Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Objective　To explore the effect of Mp1p on host macrophages through transcriptomics combined with metabolomics. Methods Firstly, a THP-1 macrophage strain (THP-1-Mp1p+) stably expressing Mp1p was constructed using lentivirus. Secondly, using high-throughput RNA sequencing (RNA Seq) technology, the expression level of intracellular mRNA was detected in transcriptomics analysis to determine differentially expressed genes; In metabolomics analysis, metabolite identification was performed through database comparison, and pathway analysis was performed on differential metabolites to reveal potential mechanisms of action. Finally, the results of metabolomics and transcriptomics were combined for analysis, and differential metabolites and genes were analyzed to further elucidate the mechanism of action of Mp1p on macrophages. Results Transcriptome analysis showed that, compared with the negative control group, the THP-1-Mp1p+ group had a total of 1 180 differentially expressed genes (DEGs), with 345 upregulated genes and 835 downregulated genes. GO enrichment analysis of DEGs showed that there were 135 differentially expressed genes, including 105 in biological processes (BP), 28 in cellular components (CC), and 2 in molecular functions (MF). The KEGG analysis results showed that the effect of Mp1p on THP-1 macrophages was highly correlated with the TNF pathway. The metabolomic analysis found that both the blank control group and the THP-1-Mp1p+ macrophage group achieved good separation between QC samples in both positive and negative ion modes. The threshold for significant differential metabolites was set at: VIP≥1 and T-test P<0.05, resulting in the identification of 488 differential metabolites, with 230 in the positive ion mode and 258 in the negative ion mode. Pathway enrichment analysis of the identified metabolites pointed to significant enrichment in metabolic pathways. The combined analysis confirmed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway were important metabolic pathways involved. Conclusions The virulence factor Mp1p may affect host macrophages by modulating the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway. The findings contribute to a better understanding of the mechanisms of action of Mp1p and may offer potential directions for the selection of relevant diagnostic and therapeutic targets in the future.

Objective:To investigate the psychology status and quality of life in patients with inflammatory bowel disease(IBD) in China, and to analyze the influencing factors.Methods:From September 2021 to May 2022, 42 hospitals in 22 provinces(autonomous regions and municipalities directly under the central government) in China, the clinical data of 2 478 IBD patients were collected, which included age, gender, weight, first visit or not, disease activity, disease course, main clinical manifestations(diarrhea, abdominal pain, hematochezia, extraintestinal manifestations), complications, treatment medication(5-aminosalicylic acid, glucocorticoids, immunosuppressive agents, and biological agents), and whether to have surgery. Anxiety, depression, sleep quality and quality of life of IBD patients were evaluated by generalized anxiety disorder-7 items, patient health questionnaire-9 items, Pittsburgh sleep quality index and inflammatory bowel disease questionnaire, and the related influencing factors were analyzed. Univariate analysis and multiple linear regression analysis were used for statistical analysis.Results:The average age of 2 478 IBD patients was 37.96 years old, and male counted for 62.43%(1 547/2 478). There were 61.82%(1 532/2 478) of the IBD patients in the active stage of disease, mostly mild or moderate(588 and 734 cases). There were 60.61%(1 502/2 478) of the IBD patients with different degrees of anxiety, 58.35%(1 446/2 478) of the IBD patients with different degrees of depression, and 48.87%(1 211/2 478) of the IBD patients had different degrees of sleep problems. The results of multiple linear regression analysis indicated that female, higher level of disease activity and longer disease course were independent risk factors of anxiety, depression and sleep quality in the IBD patients(unstandardized regression coefficient(95% confidence interval) 1.08(0.65 to 1.50), 0.45(0.23 to 0.68), 0.19(0.02 to 0.36), 0.83(0.33 to 1.32), 0.62(0.36 to 0.88), 0.28(0.08 to 0.47), 0.47(0.16 to 0.77), 0.39(0.23 to 0.55), 0.14(0.02 to 0.26); P<0.001, <0.001, =0.025 , =0.001, <0.001, =0.005, =0.003, <0.001, =0.027). The usage of biological agents was an independent protective factor of anxiety(unstandardized regression coefficient(95% confidence interval) -0.67(-1.17 to -0.17), P=0.008), and older age was an independent risk factor of sleep quality(unstandardized regression coefficient(95% confidence interval) 0.35(0.09 to 0.61), P=0.008). Higher level of disease activity, symptoms of diarrhea, abdominal pain, presence of extraintestinal manifestations, usage of 5-aminosalicylic acid and glucocorticoid, and with surgical treatment were independent risk factors of quality of life(unstandardized regression coefficient(95% confidence interval) -11.00(-12.24 to -9.76), -2.90(-5.26 to -0.55), -3.93(-6.25 to -1.61), -5.79(-9.87 to -1.71), -4.78(-7.79 to -1.76), -7.71(-11.07 to -4.35), -4.37(-8.00 to -0.73); P<0.001, =0.016, =0.001, =0.005 , =0.002, <0.001, =0.019), while the usage of biological agents was an independent protective factor of quality of life (unstandardized regression coefficient(95% confidence interval) 4.72(1.97 to 7.48), P=0.001). Conclusion:IBD patients generally have different degrees of anxiety, depression and sleep problems, which affect the quality of life of patients. Gender, disease activity and disease course are the influencing factors of mental disorders in IBD patients.

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.

Objective:To analyze the long-term efficacy and safety of thalidomide on refractory Crohn′s disease (CD).Methods:A total of 79 patients with refractory CD in the First Affiliated Hospital of Sun Yat-sen University treated with thalidomide were enrolled in this retrospective study from September 2005 to July 2018. Clinical effects and adverse drug reactions were recorded and assessed.Results:In this cohort,69 patients were treated with thalidomide for ≥6 months. Sixty-eight patients among the 69 patients achieved complete clinical remission and were followed up for a median 33.5 months (range, 7-110 months). Seventeen cases relapsed during follow-up. The cumulative probabilities of remaining in remission at 12, 24, 60 months were 88.6% (95% CI 80.6%-96.6%), 80.7% (95% CI 70.3%-91.1%), 53.7% (95% CI 32.1%-75.3%) respectively. Disease activity was the only variable associated with relapse risk, with a hazard ratio ( HR) of 3.559 for Crohn′s disease activity index (CDAI) ≥220(95% CI 1.213-10.449, P<0.05). Adverse reactions were recorded in 42 (53.2%) patients including12 (15.2%) leading to discontinuation of thalidomide. No serious side effects were observed in all subjects. Conclusions:This study suggests a long-term benefit of maintenance treatment with thalidomide in refractory CD.Moderate to severe patients have an increased risk of relapse. The high incidence of drug adverse reactions may restrain the clinical application of thalidomide.

Background/Aims: Crohn’s disease (CD) primarily affects young female adults of reproductive age. Few studies have been conducted on this population’s ovarian reserve status. The aim of study was to investigate potential risk factors associated with low ovarian reserve, as reflected by serum anti-Müllerian hormone (AMH) in women of reproductive age with CD. Methods: This was a case-control study. Cases included 87 patients with established CD, and healthy controls were matched by age, height and weight in a 1:1 ratio. Serum AMH levels were measured by enzyme-linked immunosorbent assay. Results: The average serum AMH level was significantly lower in CD patients than in control group (2.47±2.08 ng/mL vs. 3.87±1.96 ng/mL, respectively, P<0.001). Serum AMH levels were comparable between CD patients and control group under 25 years of age (4.41±1.52 ng/mL vs. 3.49±2.10 ng/mL, P=0.06), however, serum AMH levels were significantly lower in CD patients over 25 years of age compared to control group (P<0.05). Multivariable analysis showed that an age greater than 25 (odds ratio [OR], 10.03; 95% confidence interval [CI], 1.90–52.93, P=0.007), active disease state (OR, 27.99; 95% CI, 6.13–127.95, P<0.001) and thalidomide use (OR, 15.66; 95% CI, 2.22–110.65, P=0.006) were independent risk factors associated with low ovarian reserve (serum AMH levels <2 ng/mL) in CD patients. Conclusions Ovarian reserve is impaired in young women of reproductive age with CD. Age over 25 and an active disease state were both independently associated with low ovarian reserve. Thalidomide use could result in impaired ovarian reserve.

Objective To explore the diagnostic efficiency of ultrasound-guided biopsy in the diagnosis of gastrointestinal lesions.Methods The study retrospectively analyzed 41 cases who underwent ultrasound-guided biopsy and diagnosis were confirmed as gastrointestinal lesions either by surgery resections or by biopsies in our hospital from January 2006 to April 2018.The detection rate and the safety in the diagnosis of gastrointestinal lesions by ultrasound-guided biopsy were evaluated and they were compared with clinical efficiency of the endoscopic biopsy.Results (1) Of the 41 cases underwent ultrasound-guided biopsies,38 cases were confirmed by pathology.A 92.7％ detection rate had achieved by ultrasound-guided biopsies.In the 38 cases,the diagnoses were grouped in benign and malignant,with 29 malignant and 9 benign.(2) Among the 13 cases examined by both of the ultrasound-guided biopsy and endoscopic biopsy,the diagnostic accuracy of ultrasound-guided biopsy was 84.6％ and 61.5％ with endoscopy.No significant difference (P =0.378) between the two modalities.(3) No complication occurred with both of methods.Conclusions Ultrasound-guided biopsy of gastrointestinal lesions is a safe and effective method.It would be an alternative solution to provide clinicians with reliable diagnosis,especially when endoscopic diagnosis is not inapplicable or failed.

Objective To investigate the expression change of cytokines in peripheral blood and intestinal mucosa in the patients with diarrhea post-infectious irritable bowel syndrome(PI-IBS) and its relation with clinical symptoms scores.Methods Thirty outpatients and inpatients with diarrhea PI-IBS(observation group) and contemporaneous 30 individuals undergoing physical examination(control group) in the Hainan Provincial People's Hospital from January to December 2013 were selected.The peripheral blood mononuclear cells(PBMC) were separated and cultured.Then the levels of IFN-y and IL-10 in peripheral blood and cell culture supernatant fluid were detected by ELISA.The colonic mucosal tissue was taken by coloscopy.Then colonic mucosal IFN-γ and IL-10 protein expression was detected by immunohistochemistry staining.Furthermore,the correlationship between the level change of IFN-γ and IL-10 with clinical symptom score was analyzed by using the Spearman correlation method.Results Peripheral blod IL-10 and IFN-γ levels had no statistical difference between the two groups(P＞0.05).Compared with the control group,in PBMC seperation and cuture,the IFN-γ level in the observation group was increased and IL-10 level was decreased,the difference was statistically signifieant(P＜0.01).The intestinal main symptom score in the observation group had the positive correlation with IFN-γ expression level of PBMC culture supernatant fluid and colonic mucosal IFN-γ expression level(r=0.45,0.94,P＜0.01),and had the negative correlation with IL-10 expression level(r=-0.52,-0.79,P＜0.01).Conclusion The unbalance of IFN-γ and IL-10 level could be involved in the pathogenesis of diarrhea PI-IBS,which can serve as the observation indicators of disease activity.

OBJECTIVETo investigate the clinical epidemiology change trend of upper gastrointestinal bleeding (UGIB) over the past 15 years.

METHODSConsecutive patients who was diagnosed as continuous UGIB in the endoscopy center of The First Affiliated Hospital of Sun-Yat University during the period from 1 January 1997 to 31 December 1998 and the period from 1 January 2012 to 31 December 2013 were enrolled in this study. Their gender, age, etiology, ulcer classification, endoscopic treatment and hospitalization mortality were compared between two periods.

RESULTSIn periods from 1997 to 1998 and 2012 to 2013, the detection rate of UGIB was 9.99%(928/9 287) and 4.49%(1 092/24 318)(χ=360.089, P=0.000); the percentage of male patients was 73.28%(680/928) and 72.44% (791/1 092) (χ=0.179, P=0.672), and the onset age was (47.3±16.4) years and (51.4±18.2) years (t=9.214, P=0.002) respectively. From 1997 to 1998, the first etiology of UGIB was peptic ulcer bleeding, accounting for 65.2%(605/928)[duodenal ulcer 47.8%(444/928), gastric ulcer 8.3%(77/928), stomal ulcer 2.3%(21/928), compound ulcer 6.8%(63/928)],the second was cancer bleeding(7.0%,65/928), and the third was esophageal and gastric varices bleeding (6.4%,59/928). From 2012 to 2013, peptic ulcer still was the first cause of UGIB, but the ratio obviously decreased to 52.7%(575/1092)(χ=32.467, P=0.000)[duodenal ulcer 31.9%(348/1092), gastric ulcer 9.4%(103/1092), stomal ulcer 2.8%(30/1092), compound ulcer 8.6%(94/1092)]. The decreased ratio of duodenal ulcer bleeding was the main reason (χ=53.724, P=0.000). Esophageal and gastric varices bleeding became the second cause (15.1%,165/1 092, χ=38.976, P=0.000), and cancer was the third cause (9.2%,101/1 092, χ=3.352, P=0.067). The largest increasing amplitude of the onset age was peptic ulcer bleeding [(46.2±16.7) years vs. (51.9±18.9) years, t=-5.548, P=0.000), and the greatest contribution to the amplitude was duodenal ulcer bleeding [(43.4±15.9) years vs. (48.4±19.4) years, t=-3.935, P=0.000], while the onset age of esophageal and gastric varices bleeding [(49.8±14.1) years vs. (48.8±13.9) years, t=0.458, P=0.648] and cancer [(58.4±13.4) years vs. (58.9±16.7) years, t=-0.196, P=0.845] did not change significantly. Compared with the period from 1997 to 1998, the detection rate of high risk peptic ulcer rebleeding (Forrest stage I(a, I(b, II(a and II(b) increased (χ=39.958, P=0.000) in the period from 2012 to 2013. From 1997 to 1998, 54 patients underwent endoscopic treatment, and the achievement ratio of hemostasis was 79.6% (43/54). From 2012 to 2013, 261 patients underwent endoscopic treatment and the achievement ratio of hemostasis was 96.9%(253/261), which was significantly higher (χ=23.287, P=0.000). Compared to the period from 1997 to 1998, more patients with variceal bleeding or non-variceal bleeding received endoscopic treatment in time (39.0% vs. 70.3%, χ=51.930, P=0.000; 3.6% vs. 15.6%, χ=62.292, P=0.000, respectively), and higher ratio of patients staging Forrest stage I(a to II(b also received endoscopic treatment in the period from 2012 to 2013 [27.4%(26/95) vs. 68.5%(111/162), χ=40.739, P=0.000]. More qualified endoscopic hemostatic techniques were used, containing thermocoagulation (0 vs. 15.2%, χ=79.518, P=0.000), hemostatic clip (0 vs. 55.9%, χ=20.879, P=0.000), hemostatic clip combined with thermocoagulation (4.3% vs. 16.4%, χ=5.154, P=0.023), while less single injection was used (87.1% vs. 6.2%, χ=10.420, P=0.001), and single spraying for hemostasis was completely abandoned in the period from 2012 to 2013. The ratio of inpatients undergoing reoperation decreased obviously in the period from 2012 to 2013 [9.3%(86/928) vs. 6.0%(65/1092), χ=7.970, P=0.005], while no significant difference was found in mortality during hospitalization between two periods.

CONCLUSIONCompared with the period from 1997 to1998, the mean onset age of UGIB increased, and the ratio of peptic ulcer bleeding decreased due to the reduction of duodenal ulcer bleeding, the detection rate of high risk peptic ulcer rebleeding increased, the cure rate of endoscopic treatment for UGIB increased, more reasonable and immediate hemostatic methods were used, but overall mortality did not change obviously in the period from 2012 to 2013.

Adult ; Age of Onset ; Aged ; Electrocoagulation ; methods ; trends ; Endoscopy, Digestive System ; trends ; Esophageal and Gastric Varices ; pathology ; therapy ; Esophagus ; pathology ; Female ; Gastrointestinal Hemorrhage ; classification ; epidemiology ; etiology ; mortality ; Gastrointestinal Neoplasms ; pathology ; Hemostasis, Endoscopic ; methods ; trends ; Hemostatic Techniques ; trends ; Hemostatics ; therapeutic use ; Humans ; Male ; Middle Aged ; Peptic Ulcer ; pathology ; therapy ; Peptic Ulcer Hemorrhage ; pathology ; therapy ; Reoperation ; trends ; Stomach Ulcer ; pathology ; therapy ; Surgical Instruments ; trends ; Ulcer ; epidemiology ; therapy

BACKGROUND/AIMS: The past decades have seen increasing incidence and prevalence of inflammatory bowel disease (IBD) in China. This article aimed to summarize the current status and characteristics of surgical management for IBD in China. METHODS: We searched PubMed, Embase, and Chinese databases from January 1, 1990 to July 1, 2014 for all relevant studies on the surgical treatment IBD in China. Eligible studies with sufficient defined variables were further reviewed for primary and secondary outcome measures. RESULTS: A total of 74 studies comprising 2,007 subjects with Crohn's disease (CD) and 1,085 subjects with ulcerative colitis (UC) were included. The percentage of CD patients misdiagnosed before surgery, including misdiagnosis as appendicitis or UC, was 50.8%±30.9% (578/1,268). The overall postoperative complication rate was 22.3%±13.0% (267/1,501). For studies of UC, the overall postoperative complication rate was 22.2%±27.9% (176/725). In large research centers (n>50 surgical cases), the rates of emergency operations for CD (P=0.032) and in-hospital mortalities resulting from both CD and UC were much lower than those in smaller research centers (n≤50 surgical cases) (P=0.026 and P <0.001, respectively). Regarding the changes in CD and UC surgery over time, postoperative complications (P=0.045 for CD; P=0.020 for UC) and postoperative in-hospital mortality (P=0.0002 for CD; P=0.0160 for UC) both significantly improved after the year 2010. CONCLUSIONS: The surgical management of IBD in China has improved over time. However, the rates of misdiagnosis and postoperative complications over the past two decades have remained high. Large research centers were found to have relatively better capacity for surgical management than the smaller ones. Higher quality prospective studies are needed in China.
Appendicitis ; Asian Continental Ancestry Group ; China* ; Colitis, Ulcerative ; Crohn Disease ; Diagnostic Errors ; Emergencies ; Hospital Mortality ; Humans ; Incidence ; Inflammatory Bowel Diseases* ; Outcome Assessment (Health Care) ; Postoperative Complications ; Prevalence ; Prospective Studies