miRNA­21 promotes the progression of acute liver failure via the KLF6/autophagy/IL­23 signaling pathway.

Acute liver failure (ALF) is a complex syndrome characterized by overactivation of innate immunity, and the recruitment and differentiation of immune cells at inflammatory sites. The present study aimed to explore the role of microRNA (miRNA/miR)­21 and its potential mechanisms underlying inflammatory responses in ALF. Baseline serum miR­21 was analyzed in patients with ALF and healthy controls. In addition, miR­21 antagomir was injected via the tail vein into C57BL/6 mice, and lipopolysaccharide/D­galactosamine (LPS/GalN) was injected into mice after 48 h. The expression levels of miR­21, Krüppel­like­factor­6 (KLF6), autophagy­related proteins and interleukin (IL)­23, and hepatic pathology were then assessed in the liver tissue. Furthermore, THP­1­derived macrophages were transfected with a miRNA negative control, miR­21 inhibitor, miR­21 mimics or KLF6 overexpression plasmid, followed by treatment with or without rapamycin, and the expression levels of miR­21, KLF6, autophagy­related proteins and IL­23 were evaluated. The results revealed that baseline serum miR­21 levels were significantly upregulated in patients with ALF. In addition, LPS/GalN­induced ALF was attenuated in the antagomir­21 mouse group. KLF6 was identified as a target of miR­21­5p with one putative seed match site identified by TargetScan. A subsequent luciferase activity assay demonstrated a direct interaction between miR­21­5p and the 3'­UTR of KLF6 mRNA. Further experiments suggested that miR­21 promoted the expression of IL­23 via inhibiting KLF6, which regulated autophagy. In conclusion, in the present study, baseline serum miR­21 levels were highly upregulated in patients with ALF, antagomir­21 attenuated LPS/GalN­induced ALF in a mouse model, and miR­21 could promote the expression of IL­23 via inhibiting KLF6.

The intestinal microbial metabolite acetyl l-carnitine improves gut inflammation and immune homeostasis via CADM2.

Intestinal symbiotic bacteria play a key role in the regulation of immune tolerance in inflammatory bowel disease (IBD) hosts. However, the bacterial strains directly involved in this regulation and their related metabolites are largely unknown. We sought to investigate the effects of intestinal microbial metabolites on intestinal epithelium and to elucidate their therapeutic potential in regulating intestinal mucosal inflammation and immune homeostasis. Here, we used metagenomic data from Crohn's disease (CD) patients to analyze the composition of intestinal flora and identify metabolite profiles associated with disease behavior, and used the mouse model of dextran sodium sulfate (DSS)-induced colitis to characterize the therapeutic effects of the flora metabolite acetyl l-carnitine (ALC) on DSS-induced colitis. We found that intraperitoneal injection of ALC treatment could significantly alleviate the symptoms of DSS-induced colitis in mice, including prevention of weight loss, reduction in disease activity index (DAI) scores, increasing of colonic length, reduction in histological scores, and improvement in intestinal barrier function. Further, transcriptome sequencing analysis and gene silencing experiments revealed that the absence of CADM2 abolished the inhibitory effect of ALC on the TLR-MyD88 pathway in colonic epithelial cells, thereby reducing the release of inflammatory factors in colon epithelial cells. And we confirmed a significant downregulation of CADM2 expression in intestinal tissues of CD patients compared to healthy people in a population cohort. In addition, we also found that ALC increased the ratio of Treg cells in colon, and decreased the ratio of Th17 cells and macrophages, thereby improving the immune tolerance of the organism. The proposed study could be a potential approach for the treatment of CD.

The influence of sleep factors and dietary habits on the disease pattern of ulcerative colitis patients with long and short disease courses - a multicentre cross-sectional analysis.

BACKGROUND: Ulcerative colitis (UC) is a disease characterized by chronic relapsing-remitting inflammatory disorders and is associated with environmental changes. AIM: To explore the disease patterns of Chinese UC patients and to determine controllable related environmental factors. METHODS: This multicentre cross-sectional study was performed using a questionnaire survey. Data on clinical characteristics and environmental factors were collected. Patients with a disease course ≥5 years were defined as the long course group, and those with a disease course < 5 years were defined as the short course group. RESULTS: A total of 588 effective questionnaires were collected. The proportion of the chronic continuous pattern was the highest among patients with a long disease course (46.8%), and in patients with a short disease course, the proportion of the active to remission pattern was the highest (53.3%). In patients with a long disease course, a higher proportion of patients with adequate sleep was found in the active to remission pattern than in the chronic intermittent (72.1% vs. 43.3%, p = 0.008) and chronic continuous (72.1% vs. 52.4%, p = 0.016) patterns. In patients with a short disease course, the frequency of shellfish and shrimp was higher in the chronic continuous pattern group than in the active to remission pattern group (P = 0.001 and 0.017 respectively). CONCLUSIONS: For early diagnosis patients, dietary guidance should be actively carried out. With the prolongation of the disease course, attention should be given to the sleep quality of patients.

1.UC exhibits various disease patterns, which may be associated with differences in patient prognosis and treatment response.2.Environmental factors, especially sleep and dietary factors, correlated strongly with disease patterns, which varied in different disease courses.3.Early diagnosis patients should receive active dietary guidance, while patients with a prolonged disease course require attention to their sleep quality and appropriate drug interventions when necessary.

The TRAF2-p62 axis promotes proliferation and survival of liver cancer by activating mTORC1 pathway.

TRAF2 (Tumor necrosis factor receptor-associated factor 2) is a dual function protein, acting as an adaptor protein and a ubiquitin E3 ligase, which plays an essential role in mediating the TNFα-NFκB signal pathway. Dysregulated expression of TRAF2 has been reported in a variety of human cancers. Whether and how TRAF2 regulates the growth of liver cancer cells remains elusive. The goal of this study is to investigate potential dysregulation of TRAF2 and its biological function in liver cancer, and to elucidate the underlying mechanism, leading to validation of TRAF2 as an attractive liver cancer target. Here, we reported TRAF2 is up-regulated in human liver cancer cell lines and tissues, and high TRAF2 expression is associated with a poor prognosis of HCC patients. Proteomics profiling along with Co-immunoprecipitation analysis revealed that p62 is a new substrate of TRAF2, which is subjected to TRAF2-induced polyubiquitination via the K63 linkage at the K420 residue. A strong negative correlation was found between the protein levels of p62 and TRAF2 in human HCC samples. TRAF2 depletion inhibited growth and survival of liver cancer cells both in vitro and in vivo by causing p62 accumulation, which is partially rescued by simultaneous p62 knockdown. Mechanistically, TRAF2-mediated p62 polyubiquitylation activates the mTORC1 by forming the p62-mTORC1-Rag complex, which facilitates the lysosome localization of mTORC1. TRAF2 depletion inhibited mTORC1 activity through the disruption of interaction between p62 and the mTORC1 complex. In conclusion, our study provides the proof-of-concept evidence that TRAF2 is a valid target for liver cancer.

Impact of Helicobacter pylori on the gastric microbiome in patients with chronic gastritis: a systematic review and meta-analysis protocol.

INTRODUCTION: Chronic gastritis is a common disease worldwide. Studies have consistently shown that chronic gastritis is usually associated with gastric microbial dysbiosis, especially the infection of Helicobacter pylori. However, the interaction between H. pylori and non-H. pylori bacteria in patients with chronic gastritis has not been clearly identified yet. Consequently, we designed a protocol for a systematic review and meta-analysis, which focused on identifying the changes in gastrointestinal microbiota composition between patients with H. pylori-infective and non-infective chronic gastritis. METHOD AND ANALYSIS: We will search PubMed, EMBASE and Cochrane Library databases to retrieve observational studies on humans. The eligible studies must include data about the relative abundance of the gastrointestinal microbiome in patients with H. pylori-infective or non-infective chronic gastritis. Only the data of adults aged over 18 years will be analysed. Two researchers will extract the data independently, and Newcastle-Ottawa Scale will be used to assess the risk of bias. Random-effects model will be performed in quantitative analyses. Correlation analysis, bioinformatics analysis and function analysis will be performed. DISCUSSION: Currently, numerous studies have revealed the role of H. pylori in chronic gastritis. However, the alterations of non-H. pylori bacteria in patients with chronic gastritis remain an open question. The results of our study might provide new insights into future diagnosis and treatments. ETHICS AND DISSEMINATION: This study is based on published documents, unrelated to personal data, so ethical approval is not in need. The results of this study are expected to be published in journals or conference proceedings. PROSPERO REGISTRATION NUMBER: CRD42020205260; Pre-results.

The Inhibition of Bruton Tyrosine Kinase Alleviates Acute Liver Failure via Downregulation of NLRP3 Inflammasome.

There is no effective treatment for acute liver failure (ALF) except for an artificial liver support system (ALSS) and liver transplant. Bruton tyrosine kinase (Btk) plays important immunoregulatory roles in the inflammatory diseases, but its possible function in ALF remains to be characterized. In this study, we detected the phosphorylation level of Btk in ALF mouse liver and analyzed the protective effects of Btk inhibitor on survival rate and liver damage in ALF mouse models. We measured the expression levels of various inflammatory cytokines in the ALF mouse liver and primary human monocytes. In addition, we examined the expression of the NLRP3 inflammasome in mouse models with or without Btk inhibition. Clinically, we observed the dynamic changes of Btk expression in PBMCs of ALSS-treated patients. Our results showed that Btk was upregulated significantly in the experimental ALF mouse models and that Btk inhibition alleviated liver injury and reduced the mortality in these models. The protective effect of Btk inhibitors on ALF mice partially depended on the suppression of NLRP3 inflammasome signaling. Clinical investigations revealed that the dynamic changes of Btk expression in PBMCs could predict the effect of ALSS treatment. Our work shows that Btk inhibition is an effective therapeutic strategy for ALF. Moreover, Btk is a useful indicator to predict the therapeutic effect of ALSS on liver failure, which might have great value in clinical practice.

Clip or Tattooing: A Comparative Study for Preoperative Colon Cancer Endoscopic Localization.

Background and Aim: Preoperative endoscopic markers have been extensively used for the localization of colonic neoplastic lesions in laparoscopic surgery. We conducted this respective cohort study to compare the localization accuracy of two commonly used endoscopic marker strategies (endoscopic clip plus abdominal plain film and endoscopic tattooing). Methods: Patients who received preoperative colonoscopy localization for colonic neoplasia and underwent an elective laparoscopic operation afterward between 2013 and 2020 were included in this retrospective study. The localization accuracy of the two endoscopic strategies was compared, and the predictors of successful endoscopic localization were identified by multivariate regression. Results: In total, 195 patients [average age 62.4 ± 9.2 years, 123 male (63.1%)] undergoing preoperative colonoscopy localization and subsequent laparoscopic colectomy for colonic neoplasms were included. Endoscopic localization was finally proven to be successful in 150 (76.9%) patients in the surgery. Compared to the tattooing group, patients who had successful localization for colonic lesions were fewer in the clip group (64 of 101 cases, 63.4% vs. 86 of 94 cases, 91.5%, p < 0.001). The multivariate regression analysis showed that the endoscopic tattooing strategy, endoscopic clip strategy, and lesion location were all predictors for successful localization (all with p < 0.001). Conclusion: Compared with endoscopic clip plus abdominal plain film, endoscopic tattooing had higher localization accuracy and less intraoperative colonoscopy counseling; the endoscopic clip strategy, tattooing strategy, and colonic lesion location were all predictors of successful endoscopic localization.

Risk of malignancy in patients with inflammatory bowel disease: A population-based cohort study from China.

Carcinogenesis is one of the major complications for patients with inflammatory bowel disease (IBD) and causes poor prognosis. We aimed to describe cancer incidence in the Chinese IBD cohort compared to general population-based cancer registration data and further explore associated risk factors for cancer occurrence in IBD patients. IBD inpatients from January 1998 to January 2018 in Peking Union Medical College Hospital (PUMCH) were included in our study. Patients were followed-up from the date of IBD diagnosis until either the date of first cancer diagnosis or January 2019. Standardized incidence ratios (SIRs) of overall cancer and site-specific cancers were calculated. A total of 869 Ulcerative Colitis (UC) and 516 Crohn's disease (CD) patients were finally included with median follow-up time of 7 and 5 years, respectively. Fifty-three cases developed malignancies. After standardization by age and gender, SIR of total cancer occurrence in IBD patients was 1.77 (95% CI, 1.33-2.32). As for UC, digestive cancers (SIR 3.75; 95% CI, 2.29-5.80), thyroid cancer (SIR 10.34; 95% CI, 4.72-19.64) and hematological malignancies (SIR 6.25; 95% CI, 1.68-16.00) had the highest incidence, which were prominent in young and middle-aged patients. Use of steroids, immunosuppressants or infliximab did not present higher risk of malignancies in UC patients. There was no significant difference in cancer risk between CD patients and general population. In conclusion, the increased risks of multiple cancers are particularly prominent in Chinese UC patients and these findings can provide more targeted guidance for cancer monitoring in Chinese IBD patients.

The efficacy and safety of anti-tumor necrosis factor agents in the treatment of intestinal Behcet's disease, a systematic review and meta-analysis.

BACKGROUND AND AIM: Behcet's disease is a systemic vasculitis that can involve gastrointestinal tract. This is a systematic review and meta-analysis evaluating the efficacy and safety of anti-tumor necrosis factor (TNF) agents in treating patients with intestinal Behcet's disease. METHODS: We conducted searches on PubMed, Embase, and Cochrane. Data from eligible studies were used to calculate the pooled estimate of proportions of clinical remission, mucosal healing at Months 3, 6, 12, and 24 as well as the pooled incidence of adverse drug reactions. And subgroup analysis based on the specific type of anti-TNF agents was performed. RESULTS: Of the 828 studies initially identified, 13 were included finally, all of which were single-arm cohort studies. The pooled proportions of clinical remission at Months 3, 6, 12, and 24 were 0.61 (95%CI 0.48-0.78), 0.51 (95%CI 0.40-0.66), 0.57 (95%CI 0.48-0.67), and 0.38 (95%CI 0.16-0.88), respectively. The pooled proportions of mucosal healing at Months 3, 6, 12, and 24 were 0.66 (95%CI 0.50-0.86), 0.82 (95%CI 0.48-0.98), 0.65 (95%CI 0.51-0.81), and 0.69 (95%CI 0.39-1.00), respectively. The pooled estimate of proportion of overall adverse drug reactions for infliximab was 0.22 (95%CI 0.07-0.69). CONCLUSIONS: Anti-TNF agents, including infliximab and adalimumab, were an efficient therapy for intestinal Behcet's disease. The safety of anti-TNF agents used in the treatment of intestinal Behcet's disease was acceptable.

Long-term Disease Behavior and Surgical Intervention Analysis in Hospitalized Patients With Crohn's Disease in China: A Retrospective Cohort Study.

BACKGROUND: There is lack of real-world data for disease behavior and surgery of Crohn's disease (CD) from large-scale Chinese cohorts. METHODS: Hospitalized patients diagnosed with CD in our center were consecutively included from January 2000 to December 2018. Disease behavior progression was defined as the initial classification of B1 to the progression of B2 or B3. Clinical characteristics including demographics, disease classification and activity, medical therapy, development of cancers, and death were collected. RESULTS: Overall, 504 patients were included. Two hundred thirty-one (45.8%) patients were initially classified as B1; 30 (13.0%), 71 (30.7%), and 95 (41.1%) of them had disease progression at the 1-year follow-up, 5-year follow-up, and overall, respectively. Patients without location transition before behavior transition were less likely to experience behavior progression. However, patients without previous exposure to a corticosteroid, immunomodulator, or biological agent had a greater chance of experiencing behavior progression. When the long-term prognosis was evaluated, 211 (41.9%) patients underwent at least 1 CD-related surgery; 108 (21.4%) and 120 (23.8%) of these patients underwent surgery before and after their diagnosis, respectively. An initial classification as B1, no behavior transition, no surgery prior to diagnosis, and previous corticosteroid exposure during follow-up were associated with a lower risk of undergoing surgery. CONCLUSIONS: This study depicts the clinical features and factors associated with behavior progression and surgery among hospitalized CD patients in a Chinese center. Behavior progression is associated with a higher probability of CD-related surgery, and strengthened therapies are necessary for them in the early phase.

The role of cytomegalovirus colitis on short- and long-term outcomes for patients with ulcerative colitis.

BACKGROUND AND AIM: Cytomegalovirus (CMV) colitis brings great obstacles for treatment of ulcerative colitis (UC). We aimed to assess the impact of CMV colitis on prognostic outcomes and associated risk factors for UC patients. METHODS: A consecutive 77 inpatients diagnosed as UC were collected retrospectively from January 2012 to December 2015. About 33 patients were defined with CMV colitis by histological tests of colon mucosa. Clinical characteristics and outcomes were compared between patients with CMV colitis or those without. The primary outcomes were UC-related colectomy or the first time of disease relapse after discharge. RESULTS: 33 CMV colitis patients had higher frequency of recent steroid treatment (81.8% vs. 31.8%, p < .001), older age of onset (45.3 ± 13.0 vs. 44.5 ± 15.7 years, p = .028) and more severe colitis (p < .001) characterized by lower hemoglobin (99.0 ± 23.2 vs. 114.6 ± 22.6 g/L, p = .004), albumin (29.7 ± 4.6 vs. 35.4 ± 6.5 g/L, p < .001), immunoglobulin G [8.8 (5.9-10.6) vs. 12.3 (9.3-16.2) g/L, p = .003] and higher C reactive protein [48.5 (21.6-73.8) vs. 9.1 (3.6-35.0) mg/L, p < .001]. The occurrence of UC-related colectomy in patients with CMV colitis was more frequent (48.5% vs 20.5%, p<.01) and CMV colitis was proved to be one of risk factors of colectomy with a hazard ratio of 3.15 (95%CI 1.387-7.171, p = .006), mainly in a short term period. UC-related complications almost occurred within 1 year since CMV colitis diagnosis. And UC patients with CMV colitis always experienced early relapse. CONCLUSIONS: CMV colitis increases the colectomy risk mainly in a short term due to severe inflammatory response, early-onset complications or medication treatment failure. There is also potential correlation between CMV colitis and early relapse. Short-term therapy for UC patients with CMV colitis should be more concerned on controlling systemic inflammation and reducing complications whereas long-term maintenance therapy may not require more aggressive intervention.

Alterations in Gastric Mucosal Microbiota in Gastric Carcinogenesis: A Systematic Review and Meta-Analysis.

Background: The gastric microbiota profile alters during gastric carcinogenesis. We aimed to identify the alterations in the alpha diversity and relative abundance of bacterial phyla and genera of gastric microbiota in the development of gastric cancer (GC). Methods: The systematic review was performed based on a published protocol with the registration number CRD42020206973. We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2021) for observational studies reporting either the relative abundance of bacterial phyla or genera, or alpha diversity indexes in both GC and non-cancer groups. Selection of studies and data extraction were performed independently by two researchers, with disagreements resolved through discussion. Risk of bias was assessed using the self-modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD). Results: Our systematic review included 751 GC patients and 792 non-cancer patients from 14 case-control studies. Gastric cancer group had fewer operational taxonomic units (OTUs) (MD = -68.52, 95%CI: -126.65 to -10.39) and a lower Simpson index (MD = -0.13, 95%CI: -0.20 to -0.07) compared with non-cancer group. At the phylum level, gastric cancer group had a higher abundance of Firmicutes (MD = 7.11, 95%CI: 1.76 to 12.46). At the genus level, Streptococcus (MD = 3.03, 95%CI: 0.07 to 6.00) and Lactobacillus (MD = 5.15, 95%CI: 1.27 to 9.04) were found to be enriched in GCgroup. The relative abundance of the rest bacterial phyla or genera analyzed in our study did not significantly differ between two groups. Subgroup analyses indicated that the source of samples was the major source of interstudy heterogeneity. Conclusion: This systematic review suggested that gastric microbiota dysbiosis occurred in gastric carcinogenesis, with alpha diversity declined and microbiota composition altered.

Autoimmune enteropathy and primary biliary cholangitis after proctocolectomy for ulcerative colitis: A case report and review of the literature.

BACKGROUND: Autoimmune enteropathy (AIE) and primary biliary cholangitis (PBC) are both immune-mediated diseases. AIE or PBC complicated with ulcerative colitis (UC) are rare. There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before, and the pathogenesis of these comorbidities has not been revealed. CASE SUMMARY: A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease, and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016. A few months after the neoileostomy, she began to suffer from recurrent episodes of watery diarrhea. She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect. However, her symptoms of diarrhea relapsed in 2019, with different histological features of endoscopic biopsies compared with 2016, which showed apoptotic bodies, a lack of goblet and Paneth cells, and villous blunting. A diagnosis of AIE was established, and the patient's stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d. Meanwhile, her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC, and treatment with ursodeoxycholic acid (16 mg/kg per day) achieved satisfactory results. CONCLUSION: Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients. Continuous follow-up is essential for UC patients with postoperative complications.

An ultrasound image-based deep multi-scale texture network for liver fibrosis grading in patients with chronic HBV infection.

BACKGROUND & AIMS: The evaluation of the stage of liver fibrosis is essential in patients with chronic liver disease. However, due to the low quality of ultrasound images, the non-invasive diagnosis of liver fibrosis based on ultrasound images is still an outstanding question. This study aimed to investigate the diagnostic accuracy of a deep learning-based method in ultrasound images for liver fibrosis staging in multicentre patients. METHODS: In this study, we proposed a novel deep learning-based approach, named multi-scale texture network (MSTNet), to assess liver fibrosis, which extracted multi-scale texture features from constructed image pyramid patches. Its diagnostic accuracy was investigated by comparing it with APRI, FIB-4, Forns and sonographers. Data of 508 patients who underwent liver biopsy were included from 4 hospitals. The area-under-the ROC curve (AUC) was determined by receiver operating characteristics (ROC) curves for significant fibrosis (≥F2) and cirrhosis (F4). RESULTS: The AUCs (95% confidence interval) of MSTNet were 0.92 (0.87-0.96) for ≥F2 and 0.89 (0.83-0.95) for F4 on the validation group, which significantly outperformed APRI, FIB-4 and Forns. The sensitivity and specificity of MSTNet (85.1% (74.5%-92.0%) and 87.6% (78.0%-93.6%)) were better than those of three sonographers in assessing ≥F2. CONCLUSIONS: The proposed MSTNet is a promising ultrasound image-based method for the non-invasive grading of liver fibrosis in patients with chronic HBV infection.

Upfront transplantation may have better outcomes than pretransplant cytoreductive therapy for treating patients with MDS-EB-1 or MDS-EB-2.

Whether patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefit from pretransplant cytoreductive therapy remains controversial. Our study compared the outcomes of upfront transplantation with those of pretransplant cytoreductive therapy in the patients who received transplantation and those who dropped out due to cytoreductive therapy-related adverse effects. Patients with MDS-EB-1 or MDS-EB-2 were enrolled and divided into three groups based on therapy pretransplantation: upfront transplantation (upfront, n = 54), induction chemotherapy (CT, n = 66) and hypomethylating agents (HMA, n = 37) alone. One hundred fifty-seven patients were enrolled and 124 received allo-HSCT, with 5.6%, 28.8% and 29.7% of drop-out rate of transplantation in upfront, CT and HMA groups (P = .030), respectively. Overall therapy-related mortality (TRM), cytoreductive therapy and transplant-related mortality was 13.0%, 32.4% and 28.4% (P = .028), and 5-year overall survival (OS) was 73.6%, 43.4% and 46.9% (P = .033). Multivariate analysis showed that CT and HMA were risk factors for TRM and OS, and transplantation was a protective factor for OS. In transplant patients, 3-year cumulative incidence of relapse was 10.6%, 20.4% and 20.3% (P = .033), 5-year TRM was 14.5%, 20.0% and 17.6% (P = .651), OS was 77.3%, 64.3% and 68.8% (P = .047) and DFS was 74.0%, 63.0% and 65.8% (P = .042). Multivariate analysis showed that CT was a risk factor for DFS, while CT, HMA and poor karyotype were risk factors for relapse. Results suggested that pretransplant cytoreductive therapy was not associated with better outcomes in the patients who had undergone transplantation. Therefore, upfront transplantation may be preferable for MDS patients.

Clinical evaluation of traditional Chinese medicine on mild active ulcerative colitis: A multi-center, randomized, double-blind, controlled trial.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by a relapsing-remitting course owing to recurrent intestinal inflammation. UC often has symptoms such as intermittent rectal bleeding, diarrhea, and abdominal pain. As the precise etiology of UC has not completely clarified, UC has become a public health challenge worldwide. According to an epidemiological survey, there were about 350,000 new cases of IBD in China from 2005 to 2014. By 2025, the number of IBD patients in China will reach 1.5 million. Traditional Chinese medicine (TCM) has been widely used to treat UC in China, however, it is still challenging to systematically determine the efficacy of in UC. Therefore, this trial aims to evaluate the clinical efficacy and safety of CHM in the treatment of mild active UC patients. METHODS: A multi-center, double-blinding, double-dummy, active-controlled, randomized trial will be established. A total of 240 patients in 6 centers with mild active UC (Mayo score is 3-5 points) and TCM syndrome of damp-heat stasis blocking and spleen-qi deficiency will be randomly allocated in the ratio of 1:1 to 2 groups: the experimental group and the control group. The experimental group will receive Hudi enteric-coated capsules (HEC) and enteric-coated mesalazine tablets placebo; the control group will receive enteric-coated mesalazine tablets and HEC placebo. Each group will be treated for 8 weeks. The primary therapeutic outcome: the rate of clinical efficacy and clinical remission at 8 weeks of treatment (last survey point) according to the modified Mayo score. The secondary outcomes: individual symptom score, TCM syndrome score, endoscopic response rate, mucosal healing rate, and quality of life scale score. Outcomes will be assessed at baseline and the end of the trial. Besides, intestinal mucosa, stools and blood biopsies from the mild active UC patients before and after treatment will be collected to reveal the underlying mechanisms. DISCUSSION: The results of this trial will provide compelling evidence of the efficacy and safety of HEC for treatment of mild active UC and preliminarily show the potential mechanism of how HEC acts. Finally, it will widen treatment options for patients with mild active UC.

Retrospective study of the differential diagnosis between cryptogenic multifocal ulcerous stenosing enteritis and small bowel Crohn's disease.

BACKGROUND: Being a rare disease, cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is easily misdiagnosed as small bowel Crohn's disease (SBCD). AIMS: This study was aimed to compare clinical features of CMUSE to SBCD. METHODS: Fourteen patients with CMUSE and 61 patients with SBCD were retrospectively analyzed. RESULTS: Hematochezia was more frequent in CMUSE patients (10, 71.4% vs 23, 37.7%, P = 0.022), while diarrhea was more common in SBCD patients (23, 37.7% vs 0, 0.0%, P = 0.015). More patients with CMUSE developed intestinal stenosis than with SBCD (14, 100% vs 37, 60.7%, P = 0.011). 30 (50.0%) SBCD patients and none CMUSE patients had an elevated erythrocyte sedimentation rate level (P = 0.001). Extra-enteric findings found by computed tomography enterography were significantly more prevalent in SBCD patients than in CMUSE patients (25,71.4% vs 3,25%, P = 0.013). Longitudinal ulcers found by endoscopy were more common in SBCD patients (16, 37.2% vs 0, 0.0%, P = 0.041), while circumferential ulcers were more common in CMUSE patients (6, 54.6% vs 8, 18.6%, P = 0.041). All ulcers observed in CMUSE patients were within mucosal and submucosal layers, but 8 (44.4%) SBCD patients had deep ulcers that reached beyond submucosal layers (P = 0.003). Ulcers were located at strictures in 9 (90.0%) CMUSE patients but only in 1 (5.6%) SBCD patient (P = 0.000). CONCLUSIONS: Gastrointestinal symptoms, erythrocyte sedimentation rate levels, radiologic, endoscopic and pathologic features help to distinguish CMUSE from SBCD.

Similarities and differences in clinical and pathologic features of inflammatory bowel disease-associated colorectal cancer in China and Canada.

BACKGROUND: Colorectal cancer (CRC) has become one of the major life-threatening complications in patients with inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). This study aimed to explore the clinical-pathologic similarities and differences in the IBD-associated CRC (IBD-CRC) between patients in China and Canada. METHODS: Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing (China) and Calgary (Canada) over the same past 13 years, including 25 (22 UC-associated and three CD-associated) from Beijing group and 53 (32 UC-associated and 21 CD-associated) from Calgary group, were compared with regards to their clinical and pathologic characteristics. RESULTS: Several known features of IBD-CRC were seen in both groups, including long duration and large extent of colitis, active inflammation background, multifocal lesions, and advanced tumor-node-metastasis stage. Beijing group showed a significantly higher percentage of UC (88.0% vs. 60.4%, P = 0.018), younger age at diagnosis of CRC (48.6 ±â€Š12.8 years vs. 61.6 ±â€Š14.7 years, P < 0.001), lower ratio of mucinous adenocarcinoma (7.1% vs. 42.4%, P = 0.001) compared with Calgary group. None of the Beijing group had concurrent primary sclerosing cholangitis, while 5.7% of Calgary group did. Surveillance colonoscopy favored the detection rate of precancerous lesions (41.4% vs.17.0%, P = 0.002). CONCLUSIONS: As compared with patients from the Calgary group, the IBD-CRC patients in Beijing group were younger, less CD-associated and had less mucinous features, otherwise they were similar in many common features.

Pancreaticobiliary involvement in treated type 1 autoimmune pancreatitis: Imaging pattern and risk factors for disease relapse.

PURPOSE: To evaluate the imaging pattern of pancreaticobiliary lesions in patients with treated type 1AIP, to determine the incidence of disease relapse and malignancy, and to identify the risk factors. METHOD: The institutional review board approval was acquired. All patients gave written informed consent. From a prospective clinico-radiological database since 2012, consecutive patients with type 1 AIP who were treated and followed up (≥18 months) were identified. The presence/absence of pancreaticobiliary lesion(s) development during follow-up were assessed. The etiology was determined and the imaging pattern was compared to the initial attack. Risk factors were identified by univariate and multivariate analysis. RESULTS: Among 103 patients with treated type 1 AIP, 44 (42.7%) developed pancreaticobiliary lesions during follow up (median time interval to initial diagnosis: 17 months, range 3-62 months), mostly after steroid discontinuation (63.6%) or during maintenance therapy (29.5%). All lesions were disease relapse, which responded to steroid treatment. At relapse, pancreatic involvement was less frequent (81.8% vs 100%, p = 0.003), and the pancreas size was smaller (p < 0.01), whereas extra-pancreatic bile duct (ExPanBD) involvement was more severe and extensive (both p < 0.01). Multivariate analysis revealed ExPanBD involvement at initial diagnosis (hazard ratio 2.437, 95% CI 1.343-7.402, p = 0.002) and serum IgG4 response ratio at the induction phase (hazard ratio 0.357, 95% CI 0.055-0.804, p = 0.011) as significant independent predictors of relapse. CONCLUSIONS: In treated type 1 AIP, although imaging pattern may differ, pancreaticobiliary lesions are usually manifestations of disease relapse. ExPanBD involvement and poor serum response suggests high risk of relapse.