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.

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.

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.
Animals ; Autoimmune Diseases ; immunology ; Humans ; Liver ; pathology ; Liver Diseases ; immunology ; Natural Killer T-Cells ; immunology

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

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

Objective To assess and compare the efficacy and safety of ecabet sodium-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori (Hp) eradication.Methods A multicenter,randomized,positive controlled clinical trial was carried out.The object of the study were chronic gastritis patients at 8 hospitals in Xi'an,Beijing,Shanghai and Guangzhou from June 2009 to June 2011.All patients were divided into treatment group and control group.In treatment group,patients received ecabet sodium-based quadruple therapy (two times per day,omeprazole magnesium 20 mg,amoxicillin 1000 mg,clarithromycin 500 mg and ecabet sodium 1.0 g each time for 10 days.In control group,patients were assigned to receive bismuth-based quadruple therapy (two times per day; omeprazole magnesium 20 mg,amoxicillin 1000 mg,clarithromycin 500 mg and bismuth potassium citrate 220 mg each time) for 10 days.The Hp eradication was determined by 13C or 14C urea breath test at the 38th day after the treatment and the eradication rate was calculated.Side effects were recorded and analyzed.The data were analyzed by chi square test and Fisher's exact test.Results A total of 311 patients were recruited,and 155 patients were allatted in treatment group and 156 in control group.The per-protocol (PP) analysis indicated that the eradication rates of treatment group arid control group were 75.71％(106/140) and 77.37％(106/137) respectively,and there was no significant difference x2 =0.106,P=0.745).The intention-to-treat (ITT) analysis indicated that the eradication rates of treatment group and control group were 68.39％ (106/155) and 67.95％ (106/156) respectively,and there was no significant difference x2 =0.007,P=0.934).The side effects rates of treatment group and control group were 20.00％ (31/155) and 25.64％(40/156) respectively,and the difference was not statistically significant (Fisher's exact test,P=0.280).No serious side effect was observed in two groups.Conclusion The efficacy and safety of ecabet sodium-based quadruple therapy for Hp eradication in chronic gastritis patients may be the same as bismuth-based quadruple therapy.

Objective To study the correlation of fecal calprotectin and lactoferrin with intestinal mucosa lesions in Crohn′s disease (CD). Methods Eighty-eight cases of diagnosed CD patients were selected as study group and 35 irritable bowel syndrome (IBS) patients were as controls. Fecal samples of CD patients were collected in one week before colonoscopy examination and of IBS patients were collected of CD patients, CD activity index (CDAI) was calculated at same visit, and CD endoscopic index (CDEI) was calculated in the subsequent endoscopic examination. The level of fecal calprotectin and lactoferrin were tested by ELISA method. Results The median levels of facal calprotectin and lactoferrin in CD patients were 277.16 mg/kg (from 96.85 to 693.57 mg/kg) and 59.68 mg/kg (from 10.75 to 100.58 mg/kg) respectively, which were significantly higher than those of IBS patients (7.6mg/kg, from 5.54 to 32.3 mg/kg and 0.65 mg/kg from 0.23 to 4.34 mg/kg), (Z=-8.301 and -7.986, respectively both P =0.000). There were no significant difference of calprotectin and lactoferrin level between CD patients with colon pathological changes and without colon pathological changes (Z=-0.424 and -0.699,P=0.672 and 0.485, respectively). There was no significant difference of calprotectin and lacoferrin level between remission and active periods in CD patients (Z=-1.491 and -1.075, P=0.136 and 0.283, respectively). The median values of calprotectin and lactoferrin of patients in moderate and severe active period judged under endoscopy were 663.11 mg/kg (from 263.45 to 2015.63 mg/kg) and 105.64 mg/kg (from 56.52 to 187.44) mg/kg respectively, in mild active period were 344.54 mg/kg (from 132.03 to 722.67 mg/kg) and 86.68 mg/kg (from 21.07 to 100.55 mg/kg) accordingly, and in remission period were 133.94 mg/kg (from 60.54 to 583.33 mg/kg) and 45.31 mg/kg (from 7.59 to 48.31 mg/kg, respectively). Both calprotectin and lactoferrin levels were significantly higher in active period than in remission period (χ2=10.63 and 8.18, while, P=0.005 and 0.017, respectively). Conclusions The level of fecal calprotectin and lactoferrin can reflect the pathological changes and severity of the intestinal mucosa.

Objective To evaluate the effect and mechanism of 5-aminosalicylic acid (5-ASA) on bone marrow suppression caused by thiopurines, and to explore the proper dosage of thiopurines when combined with 5-ASA for inflammatory bowel diseases (IBD) patients.MethodsThe clinical data of IBD patients who took thiopurines were retrospectively analyzed. Thiopurine methyltransferase (TPMT) activity and 6-thioguanine nucleotide (6-TGN) concentration were tested.In prospective study, patients firstly treated with azathioprine (AZA) of 50 mg/d for 4 weeks, then combined with 5-ASA of 3 g/d for another 4 weeks.The concentration of 6-TGN in red blood cells (RBC) was analyzed at the end of 4th and 8th week.Results In retrospective study, there were 45 cases in AZA/6-mercaptopurine (MP) combined with 5-ASA group, 94 patients were in AZA/6-MP.alone group.The incidence of bone marrow suppression in these two groups were 46.7％ and 16.0％, respectively.Multivariates regression analysis indicated co-administration of 5-ASA was the only risk factor of increasing bone marrow suppression incidence (OR=3.45,95％ CI 1.31 ～ 9.04).There was no significant difference of TPMT activity between AZA/6-MP combined with 5-ASA group and AZA/6-MP alone group(t=-0.351 ,P=0.734).The 6-TGN concentration was significantly higher in AZA/6-MP combined with 5-ASA group than that of AZA/6-MP alone group (the median concentration was 384.9 pmol/8× 108 RBC and 286.4 pmol/8× 108 RBC,F=29.15,P=0.00).Prospective study was completed in 8 patients.After treated with AZA of 50 mg/d for 4 weeks, the 6-TGN concentration of 7 patients was lower than 230 pmol/8 × 108 RBC.After added with 5-ASA of 3 g/d for another 4weeks, the 6-TGN concentration of 7 patients was over 230 pmol/8 × 108 RBC, three patients of those was even higher than 420 pmol/8 × 108 RBC, and bone marrow suppression occurred in 2 patients.ConclusionsThe incidence of bone marrow suppression increased in Chinese IBD patients treated with recommended routine dossage of AZA/6-MP when conbined with 5-ASA.The mechanism may be related with the increased concentration of 6-TGN in RBC.To reduce the AZA dosage may possibly keep the efficacy while decrease the incidence of bone marrow suppression.