC)in diagnosing UC endoscopic activity and severity and analyze the FC correlation with endoscopic scores. Methods A total of 70 UC in-patients in our hospital from January 2016 to September 2017 were retrospectively analyzed and categorized into endoscopic remission UC [mucosal healing(n=12),mucosal lesion(n=10)]and endoscopic active UC[mild-moderate(n=30)and severe(n=18)]according to UC Endoscopic Index of Severity(UCEIS).The ROC curve was used to analyze the predictive efficacy of each laboratory indicator to identify endoscopically active UC and severe UC and evaluate the correlation of UCEIS with all these indicators. Results In UC pa-tients,the levels of FC[828.5(416.6,1079.7)μg/g],PCT[0.03(0.02,0.06)μg/L]and IL-6[13.4(7.32,21.45)ng/L]were sig-nificantly higher in endoscopically active UC than those[43.4(9.4,91.4)μg/g、0.02(0.02,0.03)μg/L、5.82(5.14,6.73)ng/L]in remission and the levels of CRP,ESR,WBC count and PLT count also increased significantly,while HB and ALB levels were signifi-cantly lower than those in remission(all P value<0.001).In endoscopically active UC patients,the levels of FC[1117.1(916.5,1492. 4)μg/g]and IL-6[18.18(12.72,33.25)ng/L]were significantly higher than those of mild-moderate UC[622.4(218.7,924.2)μg/g,8.27(7.08,16.60)ng/L](P<0.05)and the levels of CRP,ESR and WBC also increased significantly(P<0.05),while the ALB showed a significant lower level(P=0.002). When FC>175.6 μg/g,it was of higher accuracy in diagnosing UC endoscopic activity and the sensitivity,specificity,positive predictive value and negative predictive value were respectively 87.50%,90.91%,95.45%and 76.92%;When FC>781.1 μg/g,it was of higher accuracy in diagnosing severe UC and the sensitivity,specificity,positive predic-tive value and negative predictive value were respectively 88.89%,73.33%,66.66% and 91.66%. The levels of FC,PCT,IL-6, CRP,ESR,WBC and PLT all presented positive correlation with UCEIS(P<0.001),while the HB and ALB levels showed a negative correlation with UCEIS(P<0.001). Conclusion FC is a good indicator to judge UC endoscopic activity and severe UC. FC can be used as a non-invasive and surrogate marker for endoscopy to monitor UC disease activity in clinical practice.

Treating irritable bowel syndrome by wuling capsule combined pinaverium bromide: a clinical research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of wuling Capsule combined with Pinaverium Bromide in treatment of irritable bowel syndrome (IBS).</p><p><b>METHODS</b>Sixty-four IBS patients were randomized into two groups, the treatment group and the control group, 32 in each group. Patients in the treatment group took wuling Capsule (0. 33 g/capsule, 3 times per day) and Pinaverium Bromide (50 mg/tablet, one tablet each time, 3 times per day) , while those in the control group only took Pinaverium Bromide (50 mg/tablet, one tablet each time, 3 times per day). The therapeutic course for all was 6 weeks. IBS symptom score questionnaire, IBS-Quality of Life (IBS-QOL) , Self-Rating Depression Scale (SDS) , and Self-Rating Anxiety Scale (SAS) were assessed before and after treatment. Adverse reactions were also observed.</p><p><b>RESULTS</b>The improvement of abdominal pain, stool frequency, and stool properties, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). The improvement of dysphoria, body image, concerns for health, and dietary restriction of IBS-QOL, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). The improvement of SDS and SAS, as well as changing rates of integrals were significantly higher in the treatment group than in the control group (P <0. 05). No severe adverse reaction occurred in either group.</p><p><b>CONCLUSION</b>Combination therapy of wuling Capsule and Pinaverium Bromide could improve abdominal pain and defecation, attenuate depression and anxiety of IBS patients with higher safety.</p>

Clinicopathological features of colorectal neuroendocrine neoplasms and prognostic significance of WHO staging system / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics of colorectal neuroendocrine neoplasms (NENs) and the prognostic significance of the new WHO classification and staging system about gastroenteropancreatic NENs.</p><p><b>METHODS</b>The clinical and pathological records were reviewed in 73 patients with colorectal NENs (carcinoids). All slides were retrieved and reviewed, immunohistochemical staining (EnVision method) was performed and follow-up information retrieved.</p><p><b>RESULTS</b>Forty-one men and thirty-two women were included with a median age of 53 years (19 - 79 years). The location of the primary tumors in 65 patients was within 10 cm from the anorectal line. In 45 cases, the tumor diameter was ≤ 1 cm (no metastasis occurred); in 11 cases, the tumor diameter was > 1 cm but ≤ 2 cm (two patients had metastatic tumors); in 17 cases, the tumor diameter was > 2 cm (12 patients had metastatic tumors). The metastatic rate was significantly correlated with tumor size (P = 0.000). All tumors were immunoreactivity for synaptophysin and/or chromogranin A. According to the criteria of WHO classification and staging system about gastroenteropancreatic NENs, there were 65 cases of neuroendocrine tumors, including 51 cases of grade 1 (G1), 14 cases of grade 2 (G2), 4 cases of neuroendocrine carcinoma (G3) and 4 cases of mixed adenoneuroendocrine carcinoma. Following-up data showed that of the 34 patients with G1 tumor, there were no tumor-related death, but two patients showed metastases, and the remaining patients were disease free for 6 to 179 months. Of the 12 patients with G2 tumors, five developed metastasis, there were two tumor-related deaths, and the nine surviving patients were alive for 17 to 118 months. Of the four G3 patients, all developed metastasis and there were three tumor-related deaths. Of the four mixed adenoneuroendocrine carcinoma there were two tumor-related deaths. The difference of metastatic rate, tumor-related mortality, and overall survival among different grading groups in this series was statistically significant (P = 0.000).</p><p><b>CONCLUSIONS</b>Colorectal neuroendocrine neoplasm is a group of tumors with distinct prognostic difference, and most of these tumors show an indolent clinical behavior. There is a good correlation between the new WHO classification and staging system of gastroenteropancreatic NENs and their clinical behaviors.</p>

CpG methyltransferase induced down-regulation of claudin-7, -8 and its effects on proliferation and apoptosis of human colorectal cancer HT-29 cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the regulatory effect of CpG methyltransferase (M.SssI) on expression of claudin-7 and claudin-8, promoting apoptosis and inhibiting proliferation of human colorectal cancer HT-29 cells.</p><p><b>METHODS</b>HT-29 cells were treated with M.SssI (50 U/ml) for 24 hours. The methylation status of claudin-7 and claudin-8 gene promoters was assayed by bisulfite sequencing PCR (BSP). Real-time PCR with SYBR green I technique was used to detect the relative expression of claudin-7 and -8 mRNA, and claudin-7 and claudin-8 proteins were tested by cell immunofluorescence and Western blotting, while the effect on cell apoptosis was assessed by Hoechst 33342 fluorescence and flow cytometry. Inhibition of cell proliferation was measured by MTT assay.</p><p><b>RESULTS</b>The amounts of methylated claudin-7 and claudin-8 gene CpGs were 25, 10 in the M.SssI group, 9 and 5 in the PBS group, 0 and 3 in the 5-azacytidine group, respectively. Compared with the PBS group, Claudin-7 and -8 were significantly reduced by M.SssI (P < 0.05), but increased by 5-azacytidine (P < 0.05) at both mRNA and protein levels. Hoechst 33342 staining revealed that HT-29 cells treated with PBS and 5-azacytidine were not significantly different, showing even blue fluorescence, round shape and same cell volume. But the M.SssI group presented more apoptotic cells with intensive white fluorescence intensity. Cytometry indicated that early apoptotic index of the M.SssI group was increased by 84.7%, compared with that of the PBS group (P = 0.002). Measurement of MTT optical density demonstrated that cell growth of the M.SssI group was significantly lower than that of the PBS group (P = 0.002), with an inhibition rate of 32.1%, whereas the proliferation of 5-azacytidine group was similar to that of the PBS group (P = 0.084).</p><p><b>CONCLUSIONS</b>Our findings suggest that M.SssI can down-regulate claudin-7, -8 mRNA and proteins in the human colon cancer HT-29 cells by up-regulating methylation status of claudin-7 and -8 gene promoters, and finally induce apoptosis and inhibit proliferation of the tumor cells.</p>

Mutation screening of LKB1 gene in familial Peutz-Jeghers syndrome patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for potential mutations of LKB1 gene in Chinese familial Peutz-Jeghers syndrome (PJS) patients and analyze their clinical manifestations.</p><p><b>METHODS</b>Eleven PJS families were collected and genomic DNA of peripheral blood was extracted. Typically mucosal pigmentation and hamartomatous polyps were present in all 11 probands. Mutation screening of the probands were carried out by PCR and direct sequencing. Two hundred and fifty healthy adults were enrolled as normal controls, for whom genomic DNA of peripheral blood was also extracted. PCR-denaturing high performance liquid chromatography was carried out to verify the mutation identified in the patients.</p><p><b>RESULTS</b>Nine germline mutations were identified in eight PJS patients, which included 7 point mutations, 1 deletion and 1 insertion. Among these, 4 were considered to be pathogenic, of which 2 were de novel, 4 were considered to be polymorphism, and 1 was uncertain.</p><p><b>CONCLUSION</b>LKB1 gene mutations with pathogenic effect are a common cause of familial PJS in Chinese patients. Most mutations are point mutations.</p>