[Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors].

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

[Diagnostic value of different serological markers and correlation analysis with disease phenotype in inflammatory bowel disease].

Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P<0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P<0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference (P=0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) (OR=3.39, 95%CI: 1.59-7.21), dual-marker ASCA (+) ANCA (-) (OR=2.87, 95%CI: 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) (OR=3.09, 95%CI: 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) (OR=3.15, 95%CI: 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) (OR=2.69, 95%CI: 1.42-5.12) and dual-marker ANCA (+) ASCA (-) (OR=2.11, 95%CI: 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.

[Short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease].

Objective: To evaluate the short-term efficacy and safety of vedolizumab in patients with inflammatory bowel disease (IBD). Methods: Patients with moderate and severe active IBD at the first use of vedolizumab from May 1 to October 31, 2021 were retrospectively enrolled. Then the clinical characteristics, and the efficacy and safety of vedolizumab were evaluated. Meanwhile, the clinical response rate, biological response rate and endoscopic response rate were calculated. Multivariate analysis was used to evaluate the independent influencing factors of short-term clinical efficacy and safety. Results: A total of 78 patients (44 males and 34 females) with IBD were enrolled, with a mean age of (40.5±11.9) years. The clinical remission rate, clinical response rate, biological remission rate, biological response rate and endoscopic remission rate was 60.3% (47/78), 85.9% (67/78), 70.5% (55/78), 43.6% (34/78) and 47.0% (31/66) respectively after 14 weeks of treatment. Body mass index (BMI) ≥ 18.5 kg/m2 (HR=5.04, 95%CI: 1.50-16.91, P=0.009) and biological remission at 6 weeks of treatment (HR=15.22, 95%CI: 3.16-73.38, P=0.001) were predictors of endoscopic remission at 14 weeks of treatment. Adverse reactions occurred in 57 patients, with an incidence of 73.1%. The main manifestations were liver and kidney damage (37.2%) and infection (26.9%). Conclusions: More than half of patients with moderate and severe active IBD can achieve clinical remission after 14 weeks of vedolizumab treatment. Baseline BMI level and biological remission at 6 weeks of treatment are predictors of mucosal healing at 14 weeks. The incidence of adverse reactions is not low, although serious adverse reactions are rare in short-term treatment.

[Characteristic analysis of patients with type 2 diabetes mellitus combined with advanced stage chronic liver disease: a community population-based cross-sectional study in Heping District, Shenyang City (CHESS-LN 2101)].

Objective: To investigate the prevalence and independent risk factors of non-alcoholic fatty liver disease (NAFLD) and advanced chronic liver disease among the type 2 diabetes mellitus (T2DM) population in the Shenyang community, so as to provide evidence for the prevention and control of T2DM combined with NAFLD. Methods: This cross-sectional study was conducted in July 2021. 644 T2DM cases from 13 communities in Heping District, Shenyang City were selected. All the surveyed subjects underwent physical examination (measurements of height, body mass index, neck circumference, waist circumference, abdominal circumference, hip circumference, and blood pressure), infection screening (excluding hepatitis B and C, AIDS, and syphilis), random fingertip blood glucose, controlled attenuation parameter (CAP), and liver stiffness measurement (LSM). The study subjects were divided into the non-advanced chronic liver disease group and the advanced chronic liver disease group according to whether the LSM value was greater than 10 kPa. Cirrhotic portal hypertension development was indicated in patients with LSM ≥ 15 kPa. The comparison of multiple mean values among the sample groups was performed by analysis of variance when the normal distribution was met. Results: In the T2DM community population, there were 401 cases (62.27%) combined with NAFLD, 63 cases (9.78%) combined with advanced chronic liver disease, and 14 cases (2.17%) combined with portal hypertension. There were 581 cases in the non-advanced chronic liver disease group and 63 cases (9.78%) in the advanced chronic liver disease group (LSM ≥10 kPa), including 49 cases (7.61%) with 10 kPa≤LSM<15 kPa, 11 cases (1.71%) with 15 kPa ≤LSM<25 kPa, and 3 cases (0.47%) with LSM ≥ 25 kPa. Age, body mass, body mass index, neck circumference, waist circumference, hip circumference, waist-to-height ratio, systolic blood pressure, and CAP were all statistically different between the non-advanced chronic liver disease group and the advanced chronic liver disease group (F=-1.983,-2.598,-4.091,-2.062,-3.909, -4.581,-4.295,-2.474, and -5.191, respectively; P<0.05). There was a statistically significant difference in terms of whether or not there was combined cerebrovascular disease (2=4.632, P=0.031); however, there were no statistically significant differences in terms of lifestyle, diabetes complications, and other complications (P>0.05). Conclusion: Patients with T2DM have a higher prevalence of NAFLD (62.27%) than those with advanced chronic liver disease (9.78%). 2.17% of T2DM cases in the community may not have had early diagnosis and early intervention, and they might have been combined with cirrhotic portal hypertension. So, the management of these patients should be strengthened.

[The 488th case: chronic diarrhea and abnormal liver function].

A 56-year-old female was admitted to Department of Gastroenterology at Peking Union Medical College Hospital with diarrhea for seven months, and abnormal liver function for six months. She had a history of type 1 diabetes. The main clinical manifestations were recurrent fatty diarrhea and abnormal liver function, accompanied by abdominal and retroperitoneal lymphadenopathy, elevated CA19-9 and CEA. Progressive impairment of hepatic synthetic function and shrinkage of liver developed in a short period of time. The pathology of liver biopsy suggested that nodular regeneration of hepatocytes was followed by hyperplasia of thin bile ducts after submassive necrosis. Intestinal mucosa biopsies were performed twice. The pathology showed that the intestinal villi were completely blunt, accompanied with crypt hyperplasia. Goblet cells disappeared with reduced mucin. Paneth cells were barely seen without intraepithelial infiltration of lymphocytes. Rifaximin was not effective, while glucocorticoids improved clinical situation. The diagnosis of autoimmune enteropathy was finally confirmed by multidisciplinary team including departments of gastroenterology, pathology, endocrinology, hematology, infectious diseases, and rheumatology. With the administration of glucocorticoid and sirolimus, diarrhea relieved and liver function returned to normal.

[Clinical and genetic characteristics of patients with chronic enteropathy associated with SLCO2A1 gene].

Objective: To determine the clinical features and genetic characters of patients with chronic enteropathy associated SLCO2A1 gene (CEAS). Methods: Five CEAS patients diagnosed at Peking Union Medical College Hospital from January 2012 to December 2019 were enrolled in this study. The clinical manifestations, laboratory test, radiological and endoscopic findings, gene detections, treatments and prognosis of these patients were reviewed and analyzed. Results: Five male patients presented gastrointestinal symptoms after puberty, including abdominal pain, diarrhea, intermittent melena or hematochezia, incomplete bowel obstruction, anemia, hypoalbuminemia and hypokalemia. The whole gastrointestinal tract except esophagus could be involved, especially the stomach and ileum. Intestinal lesions were characterized by multiple shallow ulcers with stenosis in the layers of mucosa and submucosa. Five patients were all accompanied with primary hypertrophic osteoarthropathy (PHO), and 1 with myelofibrosis and thoracic duct dysplasia. All patients were homozygous or compound heterozygous mutations of SLCO2A1 gene. Conventional treatment of inflammatory bowel disease and COX-2 inhibitors were ineffective. Conclusions: CEAS is an autosomal recessive genetic disease which widely involves the gastrointestinal tract, and can be associated with skin and bone involvement. There is no effective treatment for CEAS at present. CEAS is a different entity from other inflammatory gastrointestinal diseases.

[Relationship between matrix Gla protein and clinical features of ulcerative colitis].

Objective: To analyze the relationship between matrix Gla protein(MGP) and clinical characteristics of patients with ulcerative colitis (UC). Methods: Fifty-one UC patients who were admitted to the gastroenterology department of Peking union medical college hospital from July 1, 2015 to May 31, 2017 were included. Twenty-seven healthy subjects in the same period were included as normal controls. The expression of MGP mRNA in the colonic mucosa was detected by real-time fluorescence quantitative PCR. Clinical data of the patients were collected during a 2-year follow-up. The public data set containing MGP gene expression profile of UC patients was downloaded from the GEO database, and was divided into four groups according to the microscopic Mayo score. The differential expression of MGP in each group was analyzed. Results: All the fifty-one UC patients were followed up. The expression of MGP mRNA in the colonic mucosa of UC patients treated with hormone and immunosuppressive agents or biological agents or surgery was higher than that of patients treated with mesalazine. MGP mRNA expression was positively correlated with C-reactive protein level. It was also higher in the colonic mucosa of UC patients with clostridium difficilis or cytomegalovirus infection than that of patients without opportunistic infection. The difference of MGP mRNA expression between groups in GEO public data set was statistically significant(P<0.01), showing an up-regulation trend with the aggravation of inflammation. The expression level of MGP was moderately correlated with the microscopic Mayo score. The relationship between MGP mRNA expression and lifestyle, lesion range, erythrocyte sedimentation rate, parenteral manifestations and recurrence frequency of UC patients was not obvious. Conclusions: MGP is associated with colonic inflammation and its abnormal expression can help to predict the disease activity of patients with UC.

[Protective effect and mechanism of Lactobacillus rhamnosus on immune checkpoint inhibitors related colitis in mice].

Objective: Modeling the immune-related adverse events (irAE) colitis in mice, and explore the protective effect and related mechanism of Lactobacillus rhamnosus GG (LGG) on irAE colitis. Methods: C57BL/6 mice were divided into dextran sodium sulfate (DSS) group (n=3), DSS+anti-programmed death receptor 1 (PD-1) group (n=4), DSS+anti-PD-1+anti-cytotoxic T lymphocyte associated protein 4 (CTLA-4) Group (n=4), DSS+anti-PD-1+anti-CTLA-4+LGG group (n=4), all were given corresponding drugs and probiotics intervention. The severity of colitis were assessed by weight loss, disease activity index (DAI), colon length, colon histopathological score. The inflammatory cytokines and T cell immunity of CD4+, CD8+, FoxP3+regulatory T cells (Treg), were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining respectively. Results: Compared to DSS group, the Day 9 weight [(87.40±1.79)% vs (94.57±0.53)%, P<0.05], colon length [(5.33±0.27)cm vs (6.63±0.12)cm, P<0.05] were lower, and DAI score(2.66±0.24 vs 0.89±0.48), colon histopathological score (12.50±1.04 vs 5.67±0.33), tumor necrosis factor-α (TNF-α) (6.73±1.68 vs 0.91±0.40) (P<0.05), as well CD8+T cells (156.80±8.84 vs 89.00±6.66) and FoxP3+Treg cells (103.80±2.66 vs 48.33±3.18) (P<0.05) were higher in DSS+anti-PD-1+anti-CTLA-4 group. Compared to DSS+anti-PD-1+anti-CTLA-4 group, the DAI score(1.83±0.17 vs 2.66±0.24), colonic histopathology score (8.75±0.63 vs 12.50±1.04), TNF-α level (1.32±0.18 vs 6.73±1.68) (P<0.05) were lower; and CD8+T cells(97.75±3.75 vs 156.80±8.84, P<0.01) level was lower with higher FoxP3+Treg cells (126.00±8.33 vs 103.80±2.66, P=0.046) in DSS+anti-PD-1+anti-CTLA-4+LGG group. Conclusion: DSS combined with anti-PD-1 and anti-CTLA-4 can successfully modeling the irAE colitis in mice, LGG can reduce irAE colitis severity by regulating Treg cells.

[Clinical characteristics and microbiome analysis in patients with anti-programmed cell death protein 1 related colitis].

Objective: To analyze clinical characteristics and monitor microbiome changes in patients with anti-PD-1 associated colitis. Methods: Two patients with non-small cell lung cancer who developed colitis after treated with anti-PD-1 antibodies were retrospectively analyzed in Peking Union Medical College Hospital from January 2019 to January 2020. The clinical symptoms, endoscopic and pathological manifestations, as well microbiome changes were analyzed and compared during pre-treatment, post-treatment and relapse. Results: The main clinical manifestations included diarrhea, elevated inflammatory indicators, colonic mucosal diffuse hyperemic edema with erosion by endoscopy. Changes in the structure of crypts were common pathological characteristics. Glucocorticoids were effective agents, which achieved clinical remission and mucosal healing. The microbiome composition of OTUs was different. After glucocorticoid treatment, the alpha diversity Observed species, Shannon, Simpson, Chao1, ACE indexes all decreased. The Firmicutes decreased with Bacteroidetes increasing in phylum level; while the Bacteroides increased with Ruminococcaceae decreasing in genus level. Lactobacillus was the potentially beneficial genus. Conclusion: Patients developing anti-PD-1 associated colitis have characteristic clinical and pathological manifestations. Glucocorticoids are effective treatment. The fecal microbiome diversity, relative abundance of major phylum and genus have changed after treatment.

[The prevalence of Crohn's disease based on the basic medical insurance system for urban employees in China in 2013].

Objective: To investigate the prevalence of Crohn's disease (CD) among urban employees in 24 provinces (municipalities and autonomous regions) in China in 2013. Method: The crude annual prevalence of CD among urban employees with medical insurance in 2013 was estimated by using the basic medical insurance database of 24 provinces (municipalities and autonomous regions), as well as the prevalence by sex, age and region. The age-standardized rate based on the 2010 census was also estimated. Results: The crude prevalence of CD among urban employees in 2013 was 3.2/100 000(95%CI:3.1/100 000-3.3/100 000) , and the sex-specific rate was 3.5/100 000 (95%CI:3.3/100 000-3.6/100 000) and 3.0/100 000 (95% CI:2.8/100 000-3.1/100 000) for male and female, respectively. The crude prevalence in different regions indicated that the highest crude prevalence was in the eastern region [5.6/100 000 (95% CI:5.4/100 000-5.8/100 000) ]. Conclusion: The prevalence of CD in China is still lower than that of the western countries, with difference varied in terms of age, gender and region.

[Study of the correlation between vitamin D status and cytokine levels in patients with Crohn's disease].

Objective: To investigate the correlations of serum total 25-hydroxyvitamin D (T-25 (OH) D) levels with serum cytokine levels including interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) and Crohn's disease activity index (CDAI) in patients with Crohn's disease (CD). Methods: A total of 60 patients with CD admitted in Peking Union Medical College Hospital from April 2014 to March 2019 who completed the tests for serum T-25 (OH) D and cytokines (IL-6, IL-8 and/or TNF-α) were retrospectively enrolled. Clinical data were collected for analysis. Results: Among 60 CD patients, there were 46 male patients, and the age was (34±13) years. There were 16 patients (26.7%) in remission and 44 cases (73.3%) in active status. The T-25(OH)D level was (16.0±7.7)µg/L. The prevalence of vitamin D sufficiency, insufficiency and deficiency was 26.7%, 40.0% and 33.3%, respectively. Correlation analysis showed that serum T-25 (OH) D level was negatively correlated with CDAI (r=-0.363,P=0.004), IL-6 level (r=-0.360,P=0.007), hsCRP level(r=-0.272, P=0.043) and ESR level(r=-0.293, P=0.024), while positively correlated with serum Alb level(r=0.372, P=0.003)、Hb(r=0.330, P=0.010) and BMI(r=0.276, P=0.033).Twenty-three cases (52.3%) of active CD patients accompanied with infection had a lower level of serum T-25 (OH) D than those without infection [(12.55±7.17) vs (17.41±6.49)µg/L, P=0.023]. Conclusion: Serum T-25 (OH) D level was negatively correlated with CDAI, serum IL-6 level and inflammatory markers in patients with CD, and it was lower in active CD patients with infection than those without infection.

[The 477th case: muscular spasms, alopecia, diarrhea].

Diarrhea is a common digestive symptom. Here, we reported a case of young patient admitted with diarrhea caused by lead poisoning and cytomegalovirus infection. Through informative medical history and multi-disciplinary team discussion, Satoyoshi syndrome was finally diagnosed.

[Clinical characteristics of metastasis-induced acute pancreatitis in patients with lung cancer].

Objective: To analyze the clinical features and prognosis of lung cancer patients with metastasis-induced acute pancreatitis (MIAP), and to provide clues for early diagnosis. Methods: The characteristics and prognosis of 8 patients with MIAP in lung cancer admitted to Peking Union Medical College Hospital from January 2002 to September 2019 were retrospectively analyzed and were compared with non-tumor-induced AP. Results: Sevencases(7/8) were Mild AP, one (1/8) was Severe AP. Four patients (4/8) presented with AP as the reporting sign and lung cancer was not diagnosed until (112±36) days after the onset of AP. Clinical manifestations included abdominal pain (8/8), weight loss (4/8), nausea and vomiting (2/8), and jaundice (1/8). Stages of lung cancer were all Ⅳ.Histopathology proved that seven cases (7/8) were small cell lung cancer, and one case (1/8) was poorly differentiated adenocarcinoma. The median survival time was 11 months. Compared with non-tumor-induced AP, lung cancer patients with MIAP were older[(62±9) vs (48±15), P=0.018], the incidence of primary pancreatic duct dilatation (37.5% vs 3.1%, P=0.004) and abdominal lymphadenopathy (37.5% vs 6.3%, P=0.017) were higher; the level of hemoglobin [105.3±15.6) g/L vs (147.9±24.8) g/L, P<0.001] and hematocrit [(31.4±5.3) vs (42.5±6.1), P<0.001] were lower. Conclusions: Patientswith MIAP in lung cancer had poor outcome and unspecific symptoms. Old age, anemia, main pancreatic duct dilatation and abdominal lymphadenopathy are diagnostic clues that merit clinical attention.

[Analysis on clinical features of patients with ulcerative colitis associated colorectal cancer].

Objective: To analyze the clinical features of ulcerative colitis associated colorectal cancer (UC-CRC). Methods: A total of 869 inpatients with Ulcerative Colitis (UC) in Peking Union Medical Hospital from January 1998 to January 2018 were continuously enrolled. Clinical data and the outcome of colorectal cancer (CRC) were collected via medical records and telephone follow-up. Chi-square test and logistic regression model were used to analyze the data. Results: There were 16 patients in 869 UC inpatients who were diagnosed with CRC during a period of 7 548 person years and the incidence rate of UC-CRC was 1.84%. Compared to UC inpatients without CRC, a longer course of disease (OR=1.087, 95% CI:1.046-1.129) , a lower usage rate of 5-Aminosalicylic Acid(5-ASA) (OR=0.218, 95% CI:0.052-0.915) and a higher incidence rate of intestinal stenosis (OR=16.533, 95% CI:3.824-71.478) were found in UC inpatients with CRC. Conclusions: A long disease course is a risk factor for UC patients developing CRC, while 5-ASA therapy can reduce the risk of suffering from CRC. For UC patients with intestinal stenosis, CRC should be warned for occurring.

[The influence of probiotics and synbiotics on intestinal inflammation and microbiota in mice with acute colitis].

Objective: To investigate the effects of probiotics and synbiotics on inflammation and microbiota of acute colitis in mice. Methods: C57BL/6J mice were divided into 4 groups randomly. Each group had 10 mice and was given 2.5% dextran sulfate sodium (DSS) drinking water for 5 days other than the blank control group. Except for model control group, other two groups were administrated with probiotics and synbiotics, respectively. Probiotics was composed of Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacterium lactis, while synbiotics was composed of the aforementioned probiotics, inulin and galactooligosaccharide. Feces of different periods and mucosa samples were collected to analyze the differences of enteric flora by 16s rDNA sequencing. Results: (1) Pathological scores in probiotics group and synbiotics group were 5.40±2.79 and 7.25±2.87, respectively, which were significantly lower than those in the model control group with scores 27.00±7.94. Model control group, probiotics group and synbiotics group showed lower flora diversity, increased Bacteroides and decreased Faecalibacterium than blank control group. The mucosal microbiota was different from fecal flora in abundance and species for each group, and Mucispirillum was more common in mucosa. Conclusions: Probiotics and synbiotics alleviate the inflammation of acute colitis in mice. Imbalance of beneficial genera to harmful genera is the characteristic of acute colitis. Supplementation of probiotics and synbiotics contributes to regulating the balance of intestinal microbiota.

[Effect of VSL#3 and S.Boulardii on intestinal microbiota in mice with acute colitis].

Objective: To investigate the effects of probiotics(VSL#3, S. Boulardii) on intestinal flora of mice with DDS-induced acute colitis. Methods: C57BL/6J mice were administered with 2.5% dextran sulfate sodium for 5 consecutive days to develop the acute colitis model except for the blank control group. Meantime,Mice were treated with drinking water (DSS model group),VSL#3 (1.5×10(9) CFU),or S.Boulardii(5×10(7) CFU) by gavage for 7 days respectively,and mice were sacrificed 2 days after the model of colitis was established. The fecal specimens before gavage (day 0),in the middle of experiment (day 4),and the end of gavage (day 7) and the intestinal mucosa after sacrifice were collected to analyze the differences between these four groups by 16s rDNA sequencing method. Results: Compared with the DSS model group, VSL#3 group showed a decrease in disease activity index (DAI) and histological scores, and there was no significant change in the S.Boulardii group. Fecal microbiota:in the middle of experiment,the alpha diversity of DSS model group,VSL#3 group and S.Boulardii group were lower than that of the blank control group(P=0.0135,P=0.0018,P=0.0151). After the end of gavage,the diversity of the VSL#3 group was lower than that of the blank control group(P=0.025), and the difference between any other two groups was not statistically significant. Mucosa-adherent microbiota:biodiversity of DSS model group,S.Boulardii group were lower than the blank control group(P=0.031,P=0.0437),while biodiversity of VSL#3 group was higher than DSS model group and S. Boulardii group(P=0.0394, P=0.0426). Compared with the blank control group, the DSS model group showed an increase in Bacteroides and a decrease in Lactobacillus. Abundance in the genus Turicibacter and Odoribacter increased in intestinal microbiota of mice with acute colitis, while VSL#3 inhibited them. Conclusions: VSL#3 alleviates inflammation in DSS-induced colitis of mice.Both VSL#3 and S.Boulardii can affect intestinal microbiota. Compared with healthy mice,mice with colitis showed a reduced diversity of microbiota both in feces and in intestinal mucosa. VSL#3 increases biodiversity of mucosal microbiota in mice with acute colitis,while it does not increase biodiversity of fecal microbiota. Genera such as Turicibacter and Odoribacter increase in mice with acute colitis, and these genera can be inhibited by VSL#3.

Serum immunoinflammation-related protein complexes discriminate between inflammatory bowel disease and colorectal cancer.

PURPOSE: Inflammatory bowel disease (IBD) is an important risk factor for colon cancer. Novel serum immunoinflammation-related protein complexes (IIRPCs) have shown associations with early cancer detection. Herein, we investigated the potential of serum IIRPCs for discriminating between IBD and colorectal cancer (CRC) patients. METHODS: Serum protein complexes of 65 healthy controls, 57 CRC, 69 (ulcerative colitis) UC, and 67 (Crohn's disease) CD patients were isolated by native-PAGE. The gray values of serum IIRPCs bands in the gel were quantified using Quantity One software. The receiver-operating characteristic (ROC) curves were constructed to assess the discriminating ability by calculating the area under the ROC curve. RESULTS: The serum IIRPCs levels in IBD and CRC patients were significantly elevated compared to healthy controls. ROC analysis indicated certain diagnostic ability of serum IIRPCs in differentiating IBD from CRC. Specifically, "a3" complex discriminated UC from CRC, with an AUC value of 0.722, sensitivity of 69.4% and specificity of 63.8%. Similarly, "b4" complex discriminated UC from CRC, with an AUC value of 0.709, sensitivity of 70.4%, and specificity of 60.0%. In addition, the "a3" complex also discriminated CD from CRC, with an AUC value of 0.785, sensitivity of 73.1%, and specificity of 74.1%, while the "b4" complex showed a tendency to discriminate CD from CRC, with an AUC value of 0.663, sensitivity of 67.9% and specificity of 50.0%. Thus, an equation based on multiple IIRPCs was built to further improve the discriminating power. CONCLUSIONS: Serum IIRPCs can be used to discriminate IBD from CRC and may also be associated with early screening of colitis-associated cancer.