Paris polyphylla extract attenuates colitis in mice by regulating PPAR-γ mediated Treg/Th17 balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Paris polyphylla Sm. (P.P), is a widely-used traditional Chinese medicine (TCM) in the treatment of wound, throat sores and snakebites. Furthermore, P.P was recorded as an anti-inflammatory drug by the Chinese Pharmacopoeia. AIM OF THE STUDY: We sought to decipher the anti-inflammatory effect of P.P on ulcerative colitis (UC); specifically, to explore whether P.P attenuates colitis by restoring the regulatory T cells (Tregs) and T helper 17 (Th17) cells balance and its mechanism. MATERIAL AND METHODS: We treated experimental colitis mice with extracts of Paris polyphylla (EPP). The percentage of Tregs and Th17 cells were measured using flow cytometry, and their secreted cytokines levels were evaluated employing ELISA. The expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) in colon tissues was detected using immunofluorescence. Furthermore, GW9662, a PPAR-γ antagonist, was used to validate the mechanism of EPP in restoring the Treg/Th17 balance. RESULTS: The EPP effectively alleviated the clinical symptoms and inflammatory cytokine levels in mice with colitis. EPP treatment also restored the impaired Treg/Th17 balance in mice. Furthermore, EPP treatment promoted PPAR-γ expression and reduced HIF-1α and p-STAT3 expression in colon tissues, whereas PPAR-γ inhibition blocked the effects of EPP in mice models. CONCLUSION: Our study indicates that EPP exhibit excellent anti-inflammatory properties via restoring PPAR-γ/STAT3/HIF-1α axis-mediated Treg/Th17 balance in colitis mice. Hence, P. polyphylla is a promising medicinal plant-based alternative for managing colitis that requires further clinical validation.

N6-methylandenosine-related immune genes correlate with prognosis and immune landscapes in gastric cancer.

Objectives: This study aimed to probe into the significance of N6-methyladenosine (m6A)-related immune genes (m6AIGs) in predicting prognoses and immune landscapes of patients with gastric cancer (GC). Methods: The clinical data and transcriptomic matrix of GC patients were acquired from The Cancer Genome Atlas database. The clinically meaningful m6AIGs were acquired by univariate Cox regression analysis. GC patients were stratified into different clusters via consensus clustering analysis and different risk subgroups via m6AIGs prognostic signature. The clinicopathological features and tumor microenvironment (TME) in the different clusters and different risk subgroups were explored. The predictive performance was evaluated using the KM method, ROC curves, and univariate and multivariate regression analyses. Moreover, we fabricated a nomogram based on risk scores and clinical risk characteristics. Biological functional analysis was performed based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The connectivity map was used to screen out potential small molecule drugs for GC patients. Results: A total of 14 prognostic m6AIGs and two clusters based on 14 prognostic m6AIGs were identified. A prognostic signature based on 4 m6AIGs and a nomogram based on independent prognostic factors was constructed and validated. Different clusters and different risk subgroups were significantly correlated with TME scores, the distribution of immune cells, and the expression of immune checkpoint genes. Some malignant and immune biological processes and pathways were correlated with the patients with poor prognosis. Ten small molecular drugs with potential therapeutic effect were screened out. Conclusions: This study revealed the prognostic role and significant values of m6AIGs in GC, which enhanced the understanding of m6AIGs and paved the way for developing predictive biomarkers and therapeutic targets for GC.

Studies on irritable bowel syndrome associated with anxiety or depression in the last 20 years: A bibliometric analysis.

Irritable bowel syndrome (IBS) associated with anxiety or depression is ubiquitous in clinical practice, and multiple related articles have been published. However, studies that utilize bibliometric analyses to address this topic are rare. In our study, we aimed to reveal research trends in IBS with anxiety or depression. Publications on IBS in relation to anxiety or depression in the last 20 years were obtained from the Web of Science Core Collection (WoSCC). CiteSpace software (5.8.R3) and GraphPad Prism 8 were used to perform bibliometric analysis of authors, countries, institutions, journals, keywords, and references involved in this topic. A total of 2,562 publications from 716 academic journals were included in this study. The majority of publications (n = 833, 32.51%) were from the USA, and the University of California, Los Angeles, contributed the most publications (n = 97, 3.79%). Active cooperations among countries and institutions were observed. Neurogastroenterology and Motility [impact factor (IF) 2020 = 3.598] published the most papers (170 publications, 6.64%), followed by Alimentary Pharmacology Therapeutics (IF 2020 = 8.171; 88 publications; 3.44%). The literatures related to IBS and anxiety or depression were primarily published in journals related to medicine/medical/clinical, neurology/sports/ophthalmology, and molecular/biology/immunology. Cryan JF and Drossman DA, with the largest number of articles (84 publications) and citations (917 citations), respectively, were considered as the most influential authors in this field. A total of 336 co-cited references were divided into 17 clusters, and #1 fecal microbiota transplantation contained most of the documents published in recent years. Moreover, the keyword "psychosocial factor" had the largest burst strength of 13.52, followed by the keyword "gut microbiota" with a burst strength of 11.71. This study shows the research performance of IBS related to anxiety or depression from 2002 to 2021 and helps researchers master the trend in this field, which should receive more attention.

Interpretation of a Quantitative Diagnosis Model of Traditional Chinese Medicine Syndromes Based on Computer Adaptive Testing.

Objectives: The aim of this study is to interpret a quantitative diagnosis model of traditional Chinese medicine (TCM) syndromes based on computer adaptive testing (CAT), from the perspective of both patients and clinicians. Methods: In this cross-sectional study, patients with postprandial distress syndrome completed the CAT model of TCM syndromes and the Chinese version of the Quality of Life Questionnaire for Functional Digestive Disorders (Chin-FDDQL); the clinicians' diagnosis was concurrently recorded. The patients completed this questionnaire again after 14 ± 2 days. The kappa test and paired chi-square test were used to evaluate the consistency between the CAT model and clinical diagnosis. Minimal clinically important differences (MCID) of the Chin-FDDQL scores were used to assess clinical efficacy from the patients' perspective. Logistic regression was used to examine the association between changes in the CAT model syndrome domain scores and changes in clinical outcomes. Results: Changes in the CAT model syndrome domain scores may affect the clinical outcomes of patients with the total scores of Chin-FDDQL (all P < 0.05). There was a correlation between changes in the CAT model syndrome domain scores and the patients' clinical outcomes. Different syndrome elements had different effects on various Chin-FDDQL domains, which was consistent with the theory of TCM. Conclusions: This study proposes a method for the clinical interpretation of the CAT model of TCM syndromes, including evidence derived from the application. It may provide a reference for future interpretation of other CAT models.

Quercetin alleviates chronic renal failure by targeting the PI3k/Akt pathway.

Chronic renal failure (CRF) threatens human health greatly and attracts worldwide concerns of health professionals in the public health sector. In our preliminary study, we found that Compound capsule (Shengqing Jiangzhuo Capsule, SQJZJN) had a significant therapeutic effect on CRF. Quercetin is one of the main components of this Compound capsule. In this study, we investigated the effect of Quercetin monomer on CRF and the regulation of PI3k/Akt pathway. Network pharmacology analysis methods were employed to analyze the SQJZJN/Quercetin/PIK3R1 network relationships. In this study, a CRF rat model was prepared using the gavage adenine solution method and detected the indicators of Creatinine (Cr), Blood Urea Nitrogen (BUN), and Uric Acid (UA). After treating the rat model with Quercetin and PIK3R1-interfering lentivirus, respectively, we observed the changes on the histological morphology of the kidney and detected apoptosis using TUNEL staining. Gene and protein expression associated with renal function were detected using qPCR, WB and immunofluorescence. Quercetin was identified as the main ingredient of SQJZJN by the network pharmacological screening and Quercetin at 1.5 and 3 g/(kg.d) concentrations could effectively alleviate the CRF symptoms, reduce the levels of Cr, BUN, and UA, and markedly inhibit cell apoptosis demonstrated by the intragastric administration. Furthermore, the protein expression of p-PI3K, p-AKT, NLRP3, caspase1, AQP1, and AQP2 in all groups was detected by immunofluorescence and western blot assays, indicating that Quercetin could reduce the expression of NLRP3, caspase1, p-PI3k, and p-Akt, and increase the expression of AQP1 and AQP2 in the renal tissues of CRF rats. Being labeled with biotin and incubated with the total protein extracted from kidney tissues, Quercetin could bind to PIK3R1. Following the PIK3R1 interference lentivirus was injected into the CRF model rats by tail vein, the CRF symptoms were effectively alleviated in the PIK3R1 interference group, consistent with the effect of Quercetin. Taken together, Quercetin, a major component of SQJZJN, might minimize renal fibrosis and apoptosis in CRF rats by inhibiting the PI3k/Akt pathway through targeting PIK3R1. By regulating AQP1 and AQP2, both water retention and toxin accumulation were reduced.

Scientometric Analysis of Medicinal and Edible Plant Coptis.

Objective: A scientometric analysis to obtain knowledge mapping of Coptis revealed the current research situation, knowledge base and research hotspots in Coptis research. Methods: Coptis-related documents published from 1987 to 2020 were selected through the Web of Science Core Collection. CiteSpace, VOSviewer and Microsoft Excel were used to construct knowledge maps of the Coptis research field. Results: A total of 367 documents and their references were analyzed. These papers were primarily published in mainland China (214), followed by Japan (57) and South Korea (52), and they each formed respective cooperation networks. The document co-citation analysis suggested that the identification of Coptis Salisb. species, the production of alkaloids, and the mechanisms of action of these alkaloids formed the knowledge bases in this field. A keyword analysis further revealed that the research hotspots were primarily concentrated in three fields of research involving berberine, Coptis chinensis Franch, and Coptis japonica (Thunb) Makino. Oxidative stress, rat plasma (for the determination of plasma alkaloid contents), and Alzheimer's disease are recent research hotspots associated with Coptis. Conclusion: Coptis research was mainly distributed in three countries: China, Japan, and South Korea. Researchers were concerned with the identification of Coptis species, the production of Coptis alkaloids, and the efficacy and pharmacological mechanism of the constituent alkaloids. In addition, the anti-oxidative stress, pharmacokinetics, and Alzheimer's disease treatment of Coptis are new hotspots in this field. This study provides a reference for Coptis researchers.

Dietary and Lifestyle Factors Related to Gastroesophageal Reflux Disease: A Systematic Review.

We performed this review to clarify which dietary and lifestyle factors are related to gastroesophageal reflux disease. Through a systematic search of the PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Chinese BioMedical Literature (CBM) databases, we identified articles with clear definitions of GERD, including nonerosive gastroesophageal reflux disease (NERD), reflux esophagitis (RE) and Barrett's esophagus (BE), that included dietary and lifestyle factors as independent factors affecting the onset of GERD (expressed as odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs)). Due to heterogeneity among the studies, we used descriptive statistical analyses to analyze and synthesize each outcome based on the disease type. In total, 72 articles were included, conducted in ten Western countries (26 articles in total) and nine Eastern countries (46 articles in total). We categorized dietary factors into 20 items and lifestyle factors into 11 items. GERD is related to many irregular dietary and lifestyle habits (such as a habit of midnight snacking: OR=5.08, 95% CI 4.03-6.4; skipping breakfast: OR=2.7, 95% CI 2.17-3.35; eating quickly: OR=4.06, 95% CI 3.11-5.29; eating very hot foods: OR=1.81, 95% CI 1.37-2.4; and eating beyond fullness: OR=2.85, 95% CI 2.18-3.73). Vegetarian diets (consumption of nonvegetarian food (no/yes); OR=0.34, 95% CI 0.211-0.545) and no intake of meat (OR=0.841, 95% CI 0.715-0.990) were negatively related to GERD, while meat (daily meat, fish, and egg intake: OR=1.088, 95% CI 1.042-1.135) and fat (high-fat diet: OR=7.568, 95% CI 4.557-8.908) consumption were positively related to GERD. An interval of less than three hours between dinner and bedtime (OR=7.45, 95% CI 3.38-16.4) was positively related to GERD, and proper physical exercise (physical exercise >30 minutes (>3 times/week): OR=0.7, 95% CI 0.6-0.9) was negatively correlated with GERD. Smoking (OR=1.19, 95% CI 1.12-1.264), alcohol consumption (OR=1.278, 95% CI 1.207-1.353) and mental state (poor mental state: OR=1.278, 95% CI 1.207-1.353) were positively correlated with GERD. RE (vitamin C: OR=0.46, 95% CI=0.24-0.90) and BE (vitamin C: OR=0.44,95% CI 0.2-0.98; vitamin E: OR=0.46, 95% CI 0.26-0.83) were generally negatively correlated with antioxidant intake. In conclusion, many dietary and lifestyle factors affect the onset of GERD, and these factors differ among regions and disease types. These findings need to be further confirmed in subsequent studies.

A Methodological and Reporting Quality Assessment of Systematic Reviews/Meta-Analyses about Chinese Medical Treatment for Gastroesophageal Reflux Disease.

OBJECTIVE: To access the methodological and reporting quality of systematic reviews (SRs)/meta-analyses (MAs) about Chinese medical treatment for gastroesophageal reflux disease (GERD). METHODS: The PubMed, Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Chinese Biomedical (CBM), Web of Science, and Cochrane Library databases were searched from inception to June 2020. Two researchers independently screened the literature considering the eligibility criteria. Overview Quality Assessment Questionnaire (OQAQ), Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to assess the methodological and reporting quality of the included reports. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the level of evidence in each report. RESULTS: Thirty-three SRs/MAs met the inclusion criteria. The OQAQ results showed that defects in the methodological quality of 17/32 reports were major, with scores of 3 points. Analyzing a single item as the object, search strategies (item 2), and risk of bias in individual studies (item 4) was considered poor. The AMSTAR 2 results showed that 25.4% of the items were not reported, and 7.8% of the items were only partially reported. The overall assessment of AMSTAR 2 showed the majority of systematic reviews and meta-analyses were of low/very low (31/33, 93.9%) methodological quality, with a lack of protocol registration and excluded study list. The PRISMA results showed that 19.9% of items were not reported, and 15.2% of items were only partially reported, due to a lack of protocol registration and study selection methods. The methodological and reporting quality of the included studies was generally poor. Evidence evaluation with GRADE showed that most (31/33) of the included studies had low or very low levels of evidence. CONCLUSION: The methodological and reporting quality of SRs/MAs about Chinese medical treatment for GERD is generally poor. The main problems included incomplete search strategies, risk of bias in individual studies, the lack of protocol registration and excluded study list, and incorrect study selection methods.

A glycolysis-related gene pairs signature predicts prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most universal malignant liver tumors worldwide. However, there were no systematic studies to establish glycolysis­related gene pairs (GRGPs) signatures for the patients with HCC. Therefore, the study aimed to establish novel GRGPs signatures to better predict the prognosis of HCC. METHODS: Based on the data from Gene Expression Omnibus, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium databases, glycolysis-related mRNAs were used to construct GRGPs. Cox regression was applied to establish a seventeen GRGPs signature in TCGA dataset, which was verified in two validation (European and American, and Asian) datasets. RESULTS: Seventeen prognostic GRGPs (HMMR_PFKFB1, CHST1_GYS2, MERTK_GYS2, GPC1_GYS2, LDHA_GOT2, IDUA_GNPDA1, IDUA_ME2, IDUA_G6PD, IDUA_GPC1, MPI_GPC1, SDC2_LDHA, PRPS1_PLOD2, GALK1_IER3, MET_PLOD2, GUSB_IGFBP3, IL13RA1_IGFBP3 and CYB5A_IGFBP3) were identified to be significantly progressive factors for the patients with HCC in the TCGA dataset, which constituted a GRGPs signature. The patients with HCC were classified into low-risk group and high-risk group based on the GRGPs signature. The GRGPs signature was a significantly independent prognostic indicator for the patients with HCC in TCGA (log-rank P = 2.898e-14). Consistent with the TCGA dataset, the patients in low-risk group had a longer OS in two validation datasets (European and American: P = 1.143e-02, and Asian: P = 6.342e-08). Additionally, the GRGPs signature was also validated as a significantly independent prognostic indicator in two validation datasets. CONCLUSION: The seventeen GRGPs and their signature might be molecular biomarkers and therapeutic targets for the patients with HCC.

Quantifying Liver-Stomach Disharmony Pattern of Functional Dyspepsia Using Multidimensional Analysis Methods.

PURPOSE: This study aims to develop and validate a quantitative model for measuring severity of a typical traditional Chinese medicine (TCM) pattern for functional dyspepsia (FD) using multidimensional analysis methods including confirmatory factor analysis (CFA) and multidimensional item response theory (MIRT). METHODS: A scale and theoretical models were constructed according to the definition of pathogenesis about "liver-stomach disharmony" patterns of FD. With data collected from 502 patients in a cross-section study, the theoretical model was validated with CFA, and the related validity and reliability were evaluated in Amos 21.0. By the use of the MIRT paradigm, psychometric properties of the scale were estimated and evaluated for pattern quantification. RESULTS: A scale consisting of 12 items was constructed detecting three latent traits of the pattern. The theoretical model was evaluated to be with adequate consistency with clinical data as RMSEA < 0.05, CFI = 0.94, and χ 2/Df = 2.29. As the correlation between symptoms and related pattern factors evaluated to be with adequate factor loading, the instrument is of preliminary interpretation. Most precision of assessment could be achieved for patients with moderate severity of the pattern as shown in test information and standard error functions. CONCLUSIONS: An instrument with an interpretable conceptual framework was developed for pattern quantification in TCM clinical practice. By constructing and evaluating both psychological and physical effects in a multidimensional model of the TCM pattern of FD, the paradigm raised in this article provided a valuable reference for interpreting complex diseases and theories such as FD and TCM patterns.

Reviews and Thoughts on the Relevance between Qualitative Chinese Medicinal Properties and Quantitative Material Components.

OBJECTIVE: Chinese Medicinal Properties (CMP) play a vital role in theoretical research and clinical practice. However, the traditional CMP system is subjective, qualitative, fixed, inconsistent, and obscured. Nowadays, quantifying CMP research achieved a notable progress. This study aims to review and reflect the relevance between qualitative CMP and quantitative material components. METHODS: A raw literature search was performed firstly in CNKI and Pubmed database to get a rough idea on the general advances in measuring CMP. Then, a strict literature search and data extraction from two dependent research studies were performed to analyze the relevance and discrimination between CMP and material components. RESULTS: The quantitative CMP research mainly focused on the microelements and chemical compositions. The largest microelements research listed 747 Chinese Materia Medica (CMM) (6780 flavors) and 120,000 element data. The measurement of chemical composition of CMM has risen rapidly in the 1990s and continues till the present. Thirty-seven articles were finally identified for the relevance analysis of CMP and material components. Of these, 18 and 19 articles correspondingly focused on the chemical compositions and microelements, and 26 and 11 articles correspondingly focused on their correlation and discrimination relationship. The most commonly used method for correlation analysis is intuitive analysis. The support vector machine maybe highly efficient and would act as the preferred method in discriminant analysis. Twelve (67%) and 5 (26%) articles' data came from the literature search in chemical compositions and microelement research studies. Four studies indicated that the research objects are the basic substances and material basis of CMP, 15 articles claimed that the chemical compositions were significantly related to CMP, 12 research studies concluded that the regularity and causality were identified between the research objects and CMP, and 9 research studies successfully established discriminant models for CMP basing on the detected substances. CONCLUSIONS: The relevance research between qualitative CMP and quantitative material components achieved a positive progress, though it is weak and defective. Standardizing the qualitative CMP system, establishing series comprehensive databases for the material components, innovating statistical and data mining methods, and integrating doctors' experiences are important and feasible for future research.

Identification of non-invasive biomarkers for chronic atrophic gastritis from serum exosomal microRNAs.

BACKGROUND: Serum exosomal microRNAs (miRNAs) have been suggested as novel biomarkers for various diseases, especially gastric cancer (GC). But circulating biomarkers for Chronic atrophic gastritis (CAG) which is defined as precancrerous lesions of GC remain largely elusive. To investigate serum exosomal miRNAs that are differently expressed in CAG patients and Chronic nonatrophic gastritis (CNAG) may be helpful for its diagnosis and therapy. METHODS: Patients were recruited according to the diagnosis and exclusioncriteria. RNA was extracted from serum exosomes of 30 CAG and 30 CNAG patients. The miRNA expression profiles were analyzed by next generation sequencing and were validated by qRT-PCR. Receiver operating characteristic (ROC) analysis has been used to evaluate the diagnostic value. RESULTS: 30 CAG patients and 30 CNAG patients were recruited in our study. sRNA-seq results showed that hsa-miR-3591-3p, - 122-3p, and - 122-5p of the top 10 miRNAs (hsa-miR-148a-3p, - 122-3p, - 486-3p, -451a, - 122-5p, - 3591-3p, - 486-5p, -151a-3p, -92a-3p, -320a) were significantly upregulated in exosomes from CAG patients versus those from CNAG patients, but hsa-miR-451a, -151a-3p, and -92a-3p were significantly downregulated. Furthermore, qRT-PCR analysis confirmed that hsa-miR-122-5p and hsa-miR-122-3p were significantly upregulated in CAG samples, but hsa-miR-122-3p hadnot a steable expression. ROC curves showed that the AUC for hsa-miR-122-5p was 0.67 (95% CI 0.52-0.82, SE 62%, SP 86%). A sum of the four miRNAs (panel 1, hsa-miR-122-5p, -451a, -151a-3p, and -92a-3p) did not significantly improve the diagnostic potential (AUC 0.63, 95% CI 0.47 to 0.78). Correlation analysis showed that the expression of hsa-miR-122-5p differed significantly between patients based on atrophic (Moderate atrophic vs. Absent, P value was 0.036.) and IM (compare moderate-severe, absent and mild P values were 0.001 and 0.014, respectively). However, there were no differences between groups based on age, gender, dysplasia, or chronic or active inflammation. CONCLUSION: These results suggested that hsa-miR-122-5p in serum exosomes might serve as a potential biomarker for CAG diagnosis. TRIAL REGISTRATION: Chinese Clinical Trial Registy ( ChiCTR-IOR-16008027 , Date of Registration:2016-03-01).

Prognostic Value of NRAS Gene for Survival of Colorectal Cancer Patients: A Systematic Review and Meta-Analysis

Introduction: NRAS gene is associated with malignant proliferation and metastasis of colorectal cancer (CRC). But its prognostic value on CRC is still unknown. The objective of this study is to perform a meta-analysis to obtain its prognostic value on survival of CRC patients. Methods: The systematic review and meta-analysis was designed, undertaken and reported using items from the PRISMA statement. Relevant articles were identified through PubMed (containing Medline), Embase, Web of Science databases and Google scholar search engines from their inception up to October 3, 2016. The articles about NRAS on prognosis of CRC patients were enrolled. The association between NRAS and CRC survival time (including overall survival [OS], progression-free survival [PFS], and disease-free survival [DFS]) was evaluated using hazard ratio (HR) with its corresponding 95% confidence interval (CI). Results: A total of fifteen articles were included. High-expression of NRAS was significantly associated with poor OS (HR: 1.36, 95% CI: 1.15­1.61), and poor PFS (HR: 1.75, 95% CI: 1.04­2.94). The combined HR of NRAS on DFS was 0.87 (95% CI: 0.37­2.03). Subgroup analysis showed that NRAS was significantly associated with poor OS for patients from Western countries (HR: 1.38, 95% CI: 1.09­1.73), but not for those from Asian countries. Conclusions: This meta-analysis demonstrate that NRAS gene could predict the poor prognosis for the CRC patients. More large-sample cohort studies are needed to further confirm this conclusion.

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats.

BACKGROUND/AIMS: MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. METHODS: We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. RESULTS: The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. CONCLUSIONS: This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

Development of a Traditional Chinese Medicine Syndrome-Specific Scale for Ulcerative Colitis: The Large Intestine Dampness-Heat Syndrome Questionnaire.

The aim of this study was to develop and validate the large intestine dampness-heat syndrome questionnaire (LIDHSQ) for patients with ulcerative colitis (UC). The domains and items of the LIDHSQ were developed according to standard procedures, namely, construct definition, item generation, language testing, content validity, pilot study, and validation study. At first, a total of 20 items in 3 domains were generated based on literature review and expert consultation. After the item selection, the LIDHSQ contains 11 items in three domains: disease-related domain (diarrhoea, abdominal pain, bloody purulent stool, and mucus stool), heat domain (fever, dry mouth, red tongue, yellow fur, and anal burning), and dampness domain (greasy fur and defecation disorder). The Cronbach's alphas of all domains were greater than 0.6. All of the intraclass correlation coefficients were greater than 0.8. The LIDHSQ and domain scores of the patients with LIDHS were higher than those of the patients with other syndromes (P < 0.001). The area under the receiver operating characteristic curve of the LIDHSQ was 0.900, with a 95% confidence interval of 0.872-0.928. When the cut-off value of the LIDHSQ was ≥ 7, the sensitivity and specificity were 0.867 and 0.854, respectively. The LIDHSQ is valid and reliable for measuring LIDHS in UC patients with good diagnostic efficacy. We recommend the use of the LIDHSQ in Chinese UC patients.

[Inspirations of Rome â £ on clinical evaluation of traditional Chinese medicine for functional gastrointestinal disease].

The Rome Foundation released the Rome Ⅳ for functional gastrointestinal diseases (FGIDs) in 2016, which fully presented the latest advances and views on the disease origin, definition, diagnosis, classification, pathology, mechanism, clinical features, influential factors, interventions, clinical evaluation, clinical research design and so on, showing high positive effects on global researches. Traditional Chinese medicines (TCM) have cognitive advantages and well-recognized and-demonstrated efficacy in the prevention and treatment for FGIDs. However, the monotonous presentation ways and weak interpretation on clinical evaluation have also hindered the inherent advantages explanation, characteristics quantization, evidence and communication accumulation. This study first analyzed the background and key points on clinical evaluation of Rome Ⅳ and corresponding inspirations, believed that its concept and viewpoints were assimilated with systematic medicine, and emphasized the important influence of subjective factors such as mental psychology and social culture on the disease and its importance in clinical evaluation. Its views on several aspects such as the theoretical model, internal and external causes, and transfer process were highly consistent with TCM. Therefore, TCM researchers should devote more dedication and courage on the innovation and collaboration with global researches to advance related studies. Then, based on 59 TCM clinical researches for FGIDs funded by national projects upon searching in CNKI with strict search strategy, the clinical evaluation methods and indexes and their correlations were summarized and analyzed, and it was found that more attention was paid to the disease symptoms and impact, symptom/syndrome score, patient report outcome, et al. However, many limitations were also founded, such as disordered relationships among different indexes, ambiguous explanation of research results, and extremely few domestic evaluation instruments in Chinese culture. Therefore, it is suggested that future research should regress and highlight the subjective features of patients and diseases, standardize the elemental structure and management mode of clinical evaluation, enhance the values and status of reported outcomes. It is highly recommended that the domestic disease-specific instruments developed in Chinese culture should be adopted as primary outcome for clinical evaluation, assisted with symptoms/signs assessment tools and doctors reporting outcome scale, et al. The common used TCM syndrome scores in current researches are not recommended as the primary outcome. However, there are some limitations in the above suggestions. We hope that more relevant researches will explore and establish a unified outcome assessment system for FGIDs and improve the quality of TCM clinical research.

[Clinical experience and academic thoughts of Professor LIU Feng-bin on case series of gastroesophageal reflux disease based on data mining].

To analyze and summarize Professor LIU Feng-bin's clinical experience and academic thoughts on gastroesophageal reflux disease (GERD), the study group adopted the retrospective study for case series and expert interview, extracted the retrospective data, including the herbs, diseases, syndrome type, medical expense and quantity of herbs of GERD patients attended the First Affiliated Hospital of Guangzhou University of Chinese Medicine. Statistical description and binary Logistic regression were used for the identification and modification of syndrome type and initial core herbs. After expert interviews were performed for the syndrome type and herbs, the final scheme were formed. A total of 112 GERD patients ages（48.97±13.13）y; male: 35 (31.3%), female: 77(68.7%) were enrolled. The numbers of patients with liver and stomach incoordination syndrome, heat stagnation of liver and stomach syndrome, syndrome of dual deficiency of Qi and Yin, syndrome of spleen deficiency and dampness-heat, spleen-stomach disharmony syndrome were 40, 26, 19, 17 and 10, respectively. The patients used totally 80 herbs, and 26 of them had significant differences among different syndrome groups. According to the logistic regression analysis on the 23 herbs used by 112 patients, the herbs scheme was modified for the second time. After the expert interviews and modification, the final consensus was reached. The main causes for GERD were dietary irregularities, moodiness, and weak constitution. The basic mechanism of GERD was spleen deficiency with Qi adverseness. The spleen-stomach disharmony syndrome was deleted by expert interviews. The 10 core herbs for GERD treatment were Taizishen(Pseudostellariae Radix), Fuling(Poria), Baizhu(Atractylodismacrocephalae Rhizoma), Gancao(Glycyrrhizae Radix Et Rhizoma), Zhebeimu(Fritillariae Thunbergii Bulbus), Haipiaoxiao(Sepiae Endoconcha), Zhiqiao(Aurantii Fructus), Chenxiang(Alosewood), Pugongying(Taraxaci Herba), Zhizitan(Cape Jasmine Fruit). The modification and psychological and diet interventions were also identified. This study summarized Professor LIU Feng-bin's clinical experience and academic thoughts of chronic atrophic gastritis based on data mining of case series and expert interviews. The quality of methodologies and report were both well. The results provide a foundation and ideas for further study on the complex intervention for GERD, and can be directly applied in clinical practice.

Quantifying Liver Stagnation Spleen Deficiency Pattern for Diarrhea Predominate Irritable Bowel Syndromes Using Multidimensional Analysis Methods.

OBJECTIVE: This study aims to offer a new approach for quantifying severity of traditional Chinese medicine pattern with multidimensional analysis methods. METHODS: A scale and theoretical models were constructed based on the definition of liver stagnation spleen deficiency pattern. Clinical data of 344 IBS-D patients from a cross-sectional study was used for feature validation of the model. Confirmatory factor analysis was used for evaluating the models. Also, multidimensional item response model was used for assessing multidimensional psychometric properties of the scale. RESULTS: Detecting two latent traits, the Cronbach's alpha of the 9-item scale was 0.745. Multidimensional model was evaluated with significant goodness of fit indices while the unidimensional model was rejected. The multidimensional item response model showed all the items had adequate discrimination. Parameters presented adequate explanation regarding mental syndromes having high factor loading on the liver stagnation factor and abdominal discomfort syndromes highly related to the spleen deficiency factor. Test information function showed that scale demonstrated the highest discrimination power among patients with moderate to high level of severity. CONCLUSIONS: The application of the multidimensional analysis methods on the basis of theoretical model construction provides a useful and rational approach for quantifying the severity of traditional Chinese medicine patterns.

Interpreting the Chinese version of quality of life questionnaire for functional digestive disorders.

BACKGROUND AND AIM: The Chinese version quality of life questionnaire for functional digestive disorders (Chin-FDDQL) is a useful health assessment instrument for functional dyspepsia. This study aims to identify its score interpretation for clinical practice. METHODS: Data of Chin-FDDQL from the functional dyspepsia patients (≥ 18 years) between November 2009 and April 2013 were enrolled in the 1st and 14th day. After baseline and responsiveness analysis, the single score interpretation and percentile ranks were established. The statistically reliable change was defined with effect size, standardized response mean, minimal detectable change, and others. Then the receiver operating characteristic curve analysis for health improvement was performed to define the clinically important change. RESULTS: Two hundred two functional dyspepsia patients, 150 healthy participants, and 25 missing data were enrolled for analysis. Compared with the intake patients, the discharged and healthy persons have significant better health status in all domains (P < 0.001, expect discomfort in discharged people, P = 0.142), totally contrast to missing data. The reliability for single total intake and discharge were both ± 1. Based on score distribution, the 25th, 50th, and 75th percentile ranks were 49, 58, and 66 for intake scores and 59, 65, and 72 for discharge scores, respectively. The minimal detectable change and Reliable Change Index were 6 and 11 for total score. Receiver operating characteristic analyses supported that total score changes 4 or more represented minimal clinically important improvement. CONCLUSIONS: The score interpretation system of the Chin-FDDQL could assist clinician's decision making during the therapy practice.

MiR-144 Increases Intestinal Permeability in IBS-D Rats by Targeting OCLN and ZO1.

BACKGROUND/AIMS: Irritable bowel syndrome with diarrhoea (IBS-D) is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs) are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i) identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii) verify in vitro whether occludin (OCLN) and zonula occludens 1 (ZO1/TJP1) were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii) determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. METHODS: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs) and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. RESULTS: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further studies confirmed that OCLN and ZO1 were direct targets of miR-144. Additionally, intestinal hyperpermeability was enhanced by miR-144 up-regulation and attenuated by miR-144 down-regulation in IBS-D rat colonic epithelial cells. Moreover, rescue experiments showed that overexpression of OCLN and ZO1 significantly eliminated the inhibitory effect of miR-144, which showed a stronger effect on the attenuation of intestinal hyperpermeability. CONCLUSION: Up-regulation of miR-144 could promote intestinal hyperpermeability and impair the protective effect of the epithelial barrier by directly targeting OCLN and ZO1. miR-144 is likely a key regulator of intestinal hyperpermeability and could be a potential therapeutic target for IBS-D.