Objective:To deepen understanding of IgG 4-related diseases (RDs), we analyzed the associated lymphocyte subtypes, and explored the pathogenesis and potential immunotherapeutic targets. Methods:Eighty-six patients with IgG 4-RDs were enrolled, and their clinical characteristics, peripheral lymphocyte subtypes, and disease course were analyzed. Results:The mean age of the participants was 36-87(62±11) years; 51 were male (59.3%) and 35 were women (40.7%); and 34.9% had a history of allergy. Follow-up lasted 4.8 (0.4, 14.1) months. The most common symptoms were abdominal pain, and submandibular gland and lacrimal gland swelling (each 20.9%). Sixty-five (75.6%) participants had multiple organ involvement, and the most frequently affected organs were the pancreas (52.3%), submandibular gland (51.2%), and lacrimal gland (34.9%). A high eosinophil count; high IgE, IgG, IgG 1, and IgG 4 concentrations; and low complement C3 and C4 concentrations were present in 18.8% (16/85), 30.0% (24/80), 72.9% (62/85), 58.3% (28/48), 89.5% (77/86), 61.2% (52/85), and 50.0% (42/84), respectively, of the participants. In addition, 64.7% (55/85) were positive for autoantibodies, and the most frequent was anti-nuclear antibody (63.5%). The proportion of CD4 +T lymphocytes increased in 25.7% (9/35) of the participants, which was accompanied by an increase in the ratio of CD4 +/CD8 +T lymphocytes (22.9%, 8/35). Importantly, most participants (90.0%, 18/20) had a high proportion of regulatory T (Treg) cells. High interleukin (IL)-2, IL-6, and IL-10 concentrations were present in 50.0% (11/22), 33.3% (10/30), and 16.7% (5/30), respectively, of the participants. Substantial lymphoplasmacytic infiltration, fibrosis, IgG 4-positive plasma cell infiltration, and lymphoid follicle hyperplasia or ectopic formation were present in 79.2% (42/53), 67.9%(36/53), 35.8%(19/53) and 30.2% (16/53), respectively, of the participants. Fifty-three participants with detailed pathologic data were also further evaluated, of whom 24.5% (13/53), 3.8% (2/53), and 67.9% (36/53) had definite, probable, and possible diagnoses; and 3.8% (2/53) could not be diagnosed. Compared with baseline, the percentage of eosinophils and the IgE, IgG, and IgG 4 concentrations decreased significantly; and the complement C3 and C4 concentrations had increased significantly after 6 months of treatment (all P<0.05). The IgG 4 concentration after 6 months of treatment negatively correlated with that of C4, and positively correlated with the baseline concentration of IgE and the IgG 4/IgG ratio. Conclusion:IgG 4-RDs are a group of diseases characterized by male predisposition; multiple organ involvement; a high eosinophil count; high IgE, IgG, IgG 1, and IgG 4 concentrations; and a low C3 concentration. Peripheral CD4 +T cells and Treg cells are also more abundant. The diseases can be controlled with glucocorticoids and immunosuppressive drugs in the majority of instances. The IgG 4 concentration after 6 months of treatment negatively correlates with the baseline complement C4 concentration and positively correlates with the IgE concentration and IgG 4/IgG ratio, which suggests that IgG 4/IgG, IgE, and complement should be closely monitored to evaluate disease activity and the efficacy of treatment in such patients.

ObjectiveDepression is common in patients with primary biliary cholangitis （PBC）， but the role of depression in disease progression remains unclear. This study aims to investigate the association between depression and treatment response and the impact of depression on liver cirrhosis in PBC patients. MethodsA retrospective analysis was performed for the clinical data of 141 patients with PBC who attended the outpatient service of autoimmune liver diseases in General Hospital of Tianjin Medical University from January 2018 to December 2020 and received standard ursodeoxycholic acid （UDCA） monotherapy for 1 year， and 170 healthy controls， matched for age and sex， who underwent physical examination in Physical Examination Center were enrolled as healthy control group. Patient Health Questionnaire-9 （PHQ-9） was used to evaluate depressive state in the patients with PBC and the healthy controls. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The binary logistic regression model and the decision tree model were used to analyze the influencing factors for liver cirrhosis in patients with PBC， as well as the influence of depression and the HLA-DRB1 gene on liver cirrhosis. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， and goodness of fit were used to evaluate model performance. All 13 variables were used to establish a classification and regression tree （CART） model， i.e.， age， sex， PHQ-9 score， the DRB1^*03∶01 gene， and the serum levels of alanine aminotransferase， aspartate aminotransferase， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin， immunoglobulin G， immunoglobulin M （IgM）， C3， and C4. The indications including AUC， sensitivity， and specificity were used to evaluate the performance of CART model in the model cohort. ResultsCompared with the normal control group， the PBC group had a significantly higher proportion of the patients with depression （53.9% vs 15.3%， χ²=57.836， P<0.001）. Compared with the PBC patients without depression， the PBC patients with depression had a significantly poorer response to UDCA treatment （χ²=7.549， P=0.006） and significant increases in the serum levels of ALP （Z=-2.157， P=0.031）， GGT （Z=-2.180， P=0.029）， and IgM （Z=-2.000， P=0.046）. Compared with the PBC patients without depression， the PBC patients carrying the HLA-DRB1^*03∶01 allele had a significant increase in the risk of liver cirrhosis （P<0.001）. The binary logistic regression model analysis showed that PHQ-9 score （OR=1.148， 95%CI： 1.050 — 1.255， P=0.002）， the HLA-DRB1^*03∶01 gene （OR=5.150， 95%CI： 1.362 — 19.478， P=0.016）， age （OR=1.057， 95%CI： 1.009 — 1.106， P=0.018）， and serum ALP level （OR=1.009， 95%CI： 1.001 — 1.017， P=0.020） were independent risk factors for liver cirrhosis in patients with PBC. The decision tree analysis showed that PHQ-9 score ≥3.5 was also a risk factor for liver cirrhosis in PBC patients. ConclusionDepression is associated with poor treatment response in patients with PBC， and it is an independent risk factor for liver cirrhosis in patients with PBC. This study highlights the important clinical significance of the identification and early management of depressive state in patients with PBC.

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Objective:To investigate the diagnostic value of a single hydrogen-methane breath test (SHMBT) for small intestinal bacterial overgrowth (SIBO).Method:The current investigation was a cross-sectional study. Questionnaires and SHMBTs were administered to 162 patients with gastrointestinal symptoms (case group) and 69 healthy volunteers (control group). Differences in SHMBT results between the two groups were assessed,and cut-off values of CH 4 (methane) and H 2 (hydrogen) were analyzed via receiver operating characteristic (ROC) curves. Lastly,archived SHMBT data from 2 655 patients with gastrointestinal symptoms (validation set) were used to evaluate the diagnostic value of the SHMBT with respect to SIBO. The Chi-square test,the Mann-Whitney U test,Spearman′s Rank correlation analysis,and the Z test were used for statistical analysis. Results:Based on the international recommended diagnostic criteria for SIBO,which are fasting CH 4 ≥10 ppm (parts per million) or H 2 ≥20 ppm,the SHMBT-positive rate in the case group was significantly higher than that of control group (35.2% vs. 21.7%, χ2=4.08, P=0.043). Levels of CH 4 and H 2 were higher in the case group than in the control group [CH 4: 3(2,7) vs. 3(1,3) ppm, H 2: 11(4,22) vs. 10(5,15) ppm],and the difference in CH 4 levels was statistically significant ( Z=6.22, P=0.001). ROC curves were generated based on whether the subjects had gastrointestinal symptoms. The areas under the ROC curves were 0.633 for CH 4 alone,0.531 for H 2 alone, and 0.620 for CH 4 combined with H 2. The cut-off values were fasting CH 4≥4 ppm,fasting H 2≥13 ppm,and fasting CH 4 ≥5 ppm (or CH 4≥4 ppm and H 2≥24 ppm),respectively. Measuring CH 4 alone and CH 4 combined with H 2 was effective for determining the presence of gastrointestinal symptoms ( P<0.05). When CH 4 alone or CH 4 combined with H 2 were used as diagnostic indicators of SIBO, the respective SHMBT-positive rates in the validation set were 34.2% and 30.4%. These rates did not significantly differ from the SIBO-positive rate of 32.0% obtained via the international recommended diagnostic criteria ( P>0.05). The specificity of CH 4 alone was 79.9%,and the accuracy of CH 4 alone was 68.8%. The specificity of CH 4 combined with H 2 was 85.0%,and the accuracy of CH 4 combined with H 2 was 71.7%. Conclusion:Rapid one-time determination of CH 4 and H 2 in exhaled breath may a viable diagnostic method for SIBO, and using CH 4 combined with H 2 ( i.e.,fasting CH 4≥5 ppm, or CH 4 ≥4 ppm and H 2 ≥24 ppm) as cutoff values may be feasible.

Objective:To compare the difference between gas volume score (GVS) method and combination of computed tomography (CT) image and calculation formula method (hereinafter referred to as CT method) in the detection of gastrointestinal gas volume in functional dyspepsia (FD) patients.Methods:From December 1, 2021 to June 30, 2022, 27 FD patients (FD group) who visited the Department of Gastroenterology and Hepatology of Tianjin Medical University General Hospital were enrolled. At the same period, 30 healthy controls were selected from the database of check-up center as the healthy control group. All the participants of the two groups underwent erect plain abdominal X-ray and abdominal CT scan. The GVS and CT methods were used to calculate and compare gastrointestinal gas volume between two groups of patients, as well as patients with FD subtypes (postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and PDS overlapping with EPS). Independent sample t-test and one-way ANOVA were used for statistical analysis. Results:Based on the GVS method, the gas volume of gastric cavity, small intestine and colorectum of FD group were 0.04±0.01, 0.06±0.01 and 0.06±0.01, respectively; and those of the healthy control group were 0.04±0.01, 0.05±0.01 and 0.05±0.01, respectively. The gas volume of small intestine and colorectum of FD group were higher than those of the healthy control group, and the differences were statistically significant( t=3.48 and 4.40, P=0.001 and <0.001). The gas volume of gastric cavity, small intestine and colorectum of FD patients with subtypes of PDS, EPS, and PDS overlapping with EPS were 0.04±0.01, 0.04±0.01 and 0.05±0.00, 0.06±0.01, 0.06±0.01 and 0.05±0.00, and 0.06±0.01, 0.06±0.01 and 0.06±0.01, respectively. There were no significant difference in the gas volume of gastric cavity, small intestine and colorectum among different subtypes ( all P>0.05 ). Based on the CT method, the gas volume of gastric cavity, small intestine and colorectum of FD group were (17 090.89±4 437.40) mm 3, (32 597.53±7 865.86) mm 3 and (49 010.20±12 972.42) mm 3, respectively; and those of the healthy control group were (13 424.43±5 211.86) mm 3, (33 567.93±9 157.23) mm 3 and (39 036.22±6 343.27) mm 3, respectively. The gas volume of gastric cavity and colorectum of FD group were higher than those of the healthy control group, and the differences were statistically significant( t=2.84 and 3.75, P=0.006 and 0.001). The gas volume of gastric cavity, small intestine and colorectum of FD patients with subtypes of PDS, EPS, and PDS overlapping with EPS were (18 464.03±4 088.57) mm 3, (14 560.97±3 771.26) mm 3 and (16 806.17±4 299.60) mm 3, (31 820.79±7 022.77) mm 3, (30 604.84±8 343.10) mm 3 and (37 140.05±8 276.58) mm 3, and (47 447.66±14 047.00) mm 3, (49 645.73±9 527.73) mm 3 and (51 181.96±16 836.97) mm 3, respectively. The gastric gas volume of FD patients with subtype of PDS was higher than that of FD patients with subtype of EPS, and the difference was statistically significant ( t=2.24, P=0.038). Conclusions:The volume of gastrointestinal gas of FD patients is higher than that of healthy controls. Gas accumulation in the gastric cavity of FD patients with subtype of PDS is more significant than that of FD patients with subtype of EPS. The CT method may assist physicians in calculating the gas volume in the gastrointestinal tract (especially in stomach) of FD patients more accurately.

Objective:To compare the efficacy of oral sulfate solution (OSS) and polyethylene glycol (PEG) electrolyte powder for colonoscopy bowel preparation.Methods:A total of 283 randomized patients from 9 centers in China taking OSS ( n=143) or PEG ( n=140) using two-day split bowel preparation regimen received colonoscopy and assessment. The primary index was the bowel preparation success rate [global Boston bowel preparation scale (BBPS)≥ 6 by independent assessment center]. Secondary indices included BBPS global and segmental scores, investigator satisfaction (5-point Likert scale) with the quality of bowel preparation, patient satisfaction assessed by questionnaires, and patient tolerance assessed by Sharma scale. Compliance and safety were compared between the two groups. Results:The bowel preparation success rates were 100.0% for OSS and 99.3% for PEG [adjusted difference 0.7% (95% CI: -5.3% - 6.7%), P<0.001 for non-inferiority]. The BBPS global score in OSS group was significantly higher than that in PEG group (8.1 VS 7.7, P<0.001). The segment BBPS scores were also higher in OSS group than those in PEG group for all 3 segments (right colon: 2.4 VS 2.3, P=0.002; transverse colon: 2.8 VS 2.7, P=0.018; left colon: 2.8 VS 2.7, P=0.007). Investigator Likert score in the OSS group was significantly higher than that in the PEG group (2.6 VS 2.3, P<0.001). There was no significant difference in compliance between OSS and PEG, except for the second dose (90.9% VS 82.6%, P=0.039). There was no significant difference in patient satisfaction, Sharma score or proportion of patients with tolerance-related symptoms between the two groups. Safety was comparable between the two groups, and all adverse events were mild to moderate. Conclusion:OSS has comparable efficacy with PEG, with higher BBPS scores in all segments, better investigator satisfaction, better compliance in split dose, and comparable patient tolerance and safety.

Objective:To evaluate the potential of receptor-interacting protein 3 (RIP3) as a therapeutic target for autoimmune hepatitis (AIH).Methods:Immunofluorescence assay was used to observe the activated expression levels of RIP3 and its downstream signal mixed lineage protein kinase domain-like protein (MLKL) in the liver tissues of patients with AIH and hepatic cyst. Concanavalin A (ConA) was injected into the tail vein to induce acute immune-mediated hepatitis in mice. Intervention was performed by intraperitoneal injection of RIP3 inhibitor GSK872 or solvent carrier. Peripheral blood and liver tissues were collected. Serum transaminases level, qPCR and flow cytometry were analyzed. The intergroup comparison was performed with an independent sample t-test. Results:The expression level of p-RIP3 (the activated forms of RIP3) and phosphorylated p-MLKL (MLKL after phosphorylation) downstream signal were significantly higher in the liver tissue of AIH patients than those of controls. Compared with the control group, the expression levels of RIP3 and MLKL mRNA were significantly increased in the liver tissue of AIH patients (relative expression levels 3.28±0.29 vs. 0.98±0.09, 4.55±0.51 vs. 1.06±0.11), and the differences were statistically significant ( t=6.71 and 6.77, respectively, and P<0.01). The expression levels of RIP3 and MLKL mRNA were significantly higher in the mice liver tissue of ConA-induced immune hepatitis than those in the control group (relative expression levels 2.35±0.09 vs. 0.89±0.11,2.77±0.22 vs. 0.73±0.16, t=10.4,6.33, P<0.01). RIP3 inhibitor GSK872 had significantly attenuated ConA-induced immune liver injury and inhibited the expression of tumor necrosis factor-α, interleukin-6, interleukin-1β and NLRP3 in liver. Compared with the control group, the proportions of CD45 +F4/80 + macrophages, CD4 + IL-17 + Th17 cells, CD4 + CD25 + regulatory T (Treg) cells and CD11b + Gr-1 + myeloid derived suppressor cells (MDSCs) were significantly increased in the liver of ConA + Vehicle group. Compared with ConA + Vehicle group, the proportion of CD45 +F4/80 + macrophages and CD4 + IL-17 + Th17 cells were significantly decreased, while the proportion of CD4 + CD25 +Treg cells and CD11b + Gr-1 + MDSCs with immunomodulatory functions were significantly increased in mice liver of ConA+GSK872 group. Conclusion:AIH patients and ConA-induced immune hepatitis mice have activated RIP3 signal in liver tissues. Inhibition of RIP3 reduces the expression and proportion of proinflammatory factors and cells, and promotes the accumulation of CD4 + CD25 + Treg cells and CD11b + Gr-1 + MDSCs with immunomodulatory functions in the liver of mice with immune hepatitis, thereby alleviating liver inflammation and injury. Therefore, the inhibition of RIP3 is expected to be a new approach for the treatment of AIH.

To compare the incidence of hypoglycemia between day-before bowel preparation and split-dose bowel preparation in colonoscopy patients. The effects of enterald ietary nutrients on the prevention of hypoglycemia and the preparation quality of the intestine during colonoscopy were compared. The patients who underwent colonoscopy were divided into the day-before bowel preparation group, the split-dose bowel preparation group, and the split-dose bowel preparation + enteral nutrient diet group. All patients had their finger blood sugar tested before colonoscopy. The peripheral blood glucose level was measured before operation. After the endoscopic examination, the intestinal cleanliness of the patients was evaluated through the Boston intestinal preparation scale by endoscopists. The incidence of day-before bowel preparation group and split-dose bowel preparation group and enteral nutrient intervention group were 14.38%(23/160), 17.50% (28/160)and 6.45% (4/62), respectively. The proportions of high quality intestinal cleaning were 31.25% (50/160), 35.00% (56/160) and 82.26% (51/62) in the three groups respectively. The incidence of hypoglycemia was higher in split-dose bowel preparation group than that in day-before bowel preparation group. Enteral nutrient intervention can effectively reduce the incidence of hypoglycemia and improve the quality of intestinal preparation, which is a recommended intestinal preparation method.

Background: Gastroesophageal reflux disease (GERD) is strongly associated with sleep disturbances. Proton pump inhibitors (PPIs) are the main treatment to improve the reflux symptoms in GERD patients. Aims: To investigate the efficacy of PPIs on nighttime reflux symptoms and associated sleep disturbances in general GERD population in North China. Methods: In this multicenter, prospective observational study, adult GERD patients with nighttime heartburn or regurgitation were recruited from 11 tertiary hospitals in North China during July 2017 to March 2018. All the patients received oral PPIs treatment. Data on nighttime reflux symptoms and associated sleep disturbances were obtained by patient diary and self-report questionnaire, the quality of sleep was defined by the Pittsburgh Sleep Quality Index (PSQI). The efficacy of PPIs was estimated by the relief rate after 4-week treatment. Results: Of the 750 GERD patients analyzed, 585 (78.0%) reported nighttime reflux-associated sleep disturbances, and 427 (56.9%) were defined as poor sleepers with a PSQI score >5. After 4-week PPIs treatment, 51.3% of the patients achieved a relief of nighttime reflux symptoms. The complete relief rates for nighttime reflux symptoms and associated sleep disturbances were 32.5% and 51.5%, respectively. PSQI score was significantly improved from 6.82 ± 3.38 at baseline to 4.56±2.50 after 4-week PPIs treatment (P<0.05). Conclusions: PPIs treatment provides an effective relief of nighttime reflux symptoms and associated sleep disturbances and improving the sleep quality in general GERD population in North China.