Comparison of pancreatic enzyme abnormalities and protease-activated receptor-2-positive eosinophils in the duodenum of patients with functional dyspepsia-irritable bowel syndrome overlap with functional dyspepsia alone in Asian populations.

BACKGROUND AND AIM: Some patients with functional gastrointestinal disorders exhibit pancreatic dysfunctions and pancreatic enzyme abnormalities. Thus, we aimed to clarify whether significant differences in clinical characteristics, prevalence of pancreatic enzyme abnormalities, duodenal inflammation, and protease-activated receptor 2 (PAR2) expression levels related to hypersensitivity exist between functional dyspepsia (FD) alone and FD-irritable bowel syndrome (IBS) overlap group. METHODS: Ninety-three patients based on the Rome IV criteria, FD alone (n = 44) and FD overlapped with IBS (n = 49) group were enrolled. The patients scored their own clinical symptoms after consuming high-fat meals. Serum trypsin, PLA2, lipase, p-amylase, and elastase-1 levels were measured. PAR2, eotaxin-3, and TRPV4 mRNA levels in duodenum were determined using real-time polymerase chain reaction methods. PRG2- and PAR2 in the duodenum were evaluated using immunostaining. RESULTS: FD score and global GSRS in patients with FD-IBS overlap were significantly higher than FD alone. Although the prevalence of pancreatic enzyme abnormalities in patients with FD alone was significantly (P < 0.01) higher than that in FD-IBS overlap, the ratio of aggravation of clinical symptoms following high-fat intake in patients with FD-IBS overlap was significantly higher (P = 0.007) than that in patients with FD alone. PAR2- and PRG2-double positive cells were localized in the degranulated eosinophils in the duodenum of patients with FD-IBS overlap. The number of PAR2- and PRG2-double positive cells in FD-IBS overlap was significantly (P < 0.01) higher than FD alone. CONCLUSIONS: Pancreatic enzyme abnormalities and PAR2 expression on degranulated eosinophils infiltrations in the duodenum may be associated with the pathophysiology of patients with FD-IBS overlap in Asian populations.

Comparison of the potency of nortriptyline and mirtazapine on gastrointestinal symptoms, the level of anxiety and depression in patients with functional dyspepsia.

Aim: In the current clinical trial study, the potency of mirtazapine and nortriptyline was compared in patients with Functional Dyspepsia (FD) who had anxiety or depression. Background: FD usually accompanies other psychosocial disorders. According to previous studies, among these disorders, anxiety and depression have the most correlation. Methods: This randomized clinical trial was organized in Taleghani hospital (Tehran, Iran). In two parallel groups, 42 patients were treated for 12 weeks, with 22 patients receiving 7.5 mg of mirtazapine and 20 patients receiving 25 mg of nortriptyline per day. To gain robust results, the patients with a positive history of antidepressant therapy, organic diseases, alcohol abuse, pregnancy, and major psychiatric disorders were excluded from the study. The subjects were examined by three questionnaires, including Nepean and Hamilton questionnaires. The patients were asked to answer the questions three times during the study: once before the onset of the treatment, second during the treatment, and third at the end of the treatment. Results: Based on Gastrointestinal (GI) manifestations, mirtazapine, in comparison to nortriptyline could significantly suppress the signs and symptoms of FD, including epigastric pains (P=0.02), belching (P=0.004), and bloating (P=0.01). Although the results from the use of mirtazapine compared to the use of nortriptyline (P=0.002) showed a lower mean depression score on the Hamilton questionnaire, no significant differences were found between the effects of these drugs on the anxiety scale of patients (P=0.091). Conclusion: Mirtazapine is more effective for GI symptoms related to gastric emptying. Considering the level of anxiety, mirtazapine, compared to nortriptyline, revealed better outcomes in FD patients suffering from depression.

Evidence and acupoint combinations in acupuncture for functional dyspepsia: an overview of systematic review and data mining study / 数字中医药（英文）

Objective@#To evaluate the methodological quality of papers that performed meta-analyzed and systematically reviewed acupoint selections for the treatment of functional dyspepsia (FD) and to identify the ideal acupoint combinations for FD.@*Methods@#Chinese databases including China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), China Biology Medicine (CBM), and Wanfang Database, as well as English databases including PubMed, Embase, and Cochrane Library were searched to retrieve papers about meta-analysis and systematic literature reviews on acupuncture for FD. The time span for the paper retrieval was set from the foundation of the databases to April 30, 2022. The Veritas scores of the papers based on their publication year, study type, Assessment of Multiple Systematic Reviews 2 (AMSTAR2), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), heterogeneity, and publication bias were rated to assess the methodological quality of the included studies. Then, randomized controlled trials (RCTs) were extracted from those meta-analysis papers or systematic literature reviews for analyzing acupoints frequency, meridian frequency, and association rules with the use of R software (V 4.3.1).@*Results@#Eight meta-analysis papers were included in the study after screening. The mean Veritas scores of the papers based on publication year, type of study, AMSTAR2, PRISMA, heterogeneity, and publication bias were 4.50, 8.00, 4.63, 4.63, 4.50, and 6.13, respectively. The analysis of the scores revealed insufficiencies in the reviews pertaining to the methodology, comprehension of the research strategy, detailed list of excluded studies, sources of funding, assessment of potential bias risks impact on meta-analysis results in each study, explanation of heterogeneity, and identification of potential conflicts of interest. Furthermore, a total of 85 RCTs were obtained from the eight meta-analysis papers involving 85 acupuncture prescriptions and 67 acupoints for subsequent data mining. The most commonly used meridian was Stomach meridian of Foot-Yangming (ST). Zusanli (ST36), Neiguan (PC6), Zhongwan (CV12), Taichong (LR3), Tianshu (ST25), Gongsun (SP4), Weishu (BL21), Pishu (BL20), Neiting (ST44), and Yinlingquan (SP9) topped the list of frequently selected acupoints. Additionally, a total of 28 association rules were identified, including 10 second-order, 15 third-order, and 3 fourth-order association rules. The top-ranking association rules in each order were “Neiguan (PC6) → Zusanli (ST36)” “Zhongwan (CV12) + Neiguan (PC6) → Zusanli (ST36)” and “Zhongwan (CV12) + Taichong (LR3) + Neiguan (PC6) → Zusanli (ST36)”, respectively.@*Conclusion@#Acupuncture could alleviate the clinical symptoms of FD. However, the quality of methodology applied in the meta-analysis papers on the subject needs to be improved. Through data mining, a combination of Neiguan (PC6), Zusanli (ST36), Zhongwan (CV12), and Taichong (LR3) was identified as an essential acupoint combination for the treatment of FD.

Evaluation of Subcortical Structure Volumes in Patients with Non-Specific Digestive Diseases.

(1) Background: To evaluate volume of subcortical structures such as hippocampus, globus pallidus, putamen, thalamus, nucleus accumbens, amygdala, caudate in patients with non-specific digestive diseases (functional dyspepsia-FD, irritable bowel syndrome-IBS) and non-specific inflammatory bowel diseases-IBD (colitis ulcerosa and Crohn's disease) in comparison to healthy control group (CON). (2) Material: The analysis included data obtained from 57 patients (FD-18, IBS-20, IBD-19) and 19 persons in control group. Both groups underwent examination in a 3T scanner (Achieva TX Philips Healthcare). (3) Results: Significant differences between the IBD group and Control group in volume of left thalamus and IBD group vs Control group in volume of right thalamus. (4) Conclusions: The brain-gut axis hypothesis explains connection between biological behavior, emotions and cognitive functions in patients with gastrointestinal disease. We found that there is a difference between volume of thalamus in IBD patients in comparison to both IBS and control group and it occurred to be smaller. Excess inflammation can be linked with psychological disorders like depressive symptoms, sleep difficulties and/or fatigue. Therefore, there is a need for using treatment both for depressive symptoms and IBD to reduce the causes and effects of inflammation.

Chinese Herbal Medicine for Functional Dyspepsia With Psychological Disorders: A Systematic Review and Meta-Analysis.

Background and Aims: Functional dyspepsia (FD) is closely associated with gut-brain interaction disorder (DGBI), characterized by the interaction of gastrointestinal symptoms and central nervous system dysregulation. Chinese herbal medicine (CHM) has a good concurrent effect in the treatment of FD, especially for patients with concurrent psychological disorders. A meta-analysis was designed to evaluate the efficacy and safety of CHMs in the treatment of FD. Methods: The PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medical Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to collect randomized controlled trials of FD treated with CHM. The retrieval time limit is from the establishment of the database till 11 April 2022. Two researchers independently searched databases, screened documents, extracted data, and evaluated the risk of bias of included studies. RevMan 5.4 software was used for meta-analysis. Results: A total of 11 studies including 951 patients were included. The study was divided into two parts. The first part included 5 clinical trials, including 471 patients. The experimental group was treated only with CHM and the control group was only treated with placebo. The results of first part showed that the total effective rate of CHM in the treatment of FD was higher than that in the placebo group (84.5 vs. 49.4%) [relative risk (RR) = 1.76; 95% confidence interval (CI) (1.13, 2.75); P = 0.01]. In addition, CHM treatment could reduce the total symptom score [standardized mean difference (SMD) = -10.05; 95% CI (-13.50, -6.59); Z = 5.70; P < 0.0001] and depression score [SMD = -7.68; 95% CI (-14.43, -0.94); Z = 2.23; P = 0.03]. The second part included 6 clinical trials, including 480 patients. The experimental group was only treated with CHM and the control group was treated with prokinetic agents combined with flupentixol melitracen (deanxit). The results of second part showed that the total effective rate of CHM in the treatment of FD was higher than that of the control group (92.6 vs. 78.8%) [RR = 1.17; 95% CI (1.09, 1.26), P < 0.0001]. In addition, CHM treatment could reduce HAMA score [mean difference (MD) = -3.19; 95% CI (-3.79, -2.59); Z = 10.40; P < 0.00001], HAMD score [MD = -4.32; 95% CI (-6.04, -2.61); Z = 4.94; P < 0.00001], and gastric emptying rate [MD = 12.62; 95% CI (5.84, 19.40); Z = 3.65; P = 0.0003]. The results of the two parts of the meta-analysis showed no serious adverse reactions, and there was no significant difference in the adverse reactions between the experimental group and the control group [MD = 1.14; 95% CI (0.53, 2.42); Z = 0.33; P = 0.74]; [MD = 0.14; 95% CI (0.01, 2.67); Z = 1.30; P = 0.19]. Conclusion: The current evidence shows that CHM treatment has great potential and safety in alleviating the symptoms of FD and improving the psychological disorders of anxiety and depression in patients with FD. Limited by the quantity and quality of the included studies and other biases, the above conclusions need more high-quality studies to be verified. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022311129].

[Effect of electroacupuncture at "Zusanli" (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD). METHODS: Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg-1•d-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1ß (IL-1ß) in duodenum was measured by ELISA. RESULTS: Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1ß in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1ß in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01). CONCLUSION: EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.

[Intestinal absorption characteristics of root tuber of Cynanchum auriculatum extract in normal and functional dyspepsia model rats via everted intestine sac model].

The study investigated the difference of intestinal absorption characteristics of root tuber of Cynanchum auriculatum extract between normal and functional dyspepsia(FD) model rats with everted intestine sac model.The content of syringic acid, scopoletin, caudatin, baishouwu benzophenone, qingyangshengenin and deacyhmetaplexigenin in the C.auriculatum extract in different intestinal segments was detected by UPLC-MS/MS.The cumulative absorption amount(Q) and absorption rate constant(K_a) of the six chemical constituents were calculated.The results showed that the six components could be absorbed into the intestinal sac and were unsaturated, which indicated that the absorption mechanism of scopoletin was active transport in the intestine, while that of the other five components were passive diffusion.For normal group, the syringic acid and baishouwu benzophenone in ileum, qingyangshengenin and deacyhmetaplexigenin in ileum and duodenum, and caudatin in colon were well absorbed and scopoletin at low, medium and high concentrations was found excellent absorption in jejunum, ileum, and colon, respectively.Whereas the best absorption site of each component was ileum in model group.The absorption characteristics of each component between normal group and model group were complex at different concentrations, showing inconsistent tendency of absorption, which suggested that the components of root tuber of C.auriculatum extract were selectively absorbed in small intestine, and the absorption characteristics of the six components could be changed under FD status.This study provided theoretical basis for the clinical drug application and development of root tuber of C.auriculatum.

Effect of electroacupuncture at "Zusanli" (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD).@*METHODS@#Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg-1•d-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA.@*RESULTS@#Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01).@*CONCLUSION@#EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.

D-galacturonic acid ameliorates the intestinal mucosal permeability and inflammation of functional dyspepsia in rats.

BACKGROUND: Functional dyspepsia (FD) is a gastrointestinal disease caused by imbalanced gastrointestinal function. Traditional treatments are deemed to be limited, and new therapeutic drugs are required. New study suggested that duodenal low-grade inflammation and increased intestinal permeability play an important role in the pathogenesis of FD. Previous studies have shown that polysaccharides containing D-galacturonic acid (GA) could modulate intestinal immune activity in vitro and in animal models. However, the ability of GA monomer to improve intestinal mucosal permeability and inflammation in FD has not been clearly elucidated. METHODS: A FD rat model was established using iodoacetamide (IA). FD Rats were administrated different doses of GA. Subsequently, the body weight and behavioral sensitivity of the rats were measured and evaluated; the permeability of the intestinal barrier was measured by determining D-lactose, lactulose/mannitol ratio (LMR), and permeability-related genes [desmocollin-2 (DSC2), TJP1, and OCLN] in FD rats. Also, inflammatory cells [cluster of differentiation (CD)3+ cells and mast cells] were assessed by immunohistochemistry, and the levels of immune-related factors, such as the Toll-like receptor-nuclear factor kappa B (TLR/NF-κB) pathway, were monitored by reverse transcription quantitative polymerase chain reaction (RT-qPCR) or western blot assays. RESULTS: Our results suggested that GA could markedly increase the body weight and attenuate the behavioral sensitivity of FD rats. Moreover, GA also has an obvious ameliorating effect on the intestinal mucosal permeability and inflammatory response of FD rats. Furthermore, we found that GA could markedly downregulate TLR2, TLR4, and NF-κB in FD rats. CONCLUSIONS: These findings indicate that GA could significantly attenuate the intestinal mucosal permeability and inflammation FD rats. The effect of GA was partially mediated by the TLR/NF-κB signaling pathway.

Effect of Chaihu Shugansan on Mitochondrial Function and Mitophagy in Gastric Tissue of Rats with Functional Dyspepsia / 中国实验方剂学杂志

Objective:To observe the effects of Chaihu Shugansan on gastric motility and mitochondrial function and mitophagy in rats with functional dyspepsia （FD） and to preliminarily reveal its mechanism in preventing and treating FD. Method:Thirty-two SD rats of SPF grade were randomly divided into the normal group， model group， Chaihu Shugansan （4.8 g·kg^-1） group， and domperidone group （4.5 mg·kg^-1） after one week of adaptive feeding， with eight rats in each group. Rats in all groups except for the normal group were exposed to modified tail-clamping stimulation for inducing FD. Four weeks later， the semi-solid nutritive medium was used to observe the gastric emptying rate of FD rats， and the serum citrate synthase （CS）， motilin （MTL）， and gastrin （GAS） were detected by enzyme-linked immunosorbent assay （ELISA）. The pathological changes in gastric tissue were observed by hematoxylin-eosin （HE） staining， the mitochondrial characteristics by transmission electron microscopy， and the expression of microtubule-associated protein light chain 3 （LC3） and voltage-dependent anion-selective channel 1 （VDAC1） by immunofluorescence co-localization. The mitochondria were extracted from fresh gastric tissue for measuring the reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels using the biochemical kits. The mitochondrial LC3， yeast Atg6 homologous（Beclin1）， and p62 protein expression was assayed by Western blot. Result:Compared with the normal group， the model group exhibited significantly reduced gastric emptying rate （<italic>P</italic><0.01） and serum CS， MTL， and GAS levels （<italic>P</italic><0.01）. HE staining showed no pathological changes like erosion or ulcer in the gastric tissue of rats in each group. However， the mitochondria in the gastric tissue were observed swollen and dilated under the transmission electron microscope， and vacuolar lesions appeared. The co-expression of LC3 with VDAC1 increased significantly （<italic>P</italic><0.01）. The mitochondrial ROS and MDA levels were elevated significantly （<italic>P</italic><0.01）， while SOD content was significantly reduced （<italic>P</italic><0.01）. The protein expression levels of LC3 and Beclin1 were significantly up-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas p62 protein expression was down-regulated significantly （<italic>P</italic><0.01）. Compared with the model group， Chaihu Shugansan and domperidone elevated the gastric emptying rate （<italic>P</italic><0.05） and serum CS， MTL， and GAS levels （<italic>P</italic><0.05， <italic>P</italic><0.01）. It was observed under the transmission electron microscope that the mitochondrial nuclear membrane of the gastric tissue was intact， with clear structure and high density of mitochondrial cristae， and mitochondrial fission and fusion were observed in some parts. The co-localization area of LC3 and VDAC1 was significantly reduced （<italic>P</italic><0.01）. The mitochondrial ROS and MDA levels declined significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas SOD level rose （<italic>P</italic><0.05）. The protein expression levels of LC3 and Beclin1 were significantly down-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， while that of p62 was obviously up-regulated （<italic>P</italic><0.01）. Conclusion:The mechanism of Chaihu Shugansan in preventing and treating FD may be related to the improvement of mitochondrial function and the inhibition of mitophagy in gastric tissue.

Imaging of Morphological Background in Selected Functional and Inflammatory Gastrointestinal Diseases in fMRI.

The study focuses on evaluation of the Default Mode Network (DMN) activity in functional magnetic resonance imaging (fMRI) in resting state in patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS), Crohn's disease and colitis ulcerosa (IBD) in comparison to healthy volunteers. We assume that etiology of both functional and non-specific inflammatory bowel diseases is correlated with disrupted structure of axonal connections. We would like to identify the network of neuronal connections responsible for presentation of symptoms in these diseases. 56 patients (functional dyspepsia, 18; Crohn's disease and colitis ulcerosa, 18; irritable bowel syndrome, 20) and 18 healthy volunteers underwent examination in MRI of the brain with assessment of brain morphology and central nervous system activity in functional imaging in resting state performed in 3T scanner. Compared to healthy controls' DMN in patients with non-specific digestive tract diseases comprised additional areas in superior frontal gyrus of left hemisphere, in left cingulum and in the left supplementary motor area. Discovered differences in the DMNs can be interpreted as altered processing of homeostatic stimuli. Our study group involved patients suffering from both functional and non-specific inflammatory bowel diseases. Nevertheless a spectrum of changes in the study group (superior frontal gyrus of the left hemisphere, in the left cingulum and in the left supplementary motor area) we were able to find common features, differentiating the whole study group from the healthy controls.

A meta-analysis of Xin kai bitter method in the treatment of functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a common, etiologically complex disease which persistently and recurrently attacks the digestive system. However, the efficacy of Western medicine in treating FD is unsatisfactory and its use is often accompanied with severe side effects. Here, this study conducted a metaanalysis on the clinical efficacy and safety of the treatment of FD with Xin kai bitter method combined with Western medicine, to produce a more objective and comprehensive systematic review to guide clinical application. METHODS: Systematic searches were conducted of the PubMed, Cochrane Library, EMBASE, Medline, Web of Science, Wanfang Databases, and Weipu (VIP) databases, as well as China National Knowledge Infrastructure (CNKI). Randomized controlled clinical trials (RCTs) of Xin kai bitter method in the treatment of FD were included in the study. The total effective rate and safety were evaluated with relative risk (RR) and the quantitative data were evaluated with standard mean difference (SMD) and 95% confidence interval (CI). The quality of the included literature was evaluated using RevMan5.3 software, and the "meta" package of R3.5.1 software was used for all other statistical analysis. RESULTS: A total of 24 papers involving 1,044 patients in the treatment group and 989 patients in the control group were included. A total of 23 articles reported the total effective rate after 1 month of treatment (I2 =0%), and the total effective rate in the treatment group was 1.21 times higher than that in the control group (95% CI: 1.17 vs. 1.26). A total of 4 articles reported the safety rate after 1 month of treatment (I2 =27%); the safety rate in the treatment group was 0.43 times than that in the control group (95% CI: 0.23 vs. 0.82). A total of 8 articles reported traditional Chinese medicine (TCM) symptom score or clinical symptoms before and after 1 month of treatment (I2 =91%), and the difference in TCM symptom score before and after treatment in the treatment group was significantly lower than that in the control group, with a SMD of -1.19 (95% CI: -1.71, -0.66). A total of 6 articles reported the motilin (MTL) level before and after 1 month of treatment, and the difference before and after treatment in MTL in the treatment group was not significantly different to that in the control group, with a SMD of 0.92 (95% CI: -0.12, 1.97). CONCLUSIONS: Compared to conventional treatment, Xin kai bitter method has a higher clinical effect and lower adverse reaction rate in patients with FD, and can improve TCM symptom score. However, highquality RCT research is still needed to further explore the safety of Xin kai bitter method for treating FD.

Specific foods can reduce symptoms of irritable bowel syndrome and functional constipation: a review.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are groups of disorders involving digestive symptoms that chronically persist despite the absence of organic abnormalities in the gastrointestinal tract. Representative FGIDs include functional dyspepsia (FD), irritable bowel syndrome (IBS), and functional constipation (FC). In particular, IBS is a disease representative of FGIDs in which abdominal pain and discomfort associated with abnormal bowel movements chronically persist and recur. These symptoms are known to be related to lifestyle habits, such as meals and stress. In recent years, according to advances in dietary therapy for IBS and FC, specific foods have been shown to alter these symptoms. In IBS, bowel movement abnormalities and abdominal discomfort have been reported to be reduced when patients eat these specific foods. MAIN TOPIC: Several studies suggest that individuals with certain attitudes toward eating or with preferences for fatty food, fast food, junk snack food, fried food, and hot/spicy food showed a higher prevalence of gastrointestinal (GI) symptoms. Those who are cognizant of nutritional balance or healthy food intake have a lower prevalence of GI symptoms. Thus, eating specific foods with higher dietary fiber and low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharaides, and polyols) is effective for relief from some GI symptoms.First, two kinds of dietary fibers are found in foods: water-soluble dietary fiber and insoluble dietary fiber. Enduring misconceptions about the physical effects of fiber in the gut have led to misunderstandings about the health benefits attributable to insoluble and soluble fiber. Previous reviews suggest that health benefits have been shown in regard to fiber, and reproducible evidence of clinical efficacy has been published.Second, the ingestion of certain carbohydrates causes gastrointestinal symptoms. Foods rich in fermentable oligosaccharides, disaccharides, monosaccharaides, and polyols (collectively known as FODMAP) have been shown to cause abdominal pain and abdominal discomfort in westerners with IBS. CONCLUSION: Dietary therapy for FGIDs should include specific foods that have been scientifically proven to be effective for managing symptoms of irritable bowel syndrome and functional constipation.

[Role of hippocampus NMDAR subunits in electroacupuncture at "Zhongwan" (CV 12) and "Weishu" (BL 21) for gastric motility].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on gastric motility, protooncogene c-fos and hippocampus N-methyl-D-aspartate (NMDA) receptor subunits in rats with functional dyspepsia (FD), and to discuss the molecular mechanism of hippocampal in EA at "Zhongwan" (CV 12) and "Weishu" (BL 21) for gastric motility. METHODS: Eighty-four Sprague Dawley (SD) rats were randomly divided into a normal group, a model group, a Zhongwan group, a Weishu group, an acupoint combination group and a non-acupoint group, 14 rats in each one. Except for the normal group, FD model were established by moderate tail-clipping infuriation method and irregular feeding. The rats in the Zhongwan group, Weishu group, acupoint combination group and non-acupoint group were treated with EA at corresponding acupoints, 20 min per treatment, once a day for 7 days. The rats in the normal group and the model group received no treatment; grabbing and fixation were applied in the model group. The stress transducer was used to record gastric motion waveforms; immunohistochemistry method was used to detect the expression of c-fos in hippocampus; Western blot method was used to detect the expression of NMDA receptor subunits NR1, NR2A and NR2B in hippocampus. RESULTS: Compared with the normal group, the gastric motility range was decreased (P<0.05), and the expression of hippocampus NR2A was reduced and the levels of NR1 and NR2B were increased in the model group (P<0.05), however, hippocampus c-fos expression was not significant different between the normal group and the model group (P>0.05). Compared with the model group, the gastric motility range was increased, the expression of hippocampus c-fos and expression of hippocampus NR2A was increased but expressions of NR1 and NR2B were reduced in the Weishu group, Zhongwan group and acupoint combination group (P<0.05). Besides, the differences of gastric motility range and expression of hippocampus c-fos, NR1, NR2A and NR2B between the model group and the non-acupoint were not significant (P>0.05). Compared with the Zhongwan group and the Weishu group, the gastric motility range was increased, the expression of hippocampus c-fos and NR2A was increased but the expression of NR1 and NR2B was reducedin the acupoint combination group (P<0.05). There was no significant difference in the frequency of gastric motility among the groups (P>0.05). CONCLUSION: EA at "Zhongwan" (CV 12) and "Weishu" (BL 21) could increase gastric motility of FD rats, which is likely to be related with activating hippocampal neurons, upregulating the level of NR2A and downregulating NR1 and NR2B.

Proton pump inhibitor monotherapy is effective to attenuate dyspepsia symptoms associated with gastroesophageal reflux disease: a multicenter prospective observational study.

BACKGROUND AND AIM: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are frequently overlapped. However, no treatment strategies have been established yet for such patients. This study compared the effects of proton pump inhibitor (PPI) treatment in patients with GERD-associated FD among three groups with varying severity levels of GERD symptoms. METHODS: The patients with GERD and FD symptoms received PPI treatment for 4 weeks after endoscopy, and the severity of the symptoms and responses to treatment were evaluated at before and after 4 weeks of treatment using the Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test (GERD-TEST). The patients were divided into three groups in accordance with the severity of the GERD symptoms as assessed by the GERD symptom subscale (SS) scores of pre-treatment. RESULTS: Data from 233 cases of 40 mild, 151 moderate and 42 severe symptoms were analyzed. Analysis of the pre-treatment scores for each symptom revealed that a higher GERD-SS score was significantly associated with higher scores on any kind of FD score. Four weeks of PPI treatment significantly and markedly alleviated any of GERD/FD symptoms. Most importantly, change in the score for each symptom after 4 weeks of treatment relative to the pre-treatment score was significantly greater in the groups with more severe GERD-SS. CONCLUSION: FD symptoms associated with more severe GERD symptoms are supposed to be acid-related dyspepsia, and PPI monotherapy is recommended as the treatment of first choice in such patients.

Role of hippocampus NMDAR subunits in electroacupuncture at "Zhongwan" (CV 12) and "Weishu" (BL 21) for gastric motility / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on gastric motility, protooncogene c-fos and hippocampus N-methyl-D-aspartate (NMDA) receptor subunits in rats with functional dyspepsia (FD), and to discuss the molecular mechanism of hippocampal in EA at "Zhongwan" (CV 12) and "Weishu" (BL 21) for gastric motility.@*METHODS@#Eighty-four Sprague Dawley (SD) rats were randomly divided into a normal group, a model group, a Zhongwan group, a Weishu group, an acupoint combination group and a non-acupoint group, 14 rats in each one. Except for the normal group, FD model were established by moderate tail-clipping infuriation method and irregular feeding. The rats in the Zhongwan group, Weishu group, acupoint combination group and non-acupoint group were treated with EA at corresponding acupoints, 20 min per treatment, once a day for 7 days. The rats in the normal group and the model group received no treatment; grabbing and fixation were applied in the model group. The stress transducer was used to record gastric motion waveforms; immunohistochemistry method was used to detect the expression of c-fos in hippocampus; Western blot method was used to detect the expression of NMDA receptor subunits NR1, NR2A and NR2B in hippocampus.@*RESULTS@#Compared with the normal group, the gastric motility range was decreased (0.05). Compared with the model group, the gastric motility range was increased, the expression of hippocampus c-fos and expression of hippocampus NR2A was increased but expressions of NR1 and NR2B were reduced in the Weishu group, Zhongwan group and acupoint combination group (0.05). Compared with the Zhongwan group and the Weishu group, the gastric motility range was increased, the expression of hippocampus c-fos and NR2A was increased but the expression of NR1 and NR2B was reducedin the acupoint combination group (0.05).@*CONCLUSION@#EA at "Zhongwan" (CV 12) and "Weishu" (BL 21) could increase gastric motility of FD rats, which is likely to be related with activating hippocampal neurons, upregulating the level of NR2A and downregulating NR1 and NR2B.

DA-9701 (Motilitone): A Multi-Targeting Botanical Drug for the Treatment of Functional Dyspepsia.

Functional dyspepsia (FD) is the most common functional gastrointestinal disorder (FGID). FD is characterized by bothersome symptoms such as postprandial fullness, early satiety, and epigastric pain or burning sensations in the upper abdomen. The complexity and heterogeneity of FD pathophysiology, which involves multiple mechanisms, make both treatment and new drug development for FD difficult. Current medicines for FD targeting a single pathway have failed to show satisfactory efficacy and safety. On the other hand, multicomponent herbal medicines that act on multiple targets may be a promising alternative treatment for FD. DA-9701 (Motilitone), a botanical drug consisting of Corydalis Tuber and Pharbitidis Semen, has been prescribed for FD since it was launched in Korea in 2011. It has multiple mechanisms of action such as prokinetic effects, fundus relaxation, and visceral analgesia, which are mediated by dopamine D2 and several serotonin receptors involved in gastrointestinal (GI) functions. In clinical studies, DA-9701 has been found to be beneficial for improvement of FD symptoms and GI functions in FD patients, while showing better safety compared to that associated with conventional medicines. In this review, we provide updated information on the pharmacological effects, safety, and clinical results of DA-9701 for the treatment of FGIDs.

New Approaches to Diagnosis and Treatment of Functional Dyspepsia.

PURPOSE OF REVIEW: The purpose of this article is to review the recent literature and discuss the new approaches to the diagnosis and treatment of functional dyspepsia (FD). RECENT FINDINGS: According to the recent American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guideline for dyspepsia, Helicobacter pylori (H. pylori) eradication is recommended as a first treatment option, and proton pump inhibitors (PPIs), tricyclic antidepressants, and prokinetics are listed as second-line therapy. On the other hand, in the Japanese guideline for FD, PPIs and prokinetics are recommended as the first-line treatment. In Japan, acotiamide, a recently launched prokinetic, showed significant efficacy in several clinical trials performed either in Japan or Europe. Regarding non-pharmacological treatment, recent topics include acupuncture, electrical stimulation, gastric peroral endoscopic myotomy, and meal and lifestyle modification. These treatments have provided significant efficacy, which provides some insights into the main pathophysiology of this disease. Although FD is common among functional gastrointestinal disorders, it is not easy to relieve the dyspeptic symptoms of FD patients. Combinations of pharmacological and non-pharmacological treatment options are expected.