Comprehensive bibliometric and visualized analysis of research on gut-liver axis published from 1998 to 2022.

Background: The concept of the gut-liver axis was proposed by Marshall in 1998, and since then, this hypothesis has been gradually accepted by the academic community. Many publications have been published on the gut-liver axis, making it important to assess the scientific implications of these studies and the trends in this field. Methods: Publications were retrieved from the Web of Science Core Collection. Microsoft Excel, CiteSpace, VOSviewer, and Scimago Graphica software were used for bibliometric analysis. Results: A total of 776 publications from the Web of Science core database were included in this study. In the past 25 years, the number of publications on the gut-liver axis has shown an upward trend, particularly in the past 3 years (2020-2022). China had the highest number of publications (267 articles, 34.4%). However, the United States was at the top regarding influence and international cooperation in this field. The University of California San Diego had contributed the most publications. Suk, Ki Tae and Schnabl, Bernd were tied for the first rank in most publications. Thematic hotspots and frontiers were focused on gut microbiota, microbial metabolite, intestinal permeability, bacterial translocation, bile acid, non-alcoholic steatohepatitis, and alcoholic liver disease. Conclusion: Our study is the first bibliometric analysis of literature using visualization software to present the current research status of the gut-liver axis over the past 25 years. The damage and repair of intestinal barrier function, as well as the disruption of gut microbiota and host metabolism, should be a focus of attention. This study can provide a reference for later researchers to understand the global research trends, hotspots, and frontiers in this field.

Modified Gegen Qinlian decoction ameliorated ulcerative colitis by attenuating inflammation and oxidative stress and enhancing intestinal barrier function in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Gegen Qinlian decoction (MGQD), which was first documented in Treatise on Febrile Disease, is recognized as a classic prescription to treat ulcerative colitis (UC). However, its protective mechanism against UC remains to be fully elucidated. AIM OF THE STUDY: To explore the impact and the potential molecular mechanism of MGQD on dextran sodium sulfate (DSS)-induced UC mice and tumor necrosis factor alpha (TNF-α)-induced Caco-2 cell monolayer model of intestinal barrier. MATERIALS AND METHODS: The chemical components of MGQD and MGQD drug containing serum (MGQD-DS) were characterized by LC-MS/MS. The therapeutic effect of MGQD on DSS-induced UC was evaluated based on body weight, disease activity index (DAI), colon length, colonic histopathological injury, inflammatory cytokines, oxidative stress response and intestinal barrier function. Cell Counting Kit (CCK)-8 assay was applied to detect the effect of MGQD-DS on the viability of Caco-2 cells. Additionally, TNF-α-induced Caco-2 cell monolayer model of intestinal barrier was established in vitro. The Caco-2 cell monolayers were administered blank serum or MGQD-DS to observe the effects of MGQD-DS on transepithelial electrical resistance (TEER), permeability of fluorescein isothiocyanate (FITC)-dextran, inflammatory cytokines, oxidative stress indicators and intestinal epithelial barrier (IEB). RESULTS: MGQD significantly improved symptoms and pathological damage in UC mice by downregulating the expression of interleukin (IL)-1ß and malondialdehyde (MDA), attenuating the loss of goblet cells and the destruction of intestinal epithelial ultrastructure, and upregulating the expression of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), zonula occludens-1 (ZO-1), Occludin, Claudin-1 and E-cadherin. In vitro, MGQD-DS significantly reduced the flux of FITC-dextran, increased the TEER, inhibited the expression of IL-21, IL-17A and MDA, and promoted the expression of IL-4, IL-10, transforming growth factor-ß (TGF-ß), SOD, CAT, GSH, Occludin and E-cadherin in TNF-α-induced Caco-2 cell monolayer model of intestinal barrier. CONCLUSION: MGQD can ameliorate DSS-induced UC mice and TNF-α-induced Caco-2 cell monolayer model of intestinal barrier, and the protective effect is related to its inhibition of inflammation, alleviation of oxidative stress, and repair of intestinal barrier damage.

Research trends in the field of the gut-brain interaction: Functional dyspepsia in the spotlight - An integrated bibliometric and science mapping approach.

Objectives: This study aims to perform a bibliometric analysis of functional dyspepsia (FD), which includes visualizing bibliographic information, in order to identify prevailing study themes, topics of interest, contributing journals, countries, institutions, and authors as well as co-citation patterns. Methods: The Web of Science™ Core Collection Database was used to retrieve all peer-reviewed scientific publications related to FD research. The validated search terms were entered into the "title" and "author keywords" fields, and the results were sorted by publication year from 2006 to 2022. There were no restrictions on language. On 12 February 2023, a manual export of the complete metadata for each original publication and review article was performed. CiteSpace was used to reveal co-authorship, publication, and co-citation patterns to find prominent authors, organizations, countries, and journals in FD research as well as to identify author keywords with strong citation bursts, which could indicate an emerging research area. VOSviewer was used to build the co-occurrence indicator (co-word) to identify the main author keywords on which previous studies focused and to induce clustered scientific landscape for two consecutive periods to identify intriguing areas for future research. Results: A search of the database retrieved 2,957 documents. There was a wave-like pattern in the number of publications until 2017, after which there was a spike in publication volume. The USA, China, and Japan provided the majority of contributions. In terms of institution, Mayo Clin, Univ Newcastle, and Katholieke Univ Leuven were found to be the prolific institutions. Additionally, the results indicate that eastern Asian researchers contributed significantly to the global knowledge of literature that led other countries; however, Canada, the USA, Australia, England, and Germany were found to have the highest degree of betweenness centrality. Nicholas J. Talley, Jan Tack, Gerald Holtmann, Michael Camilleri, Ken Haruma, and Paul Moayyedi occupied the top positions based on productivity and centrality indicators. Six thematic clusters emerged (Helicobacter pylori infection; pathophysiological mechanisms of FD; extraintestinal co-morbidities and overlap syndromes associated with FD; herbal medicine in FD; diabetic gastroparesis; and dietary factors in FD). "Acupuncture," "duodenal eosinophilia," "gut microbiota," and others were among the author keywords with rising prevalence. Conclusion: In FD research, eastern Asian countries have established themselves as major contributors with the highest publishing productivity; however, research has primarily been driven by North America, Europe, and Australia, where cooperation is generally more active and highly influential scientific results are produced. Our analysis suggests that increased investments, training of human resources, improved infrastructures, and expanded collaborations are essential to improving the quality of FD research in Asia. The emerging author keyword analysis suggests that eosinophil-mast cell axis, gut microbiota, mental disorders, and acupuncture are the key areas that attract researchers' attention as future research boulevards. There is a highly skewed distribution of research output across Asia, with most focus on complementary and alternative medicine (CAM) coming from Chinese, Japanese, and South Korean centers. However, CAM remains an underexplored area of research in the context of FD, and it deserves greater research efforts in order to obtain quality scientific evidence. Furthermore, we propose that the research framework of CAM should not be limited to dysmotility; rather, it could be interpreted within a more holistic context that includes the brain-gut-microbiota axis, as well as novel concepts such as duodenitis, increased mucosal permeability, and infiltration and activation of eosinophils and mast cells, among others. Overall, we provided bibliometrics-based overviews of relevant literature to researchers from different backgrounds and healthcare professionals to provide an in-depth overview of major trends in FD research.

Chinese integrated guideline on the management of gastric precancerous conditions and lesions.

The standardized diagnosis and management of gastric precancerous conditions and lesions are important to prevent gastric cancer. This guideline, created by 5 traditional Chinese medicine and Western medicine associations, based on the current morbidity and diagnosis and treatment of gastric precancerous conditions and lesions, provides specific key points and strategies for diagnosis and treatment in the following five aspects: definition and epidemiology, diagnosis and stage, surveillance, treatment and efficacy evaluation. It is hoped that these aspects, assessed by integrating Western medicine and traditional Chinese medicine and involving multidisciplinary participation, will play a guiding role in clinical diagnosis and treatment and achieve effective secondary prevention of gastric cancer.

Chinese herbal compound prescriptions combined with Chinese medicine powder based on traditional Chinese medicine syndrome differentiation for treatment of chronic atrophic gastritis with erosion: a multi-center, randomized, positive-controlled clinical trial.

BACKGROUND: In this study, Chinese herbal compound prescriptions combined with Chinese medicine powder were evaluated for the treatment of chronic atrophic gastritis with erosion. METHODS: This multi-center, randomized, positive drug control clinical trial randomly assigned 216 patients with chronic atrophic gastritis with erosion to three groups: (1) control group: aluminum plus magnesium suspension thrice per day for 4 weeks; (2) test group 1: Chinese herbal compound prescriptions twice a day plus Sanqi (Panax notoginseng) powder twice a day for 4 weeks; (3) test group 2: Chinese herbal compound prescriptions twice a day plus Sanqi (Panax notoginseng) powder and Zhebeimu (Fritillaria thunbergii Miq.) powder twice a day for 4 weeks. The primary endpoint (improvement of gastric mucosal erosion; improvement of gastric mucosal pathology) and secondary endpoints (improvement of clinical symptoms scores; improvement of the patient-reported outcome [PRO] instrument for chronic gastrointestinal diseases) were assessed using endoscopy at week 4 following the treatment. Drug-related adverse events (AEs) and adverse drug reactions (ADRs) were also compared. RESULTS: The final analysis included 202 patients (control group, 63; test group 1, 69; test group 2, 70). At week 4, using within-group comparison, gastric mucosal erosion improved in each group following treatment with a significant difference (P < 0.05); there were no statistically significant differences in gastric mucosal erosion scores among the groups after treatment (P > 0.05); in terms of improvement of gastric mucosal erosion, the efficacy rate of the control group was 69.12%, the efficacy rate of the test group 1 was 73.24%, and the efficacy rate of the test group 2 was 69.01% and efficacy rate among the groups was not statistically significant (P > 0.05). As determined by acute inflammation, chronic inflammation, atrophy, intestinal metaplasia, and dysplasia, the pathological score (total score and the highest score) did not differ statistically among groups following treatment (P > 0.05); within the control group, the total scores of acute inflammation, chronic inflammation, atrophy, and intestinal metaplasia were significantly decreased (P < 0.05), but there was no significant improvement in dysplasia (P > 0.05); in the test group 1, chronic inflammation, atrophy, and intestinal metaplasia and dysplasia scores were significantly decreased (P < 0.05), but acute inflammation did not improve (P > 0.05); there was a significant reduction in the atrophy score in test group 2 (P < 0.05), but no improvement in the scores of acute inflammation, chronic inflammation, intestinal metaplasia, and dysplasia was observed (P > 0.05). Similarly, within the control group, the highest scores of acute inflammation, chronic inflammation, atrophy, and intestinal metaplasia were significantly decreased (P < 0.05), but there was no significant improvement in dysplasia (P > 0.05); there was a significant reduction in highest scores of atrophy, intestinal metaplasia, and dysplasia (P < 0.05) in test group 1, but the highest scores didn't not improve with acute inflammation and chronic inflammation (P > 0.05); there was a significant reduction in the highest atrophy score in test group 2 (P < 0.05), but no improvement in the highest scores of acute inflammation, chronic inflammation, intestinal metaplasia, and dysplasia was observed (P > 0.05). Compared to the control group, the main symptom scores and total symptom scores in the test groups were lower following treatment, with a statistically significant difference (P < 0.05); the analysis of covariance with center, erosion type, and group as factors was applied, and the comparison among the groups in dyspepsia, defecation, and total PRO instrument scores were statistically significant (P < 0.05). In the study period, AEs were reported in 3 (4.23%) patients in the test group 1 and 3 (4.41%) patients in the control group; ADRs were confirmed in 3 (4.23%) patients from the test group 1 and 2 (2.94%) from the control group. AEs and ADRs were not statistically significantly different among groups (AE, P = 0.2213; ADR, P = 0.2872). No serious AE or ADR was reported. CONCLUSIONS: This study has shown that both aluminum plus magnesium suspension and Chinese herbal compound prescriptions together with Panax notoginseng powder are capable of improving gastric mucosal erosion and reducing gastric mucosal pathological scores, and there were no statistically significant differences among the groups in primary endpoints, indicating that Chinese herbal therapy can achieve similar efficacy than antacids in terms of primary outcomes. The aluminum plus magnesium suspension is comparable to Chinese herbal therapy in improving atrophy and intestinal metaplasia, and is inferior to Chinese herbal therapy in improving dysplasia. In addition, the Chinese herbal therapy significantly outperforms the aluminum plus magnesium suspension in improving symptoms. Therefore, the overall clinical outcome of Chinese herbal compound prescriptions together with Panax notoginseng powder based on TCM syndrome patterns in the treatment of erosive gastritis is superior to that of antacids. Trial registration ChiCTR, ChiCTR-IPR-15005905. Registered 22 January 2015, https://www.chictr.org.cn/showproj.aspx?proj=10359.

Revealing immune infiltrate characteristics and potential diagnostic value of immune-related genes in ulcerative colitis: An integrative genomic analysis.

Objectives: Ulcerative colitis (UC) is an autoimmune disease of the colon. The aim of this study was to explore the characteristics of immune infiltrates in UC patients and identify immune-related diagnostic biomarkers for UC. Methods: Three gene expression profiles were acquired from the GEO database, followed by identification of differentially expressed genes (DEGs) by Linear Modeling of Microarray Data. Enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Disease Ontology (DO) were performed to analyze the biological functions of DEGs. Subsequently, the single sample gene set enrichment analysis (ssGSEA) was performed to identify immune infiltration characteristics of UC. Correlations between diagnostic genes and immune infiltration were explored to identify markers with the greatest diagnostic potential, and a UC diagnostic model was subsequently constructed. Finally, the prediction performance of the model was quantified by nomogram, non-correlated nomogram, and ROC curve. Results: A total of 3111 DEGs (1,608 up-regulated and 1,503 down-regulated genes) were identified. DEGs were significantly involved in the immune system and UC-related pathways. Immune infiltration profiles of colonic tissue were significantly different between healthy individuals and UC patients. High proportions of resting of aDCs, B cells, CD8+ T cells, DCs, iDCs, Macrophages, Neutrophils, pDCs, T helper cells, Tfh, Th1 cells, Th2 cells, TIL and Treg were found in UC samples. A 5-gene based diagnostic prediction model was constructed and the results of nomogram, non-correlated nomogram and ROC curve suggested the powerful diagnostic value of the model. Conclusions: This study identified the immune infiltrate characteristics and 5 immune-related genes for UC. The model based on the immune-related genes facilitates the early diagnosis of UC and provides a basis for the evaluation of the prognosis of UC.

Comprehensive analysis of cuproptosis-related genes in immune infiltration and diagnosis in ulcerative colitis.

Objectives: Cuproptosis is a recently discovered form of programmed cell death; however, its role in ulcerative colitis (UC) remains a void. Methods: Three gene expression profiles were acquired from the GEO database. Subsequently, the single sample gene set enrichment analysis (ssGSEA) was performed to identify the immune infiltration characteristics of UC. Correlation analysis between cuproptosis and immune infiltration was further conducted, and the cuproptosis-related genes were applied to construct a UC diagnostic model. Subsequently, analysis results of microarray data were experimentally validated by DSS-induced colitis in mice. Finally, therapeutic agents for the cuproptosis-related genes were screened owing to the gaping field of therapeutic agents on cuproptosis. Results: Three gene expression profiles with 343 samples (290 UC and 53 healthy samples) were included. Immune infiltration revealed that UC patients had a higher level of DCs, B cells, CD8+ T cells, iDCs, Macrophages, neutrophils, pDCs, T helper cells, Tfh, Th1 cells, Th2 cells, TIL and Treg than normal subjects. Moreover, almost all cuproptosis-related genes were significantly negatively associated with immune infiltration in UC patients. The risk prediction model based on cuproptosis-related genes showed an excellent discrimination for UC. Animal experiments revealed significant alterations in genes essential for cuproptosis between DSS-induced colitis mice and healthy controls, providing experimental validation for the analysis results of microarray data. Further analysis revealed that latamoxef, vitinoin, clomipramine, chlorzoxazone, glibenclamide, pyruvic acid, clindamycin, medrysone, caspan, and flavin adenine dinucleotide might be the target agents for cuproptosis-related genes. Conclusions: In conclusion, cuproptosis was significantly associated with immune infiltration in UC, and the cuproptosis-related genes showed an excellent discrimination for UC.

Comprehensive bibliometric and visualized analysis of research on fecal microbial transplantation published from 2000 to 2021.

BACKGROUND: Fecal microbial transplantation has emerged in recent years as a method of treating disease by rebuilding the intestinal flora. However, few bibliometric analyses have systematically studied this area of research. We aimed to use bibliometric analysis to visualize trends and topical research in fecal microbial transplantation to help provide insight into future trends in clinical and basic research. MATERIALS AND METHODS: Articles and reviews related to fecal microbial transplantation were collected from the Web of Science Core Collection. Significant information associated with this field was visually analyzed by using Biblioshiny and CtieSpace software. RESULTS: A total of 3144 articles and overviews were included. The number of publications related to fecal microbial transplantation significantly increased yearly. These publications mainly came from 100 countries, led by the US and China, and 521 institutions. The most prolific and influential author is KHORUTS A. The main disciplines and application fields of fecal microbial transplantation included molecular /biology/immunology and medicine/clinical medicine, and the research foundation of fecal microbial transplantation was molecular /biology/genetics and health/nursing/medicine. An alluvial flow visualization showed several landmark articles. New developments were identified in terms of reference and keyword citation bursts. Data analysis showed that different FMT preparation and delivery methods gradually appeared as research hotspots. The main research keywords in the last 3 years were chain fatty acids, Akkermansia muciniphila, and insulin sensitivity, other keywords were current and developing research fields. CONCLUSION: Research on fecal microbial transplantation is flourishing and many new applications of fecal microbial transplantation are emerging. Microbial metabolites such as short-chain fatty acids and the microbiota-gut-brain axis have become the focus of current research and are future research trends.

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.

Trends in gastroesophageal reflux disease research: A bibliometric and visualized study.

Background: Gastroesophageal reflux disease (GERD), a disorder resulting from the retrograde flow of gastric contents into the esophagus, affects an estimated 10-30% of the Western population, which is characterized by multifactorial pathogenesis. Over the past few decades, there have been many aspects of uncertainty regarding GERD leading to an ongoing interest in the field as reflected by a large number of publications, whose heterogeneity and variable quality may present a challenge for researchers to measure their scientific impact, identify scientific collaborations, and to grasp actively researched themes in the GERD field. Accordingly, we aim to evaluate the knowledge structure, evolution of research themes, and emerging topics of GERD research between 2012 and 2022 with the help of bibliometric approaches. Methods: The literature focusing on GERD from 2012 to 2022 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. The overall publication performance, the most prolific countries or regions, authors, journals and resources-, knowledge- and intellectual-networking, as well as the co-citation analysis of references and keywords, were analyzed through Microsoft Office Excel 2019, CiteSpace, and VOSviewer. Results: A total of 8,964 publications were included in the study. The USA published the most articles (3,204, 35.74%). Mayo Clin ranked first in the number of articles published (201, 2.24%). EDOARDO SAVARINO was the most productive author (86, 0.96%). The most productive journal in this field was SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES (304, 3.39%). AMERICAN JOURNAL OF GASTROENTEROLOGY had the most co-citations (4,953, 3.30%). Keywords with the ongoing strong citation bursts were transoral incision less fundoplication, eosinophilic esophagitis, baseline impedance, and functional heartburn. Conclusion: For the first time, we obtained deep insights into GERD research through bibliometric analysis. Findings in this study will be helpful for scholars seeking to understand essential information in this field and identify research frontiers.

Research trends in ulcerative colitis: A bibliometric and visualized study from 2011 to 2021.

Background: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease with repeated relapses and remissions. Despite decades of effort, numerous aspects, including the initiating event and pathogenesis of UC, still remain ambiguous, which requires ongoing investigation. Given the mass of publications on UC, there are multidimensional challenges to evaluating the scientific impact of relevant work and identifying the current foci of the multifaceted disease. Accordingly, herein, we aim to assess the global growth of UC research production, analyze patterns of research areas, and evaluate trends in this area. Methods: The Web of Science Core Collection of Clarivate Analytics was searched for articles related to UC published from 2011 to 2021. Microsoft Office Excel 2019 was used to visualize the number of publications over time. Knowledge maps were generated using CiteSpace and VOSviewer to analyze collaborations among countries, institutions, and authors and to present the journey of UC research as well as to reveal the current foci of UC research. Results: A total of 5,088 publications were evaluated in the present study. China had the most publications (1,099, 22.5%). Univ Calif San Diego was the most productive institution (126, 2.48%). William J Sandborn published the greatest number of articles (100, 1.97%). Toshifumi Hibi was the most influential author in the field with a betweenness centrality of 0.53. Inflammatory bowel diseases was identified as the most prolific journal (379, 7.45%). Gastroenterology was the most co-cited journal (3,730, 4.02%). "Vedolizumab," "tofacitinib," "Faecalibacterium prausnitzii," "fecal microbiota transplantation (FMT)," "toll-like receptor 4," and "nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome" were considered the hot topics. Conclusion: In UC research, manuscripts that had high impacts on the scientific community provided an evidence base. UC therapy has entered the era of personalized and precision therapy. As research on FMT, anti-integrin antibodies, Janus kinase inhibitors, and anti-tumor necrosis factor drugs continues to grow, their use in the clinical setting may also expand.

External therapy of traditional Chinese medicine for treating irritable bowel syndrome with diarrhea: A systematic review and meta-analysis.

Background: Irritable bowel syndrome with diarrhea (IBS-D) is a chronic functional gastrointestinal disorder that has a significant impact on quality of life, work productivity, and healthcare resources. External therapy of traditional Chinese medicine (TCM) has positive effects on IBS-D and is simple, convenient, and low-cost. This study aimed to systematically evaluate the efficacy and safety of external therapy of TCM for IBS-D. Methods: This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals (VIP), Wan Fang, and Chinese Biomedical (CBM) databases were electronically searched to collect randomized controlled trials comparing external therapy of TCM with Western medicine for IBS-D from inception to 31 December 2021. Two authors independently screened, extracted, and assessed the selected studies. The Jadad scale and Cochrane Collaboration Risk of Bias tool were used to evaluate study quality. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). The meta-analysis was performed using the Review Manager software (version 5.3). Results: Twenty-one studies involving 1,862 subjects were included. Acupuncture and moxibustion were the most commonly used external therapies. The meta-analysis showed that based on total effective rate with moderate certainty of evidence (n = 21 studies, n = 1,862 participants, RR = 1.25, 95% CI [1.2, 1.31], I2 = 0%, P < 0.00001), clinical cure rate with low certainty of evidence (n = 17 studies, n = 1,502 participants, RR = 1.66, 95% CI [1.4, 1.96], I2 = 1%, P < 0.00001), recurrence rate with very low certainty of evidence (n = 5 studies, n = 260 participants, RR = 0.44, 95% CI [0.34, 0.58], I2 = 0%, P < 0.00001), total symptom score (MD = -4.9, 95% CI [-7.34, -2.47]), and IBS severity scoring system score (IBS-SSS) with moderate certainty of evidence (MD = -52.72, 95% CI [-63.9, -41.53]), the experimental group had significant advantages compared with the control group. The sensitivity analysis further confirmed the robustness of the primary outcomes. The improvement in quality of life associated with IBS (IBS-QOL) was superior in the experimental group compared to the control group, and the difference was statistically significant; however, the clinical heterogeneity was strong. The inverted funnel plot of the included studies indicated a potential publication bias. Conclusion: External therapy of TCM for IBS-D alleviated abdominal symptoms, improved clinical effectiveness, and reduced recurrence with great safety. However, because of the limitations of publication bias in trials, more rigorous studies with a clinical design are necessary for further verification of the outcomes. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42020222993].

Global Research Trends in Irritable Bowel Syndrome: A Bibliometric and Visualized Study.

Background: There are about 10-23% of adults worldwide suffering from irritable bowel syndrome (IBS). Over the past few decades, there are many aspects of uncertainty regarding IBS leading to an ongoing interest in the topic as reflected by a vast number of publications, whose heterogeneity and variable quality may challenge researchers to measure their scientific impact, to identify collaborative networks, and to grasp actively researched themes. Accordingly, with help from bibliometric approaches, our goal is to assess the structure, evolution, and trends of IBS research between 2007 and 2022. Methods: The documents exclusively focusing on IBS from 2007 to 2022 were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. The annual productivity of IBS research, and the most prolific countries or regions, authors, journals and resource-, intellectual- and knowledge-sharing in IBS research, as well as co-citation analysis of references and keywords were analyzed through Microsoft Office Excel 2019, CiteSpace, and VOSviewer. Results: In total, 4,092 publications were reviewed. The USA led the list of countries with the most publications (1,226, 29.96%). Mayo Clinic contributed more publications than any other institution (193, 4.71%). MAGNUS SIMREN stood out as the most active and impactful scholar with the highest number of publications and the greatest betweenness centrality value. The most high-yield journal in this field was Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society (275, 6.72%). Gastroenterology had the most co-citations (3,721, 3.60%). Keywords with the ongoing strong citation bursts were chromogranin A, rat model, peptide YY, gut microbiota, and low-FODMAP diet, etc. Conclusion: Through bibliometric analysis, we gleaned deep insight into the current status of literature investigating IBS for the first time. These findings will be useful to scholars interested in understanding the key information in the field, as well as identifying possible research frontiers.

Effectiveness of peer-mediated intervention on social skills for children with autism spectrum disorder: a randomized controlled trial.

Background: Peer-mediated intervention (PMI) is an intervention that teaches normally developing peers to help children with autism spectrum disorder (ASD) actively participate in social interactions. Previous studies have shown that PMI applied to school settings is effective for children with ASD, but more multiple-baseline single-subject design. Many questions are still not clear due to the large clinical variability in children with ASD. This study investigated the effectiveness of PMI on social skills of children with ASD at varying symptom levels and analyzed the specific changes. Methods: This study used a randomized, single-blind, parallel-controlled design to analyze the effect of PMI in a hospital setting. Fifty-five children aged 4-12 years were diagnosed with ASD by clinicians using the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and stratified randomly allocated to either the experimental group or the control group using the envelope method. The experimental group utilized PMI, whereas the control group utilized behavioral therapy based on applied behavior analysis (ABA) [early intensive behavioral intervention (EIBI)]. This study primarily utilized the Social Responsiveness Scale (SRS) to evaluate the social performance of autistic children prior to and after the intervention. Results: Fifty-five participants were recruited and analyzed, the experimental group (n=29; mild to moderate n=18, severe n=11) and the control group (n=26; mild to moderate n=15, severe n=11). After the intervention, the experimental group's SRS score fell significantly more than the control group's (t=-3.918, P=0.000), d=-1.043; the mild to moderate subgroup experienced the same situation (H=17.811, P=0.009), d=-1.642. At the same time, the decline in social communication scores was significantly greater in the experimental group compared to the control group (t=-3.869, P=0.000), and the 95% confidence interval was -10.067 to -3.193. The social motivation of the mild-to-moderate subgroup of the experimental group (H=16.894, P=0.011), -3.000 (25th percentile, 75th percentile: -3.000, 0.000), and the behavioral patterns of autism (H=18.150, P=0.006), -3.000 (25th percentile, 75th percentile: -5.000, 0.000), the decreased value was significantly larger. Conclusions: PMI therapy can increase social motivation in children with mild to moderate ASD, minimize undesirable behavior patterns, effectively improve overall social skills and enhance effective social communication with others. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100049185.

Treatment of the Gastroesophageal Reflux Disease with Chinese Herbal Medicine (BanxiaXiexin Decoction): Evidence from Meta-Analysis.

Objectives: Systematic reviews/meta-analyses (SRs/MAs) are still controversial on the effectiveness of Banxia Xiexin decoction (BXD) to treat gastroesophageal reflux disease (GERD). To assess the evidence reliability and inform the clinical use of BXD, we performed a meta-analysis from previous SRs/MAs to collate, critically appraise, and synthesize the effectiveness of BXD treatment in GERD. Methods: SRs/MAs were collected by searching major medical databases. The included studies were evaluated in terms of methodological quality and quality of evidence using criteria from the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system, respectively. Results: Six SRs/MAs were included in this study. The methodological quality of SRs/MAs was generally unsatisfactory. Unregistered protocols, failure to provide a list of excluded trials, and lack of a comprehensive search strategy were the main limitations of previous SRs/MAs. No high-quality evidence was found to support the effect of BXD on GERD patients. The qualitative data synthesis relied on low-quality trials with a small sample size, which was the main factor for evidence degradation. Conclusions: BXD seems to have promising efficacy to treat GERD patients. Although the quality of SRs/MAs was generally low and defects were frequent, our study highlights areas where methodologies need to be improved.

A Bibliometric Analysis of Atrophic Gastritis From 2011 to 2021.

BACKGROUND: Atrophic gastritis (AG), which is characterized by a decreased number or disappearance of the glandular structures and secretory dysfunction, is linked to chronically inflamed stomach. It has been estimated that the annual incidence of gastric cancer (GC) is 0.1% for patients with AG. Early eradication of Helicobacter pylori (H. pylori) can reduce the risk of GC development. Additionally, the follow-up and management of AG are necessary to prevent GC. Exploring novel methods of the automatized analysis of data for apprehending knowledge in any medical field is encouraged, especially when a body of literature suggests the necessity of doing so. Accordingly, herein, we aim to systematically review the current foci and status of AG research using bibliometric analysis. METHODS: Articles and reviews related to AG published from 2011 to 2021 in the Web of Science Core Collection were retrieved. Microsoft Office Excel 2019 and GraphPad Prism were used to show the annual number of publications and scientific productivity of authors through time. CiteSpace and VOSviewer were used to generate network maps about the collaborations among countries, institutions, and authors as well as reveal hotspots of AG research. The relationships among the author's keywords, cited references, and the top authors were summarized by a Sankey plot (three-fields plot). RESULTS: A total of 1,432 publications were included in the present study. China remained the most productive country, with the highest number of publications (377, 26.32%). Vanderbilt University contributed the most publications of any single institution (56, 3.91%). James R Goldenring was the most active and influential scholar, with the highest number of publications and greatest centrality. The most prolific journal in this field was World Journal of Gastroenterology (62, 4.32%). Gastroenterology (997, 69.62%) was the most co-cited journal. Exploring the origin of gastric metaplasia, especially spasmolytic polypeptide-expressing metaplasia (SPEM) was a major topic in AG research. CONCLUSIONS: This bibliometric study provides a comprehensive analysis of the scientific progress of AG over the past decade. Metaplasia is a hot topic and could be a promising area of research in the coming years.

JianpiQinghua granule reduced PPI dosage in patients with nonerosive reflux disease: A multicenter, randomized, double-blind, double-dummy, noninferiority study.

BACKGROUND: Proton pump inhibitors (PPIs) play an important role in the treatment of nonerosive reflux disease (NERD), but their long-term and excessive uses have been associated with safety concerns. Chinese herbal medicine (CHM) has become a popular alternative treatment for this condition. METHODS: A total of 204 patients were randomly assigned to the combination group or PPI group (1:1 ratio). They were given JianpiQinghua (JQ) granules (34.8 g) plus omeprazole (10 mg) plus dummy omeprazole (10 mg) or dummy JQ granules (34.8 g) plus omeprazole (20 mg) daily for 4 weeks. The primary endpoints were the rate of sufficient relief and complete resolution of GERD Q at week 4. Metabonomics and the gut microbiota were also assessed. RESULTS: Complete resolution was observed in 40.8% of patients in the combination group and 26.8% of patients in the PPI group after 4 weeks (FAS analysis, OR, 1.88; 95% CI, 1.03-3.44; p = 0.039). Sufficient relief was observed in 50% of patients in the combination group and 43.30% of patients in the PPI group after 4 weeks (FAS analysis, OR, 1.31; 95% CI, 0.74-2.30; p = 0.35). Three patients had liver dysfunction, one of whom had a mild case and 2 of whom had moderate-to-severe cases in the combination group. Patients in the combination group showed a significant increase in richness and diversity of their gut microbiota compared with those in the PPI group. Metabonomics showed that the combination therapy could correct the glutamate metabolism pathway. CONCLUSION: Our findings demonstrate the superior efficacy of JQ granules combined with omeprazole (10 mg) vs. omeprazole (20 mg) in terms of symptom relief in patients with NERD. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02892357. Registered on 14 February 2019.

A comprehensive review on recent developments of radio frequency treatment for pasteurizing agricultural products.

Recent pathogen incidents have forced food industry to seek for alternative processes in postharvest pasteurization of agricultural commodities. Radio frequency (RF) heating has been used as one alternative treatment to replace chemical fumigation and other conventional thermal methods since it is relatively easy to apply and leaves no chemical residues. RF technology transfers electromagnetic energy into large bulk volume of the products to provide a fast and volumetric heating. There are two types of RF technology commonly applied in lab and industry to generate the heat energy: free running oscillator and 50-Ω systems. Several reviews have been published to introduce the application of RF heating in food processing. However, few reviews have a comprehensive summary of RF treatment for pasteurizing agricultural products. The objective of this review was to introduce the developments in the RF pasteurization of agricultural commodities and to present future directions of the RF heating applications. While the recent developments in the RF pasteurization were presented, thermal death kinetics of targeted pathogens as influenced by water activity, pathogen species and heating rates, non-thermal effects of RF heating, combining RF heating with other technologies for pasteurization, RF heating uniformity improvements using computer simulation and development of practical RF pasteurization processes were also focused. This review is expected to provide a comprehensive understanding of RF pasteurization for agricultural products and promote the industrial-scale applications of RF technology with possible process protocol optimization purposes.

Comparative proteomic analysis of the brain and colon in three rat models of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) has been gradually recognized as a disorder of the brain-gut interaction, but the molecular changes in the brain and colon that occur in disease development remain poorly understood. We employed proteomic analysis to identify differentially expressed proteins in both the brain and colon of three IBS models. METHODS: To explore the relevant protein abundance changes in the brain and colon, isobaric tags for relative and absolute quantitation (iTRAQ), liquid chromatography and tandem mass spectrometry (LC-MS) and Western blotting methods were used in three IBS models, including maternal separation (MS, group B), chronic wrap restraint stress (CWRS, group C) and a combination of MS and CWRS (group D). RESULTS: We identified 153, 280, and 239 proteins that were common and differentially expressed in the two tissue types of groups B, C and D, respectively; 43 differentially expressed proteins showed the same expression changes among the three groups, including 25 proteins upregulated in the colon and downregulated in the brain, 7 proteins downregulated in the colon and upregulated in the brain, and 3 proteins upregulated and 8 downregulated in both tissues. Gene ontology analysis showed that the differentially expressed proteins were mainly associated with cellular assembly and organization and cellular function and maintenance. Protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the differentiated proteins were mainly involved in the protein ubiquitination pathway and mitochondrial dysfunction. CONCLUSIONS: Taken together, the data presented represent a comprehensive and quantitative proteomic analysis of the brain and colon in IBS models, providing new evidence of an abnormal brain-gut interaction in IBS. These data may be useful for further investigation of potential targets in the diagnosis and treatment of IBS.

Chang'an II Decoction ( II )-Containing Serum Ameliorates Tumor Necrosis Factor-α-Induced Intestinal Epithelial Barrier Dysfunction via MLCK-MLC Signaling Pathway in Rats.

OBJECTIVE: To investigate the effect of Chang'an II Decoction ( II ))-containing serum on intestinal epithelial barrier dysfunction in rats. METHODS: Tumor necrosis factor (TNF)-α-induced injury of Caco-2 monolayers were established as an inflammatory model of human intestinal epithelium. Caco-2 monolayers were treated with blank serum and Chang'an II Decoction-containing serum that obtained from the rats which were treated with distilled water and Chang'an II Decoction intragastrically at doses of 0.49, 0.98, 1.96 g/(kg·d) for 1 week, respectively. After preparation of containing serum, cells were divided into the normal group, the model group, the Chang'an II-H, M, and L groups (treated with 30 ng/mL TNF-α and medium plus 10% high, middle-, and low-doses Chang'an II serum, respectively). Epithelial barrier function was assessed by transepithelial electrical resistance (TER) and permeability of fluorescein isothiocyanate (FITC)-labeled dextran. Transmission electron microscopy was used to observe the ultrastructure of tight junctions (TJs). Immunofluorescence of zonula occludens-1 (ZO-1), claudin-1 and nuclear transcription factor-kappa p65 (NF-κ Bp65) were measured to determine the protein distribution. The mRNA expression of myosin light chain kinase (MLCK) was measured by real-time polymerase chain reaction. The expression levels of MLCK, myosin light chain (MLC) and p-MLC were determined by Western blot. RESULTS: Chang'an II Decoction-containing serum significantly attenuated the TER and paracellular permeability induced by TNF-α. It alleviated TNF-α-induced morphological alterations in TJ proteins. The increases in MLCK mRNA and MLCK, MLC and p-MLC protein expressions induced by TNF-α were significantly inhibited in the Chang'an II-H group. Additionally, Chang'an II Decoction significantly attenuated translocation of NF-κ Bp65 into the nucleus. CONCLUSION: High-dose Chang'an II-containing serum attenuates TNF-α-induced intestinal barrier dysfunction. The underlying mechanism may be involved in inhibiting the MLCK-MLC phosphorylation signaling pathway mediated by NF-κ Bp65.