OBJECTIVE: To explore the peripheral neural mechanism underlying representation along the distribution of stomach meridian induced by intestinal inflammatory reaction using diarrhea predominant-irritable bowel syndrome (IBS-D) mice. METHODS: Among 62 healthy male C57BL/6 mice of clean grade, 12 mice were randomly selected and divided into a control group and a model group, 6 mice in each group, additionally, 12 mice were randomly selected and divided into a Tianshu group, a Liangqiu group and a Zusanli group, 4 mice in each group. In the model group, citrobacter was administered orally to establish IBS-D model. In the control group and the model group, the visceral pain threshold was observed using fecal colorectal distension (fCRD) induced electromyography of external oblique muscle, the positive cell number of neutrophil in the colonic muscularis was detected by myeloperoxidase (MPO) staining, the number, location and distribution rule of Evans blue (EB) extravasation points were observed by injection of EB staining solution into the tail vein. In the Tianshu group, the Liangqiu group and the Zusanli group, fluorescent dye Dil was injected at bilateral "Tianshu" (ST25), "Liangqiu" (ST34) and "Zusanli" (ST36) respectively, to observe the dye-positive cell number in different dorsal root ganglion (DRG) segments. In the control group and the model group, the activation of satellite glial cells (SGCs) in different DRG segments was observed by immunofluorescence. RESULTS: Compared with the control group, in the model group, the area under curve of electromyography of external oblique muscle was increased at fCRD of 25, 50 and 75 μL distilled water (P<0.001, P<0.01); the MPO-positive cell number of neutrophil in the colonic muscularis was increased (P<0.01). Few EB extravasation points could be found in the control group, while there were much more EB extravasation points observed in the model group, which was specially distribution in the area of stomach meridian, from "Huaroumen" (ST24) to "Zusanli" (ST36), as well as the surface area dominated by L₂-L₅ segment of the spinal cord. The Dil-positive cells were mainly exhibited in the DRG of T₁₁, L₅ and L₄ segments in the Tianshu group, the Liangqiu group and the Zusanli group, respectively. Compared with the control group, the ratio of glial fibrillary acidic protein (GFAP)/glutamine synthetase (GS) co-expression was increased in the DRG of T₁₁, L₄ and L₅ segments in the model group (P<0.05, P<0.01). CONCLUSION The activation of SGCs within DRG of T₁₁, L₄ and L₅ segments may relate closely to the occurrence of the representation along the stomach meridian distribution in IBS-D mice.
Animals ; Male ; Mice ; Irritable Bowel Syndrome/therapy* ; Mice, Inbred C57BL ; Meridians ; Stomach/physiopathology* ; Humans ; Acupuncture Points ; Disease Models, Animal

OBJECTIVE: To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms. METHODS: Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy. RESULTS: Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD₈⁺ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD₄⁺ T subset and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD₄⁺ T subset, and CD₄⁺/CD₈⁺, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged. CONCLUSION Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals ; Irritable Bowel Syndrome/immunology* ; Rats ; Moxibustion ; Intestinal Mucosa/immunology* ; Female ; Diarrhea/therapy* ; Intestine, Small/immunology* ; Male ; Humans ; Rats, Sprague-Dawley ; Disease Models, Animal

OBJECTIVE: To observe the effects of moxibustion on the stem cell factor (SCF)/tyrosine kinase receptor (c-kit) signaling pathway and immune function in rats with diarrhea irritable bowel syndrome (IBS-D), and to explore the mechanism of moxibustion for IBS-D. METHODS: Among 52 young rats born from 6 healthy pregnant SPF rats, 12 rats were randomly selected into the normal group, and the remaining 40 rats were treated with the three-factor combination method of maternal separation, acetic acid enema and chronic restraint stress to establish the IBS-D rat model. Thirty-six rats with successful IBS-D model were randomly divided into a model group, a moxibustion group, and a medication group, 12 rats in each group. The rats in the moxibustion group were treated with suspension moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the medication group were treated with intragastric administration of rifaximin suspension (150 mg/kg). All the treatments were given once a day for 7 consecutive days. The body mass, loose stool rate (LSR), the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were measured before acetic acid enema (35 days old), after modeling (45 days old), and after intervention (53 days old). After intervention (53 days old), HE staining was used to observe the morphology of colon tissue, and spleen and thymus coefficients were measured; ELISA method was used to detect serum inflammatory factors (tumor necrosis factor a [TNF-a], interleukin [IL]-10, IL-8), T-lymphocyte subsets (CD⁺₄, CD⁺₈, CD⁺₄₅), value of CD⁺₄/CD⁺₈ and immune globulin (IgA, IgG, IgM); real-time PCR method and Western blot method was used to detect the expression of SCF, c-kit mRNA and protein in colon tissue; immunofluorescence staining method were used to detect positive expression of SCF and c-kit. RESULTS: After intervention, compared with the normal group, in the model group, the body mass and the minimum volume threshold when AWR scored 3 were decreased (P<0.01), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD⁺₄, CD⁺₄₅, CD⁺₄/CD⁺₈, IgA, IgG, IgM were increased (P<0.01), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were decreased (P<0.01), and the positive expression of SCF and c-kit was decreased (P<0.01). Compared with the model group, in the moxibustion group and the medication group, the body mass and the minimum volume threshold when AWR scored 3 were increased (P<0.01, P<0.05), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD⁺₄, CD⁺₈, CD⁺₄₅, CD⁺₄/CD⁺₈, IgA, IgG, IgM were decreased (P<0.01, P<0.05), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were increased (P<0.01), and the positive expression of SCF and c-kit was increased (P<0.01). Compared with the medication group, in the moxibustion group, the level of serum CD⁺₄ was decreased (P<0.05), the value of CD⁺₄/CD⁺₈ was increased (P<0.01), and there was no significant difference in other indexes (P>0.05). The expression of SCF and c-kit mRNA was positively correlated with the minimum volume threshold when AWR scored 3 and IL-10 (P<0.01), and negatively correlated with remaining indexes (P<0.01, P<0.05). CONCLUSION Moxibustion could reduce visceral hypersensitivity, improve symptoms of abdominal pain and diarrhea in IBS-D rats, and its mechanism may be related to up-regulation of the expression of SCF/c-kit signaling pathway and improvement of IBS-D immune function.
Rats ; Animals ; Irritable Bowel Syndrome/therapy* ; Moxibustion/methods* ; Rats, Sprague-Dawley ; Interleukin-10 ; Interleukin-8 ; Maternal Deprivation ; Tumor Necrosis Factor-alpha ; Diarrhea ; Signal Transduction ; Homeostasis ; Receptor Protein-Tyrosine Kinases ; Immunity ; Immunoglobulin A ; Immunoglobulin M

To provide proof of the evidence-based medicine and decision-making information for the clinical decision of functional gastrointestinal disorders(FGIDs), this study evaluated and compared the efficacy, safety, and economy of four oral Chinese patent medicines(CPMs) in the treatment of FGIDs using the method of rapid health technology assessment. The literature was systematically retrieved from CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library and ClinicalTrials.gov from the establishment of the databases to May 1, 2022. Two evaluators screened out the literature, extracted data, evaluated the quality of the literature, and descriptively analyzed the results according to the prepared standard. Eventually, 16 studies were included, all of which was rando-mized controlled trial(RCT). The results showed that Renshen Jianpi Tablets, Renshen Jianpi Pills, Shenling Baizhu Granules, and Buzhong Yiqi Granules all had certain effects on the treatment of FGIDs. Renshen Jianpi Tablets treated FGIDs and persistent diarrhea. Shenling Baizhu Granules treated diarrhea with irritable bowel syndrome and FGIDs. Buzhong Yiqi Granules treated diarrhea with irritable bowel syndrome, FGIDs, and chronic diarrhea in children. Renshen Jianpi Pills treated chronic diarrhea. The four oral CPMs all have certain effects on the treatment of FGIDs and have specific advantages for specific patients. Compared with other CPMs, Renshen Jianpi Tablets have higher clinical universality. However, there are problems such as insufficient clinical research evidence, generally low quality of evidence, lack of comparative analysis among medicines, and lack of academic evaluation. More high-quality clinical research and the economic research should be carried out in the future, so as to provide more evidence for the evaluation of the four CPMs.
Child ; Humans ; Irritable Bowel Syndrome ; Technology Assessment, Biomedical ; Gastrointestinal Diseases ; Diarrhea

Blastocystis is a common unicellular intestinal protozoa in humans and animals, and the most common clinical manifestations of infections include abdominal pain and diarrhea. Based on the sequence of the small-subunit ribosomal RNA (SSU rRNA) gene, 28 subtypes of B. hominis (ST1 to ST17, ST21 and ST23 to ST32) have been characterized. Previous studies have demonstrated that B. hominis infection is strongly associated with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other intestinal diseases, which threatens the health and quality of life among patients with B. hominis infection and is considered as an important public health problem. This review summarizes the progress of researches on B. hominis infection among IBD and IBS patients during the past 20 years, so as to provide insights into management of blastocystosis in China.
Animals ; Humans ; Irritable Bowel Syndrome/parasitology* ; Blastocystis Infections/complications* ; Quality of Life ; Blastocystis hominis/genetics* ; Feces/parasitology* ; Inflammatory Bowel Diseases/parasitology*

This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.
Rats ; Male ; Animals ; Irritable Bowel Syndrome/metabolism* ; Water ; Chromatography, Liquid ; Tryptophan ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Diarrhea/drug therapy* ; Biomarkers ; Riboflavin

Abnormal brain-gut interaction is considered the core pathological mechanism behind the disorders of gut-brain interaction (DGBI), in which the intestinal microbiota plays an important role. Microglia are the "sentinels" of the central nervous system (CNS), which participate in tissue damage caused by traumatic brain injury, resist central infection and participate in neurogenesis, and are involved in the occurrence of various neurological diseases. With in-depth research on DGBI, we could find an interaction between the intestinal microbiota and microglia and that they are jointly involved in the occurrence of DGBI, especially in individuals with comorbidities of mental disorders, such as irritable bowel syndrome (IBS). This bidirectional regulation of microbiota and microglia provides a new direction for the treatment of DGBI. In this review, we focus on the role and underlying mechanism of the interaction between gut microbiota and microglia in DGBI, especially IBS, and the corresponding clinical application prospects and highlight its potential to treat DGBI in individuals with psychiatric comorbidities.
Humans ; Gastrointestinal Microbiome ; Irritable Bowel Syndrome/therapy* ; Microglia ; Brain Diseases ; Brain

OBJECTIVE: To compare the clinical efficacy between herbal-moxa plaster and moxa-box moxibustion for diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: Eighty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a herbal-moxa plaster group and a moxa-box moxibustion group, 40 cases in each group. The patients in the two groups were treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 24⁺), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Yinlingquan (SP 9), and Taixi (KI 3), etc. In addition, the patients in the herbal-moxa plaster group were treated with herbal-moxa plaster (Wenyang Fuzheng ointment, composed of prepared monkshood, prepared evodia rutaecarpa, dried ginger, cinnamon, etc.) at Shenque (CV 8), Guanyuan (CV 4), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Shenshu (BL 23) and Shangjuxu (ST 37); the patients in the moxa-box moxibustion group were treated with moxa-box moxibustion at the same acupoints as the herbal-moxa plaster group. The acupuncture-moxibustion treatment was provided once every other day for 4 weeks (14 treatments). Before and after treatment, the scores of clinical symptom of TCM, irritable bowel syndrome (IBS) symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Compared with those before treatment, each item scores and total scores of clinical symptom of TCM, and IBS-SSS scores in the two groups were reduced after treatment (P<0.05). The abdominal bloating score, stool frequency score and total score of clinical symptom of TCM as well as IBS-SSS score in the herbal-moxa plaster group were lower than those in the moxa-box moxibustion group (P<0.05). Compared with those before treatment, the IBS-QOL scores in the two groups were increased after treatment (P<0.05), and the IBS-QOL score in the herbal-moxa plaster group was higher than that in the moxa-box moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the herbal-moxa plaster group, which was higher than 85.0% (34/40) in the moxa-box moxibustion group (P<0.05). CONCLUSION On the basis of conventional acupuncture treatment, herbal-moxa plaster could effectively improve the clinical symptoms and quality of life in IBS-D patients of spleen and kidney yang deficiency, and its efficacy is superior to that of moxa-box moxibustion.
Humans ; Spleen ; Irritable Bowel Syndrome/drug therapy* ; Quality of Life ; Yang Deficiency/drug therapy* ; Kidney ; Diarrhea

BACKGROUND: Cholecystectomy is a standard surgery for patients suffering from gallbladder diseases, while the causal effects of cholecystectomy on colorectal cancer (CRC) and other complications are still unknown. METHODS: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level ( P value <5 × 10 -8 ) as instrumental variables (IVs) and performed Mendelian randomization (MR) to identify the complications of cholecystectomy. Furthermore, the cholelithiasis was also treated as the exposure to compare its causal effects to those of cholecystectomy, and multivariable MR analysis was carried out to judge whether the effect of cholecystectomy was independent of cholelithiasis. The study was reported based on Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. RESULTS: The selected IVs explained 1.76% variance of cholecystectomy. Our MR analysis suggested that cholecystectomy cannot elevate the risk of CRC (odds ratio [OR] =1.543, 95% confidence interval [CI]: 0.607-3.924). Also, it was not significant in either colon or rectum cancer. Intriguingly, cholecystectomy might decrease the risk of Crohn's disease (OR = 0.078, 95% CI: 0.016-0.368) and coronary heart disease (OR = 0.352, 95% CI: 0.164-0.756). However, it might increase the risk of irritable bowel syndrome (IBS) (OR = 7.573, 95% CI: 1.096-52.318). Cholelithiasis could increase the risk of CRC in the largest population (OR = 1.041, 95% CI: 1.010-1.073). The multivariable MR analysis suggested that genetic liability to cholelithiasis could increase the risk of CRC in the largest population (OR = 1.061, 95% CI: 1.002-1.125) after adjustment of cholecystectomy. CONCLUSIONS The study indicated that cholecystectomy might not increase the risk of CRC, but such a conclusion needs further proving by clinical equivalence. Additionally, it might increase the risk of IBS, which should be paid attention to in clinical practice.
Humans ; Mendelian Randomization Analysis ; Irritable Bowel Syndrome ; Colorectal Neoplasms/genetics* ; Cholelithiasis/complications* ; Cholecystectomy/adverse effects* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

OBJECTIVES: To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship. METHODS: (1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting. RESULTS: (1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99. CONCLUSIONS When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.
Humans ; Siblings ; Genetic Markers ; Computer Simulation ; Irritable Bowel Syndrome/genetics* ; Reproducibility of Results ; Genotype