Significant improvement of physicians' knowledge and clinical practice: an opportune, effective, and convenient continuing medical education program on functional dyspepsia.

Aims: This cohort study aimed to explore the effect of a one-day online continuing medical education (CME) on the improvement of physicians' knowledge and clinical practice on functional dyspepsia (FD). Methods: Physicians were invited to participate in this CME via medical education applications. FD training videos made in advance were sent to participants via a weblink. Before and after training, participants were required to finish the FD knowledge test and provide case information of FD patients. McNemar test, Wilcoxon rank-sum test, Freidman test, Chi-square test, quantile regression, and generalized estimating equations (GEE) were used to perform statistical analysis. Results: There were 397 of 430 (92.33%) physicians finished this CME program. The total score of the FD knowledge test after training was significantly higher compared with before training [488.3 (468.3-510.0) vs. 391.7 (341.7-450.0), p < 0.001]. Particularly, physicians from primary hospitals show more increase in total scores than physicians from secondary and tertiary hospitals. According to the GEE model, receiving this online training was an independent predictor of physicians' choice of upper gastrointestinal endoscopy in patients with FD [OR 1.73, 95%CI (1.09-2.73), p = 0.020], especially in PDS. Also, it was an independent predictor of physicians' choice of acid-suppressive drugs in patients with FD [OR 1.30, 95%CI (1.03-1.63), p = 0.026], especially in EPS and PDS overlapping EPS. Conclusion: This one-day online CME program effectively and conveniently improved physicians' knowledge and clinical practice, providing new ideas for future CME and facilitating precise clinical management of FD patients with different subtypes especially in primary hospitals.

Case report: Successful treatment of ulcerative colitis-related post-colectomy enteritis refractory to multiple therapies with ustekinumab.

Ulcerative colitis-related severe post-colectomy enteritis is a rare condition. A few cases have undergone successful treatment with corticosteroids, Cyclosporine, Azathioprine, and Infliximab. We aim to evaluate the treatment outcome of ustekinumab in this rare case. Here we describe a 56-year-old woman with post-colectomy enteritis refractory to multiple therapies. Finally, the patient was administered with ustekinumab treatment. Under monitoring, the feces volume of the patient decreased from 5000-7000 mL per day to 1700-2000 mL. Over a one-year follow-up period, the patient gradually gained body weight, with the stoma drainage of formed brown stool. And the villi of the small intestinal mucosa restore growth. To our knowledge, this is the first report that indicates ustekinumab could be a treatment selection for ulcerative colitis-related severe post-colectomy enteritis.

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.

BACKGROUND: Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non-response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF-α (tumour necrosis factor-α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond. METHODS: We designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage-expressed membrane TNF-α (hmTNF-α) and IL-23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb-Fc.  Our study encompassed in vitro and in vivo characterization of BsNb and BsNb-Fc. RESULTS: BsNb-Fc exhibited an improved serum half-life, targeting capability and effector function than BsNb. It's demonstrated that BsNb-Fc exhibited superior anti-inflammatory effects compared to the anti-TNF-α mAb (infliximab, IFX) combined with anti-IL-12/IL-23p40 mAb (ustekinumab, UST) by Transwell co-culture assays. Notably, in murine models of acute colitis brought on by 2,4,6-trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb-Fc effectively alleviated colitis severity. Additionally, BsNb-Fc outperformed the IFX&UST combination in TNBS-induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS. CONCLUSION: These findings highlight an enhanced efficacy and improved biostability of BsNb-Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF-α inhibition. KEY POINTS: A bispecific nanobody (BsNb) was created to target TNF-α and IL-23p19, exhibiting high affinity and remarkable stability. BsNb-Fc inhibited the release of cytokines in CD4+T cells during co-culture experiments. BsNb-Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination.

Ulcerative colitis overall disease severity index predicts colectomy: a prospective cohort study.

BACKGROUND: ulcerative colitis (UC) overall disease severity index (DSI) has been established. A prospective cohort study was performed to find the value of DSI to predict colectomy within one and four years and explored the association between DSI and other indexes. METHODS: the hospitalized UC patients were enrolled from March 2018 to January 2019 in this single center study. DSI, Truelove and Witts criteria, Mayo index and Seo index were assessed by medical records. Outcome was whether to undergo colectomy within one and four years and was obtained by telephone survey or medical records. Index values of predicting colectomy within one and four years were evaluated using receiver operating characteristics (ROC) curves. RESULTS: one hundred and thirty-eight of 233 hospitalized UC patients were enrolled. Within one year, the follow-up period was less than one year for six patients and two patients had died. A further nine patients underwent colectomy. The Spearman correlation coefficient between DSI and Truelove and Witts criteria, Mayo index and Seo index were 0.730, 0.839 and 0.843, respectively. Using these indices to predict colectomy within one and four years, the area under the curve of DSI was more than those of other indices and the cut-off value of DSI was 79. CONCLUSIONS: a good correlation of DSI with other indexes was demonstrated. DSI can be used to predict the need for colectomy within one or four years.

Ulcerative colitis overall disease severity index predicts colectomy: a prospective cohort study

Background: ulcerative colitis (UC) overall disease severity index (DSI) has been established. A prospective cohort study was performed to find the value of DSI to predict colectomy within one and four years and explored the association between DSI and other indexes. Methods: the hospitalized UC patients were enrolled from March 2018 to January 2019 in this single center study. DSI, Truelove and Witts criteria, Mayo index and Seo index were assessed by medical records. Outcome was whether to undergo colectomy within one and four years and was obtained by telephone survey or medical records. Index values of predicting colectomy within one and four years were evaluated using receiver operating characteristics (ROC) curves. Results: one hundred and thirty-eight of 233 hospitalized UC patients were enrolled. Within one year, the follow-up period was less than one year for six patients and two patients had died. A further nine patients underwent colectomy. The Spearman correlation coefficient between DSI and Truelove and Witts criteria, Mayo index and Seo index were 0.730, 0.839 and 0.843, respectively. Using these indices to predict colectomy within one and four years, the area under the curve of DSI was more than those of other indices and the cut-off value of DSI was 79. Conclusions: a good correlation of DSI with other indexes was demonstrated. DSI can be used to predict the need for colectomy within one or four years (AU)

International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by Board of Specialty Committee of Digestive System Disease of World Federation of Chinese Medicine Societies (2023).

Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework. Additionally, it incorporated insights from ancient Chinese medical sources, employing the evidence grading method found in traditional TCM literature. The development process involved collaboration with multidisciplinary experts and included input from patients with UC. The guideline, based on a comprehensive review of available evidence, present 40 recommendations. They offer a condensed overview of TCM's role in understanding the pathogenesis, diagnosis, and treatment of UC, along with an assessment of the efficacy of various TCM-based treatments. TCM exhibits promising outcomes in the treatment of UC. However, to establish its efficacy conclusively, further high-quality clinical studies on TCM for UC are essential.

Iatrogenic Small Intestinal Obstruction / Obstrucción iatrogénica del intestino delgado

An 83-year-old female, suffering from abdominal pain, nausea, and vomiting, was admitted to our hospital. Gas-liquid level and tumor was not seen on the abdominal computed tomography scan. Instead, two high density balloon which were 2.7cm(distal) and 3.3cm(proximal) in diameter separately were shown (Figure A) in small intestine. The balloons proved to be part of ileus tube and iohexol which was incorrectly injected into the balloons caused a blockage in the tube. During colonoscopy, we were surprised to find that the distal balloon had passed through the ileocecal valve and we punctured it easily (Figure B). However, affected by the broken distal balloon, we could not reach another one. Finally, we cut off the connector fixed to the face and instructed the patient to take some oral paraffin oil and exercise appropriately. The next day, the balloons were discharged with the symptoms alleviated. It is rare for iatrogenic foreign body to cause ileal obstruction).(AU)

Three-dimensional printed cast assisted screw fixation of calcaneal fractures: a prospective study.

BACKGROUND: Treatment of displaced intra-articular calcaneal fractures (DIACFs) with percutaneous screw fixation remains defective in some aspects. A novel three-dimensional (3D) printed cast was devised to assist screw placement. This study assessed the radiological and functional outcomes of 3D-printed cast assisted screw fixation for patients with DIACFs. METHODS: Patients with unilateral Sanders type II or III DIACFs admitted to a single-centre hospital underwent either 3D-printed cast assisted screw fixation (3D group) or minimally invasive plate fixation (control group) from September 2020 to November 2022. All patients were assessed at one, two, three, and six months of follow-up. Comparison between groups was conducted in operative duration, fluoroscopic times, radiographic measurements of the calcaneus, and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score. RESULTS: A total of 32 patients were enrolled (19 in the 3D group versus 13 in the control group). Significant differences were detected between the 3D group and control group in operative duration (53.63±8.95 min, 95.08±8.31 min, P <0.001), fluoroscopic times (7.37±1.21, 16.85±1.57, P <0.001). At a follow-up of six months, the 3D group showed better restoration than the control group in calcaneal width, height, Bohler angle, and AOFAS Ankle-Hindfoot scores (all P <0.001). No significant differences were shown in calcaneal length and Gissane angle (P >0.05). No wound-related complications occurred in either group. CONCLUSION: The 3D-printed cast assisted screw fixation has shown superiority over minimally invasive plate fixation in the operative duration, fluoroscopic exposure, morphological restoration of the calcaneus, and functional outcomes in the treatment of DIACFs.

A rare complication of people with inflammatory bowel disease after ileostomy: A case report.

RATIONALE: Venous thromboembolism is one of the common complications of inflammatory bowel disease (IBD), which is a significant health problem worldwide. Factors such as inflammation, medications, and abdominal surgery, contribute to the increased risk of venous thromboembolism in patients with IBD. Cavernous transformation of the portal vein (CTPV) is a relatively rare complications of IBD. Subsequent portal hypertension could be fatal and the clinical treatment is difficult. Thus, early prevention is very crucial. PATIENT CONCERNS: A 55-year-old man presented to our department with asthenia, hematemesis, and diarrhea. He was diagnosed with Crohn disease for 9 years. Two years ago, He suffered intestinal perforation and received enterectomy and ileostomy. And, anticoagulants were not given during perioperative period and after surgery because of the history of gastrointestinal bleeding. DIAGNOSES: The patient was given endoscopy inspection showing the varices of esophagus and gastric fundus near cardia. Contrast enhancement CT scan showed portal hypertension, CTPV, gastroesophageal varices, and splenomegaly. Then percutaneous transhepatic portography was performed to make a clear diagnosis. INTERVENTIONS: Concerned about the risk of surgery, he refused surgical shunting. Conservative treatment was recommended due to technical difficulties instead of interventional therapy. OUTCOMES: And after a period of fasting, blood transfusion, and parenteral nutrition treatment, the patient did not experience any further vomiting or hematemesis. LESSONS: Early identification and treatment of CTPV is difficult. Prevention such as early application of anticoagulant is necessary for patients with IBD undergoing surgery, particularly with simultaneous stoma formation. For IBD patients who are not suitable for anticoagulant therapy, postoperative follow-up monitoring should be more frequent and monitoring time should be extended.

Iatrogenic Small Intestinal Obstruction.

An 83-year-old female, suffering from abdominal pain, nausea, and vomiting, was admitted to our hospital. Gas-liquid level and tumor was not seen on the abdominal computed tomography scan. Instead, two high density balloon which were 2.7cm(distal) and 3.3cm(proximal) in diameter separately were shown (Figure A) in small intestine. The balloons proved to be part of ileus tube and iohexol which was incorrectly injected into the balloons caused a blockage in the tube. During colonoscopy, we were surprised to find that the distal balloon had passed through the ileocecal valve and we punctured it easily (Figure B). However, affected by the broken distal balloon, we could not reach another one. Finally, we cut off the connector fixed to the face and instructed the patient to take some oral paraffin oil and exercise appropriately. The next day, the balloons were discharged with the symptoms alleviated. It is rare for iatrogenic foreign body to cause ileal obstruction).

Probiotic Escherichia coli Nissle 1917 Expressing Elafin Protects Against Inflammation and Restores the Gut Microbiota.

Intestinal mucosal inflammation and epithelial barrier dysfunction have been implicated as pathological factors in inflammatory bowel disease (IBD). An emerging area of IBD research focuses on probiotics. The probiotic Escherichia coli Nissle 1917 (EcN) is an excellent choice for engineering therapeutic microbes. Elafin is an endogenous specific inhibitor of neutrophil elastase (NE) and proteinase 3, and we previously found Elafin can effectively suppress the development of colitis. Here, we genetically engineered EcN to deliver Elafin (EcN-Elafin) directly to the colonic mucosa and explored the protective effects of EcN-Elafin against colitis in mice. EcN-Elafin significantly alleviated dextran sodium sulfate (DSS) induced colitis. Compared with wild-type EcN, oral administration of EcN-Elafin displayed better effects on loss of weight, colon length shortening, elevated expression of myeloperoxidase (MPO), and proinflammatory cytokines and chemokine in colonic tissues. In addition, EcN-Elafin restored the expression and distribution of tight junction protein ZO-1 in colonic tissues back to normal. In a damaged colonic epithelial model utilizing Caco-2 cells stimulated with TNF-α, EcN-Elafin efficiently downregulated the activation level of NF-κB signaling. EcN-Elafin was also found to have restored the dysbiosis in gut caused by DSS administration. Moreover, EcN-Elafin significantly enhanced the concentrations of butyrate and valerate in the gut lumen. Thus, our findings demonstrated that EcN-Elafin enhanced the colonic epithelial barrier, promoted the resolution of inflammation, modulated the gut microbiota, and elevated concentrations of short-chain fatty acids (SCFAs) in the gut. EcN-Elafin may be a potential therapeutic method for IBD.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Menstrual blood-derived mesenchymal stem cells attenuate inflammation and improve the mortality of acute liver failure combining with A2AR agonist in mice.

BACKGROUND AND AIM: Acute liver failure (ALF) poses a serious public health issue. The menstrual blood-derived mesenchymal stem cells (MenSCs) have been applied to cure various liver-related diseases. However, the efficacy and mechanism are far from clear. This study aims to explore the efficacy and potential mechanism of MenSCs to cure ALF. METHODS: We investigate the potential mechanism of MenSCs on the ALF in vitro and in vivo. A2A adenosine receptor (A2AR) activation was investigated as the potential reinforcer for MenSCs treatment. Lipid polysaccharide/d-galactosamine (d-GalN) was employed to induce ALF. Diverse techniques were used to measure the inflammatory cytokines and key signaling molecules. Hematoxylin-eosin stain and aminotransaminases were applied to evaluate the liver injury. Flow cytometry was employed to assess the T cells. RESULTS: The MenSCs can decrease the lipid polysaccharide-induced inflammatory cytokine elevation and related signaling molecules in ALF, including TLR4, phosphorylated-NF-kBp65 (p-NF-kBp65), PI3K, and p-AKT, p-mTOR and p-IKK in vitro. Moreover, MenSCs also can significantly reverse the liver injury, inflammatory cytokines elevation and related signaling molecules increase, and Treg/Th17 ratio decrease in vivo. In addition, MenSCs plus A2AR agonist can enhance the above changes. CONCLUSIONS: The MenSCs can attenuate the ALF-induced liver injury via inhibition of TLR4-mediated PI3K/Akt/mTOR/IKK signaling. Then, this inhibits the p-NF-κBp65 translocate into nuclear, which causes a decrease of inflammatory cytokines release. Moreover, A2AR agonist can play a synergic role with MenSCs and enhance the above-mentioned effects.

HCP5 Promotes Proliferation and Contributes to Cisplatin Resistance in Gastric Cancer Through miR-519d/HMGA1 Axis.

INTRODUCTION: The long-non-coding RNA HCP5 (HLA complex P5) has been extensively linked to the ability of cancer cells to resist chemotherapeutic interventions. Here, we investigated the role of HCP5 in gastric cancer (GC) which to-date has been poorly characterized. Our results indicated that HCP5 expression was up-regulated in GC cells. METHODS: HCP5, miR-519d, and high mobility group A1 (HMGA1) expression levels in GC cells were measured using quantitative real-time PCR (qRT-PCR) and Western blot analysis. Drug sensitivity and apoptosis of tumor cells were assessed using cell counting kit-8, flow cytometry, and caspase activity assay. Bioinformatics and luciferase reporter assays were employed for analyzing the interactions between HCP5, miR-519d, and HMGA1. RESULTS: HCP5 knockdown suppressed proliferation and weakened the resistance to cisplatin (DDP) of GC cells. miR-519d was down-regulated in GC cells and sponged by HCP5. HMGA1 was directly inhibited by miR-519d and its expression was up-regulated in GC cells. HCP5 exacerbated the resistance to cisplatin of GC cells in vitro by enhancing HMGA1 expression via sponging miR-519d. CONCLUSION: In summary, HCP5 promoted proliferation and contributed to DDP resistance in GC cells through miR-519d/HMGA1 axis.

A Seven-NF-κB-Related Gene Signature May Distinguish Patients with Ulcerative Colitis-Associated Colorectal Carcinoma.

PURPOSE: Ulcerative colitis (UC) patients have an increased risk of colorectal cancer (CRC), and compared with sporadic CRC, ulcerative colitis-associated colorectal cancer (CAC) is more aggressive with a worse prognosis. This study aimed to identify a gene signature to predict the risk of CAC for patients with UC in remission. PATIENTS AND METHODS: Series of quiescent UC-related transcriptome data obtained from the Gene Expression Omnibus (GEO) data set were divided into a training set and a validation set. Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), and \Weighted Correlation Network Analysis (WGCNA) combined with protein-protein interaction (PPI) analysis were used to identify the pathways and gene signatures related to tumorigenesis among quiescent UC patients. A generalized linear model (GLM) of Poisson regression based on the training set was applied to estimate the diagnostic power of the gene signature in our validation set. RESULTS: The tumor necrosis factor (TNF) signaling via NF-κB pathway was significantly augmented with the highest normalized enrichment score (NES). The genes in the brown module from WGCNA have shown a significant correlation with CAC (Pearson coefficient = 0.83, p = 6e-06). A subset of NF-κB related genes (FOS, CCL4, CXCL1, MYC, CEBPB, ATF3, and JUNB) were identified with a relatively higher expression level in CAC samples. The diagnostic value of this 7-gene biomarker was estimated by the receiver operating characteristic (ROC) curve with an area under the ROC curve (AUC) at 0.82 (p<0.0001, 95% CI: 0.7098-0.9400) in the validation cohort. CONCLUSION: In summary, the increased expression of this seven-NF-κB-related gene signature may act as a powerful index for tumorigenesis prediction among patients with UC in remission.

Efficacy of Sucralfate-Combined Quadruple Therapy on Gastric Mucosal Injury Induced by Helicobacter pylori and Its Effect on Gastrointestinal Flora.

BACKGROUND: This study explored the therapeutic efficacy of standard triple therapy combined with sucralfate suspension gel as well as the mechanisms of action in mouse models of H. pylori infection. MATERIALS AND METHODS: C57BL/6J mice were randomly divided into 5 groups: NC (natural control), HP (H. pylori infection), RAC (rabeprazole, amoxicillin, and clarithromycin), RACS (RAC and sucralfate suspension gel), and RACB (RAC and bismuth potassium citrate). HE staining and electron microscopy were performed to estimate histological and ultrastructural damages. The IL-8, IL-10, and TNF-α of gastric antrum tissues were measured by immunohistochemistry and qRT-PCR. ZO-1 and Occludin were also detected with immunohistochemistry. The genomes of gastric and fecal microbiota were sequenced. RESULTS: The eradication rate of H. pylori in the RACS group was higher than the RAC group. RACS therapy had protective effects on H. pylori-induced histological and ultrastructural damages, which were superior to the RAC group. RACS therapy reduced the protein and mRNA levels of IL-8 compared with the RAC group. The expression of Occludin in the RACS group was significantly higher than that of the RAC group. The composition of gastric and fecal microbiota for RACS was similar to the RACB group according to PCA. CONCLUSIONS: The RACS regimen eradicated H. pylori infection effectively and showed RACS had protective effects against H. pylori-induced histological and ultrastructural damage. The mechanisms of RACS effects included decreasing IL-8, enhancing Occludin, and transforming gastric microbiota. Moreover, RACS and RACB have a similar effect on gastrointestinal flora.

The relationship between dectin-1 and mast cells in patients with diarrhea-predominant irritable bowel syndrome.

Background/Aims: Currently, the role of the microbiome GBA is being widely studied in the pathogenesis of visceral hypersensitivity in IBS. To investigate the role of fungus, the current study aimed to i) investigate the expression of Syk/CARD9-coupled Dectin-1 receptors in the ileocecal mucosa in D-IBS patients and (ii) explore the relationships between Dectin-1 and plasma MCT levels as well as anorectal sensory function in patients with D-IBS.Methods: Thirty-eight D-IBS patients who met the Rome III criteria and 2 groups of age- and sex-matched asymptomatic healthy controls were recruited from March 2015 to January 2017. Anorectal sensory function was quantified by HR-ARM. Plasma MCT titers were identified by ELISA, while the expression of Syk/CARD9 Dectin-1 receptors in ileocecal mucosa was identified by RT-qPCR.Results: (i) The expression of Syk/CARD9-coupled Dectin-1 receptors was significantly higher in D-IBS patients than in controls (p < .001). ii) The threshold values of first sensation and desire to defecate were significantly lower in D-IBS patientsthan in controls (the P value was0.007 and 0.001 respectively). (iii) There were negative correlations between plasma MCT levels and first sensation thresholds in D-IBS patients (r = -0.513, p = .012) and the desire to defecate thresholds (r = -0.423, p = .044). (iiii) There was a positive correlation between plasma MCT titers and the expression of Dectin-1 receptors in D-IBS patients (r = 0.565, p = .005).Conclusions: These results suggested that fungi may partially participate in the genesis of visceral hypersensitivity by activating mast cells, which is mediated by activation of the Dectin-1 receptor-mediated Syk/CARD9 signaling pathway.