QingChang-XiaoPi decoction ameliorates intestinal inflammation of ulcerative colitis by regulating the pathogenicity of Th17 cells.

BACKGROUND: QingChang-XiaoPi Decoction (QCXPY), a Chinese herbal prescription, has been employed in the treatment of ulcerative colitis (UC) in China. However, its molecular mechanism of action in UC remains unclear. PURPOSE: To elucidate the therapeutic effects of QCXPY against UC and reveal its mechanism of action. STUDY DESIGN: We conducted a single-arm observation to evaluate the clinical efficacy of QCXPY in patients with mild-to-moderate UC. Inclusion and exclusion criteria were established to ensure the eligibility of participants, with a focus on excluding patients with specific conditions or complications that could confound the results. METHODS: The expression of inflammatory factors in patients' serum was detected using a Luminex assay. The main components of QCXPY were identified using UHPLC-Q-TOF-MS. Network pharmacology was employed to predict potential therapeutic targets and their mechanisms of action. The efficacy of QCXPY was evaluated using a dextran sulfate sodium (DSS)-induced mouse model. Disease activity index (DAI), histopathological score, cytokine detection by ELISA, T-helper 17 (Th17) cell proportion by flow cytometry, expression of the IL-23/IL-17 axis, and changes in the levels of its downstream effectors were detected by immunohistochemistry, immunofluorescence, and western blotting. RESULTS: QCXPY could alleviate the symptoms of diarrhea, abdominal pain, abdominal distension, and purulent stool in patients with mild-to-moderate UC. Moreover, it reduced the expression of IL-6, IL-17, and IL-23 in serum; alleviated DSS-induced experimental colitis in mice; reduced DAI, pathological scores, and the expressions of IL-6, IL-17, and IL-23 in colon tissue; and decreased the proportion of pathogenic Th17 cells and the expression of STAT3 and phospho-STAT3. CONCLUSION: This study confirmed for the first time that QCXPY could alleviate intestinal symptoms, reduce the levels of serum inflammatory factors, and improve the quality of life of patients with mild-to-moderate UC. Its mechanism of action may involve reducing the secretion of inflammatory cytokines, moderating the pathogenicity of Th17 cells, and inhibiting STAT3 phosphorylation, thereby alleviating intestinal inflammation in UC.

The function of the gut microbiota-bile acid-TGR5 axis in diarrhea-predominant irritable bowel syndrome.

Imbalanced gut microbiota (GM) and abnormal fecal bile acid (BA) are thought to be the key factors for diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying mechanism remains unclear. Herein, we explore the influence of the GM-BA-Takeda G-protein-coupled receptor 5 (TGR5) axis on IBS-D. Twenty-five IBS-D patients and fifteen healthy controls were recruited to perform BA-related metabolic and metagenomic analyses. Further, the microbiota-humanized IBS-D rat model was established by fecal microbial transplantation (FMT) to investigate the GM-BA-TGR5 axis effects on the colonic barrier and visceral hypersensitivity (VH) in IBS-D. Finally, we used chenodeoxycholic acid (CDCA), an important BA screened out by metabolome, to evaluate whether it affected diarrhea and VH via the TGR5 pathway. Clinical research showed that GM associated with bile salt hydrolase (BSH) activity such as Bacteroides ovatus was markedly reduced in the GM of IBS-D, accompanied by elevated total and primary BA levels. Moreover, we found that CDCA not only was increased as the most important primary BA in IBS-D patients but also could induce VH through upregulating TGR5 in the colon and ileum of normal rats. TGR5 inhibitor could reverse the phenotype, depression-like behaviors, pathological change, and level of fecal BSH in a microbiota-humanized IBS-D rat model. Our findings proved that human-associated FMT could successfully induce the IBS-D rat model, and the imbalanced GM-BA-TGR5 axis may promote colonic mucosal barrier dysfunction and enhance VH in IBS-D. IMPORTANCE: Visceral hypersensitivity and intestinal mucosal barrier damage are important factors that cause abnormal brain-gut interaction in diarrhea-predominant irritable bowel syndrome (IBS-D). Recently, it was found that the imbalance of the gut microbiota-bile acid axis is closely related to them. Therefore, understanding the structure and function of the gut microbiota and bile acids and the underlying mechanisms by which they shape visceral hypersensitivity and mucosal barrier damage in IBS-D is critical. An examination of intestinal feces from IBS-D patients revealed that alterations in gut microbiota and bile acid metabolism underlie IBS-D and symptom onset. We also expanded beyond existing knowledge of well-studied gut microbiota and bile acid and found that Bacteroides ovatus and chenodeoxycholic acid may be potential bacteria and bile acid involved in the pathogenesis of IBS-D. Moreover, our data integration reveals the influence of the microbiota-bile acid-TGR5 axis on barrier function and visceral hypersensitivity.

Biomarkers prediction and immune landscape in ulcerative colitis: Findings based on bioinformatics and machine learning.

BACKGROUND: Ulcerative colitis (UC) presents diagnostic and therapeutic difficulties. The primary objective of this study is to identify efficacious biomarkers for diagnosis and treatment, as well as acquire a deeper understanding of the immuneological characteristics associated with the disease. METHODS: Datasets relating to UC were obtained from GEO database. Among these, three datasets were merged to create a metadata for bioinformatics analysis and machine learning. Additionally, one dataset specifically utilized for external validation. Least absolute shrinkage and selection operator (LASSO) and random forest (RF) were employed to screen signature genes. The artificial neural network (ANN) model and receiver operating characteristic (ROC) curve were used to assess the diagnostic performance of signature genes. The single sample gene set enrichment analysis (ssGSEA) was applied to reveal the immune landscape. Finally, the relationship between the signature genes, immune infiltration, and clinical characteristics was investigated through correlation analysis. RESULT: By intersecting the result of LASSO, RF and WGCNA, 8 signature genes were identified, including S100A8, IL-1B, CXCL1, TCN1, MMP10, GREM1, DUOX2 and SLC6A14. The biological progress of this gene mostly encompasses acute inflammatory response, aggregation and chemotaxis of leukocyte, and response to lipopolysaccharide by mediating IL-17 signaling pathway, NF-kappa B signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway. Immune infiltration analysis shows 25 immune cells are significantly elevated in UC samples. Moreover, these signature genes exhibit a strong correlation with various immune cells and a mild to moderate correlation with the Mayo score. CONCLUSION: S100A8, IL-1B, CXCL1, TCN1, MMP10, GREM1, DUOX2 and SLC6A14 have been identified as credible potential biomarkers for the diagnosis and therapy of UC. The immune response mediated by these signature biomarkers plays a crucial role in the occurrence and advancement of UC by means of the reciprocal interaction between the signature biomarkers and immune-infiltrated cells.

Therapeutic targets and pharmacological mechanisms of Coptidis Rhizoma against ulcerative colitis: Findings of system pharmacology and bioinformatics analysis.

Evidence of the advantages of Coptidis Rhizoma (CR) for the treatment of ulcerative colitis (UC) is accumulating. However, research revealing the targets and molecular mechanisms of CR against UC is scarce. In this research, a bioinformatics analysis was performed to carry out the physicochemical properties and biological activities of phytochemicals in CR and analyze the binding activities, targets, biological functions and mechanisms of CR against UC. This research shows that the CR's key phytochemicals, which are named Coptisine, Berberrubine, Berlambine, Berberine, Epiberberine, Obacunone, Worenine, Quercetin, (R)-Canadine, Magnograndiolide, Palmatine and Moupinamide, have ideal physicochemical properties and bioactivity. A total of 1,904 potential phytochemical targets and 17,995 UC-related targets are identified, and we finally acquire 233 intersection targets between key phytochemicals and disease. A protein-protein interaction network of 233 common targets was constructed; and six hub targets were acquired with a degree greater than or equal to median, namely TP53, HSP90AA1, STAT3, ESR1, MYC, and RELA. The enrichment analysis suggested that the core targets may exert an impact on anti-inflammatory, immunoregulatory, anti-oxidant and anti-fibrosis functions mainly through the PI3K/ART signaling pathway, Th17 differentiation signaling pathway, inflammatory bowel disease signaling pathway, etcetera. Also, a molecular docking analysis shows that the key phytochemicals have strong affinity for binding to the core targets. Finally, the interaction network of CR, phytochemicals, targets, GO functions, KEGG pathways and UC is constructed. This study indicates that the key phytochemicals in CR have superior drug likeness and bioactivity, and the molecular mechanism of key phytochemicals against UC may be via the signaling pathway mentioned above. The potential and critical pharmacological mechanisms provide a direction for future research.

Traditional Chinese medicine based on Tongjiang methodology combined with proton pump inhibitor (PPI) step-down in treating non-erosive reflux disease: a study protocol for a multicentered, randomized controlled clinical trial.

BACKGROUND: Non-erosive reflux disease (NERD) is characterized by typical gastroesophageal reflux symptoms, such as heartburn and regurgitation but an absence of esophageal mucosal damage during upper gastrointestinal endoscopy. Although proton pump inhibitors (PPIs) are the first line therapy, almost 50% of patients with NERD fail to respond to this treatment. Traditional Chinese medicine (TCM) can better relieve the symptoms of NERD. Therefore, a randomized controlled trial (RCT) was designed to investigate the efficiency of TCM granules based on Tongjiang (TJ) methodology combined with PPI step-down therapy for NERD patients who did not respond to PPIs alone. METHOD: This multicentered, double-blinded, RCT with two parallel groups will recruit 174 participants who will be randomized into the TCM granules combined with PPI step-down group (n = 87) and the TCM granules placebo combined with PPI step-down group (n = 87). Both groups of participants will receive 6 weeks of treatment and 4 weeks of follow-up, and all participants will be assessed for related symptoms, mental health status, and quality of life at each visit. The primary outcome measurements include visual analog scale (VAS) for heartburn and regurgitation and the major symptoms scale. The secondary outcome measurements include PPI withdrawal rate, symptom recurrence rate, minor symptoms scale, SF-36, PRO, SAS, SDS, GERD-HRQL, and TCM syndromes scales. DISCUSSION: Previous research has shown that TCM is capable to alleviate NERD symptoms. This trial will help to provide a better understanding of the synergistic efficiency of the combination of TCM and PPIs, to explore whether the dosage of PPIs can be reduced after the supplement of TCM granules and to provide a feasible plan to reduce dependencies or withdraw NERD patients from PPIs. The outcome of this trial is expected to reduce the symptom recurrence rates, lessen patients' physical and psychological burdens, and achieve good social benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT04340297. Registered on April 9, 2020.

Tong-Xie-Yao-Fang alleviates diarrhea-predominant irritable bowel syndrome in rats via the GCN2/PERK-eIF2α-ATF4 signaling pathway.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disease. Tong-Xie-Yao-Fang (TXYF), the traditional Chinese herbal medicine prescription, is a classic and effective prescription for the treatment of IBS-D, but its mechanism of action is not fully clarified. OBJECTIVE: To evaluate the efficacy of TXYF in the treatment of IBS-D and to explore its potential mechanism of action. METHODS: Changes in the serum levels of 50 free amino acids were targeted for detection by high-performance liquid chromatography (HPLC), and the expression of glucose-regulated protein 78 (GRP78), general control nonderepressible 2 (GCN2), and endoplasmic reticulum-resident kinase (PERK) was detected by immunohistochemistry examinations in healthy volunteers and IBS-D patients. The IBS-D rat was constructed by the three-factor superposition method of neonatal maternal separation, 2,4,6-trinitrobenzene sulfonic acid enema, and chronic unpredictable stress stimulation. The treatment effect of TXYF on IBS-D rats was observed by recording the body weight, grasp force, fecal water content (FWC), and abdominal withdrawal reflex (AWR) of rats before and after treatment. The effects of GCN2/PERK-eukaryotic initiation factor-2 (eIF2α) -activating transcription Factor 4 (ATF4) pathway proteins and gene expression were analyzed by western blotting, reverse transcription-polymerase chain reaction (RT-qPCR), and immunohistochemistry evaluations. RESULTS: Compared with healthy volunteers, IBS-D patients exhibited lower levels of cysteine, γ-aminoacetic acid (GABA), homoproline, and lysine, and immunohistochemistry showed strong activation of GRP78, a marker of endoplasmic reticulum stress. Differential expression of GCN2 and PERK proteins was detected in IBS-D patients and rat colons. In the IBS-D rats, TXYF improved the body weight and grasp force, reduced the FWC, and improved the AWR score. TXYF increased the levels of p-GCN2 and GCN2 and reduced the levels of GRP78, p-PERK, PERK, p-eIF2α, and eIF2α, thereby affecting the expression of the apoptosis-related transcription factors ATF4, CHOP, Caspase-3, and Bcl-2. CONCLUSION: Our study showed that TXYF improved IBS-D by inhibiting apoptosis. The anti-apoptosis effects were potentially mediated by regulating the GCN2/PERK-eIF2a-ATF4 signaling pathway.

The Association between Coparenting Behavior and Internalizing/Externalizing Problems of Children and Adolescents: A Meta-Analysis.

This study aimed to determine the association between coparenting behavior and children's externalizing and internalizing problems and possible factors that may moderate their associations. A meta-analysis of 93 studies involving 41,207 participants found that coparenting behavior was slightly and significantly related to externalizing problems, r = -0.17, 95% CI [-0.194, -0.15], and internalizing problems, r = -0.16, 95% CI [-0.18, -0.14]. In addition, coparenting integrity, cooperation, conflict, competitiveness, and triangulation were significantly related to externalizing and internalizing problems. Moderation analyses revealed the following findings: (a) data reporter moderated the association between coparenting and internalizing problems, with children-report coparenting showing a significantly stronger relation with internalizing symptom than father-report coparenting; (b) developmental stage was found to moderate the association between coparenting behavior and externalizing problems, with stronger association found in childhood than in toddlerhood; (c) female percentage, individualism-collectivism culture, research methods, and publication year were not found to moderate the association between coparenting behavior and externalizing or internalizing problems. These findings help summarize the previous studies and provide an empirical basis for the relation between coparenting and child externalizing/internalizing problems, and benefits targeted interventions towards coparenting behaviors.

Shenling Baizhu Powder Alleviates TNBS-Induced Colitis in Rats by Improving Intestinal Epithelial Permeability and Inhibiting Inflammation Through the TLR5/MyD88/NF-κB Pathway.

Aim of the study: To evaluate the protective effect and mechanism of shenling baizhu powder (SBP) on TNBS-induced colitis. Methods: Rats were given TNBS to establish the model of colitis and subsequently treated with different doses of SBP or mesalamine (MES). In addition, the expression of the TLR5/MyD88/NF-κB signaling pathway and critical targets of the intestinal mucosal barrier was detected by immunochemical analysis techniques. Results: SBP significantly ameliorated the symptoms of TNBS-induced colitis in rats and reduced the secretion of pro-inflammatory cytokines. SBP could effectively strengthen epithelial barrier integrity in TNBS-induced colitis by increasing the secretion of mucin and tight junction and inhibiting apoptosis. Furthermore, we identified the crucial role of the TLR5/MyD88/NF-κB signaling pathway in exerting the therapeutic effect of SBP. Conclusion: The results of our study suggest that SBP has therapeutic effects on TNBS-induced colitis and potential value in treating and maintaining remission of colitis.

Efficacy and safety of Chinese medicine combined with balloon dilatation vs. balloon dilatation alone for achalasia patients: a systematic review and meta-analysis.

Background: Balloon dilatation is widely used for patients with achalasia; however, the efficacy and safety of Chinese medicine combined with balloon dilatation for achalasia patients is still unclear. Therefore, we conducted a meta-analysis to compare the treatment effectiveness of treatment with Chinese medicine plus balloon dilatation versus balloon dilatation alone for patients with achalasia. Methods: Randomized controlled trials (RCTs) compared the effectiveness of Chinese medicine plus balloon dilatation with balloon dilatation as examined in studies in the PubMed, Springer, Embase, Wiley-Blackwell, Chinese Journal Full-text Database, and the Cochrane library from their inception up to May 2019. The odds ratios (ORs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were used to calculate categories and continuous outcomes using the random-effects model. The inclusion of studies according to the PICOS (participants, interventions, comparisons, outcomes) criteria, the assessment of risk of bias of included studies adhered to the Cochrane criteria guidelines. Results: The initial electronic searches produced 378 records, and 10 RCTs that recruited 504 achalasia patients were included in the final quantitative analysis. Except for other potential biases with moderate to high-risk bias of 20-40%, the other six items had a low-risk bias of 80-90%. Overall, we noted that patients who received the Chinese medicine plus balloon dilatation treatment had a greater incidence of improvement at 1 year (OR: 2.20; 95% CI: 1.45-3.33; P<0.001), and 5 years (OR: 1.83; 95% CI: 1.23-2.74; P=0.003), and reduced the risk of gastroesophageal reflux (OR: 0.42; 95% CI: 0.24-0.76; P=0.004) than patients who underwent balloon dilation only. However, patients who received the Chinese medicine plus balloon dilatation treatment did not have a greater risk of perforation (OR: 0.53; 95% CI: 0.24-1.19; P=0.123) compared with patients undergoing balloon dilation. Finally, Chinese medicine plus balloon dilatation was associated with high esophageal sphincter pressure (WMD: 2.01; 95% CI: 1.19-2.84; P<0.001) compared with patients who underwent balloon dilatation only. Conclusions: Chinese medicine plus balloon dilatation had better effects after treatment than balloon dilatation alone for achalasia patients. Given the risk of bias of included studies, the conclusion should be made with cautions.

Comparison of five diarrhea-predominant irritable bowel syndrome (IBS-D) rat models in the brain-gut-microbiota axis.

The brain-gut-microbiota (BGM) axis is known to be essential for diarrhea-predominant irritable bowel syndrome (IBS-D). In order to evaluate the effects of IBS-D rat models (the central sensitization model, the peripheral sensitization model and the compound model) on the BGM axis, five models were induced in Wistar rats with 4% acetic acid (AD, dissolved 0.4 ml of AD in 9.6 ml of ultrapure water) + wrap restrain stress (WRS), 4% AD, colorectal distention (CRD), WRS, and neonatal maternal separation (NMS). Abdominal withdrawal reflex (AWR) scale scores and the moisture content of feces (MCF) were evaluated on the day of completing modeling. Body weight was measured every 7 days during modeling. Brain gut peptides, cytokine levels, the activity of spinal cord neurons, intestinal mucosal barrier function, and gut microbiota were determined after induction of IBS-D. We found intervention with 4% AD + WRS, 4% AD, CRD, WRS, and NMS induced a similar course of effects on the BGM axis. Among the five models, AWR scores (60 mmHg, 80 mmHg) were all increased. The levels of 5-hydroxytryptamine, corticotropin-releasing factor, substance P, and calcitonin gene-related protein in serum rapidly increased, whereas that of neuropeptide Y decreased. C-fos in the spinal cord showed increased neuronal activity. The intestinal permeability was increased and the composition and structure of gut microbiota were changed. In conclusion, the five models could cause changes in BGM axis, but the 4% AD + WRS model was closer to the changes BGM axis of post-inflammatory models of IBS-D.

Clinical evidence of acupuncture and moxibustion for irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials.

Background: Acupuncture and moxibustion have been widely used in the treatment of Irritable Bowel Syndrome (IBS). But the evidence that acupuncture and moxibustion for IBS reduction of symptom severity and abdominal pain, and improvement of quality of life is scarce. Methods: PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wanfang Database, China Biomedical Literature Service System (SinoMed), and unpublished sources were searched from inception until June 30, 2022. The quality of RCTs was assessed with the Cochrane Collaboration risk of bias tool. The strength of the evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation system (GRADE). Trial sequential analysis (TSA) was conducted to determine whether the participants in the included trials had reached optimal information size and whether the cumulative data was adequately powered to evaluate outcomes. Results: A total of 31 RCTs were included. Acupuncture helped reduce the severity of symptoms more than pharmaceutical drugs (MD, -35.45; 95% CI, -48.21 to -22.68; I 2 = 71%). TSA showed the cumulative Z score crossed O'Brien-Fleming alpha-spending significance boundaries. Acupuncture wasn't associated with symptom severity reduction (SMD, 0.03, 95% CI, -0.25 to 0.31, I 2 = 46%), but exhibited therapeutic benefits on abdominal pain (SMD, -0.24; 95% CI, -0.48 to -0.01; I 2 = 8%) compared to sham acupuncture. Moxibustion show therapeutic benefits compared to sham moxibustion on symptom severity (SMD, -3.46, 95% CI, -5.66 to -1.27, I 2 = 95%) and abdominal pain (SMD, -2.74, 95% CI, -4.81 to -0.67, I 2 = 96%). Acupuncture (SMD, -0.46; 95% CI, -0.68 to -0.24; I 2 = 47%) and the combination of acupuncture and moxibustion (SMD, -2.00; 95% CI, -3.04 to -0.96; I 2 = 90%) showed more benefit for abdominal pain compared to pharmacological medications as well as shams. Acupuncture (MD, 4.56; 95% CI, 1.46-7.67; I 2 = 79%) and moxibustion (MD, 6.97; 95% CI, 5.78-8.16; I 2 = 21%) were more likely to improve quality of life than pharmaceutical drugs. Conclusion: Acupuncture and/or moxibustion are beneficial for symptom severity, abdominal pain and quality of life in IBS. However, in sham control trials, acupuncture hasn't exhibited robust and stable evidence, and moxibustion's results show great heterogeneity. Hence, more rigorous sham control trials of acupuncture or moxibustion are necessary. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=262118, identifier CRD42021262118.

The Chinese herbal formula Huoxiang Zhengqi for diarrhea-predominant irritable bowel syndrome (CHAIRS): a study protocol for a double-blinded randomized controlled trial.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic digestive disease. Recent observational studies have reported that the Chinese herbal formula Huoxiang Zhengqi (HXZQ) can relieve IBS-D symptoms, but no high-level evidence is presented. Therefore, we want to evaluate the efficacy and safety of HXZQ for IBS-D patients. METHODS: This is a double-blind, randomized, placebo-controlled trial. The 212 eligible patients with IBS-D will be randomly assigned to receive either HXZQ oral liquid or a placebo, at a 1:1 ratio, for 4 weeks with a 4-week follow-up period. Adequate relief will be the primary outcome measures. IBS symptom severity score, IBS quality-of-life questionnaire, EQ-5D-5L, and Chinese medicine symptom questionnaire will be the secondary outcome measures. DISCUSSION: This trial aims to demonstrate the efficacy and safety of HXZQ for IBS-D, which is expected to be an effective IBS-D treatment. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry, ChiCTR1900026837 . Registered on 24 October 2019.

Efficacy of opioid receptor modulators in patients with irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: While irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal diseases in clinical practice, it has diverse pathogenesis. Because of its sudden and lingering intractable symptoms, it seriously affects patients work and life. Opioid receptors are G protein-coupled receptors distributed across the brain, spinal cord, skin, and gastrointestinal tract, and each of the subtypes has a unique role and specific distribution. They play a role in regulating gastrointestinal motility, secretion, and visceral sensations in the gastrointestinal tract. Therefore, this meta-analysis aims to evaluate the effects of opioid receptor modulators on improving the symptoms of IBS. METHODS: Searching the key words (Irritable Bowel Syndromes or Syndrome, Irritable Bowel OR Syndromes, Irritable Bowel OR Colon, Irritable OR Irritable Colon OR Colitis, Mucous OR Colitides, Mucous OR Mucous Colitides OR Mucous Colitis) AND (opioid receptor modulators OR eluxadoline OR Viberzi OR asimadoline OR loperamide), a preliminary search on PubMed (English), EMBASE (English), Cochrane Library (English), China National Knowledge Infrastructure Database (CNKI, Chinese), WanFang (Chinese), VIP citation databases (Chinese) and SinoMed (Chinese) databases yielded 1023 papers published in English and Chinese from inception to July 1, 2019. Nine studies were included in the final meta-analysis. Because this is a systematic review and meta-analysis, ethical approval is not necessary. RESULTS: The random-effects meta-analysis based on these 9 studies and their 4156 patients found that opioid receptor modulators have a statistically significant beneficial effect on IBS global symptoms (RR = 0.85, 95%CI = 0.79-0.92, P < .01) and bowel movement frequency (SMD = -1.26, 95%CI = -2.49--0.04, P < .05), and while there was an improvement trend in stool consistency and quality of life, these findings were not statistically significant. CONCLUSIONS: This is the first meta-analysis to examine the use of opioid receptor modulators in IBS, and few adverse events were reported in the available trials. Compared with the control group, eluxadolin has a better effect in improving IBS global symptoms and abdominal pain and has statistical significance and showed a low rate of constipation development in IBS patients in comparison with known effects of other opioid receptor modulators. However, current findings are based on a considerably limited evidence base with marked heterogeneity. Future studies should aim to identify subpopulations of patients with IBS and need to evaluate the long-term safety of these therapies.PROSPERO registration number: CRD42020141597.

Negative Emotions and Job Burnout in News Media Workers: A Moderated Mediation Model of Rumination and Empathy.

News media workers are in stressful and competitive professions susceptible to negative emotions. Although the relationship between negative emotions and job burnout has been evidenced in some professional fields, it has not yet been examined in the population of news media workers. Far few studies have revealed the mediating and moderating mechanism between negative emotions and job burnout. Based on Resource Allocation Theory and Theory of Compassion Fatigue, this study examined (a) the mediating role of rumination in the relationship between negative emotions and job burnout, (b) the moderating role of empathy in the direct and indirect effect of negative emotions on job burnout, and (c) the moderating role of gender in the direct effect of negative emotions on rumination. Two hundred and eleven Chinese news media workers filled out questionnaires regarding negative emotions, job burnout, rumination, and empathy. The results indicated that negative emotions were positively correlated with job burnout. Mediation analysis revealed that rumination partially mediated the association between negative emotions and job burnout. Moderated mediation analysis further indicated that empathy moderated the effect of negative emotions on rumination, with a high level of empathy strengthening the association between negative emotions and rumination; gender moderated the effect of negative emotions on rumination, with the association between negative emotions and rumination was stronger among males than females. These findings encourage to design psychological interventions to reduce rumination and express proper empathy in the face of stress or negative affective status to avoid job burnout among news media workers.

Gut Microbiota-Bile Acid Crosstalk in Diarrhea-Irritable Bowel Syndrome.

The occurrence of diarrhea-predominant irritable bowel syndrome (IBS-D) is the result of multiple factors, and its pathogenesis has not yet been clarified. Emerging evidence indicates abnormal changes in gut microbiota and bile acid (BA) metabolism have a close relationship with IBS-D. Gut microbiota is involved in the secondary BA production via deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, and esterification reactions respectively. Changes in the composition and quantity of gut microbiota have an important impact on the metabolism of BAs, which can lead to the occurrence of gastrointestinal diseases. BAs, synthesized in the hepatocytes, play an important role in maintaining the homeostasis of gut microbiota and the balance of glucose and lipid metabolism. In consideration of the complex biological functional connections among gut microbiota, BAs, and IBS-D, it is urgent to review the latest research progress in this field. In this review, we summarized the alterations of gut microbiota in IBS-D and discussed the mechanistic connections between gut microbiota and BA metabolism in IBS-D, which may be involved in activating two important bile acid receptors, G-protein coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR). We also highlight the strategies of prevention and treatment of IBS-D via regulating gut microbiota-bile acid axis, including probiotics, fecal microbiota transplantation (FMT), cholestyramine, and the cutting-edge technology about bacteria genetic engineering.

Tojapride prevents CaSR-mediated NLRP3 inflammasome activation in oesophageal epithelium irritated by acidic bile salts.

Impairment of the oesophageal epithelium in patients with reflux oesophagitis (RE) is a cytokine-mediated injury rather than a chemical burn. The present study was conducted to explore CaSR/NLRP3 inflammasome pathway activation and cytokines IL-1ß and IL-18 release in oesophageal epithelia injured by refluxates and the effects of Tojapride on that signal regulation. Using a modified RE rat model with Tojapride administration and Tojapride-pretreated SV40-immortalized human oesophageal epithelial cells (HET-1A) exposed to acidic bile salts pretreated with Tojapride, we evaluated the therapeutic effects of Tojapride on oesophageal epithelial barrier function, the expression of CaSR/NLRP3 inflammasome pathway-related proteins and the release of downstream cytokines in response to acidic bile salt irritation. In vivo, Tojapride treatment ameliorated the general condition and pathological lesions of the oesophageal epithelium in modified RE rats. In addition, Tojapride effectively blocked the CaSR-mediated NLRP3 inflammasome activation in modified RE rats. In vitro, Tojapride treatment can reverse the harmful effect of acidic bile salts, which reduced transepithelial electrical resistance (TEER), up-regulated the CaSR-mediated NLRP3 inflammasome pathway and increased caspase-1 activity, LDH release and cytokines secretion. Taken together, these data show that Tojapride can prevent CaSR-mediated NLRP3 inflammasome activation and alleviate oesophageal epithelial injury induced by acidic bile salt exposure.

Effect of Chinese Herbal Medicines on Helicobacter pylori-associated gastroduodenal ulcers: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the effect and safety of Chinese herbal medicines on Helicobacter pylori (HP)-associated gastroduodenal ulcers. METHODS: All randomized controlled trials (RCTs) listed in the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure Database, WanFang, China Science and Technology Journal Database and SinoMed databases that were published in English or Chinese were searched, and the retrieval time range was from database inception to December 31, 2018. A comprehensive Meta-analysis of all publications was performed with RevMan 5.3 software, and the quality of the evidence reported in the results of Meta-analysis was analyzed with GRADE profiler software (version 3.6.1). Dichotomous data were analyzed by calculating odds ratios and 95% confidence intervals (CIs). Outcome measures included the HP clearance rate and percentage of adverse effects. RESULTS: Eight trials with 919 participants were included in this Meta-analysis. Compared with the effects of single drug therapy on HP-associated gastroduodenal ulcers, according to the statistical analysis, odds ratios for the HP clearance rate and percentage of adverse effects of Chinese herbal medicines administered as complementary medicines combined with drugs were 3.10 [95% CI (2.21, 4.36), P < 0.01] and 0.28 [95% CI (0.15, 0.52), P < 0.01], respectively, and the differences were statistically significant. According to the GRADE analysis, the quality of evidence for the HP clearance rate and percentage of adverse effects were both very low. CONCLUSION: Compared with using the drug therapy only, the combination of Chinese herbal medicines with the drug therapy more effectively eliminates HP and alleviates adverse reactions. However, the available studies were of low quality, and therefore more well-designed studies are required to further confirm the findings.

[Differentiation Study of Chinese Medical Syndrome Typing for Diarrhea-predominant Irritable Bowel Syndrome Based on Information of Four Chinese Medical Diagnostic Methods and Brain-gut Peptides].

OBJECTIVE: To establish discriminant functions of diarrhea-predominant irritable bowel syndrome (IBS-D) by studying it from quantitative diagnosis angle, hoping to reduce interference of subjective factors in diagnosing and differentially diagnosing Chinese medical syndromes of IBS-D. METHODS: A Chinese medical clinical epidemiological survey was carried out in 439 IBS-D patients using Clinical Information Collection Table of IBS. Initial syndromes were obtained by cluster analysis. They were analyzed using step-by-step discrimination by taking information of four Chinese medical diagnostic methods and serum brain-gut peptides (BGP) as variables. RESULTS: Clustering results were Gan stagnation Pi deficiency syndrome (GSPDS), Pi-Wei weakness syndrome (PWWS), Gan stagnation qi stasis syndrome (GSQSS), Pi-Shen yang deficiency syndrome (PSYDS), Pi-Wei damp-heat syndrome (PWDHS), cold-damp disturbing Pi syndrome (CDDPS). Of them, GSPDS was mostly often seen with effective percentage of 34. 2%, while CDDPS was the least often seen with effective percentage of 5.5%. A total of 5 discriminant functions for GSPDS, PWWS, GSQSS, PSYDS, and PWDHS were obtained by step-by-step dis- crimination method. The retrospective misjudgment rate was 4.1% (16/390), while the cross-validation misjudgment rate was 15.4% (60/390). CONCLUSION: The establishment of discriminant functions is of value in objectively diagnosing and differentially diagnosing Chinese medical syndromes of IBS-D.