Randomized Double-blind Placebo-controlled Trial of Modified Zuojinwan Granules in Treating Reflux Esophagitis and Functional Dyspepsia with Same Syndrome with Disharmony Between Liver and Stomach / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of modified Zuojinwan granules in treating reflux esophagitis （RE） and functional dyspepsia （FD） with the same syndrome with disharmony between liver and stomach）. MethodA randomized double-blind placebo-controlled clinical trial was conducted to enroll 144 patients with disharmony between liver and stomach， including 72 patients with RE and 72 patients with FD. These patients were then randomly divided into observation and control groups， with 36 patients in each group. The observation group was given modified Zuojinwan granules orally， and the control group was given placebo granules orally. They both were treated with two packs each time， twice a day， for four weeks. The traditional Chinese medicine （TCM） syndrome scores， cerebrointestinal peptides ［calcitonin gene-associated titanium （CGRP）， vasoactive intestinal peptide （VIP）， 5-hydroxytryptamine （5-HT）， and substance P （SP）］， inflammatory factors ［tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6）］， common gastrointestinal related hormones ［gastrin （GAS） and motilin （MTL）］， and other indicators in the two groups were compared before and after treatment， and the curative effect of TCM syndromes and the occurrence of adverse reactions were determined. At the same time， the changes in the above indicators and the curative effect of TCM syndromes in the two groups of patients with the same disease were analyzed. ResultAfter treatment， CGRP， VIP， 5-HT， SP， TNF-α， IL-6， GAS， MTL， and TCM syndrome scores in the observation group and control group were significantly improved （P<0.05）. After treatment， the improvement of CGRP， VIP， 5-HT， SP， TNF-α， IL-6， GAS， MTL， and TCM syndrome scores in the observation group was better than that in the control group （P<0.05）. After treatment， CGRP， VIP， 5-HT， SP， TNF-α， IL-6， GAS， MTL， and TCM syndrome scores in both groups of RE patients and FD patients were significantly improved （P<0.05）. After treatment， the improvement of CGRP， VIP， 5-HT， SP， TNF-α， IL-6， GAS， MTL， and TCM syndrome scores in RE patients and FD patients in the observation group were better than that in the control group （P<0.05）. In the observation group and the control group， the incidence of nausea， vomiting， fatigue， dry mouth， and other adverse reactions was lower， and there was no statistical significance. ConclusionModified Zuojinwan granules can effectively improve the TCM syndromes of disharmony between liver and stomach of RE and FD， brain and intestinal peptide， gastrointestinal hormone， and inflammatory factors and provide evidence for the clinical application of TCM theory of "treating different diseases with the same method".

Omeprazole combined with different probiotics regulates intestinal microbiota to alleviate functional dyspepsia in children / 基础医学与临床

Objective To explore the effect of omeprazole combined with different probiotics on regulating intestinal flora in reducing functional dyspepsia(FD)in children.Methods Two hundreds children with FD admitted to the Pediatric Department of Foshan Maternal and Child Health Hospital from January 2022 to February 2023 were se-lected as the study subjects.They were randomly divided into omeprazde(omep)group,groups of omeprazole+yeast(yeast group),+clostridium butyricum(clos group),and+bifidobacterium(bifi group)respectively.Results After treatment,serum level of IL-6,TNF-α,IL-1β,hs-CRP,VIP,SS,Enterobacter and Enterococcus in all groups significantly decreased as compared with the finding before treatment(P<0.05).Those targets in the three combined treatment groups were significantly lower compared to the ome group;After treatment,the serum MOT level,bifidobacteria,and lactobacilli in each group were significantly increased(P<0.05),and the results from three combined treatment groups demonstrated notably higher levels compared to the omep group(P<0.05);The scores of symptoms in all groups showed a significant alleviation after the treatment(P<0.05).Additionally,the three combined treatment groups exhibited significantly lower symptom scores than the group treated with omeprazole alone(P<0.05).There was no difference in the incidence of adverse reactions during treatment among the groups.Conclusions Omeprazole combined with different probiotics have achieved good results in the treatment of FD in children.

Mechanism of Electroacupuncture in Functional Dyspepsia Rats Based on Hypothalamic-Pituitary-Adrenal Axis / 世界科学技术-中医药现代化

Objective We aimed to explore the therapeutic mechanism of electroacupuncture at Yintang(EX-HN3),Neiguan(PC6)and Zusanli(ST36)on the Hypothalamic-Pituitary-Adrenal axis(HPA)of functional dyspepsia(FD)rats.Methods Forty SD rats were randomly divided into blank group,model group and EA group.The FD model was replicated by tail clamping,irregular diet,and filling the stomach with ice of Saline Solution.After modeling,the EA group received acupuncture treatment for 1 time day,30 minutes time,for 14 days.Recording the general state of the rat.Detection of locomotion and catatonia in rats by open field test.HE staining to observe the morphology and inflammation of gastric mucosa in rats.PCR detection of mRNA expression of 5-hydroxytryptamine3 receptor and corticotropin-releasing hormone in rat hypothalamus.Detection of corticotropin-releasing hormone receptor-2 and NOD-like receptor protein 6 inflammasome protein expression in rat duodenum by Western blotting.Alcian blue staining was used to detect the expression of rat duodenum goblet cells.Results Compared with the blank group,the general state,distance,speed,duodenum CRHR2 and NLRP6 proteins in the model group were significantly decreased(P<0.05),the hypothalamic 5-HT3R and CRH mRNA were significantly increased(P<0.05).Compared with the model group,the general state,distance,speed,expression of CRHR2,NLRP6 protein and goblet cells in the duodenum of rats in the EA group were significantly increased(P<0.05),the 5-HT3R and CRH mRNA in the hypothalamus were significantly decreased(P<0.05).In the model group,the connective tissue of the gastric mucosa was loosely arranged,the submucosa had mild edema,and there were some lymphocytes.The connective tissue of the gastric mucosa of the rats in the blank group and the electroacupuncture group was closely arranged,and there was no obvious proliferation of interstitial cells and no inflammatory cells.Conclusion EA can increase the expression of CRHR2,NLRP6 protein and goblet cells in the duodenum,and inhibit the expression of 5-HT3R and CRH in the hypothalamus.EA can improve gastrointestinal motility and locomotion,relieve anxiety,repair the mucosal barrier of the defective intestine,and restore the function of the Hypothalamic-Pituitary-Adrenal axis.

Effect of Wenweiyang decoction on mast cell activation and SCF/c-Kit signaling pathway in rats with functional dyspepsia / 中国病理生理杂志

AIM:To investigate the mechanism of action of Wenweiyang decoction(WWYD)in treating func-tional dyspepsia in rats based on mast cell activation and stem cell factor(SCF)/receptor tyrosine kinase c-Kit signaling pathway.METHODS:Sixty SD rats were randomly divided into control group,model group,ranitidine hydrochloride capsule group,and low-,medium-and high-dose WWYD groups,with 10 rats in each group.The rat model of functional dyspepsia was established by tail clamping and irregular feeding compound senna method.After modeling,the rats in con-trol group and model group were given normal saline,while those in low-,medium-and high-dose(0.743 g/mL,1.485 g/mL and 2.970 g/mL)WWYD groups and ranitidine hydrochloride capsule(3 g/L)group were treated with corresponding drugs by intragastric administration.After treatment,the propulsion rate of the small intestine was measured by the carbon ink propulsion method.Rat duodenal mast cells were observed and counted by toluidine blue staining.ELISA was used for determination of mast cell tryptase(MCT)and histamine(HA)content in rat duodenum.The mRNA levels of SCF and c-Kit in duodenum were detected by RT-qPCR.Western blot and immunohistochemistry were employed to determine the ex-pression levels of SCF and c-Kit in the duodenum.RESULTS:Compared with model group,WWYD treatment signifi-cantly increased the propulsion rate of the small intestine in rats(P<0.05).ELISA results showed that WWYD reduced the number of mast cells and the content of MCT and HA in the duodenal mucosa tissue of rats(P<0.05).Western blot and immunohistochemistry results suggested that WWYD up-regulated the protein expression levels of c-Kit and SCF in the duodenal tissue of rats(P<0.05),and increased the numbers of SCF and c-Kit positive cells.RT-qPCR results indicated that WWYD up-regulated the mRNA expression of c-Kit and SCF in the duodenum of rats(P<0.05).Moreover,the small intestinal propulsion rate was negatively correlated with MCT and HA content,and positively correlated with the expres-sion of SCF and c-Kit.CONCLUSION:Wenweiyang decoction promotes rat duodenal motility,and its mechanism may be related to the inhibition of rat duodenal MCT and HA production and activation of SCF/c-Kit signaling pathway.

Meta-Analysis of the Placebo Effect of Chinese Herbal Medicine in Clinical Trials of Traditional Chinese Medicine for Functional Dyspepsia / 中医杂志

ObjectiveTo analyse the current implementation status of Chinese herbal medicine （CHM） placebo and systematically evaluate the placebo effect in randomised controlled trials （RCTs） of traditional Chinese medicine （TCM） for the treatment of functional dyspepsia （FD）. MethodsA combination of medical subject terms and free words was used to search six databases， including PubMed， EMBASE， Cochrane Library， Web of Science， China National Knowledge Infrastructure， and Wanfang， for RCTs with CHM placebo group for FD published from January 31st， 1994 to September 30th， 2023. The dosage forms， composition， and methodological quality were collected and evaluated. The quality of the included articles was evaluated by Cochrane risk of bias assessment tool， and meta-analysis was performed on the CHM placebo response rate of patients with FD， and subgroup analysis and meta-regression was performed according to diagnostic criteria， efficacy criteria， duration of treatment， type of placebo， whether it contained active ingredient， and whether it evaluated placebo effects. ResultsA total of 34 publications were included involving 5046 participants， of which 2221 FD patients received CHM placebo treatment. Granules were the predominant placebo preparation， accounting for 71% （24/34）； 32.35% （11/34） of the studies added real CHM to the placebo， and only 12 （35%） of the studies described appearance， odour， and taste. The placebo response rate in FD patients in the placebo group was 41% （95% CI： 0.35 to 0.47； P＜0.01， I2 = 87%）； there was significant difference between groups with different diagnostic criteria and different treatment durations （P＜0.05 or P＜0.01）， but there was no significant difference between the different efficacy evaluation criteria， the different placebo preparation， the presence of a low-dose active ingredient， and the presence or absence of placebo assessment （P＞0.05）. ConclusionThere was a significant CHM placebo effect in patients with FD， with granules as the main preparation of placebop. Different diagnostic criteria and different treatment times may affect the response rate of patients， and the addition of low-dose real medicine to the CHM placebos has not been seen to have an effect on the response rate. Clinical investigators have not paid enough attention to placebos， and there is a lack of uniform standards and norms for the preparation and evaluation of CHM placebos.

Chaihu Shugansan and Its Modified Formulas in Treatment of Functional Dyspepsia： A Review / 中国实验方剂学杂志

Chaihu Shugansan composed of Bupleuri Radix， Paeoniae Radix Alba， Chuanxiong Rhizoma， Aurantii Fructus， Citri Reticulatae Pericarpium， Cyperi Rhizoma， and Glycyrrhizae Radix et Rhizoma has the effects of soothing liver， relieving depression， regulating Qi movement， and relieving pain. It is a classic formula for treating gastric distension recommended by doctors of later ages. This article systematically reviews the clinical application and basic experimental progress of Chaihu Shugansan in the treatment of functional dyspepsia. In modern clinical practice， Chaihu Shugansan and its modified formulas are used to treat functional dyspepsia， and they can be applied in combination with other formulas （Si Junzitang， Jinlingzisan， Zhizhuwan， etc.）， western medicine （domperidone tablets， deanxit， Saccharomyces boulardii， etc.）， traditional Chinese medicine （TCM） acupuncture and other therapies. The results of clinical studies have shown that Chaihu Shugansan and its modified formulas can significantly reduce the Hamilton depression scale （HAMD） score， Hamilton anxiety scale （HAMA） score， and TCM syndrome score， ameliorate the symptoms， improve the quality of life， and decrease the recurrence rate. The experimental pharmacological studies have demonstrated that Chaihu Shugansan can inhibit the autophagy of Cajal interstitial cells， regulate the endoplasmic reticulum stress signaling pathway， and modulate the brain-gut peptide level to improve the gastrointestinal motility. Chaihu Shugansan can inhibit the expression of 5-hydroxytryptamine in the colon tissue and reduce the abdominal withdrawal reflex （AWR） score to improve visceral hypersensitivity. Furthermore， Chaihu Shugansan can lower the levels of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α to repair duodenal mucosal inflammation. In addition， it can regulate intestinal flora to maintain intestinal flora balance. The main active ingredients such as saikosaponin， paeoniflorin， hesperidin， and naringin in Chaihu Shugansan can exert anti-inflammatory， antioxidant， and antimicrobial effects.

Oral Chinese Patent Medicines for Adult Functional Dyspepsia:A Scoping Review of Clinical Evidence and Drug Package Inserts / 世界科学技术-中医药现代化

Objective To systematically review the present status of oral Chinese patent medicines(CPMs)for treating functional dyspepsia(FD),explore the formation rules of CPMs,and reveal the potential problems by referring to the methods and procedures of Scoping review.Methods First,we screened all CPMs from the domestic-related drug catalogs which are generally accepted and own the force of law,then we sorted the CPMs based on the drug instructions while carrying out Chinese and English database document retrieval to review the clinical studies.Descriptive analysis of the basic feature and clinical research evidence of CPMs was performed combined with visual charts.Results This study included 42 CPMs for treating FD.Among the formulas of CPMs,Tangerine peel,Radices saussureae,Poria cocos,Glycyrrhiza,Atractylodes macrocephala,and Six Divine Qu appeared frequently.In addition,96 studies involving 21 CPMs were included,among which Zhizhu Kuanzhong Capsule,Liuwei Anxiao capsule,and Dalitong granules had more clinical literature.By analyzing the included 96 clinical studies,we found that the combination of Chinese and Western medicine was the main intervention,and the effective rate,clinical symptom score,and adverse reactions were the main outcomes that were concerned.In addition,8 studies had off-label use of diseases,involving the Wuling capsule to treat the FD whether the disease was accompanied by depression and anxiety symptoms or not,and Zhizhu Kuanzhong Capsule to treat the FD with anxiety and depression.Although the Wuling capsule and Zhizhu Kuanzhong capsule were off-label used in clinical practice,there was no beyond the scope of the guideline.Conclusion The qi-regulating drug,spleen-strengthening drug and digestant drugs are the usual Chinese medicines used for treating adult FD.In recent years,research on CPMs for treating adult FD has increased rapidly.But there is insufficient reflection of CPMs treatment characteristics,ambiguous differences from the primary and secondary outcomes,multiple composite outcomes,and not explicit information on FD or its symptoms in drug package insert,which needs to be improved in the future.

Exploring the Application of Auricular Concha Eletro-Acupuncture in Functional Dyspepsia from the"Ear-Brain-Liver-Spleen"Correlation / 世界科学技术-中医药现代化

Based on the traditional medical theory,the theory of"ear-brain-liver-spleen correlation"was proposed by linking the ear with the brain,liver and spleen.Then,by combining the Chinese medical etiology of Functional Dyspepsia(FD)and the corresponding modern medical mechanism,we realized that the close connection between the ear,brain,liver and spleen is the theoretical basis for treating FD from the ear.In recent years,a new type of vagus nerve stimulation therapy,auricular concha eletro-acupuncture(ACEA),has been developed to treat FD by regulating the liver and spleen through the regulation of the brain,relieving liver depression and strengthening spleen and qi,thus treating FD.In terms of modern medicine,this is related to its ability to reduce anxiety and depression,reduce pain perception,enhance gastrointestinal motility and reduce central and peripheral inflammation by regulating the activity of the corresponding brain functional areas.By exploring the application of auricular concha eletro-acupuncture in FD on the basis of the"ear-brain-liver-spleen correlation",we will better understand the unique role of auricular stimulation in regulating the brain and the blood of the liver and spleen,and promote the inheritance,innovation and development of TCM theory.

Progress of Research on Application of Transcutaneous Auricular Vagus Nerve Stimulation in Treatment of Digestive System Diseases / 胃肠病学

Transcutaneous auricular vagus nerve stimulation(taVNS)is a non-invasive alternative treatment for vagus nerve stimulation.In the early stage,it was used to treat epilepsy,depression,blood pressure control,insomnia,and so on.After continuous exploration,it was gradually applied to the treatment of functional dyspepsia,irritable bowel syndrome,and other digestive system diseases.TaVNS is the stimulation of auricular branch of vagus nerve distributed in the receptive field of the external ear with a specific frequency of the current,which directly or indirectly affects the vagal tension and regulates the gastrointestinal nerve reflex,to achieve the purpose of treatment.The exact mechanism of taVNS is still unclear,but the results of research in the last decade indicate that taVNS has been used as an alternative or adjuvant treatment for drug therapy in many digestive system diseases.This article reviewed the progress of research on taVNS in the treatment of digestive system diseases.

Occurrence of Emotional Disorders in Patients With Functional Gastrointestinal Disorders Overlapping Syndrome / 胃肠病学

Background:The pathological and physiological mechanisms of functional gastrointestinal disorders(FGIDs)are complex.In recent years,FGIDs have been referred to as gut-brain interaction disorders.Emotional disorders are widely present in patients with FGIDs.Our study aims to analyze the occurrence of emotional disorders in patients with functional dyspepsia(FD)overlap with other FGIDs.Aims:To explore whether detailed consultation and comprehensive analysis can provide more accurate treatment for patients with FD.Methods:This study included 137 patients with FD,who complete a detailed gastrointestinal symptom survey questionnaire.We evaluated their emotional status through an anxiety and depression scale.Results:Among patients with anxiety or depression disorder,the symptoms of FD were more severe thanthose without anxiety or depression(P=0.003,P=0.003).There was a statistically significant difference in the distribution of anxiety and depression scores between patients with simple FD and those with overlapping 1,2,and 3 FGIDs(P=0.021,P=0.010).Compared with patients with simple FD and overlapping 1,2 and 3 FGIDs,there was a statistically significant difference in the proportion of anxiety and depression patients(P=0.005,P=0.005).The chi square test showed a significant trend in the proportion of anxiety patients(P=0.009),indicating that patients with FGIDs overlapping syndrome are more likely to develop anxiety or depression disorders,and the more overlapping quantities,the more likely they are to develop anxiety disorders.There is a significant difference in the distribution of quantities of FGIDs between patients with and without anxiety(P=0.010),indicating that patients with anxiety disorders are more likely to suffer from two or more types of FGIDs.The score of gastrointestinal symptoms is positively correlated with the score of anxiety and depression,and this correlation is statistically significant(P=0.009,P=0.021).Conclusions:The prevalence of FGIDs overlapping syndrome is closely related to emotional disorders.Clinicians,especially grassroots general practitioners and gastroenterologists,should pay attention to the emotional state of patients with gastrointestinal symptoms,especially those with extensive and diverse symptoms.Timely psychological state assessment should be conducted,and if necessary,psychiatric specialists should be recommended for consultation.

Research progress in TCM treatment of Helicobacter pylori positive functional dyspepsia / 国际中医中药杂志

The incidence rate of functional dyspepsia (FD) is high. Helicobacter pylori (Hp) infection is one of the main causes of FD. Eradication of Hp is the current first-line treatment. However, the actual efficacy of eradicating Hp with the triple/quadruple therapy of Western medicine alone is not satisfactory for Hp-positive FD patients. TCM-assisted triple/quadruple therapy for Hp positive FD has a good efficacy, which has the effects of anti-Hp, regulating gastrointestinal hormones and gastric electrical parameters, and improving gastrointestinal motility. It can improve the eradication rate of Hp, effectively alleviate the clinical symptoms of patients, and improve the pathological conditions such as abnormal gastrointestinal secretion, abnormal motility, and abnormal sensation. The diagnostic and treatment idea of integrated TCM and Western medicine is worthy of summary and promotion.

Overview of systematic review on TCM for functional dyspepsia / 国际中医中药杂志

Objective:To re-evaluate the reliability of the conclusions of the systematic reviews (SR)/meta-analysis (MA) of Traditional Chinese Medicine (TCM) in the treatment of functional dyspepsia (FD).Methods:CNKI, CBM, WanFang Data, VIP, PubMed, Cochrane Library, and Embase were searched from the establishment of the database to March 30, 2022. Two researchers independently screened literature and extracted data, and included SRs/MAs in the treatment of FD with TCM. The AMSTAR 2 and GRADE tools were used to evaluate the included the study carried out methodological quality evaluation, outcome evidence quality grading, and descriptive analysis of the main outcome.Results:A total of 28 SRs/MAs were included, with 34 outcome indicators. According to the AMSTAR 2 evaluation results, 21 SRs/MAs were of medium quality, and 7 SRs/MAs were of low quality. The GRADE quality of evidence grading results showed that of the 100 evidence bodies, 13 were of high quality, 58 were of moderate quality, 24 were of low quality, and 5 were of very low quality.Conclusion:TCM in the treatment of FD can improve the clinical efficiency, improve the cure rate, reduce the recurrence rate, and improve the clinical symptoms, but the methodological quality and evidence quality of related SRs/MAs have certain defects, so this conclusion should be treated with caution.

Effects of Chaihu Shugan Powder （柴胡疏肝散） on Duodenal Mucosal Barrier and Intestinal Flora in Functional Dyspepsia Model Rats / 中医杂志

ObjectiveTo study the possible mechanism of Chaihu Shugan Powder （柴胡疏肝散， CSP） in the treatment of functional dyspepsia （FD）. MethodsTwenty-four SD rats were randomly divided into a normal group， a model group， a CSP group and a probiotic group， with six rats in each group.The tail-clamping provocation method was used in all groups except for the normal group to replicate the FD rat model. Simultaneously， the normal group and the model group were given 10 ml/（kg·d） of saline by gavage， while the CSP group and the probiotic group were given 9.6 g/（kg·d） of CSP aqueous decoction and 0.945 g/（kg·d） of probiotic aqueous solution by gavage， respectively， twice daily for four weeks. After four weeks， the gastric emptying and small intestinal propulsion rates were detected in each group of rats. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the gastric sinusoids and duodenum of the rats. The changes in the intestinal flora were analyzed by 16s rDNA high-throughput gene sequencing， and the expressions of the duodenal zona occludin 1 （ZO-1） and Occludin were detected by immunohistochemistry and western blotting. Pearson correlation analysis was performed on intestinal flora and ZO-1 and Occludin protein expression. ResultsThe gastric antrum tissue structure was clear in all groups， and the gland structure was regular， with smooth gastric tissue mucosa and no pathological changes such as erosion and ulcer. Compared to those in the normal group， the intestinal villi in the duodenal tissue in the model group were significantly reduced or atrophied， and the goblet cells were arranged in disorder， with eosinophilic infiltration； the gastric emptying rate and small intestinal propulsion rate， as well as ZO-1 and Occludin protein expression in duodenal tissue significantly decreased （P＜0.01）. Compared to those in the model group， the duodenal tissue structure was clear， and the length intestinal villi was longer， with goblet cells neatly arranged in the CSP group and the probiotic group； no obvious eosinophil infiltration was found， and the gastric emptying rate and small intestinal propulsion rate as well as ZO-1 and Occludin protein expression significantly increased in the CSP group； a small amount of eosinophil infiltration was found， and the gastric emptying rate and Occludin protein expression significantly increased in the probiotic group （P＜0.05 or P＜0.01）. Beta diversity analysis of intestinal flora showed that the overall structure of intestinal flora in the model group changed significantly compared to that in the normal group （P＜0.01）. The overall structure of the intestinal flora in the CSP group and the probiotic group was closer to the normal group than the model group. Species composition analysis showed that the relative abundance of the Firmicutes decreased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae increased， and the Bacteroidetes/Firmicutes value increased in the model group than those in the normal group （P＜0.05 or P＜0.01）. Compared to those in the model group， the relative abundance of the Firmicutes increased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae， as well as the Bacteroidetes/Firmicutes value decreased in the CSP group and the probiotic group （P＜0.05 or P＜0.01）. There was no statistically significant difference in each indicator between the probiotic group and the CSP group （P＞0.05）. Pearson correlation analysis showed that at the phylum level， Firmicutes was positively correlated with ZO-1 （r=0.610， P=0.016） and Occludin （r=0.694， P=0.004） protein expression. Bacteroidetes was negatively correlated with ZO-1 （r=-0.557， P=0.031） and Occludin （r=-0.662， P=0.007） protein expression. At the genus level， norank_f_Muribaculaceae was negatively correlated with ZO-1 （r=-0.727， P=0.002） and Occludin （r=-0.760，P=0.001） protein expression. ConclusionCSP can restore the structure of intestinal flora， regulate the abundance levels of Firmicutes， Bacteroidetes and norank_f_Muribaculaceae， up-regulate ZO-1 and Occludin proteins， and thus repairing the duodenal mucosal barrier， and playing a therapeutic role in FD rats.

Functional dyspepsia treated with acupuncture of different frequencies: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy of acupuncture with different frequencies in the treatment of patients with functional dyspepsia (FD).@*METHODS@#A total of 90 patients with FD were randomly divided into a 3-time acupuncture treatment per week group (3-A group, 31 cases, 2 cases dropped off), a 1-time acupuncture treatment per week group (1-A group, 30 cases, 2 cases dropped off) and a control group (29 cases, 2 cases dropped off). In the two acupuncture groups, the acupoints were Zhongwan (CV 12) and bilateral Tianshu (ST 25), Neiguan (PC 6), Liangqiu (ST 34), Yanglingquan (GB 34), Zusanli (ST 36) and Taichong (LR 3), stimulated 3 times a week and once a week, respectively; and the treatment was given consecutively for 4 weeks. In the control group, no intervention was adopted, but the compensatory therapy was provided after the end of follow-up. The scores of the symptom index of dyspepsia (SID), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were compared among the 3 groups before treatment, after 4 weeks of treatment and in 4 and 8 weeks after treatment completion separately. The score of Nepean dyspepsia life quality index (NDLQI) was evaluated before treatment, after 2 and 4 weeks of treatment and in 4 and 8 weeks after treatment completion.@*RESULTS@#After 4 weeks of treatment and in 4 and 8 weeks after treatment completion, the scores of SID, SAS and SDS were all reduced in the 3-A group and the 1-A group when compared with the scores before treatment (P<0.000 1, P<0.05). After 4 weeks of treatment, the scores of SID, SAS and SDS in the two acupuncture groups were lower than those in the control group (P<0.000 1). After 2 and 4 weeks of treatment, the increased values of NDLQI score in the two acupuncture groups were all higher than those in the control group (P<0.05). In 4 and 8 weeks after treatment completion, the scores of SID, SAS and SDS in the 3-A group were lower than those in the 1-A group (P<0.001, P<0.05), and the increased values of NDLQI score in the 3-A group were higher than those in the 1-A group (P<0.000 1).@*CONCLUSION@#Acupuncture given 3 times per week is superior to the treatment given once per week in the aspects of relieving the clinical symptoms, improving the quality of life and regulating the emotional state in patients with FD. This efficacy is persistent for 8 weeks after treatment completion.

Meta-analysis of Simotang Oral Liquid in treatment of functional dyspepsia in adults / 中国中药杂志

This study was conducted to evaluate the efficacy and safety of Simotang Oral Liquid in the treatment of functional dyspepsia in adults. "Simotang Oral Liquid" "Simotang" "Si Mo Tang" "Si Mo Tang Oral Liquid" were used for retrieval of the relevant papers from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, Springer Link, and Web of Science from database inception to June 2021. Randomized controlled trial(RCT) of Simotang Oral Liquid in the treatment of functional dyspepsia in adults was screened out for Meta-analysis which was conducted in RevMan 5.3. A total of 16 RCTs were included. Meta-analysis showed that compared with the control group, Simotang Oral Liquid increased the total response rate and lowered the traditional Chinese medicine syndrome scores, serum cholecystokinin(CCK), serum nitric oxide(NO), and incidence of adverse reactions. However, the serum substance P(SP) had no statistical difference between the two groups. Simotang Oral Liquid is effective and safe in the treatment of functional dyspepsia in adults. However, this study has evidence and limitations, so the conclusions need to be further verified by large sample and multicenter clinical studies.

Effect of electroacupuncture at "Neiguan" (PC 6) and "Zusanli" (ST 36) on gastrointestinal hormone in the antral tissue of rats with functional dyspepsia / 中国针灸

OBJECTIVES@#To observe the effects of electroacupuncture (EA) at "Neiguan" (PC 6) and "Zusanli"(ST 36) on the gastric emptying rate, the level of serotonin (5-HT) and the protein expression of motilin (MTL), ghrelin, substance P (SP) and vasoactive intestinal peptide (VIP) in the antral tissue of the rats with functional dyspepsia (FD) and explore the effect mechanism of EA in treatment of FD.@*METHODS@#A total of 21 SPF male SD rat pups were randomly divided into a normal group, a model group and an EA group, with 7 rats in each group. In the model group and the EA group, FD model was prepared by the gavage with 0.1% sucrose iodoacetamide solution combined with the modified small platform method. After the successful modeling, EA was applied to "Neiguan" (PC 6) and "Zusanli"(ST 36) in the rats of the EA group, with disperse-dense wave, 20 Hz/100 Hz in frequency, stimulated for 30 min, once daily, for 7 days consecutively. Before and after intervention, the general condition of the rats was observed in each group. After the completion of intervention, the gastric emptying rate was measured, the morphological changes of gastric antral tissue were observed using HE staining, the level of 5-HT was detected with ELISA method, and the protein expression of MTL, ghrelin, SP, and VIP was determined with Western blot method in the antral tissue of rats.@*RESULTS@#In the normal group, the rats were in a good mental state, with lustrous fur, flexible movement and the increase of food intake and body mass. In the model group, the rats were poor in mental state, lack of lustre in fur, preference for the body curled up, reduced activity and response; and a part of rats had loose stool, obviously enlarged gastric body and gastric food retention. In the EA group, the general condition of rats, e.g. the mental state, food intake and activity, were improved, the gastric body got smaller obviously and the gastric food retention was reduced when compared with the model group. The antral structure was intact, the glands were rich and no injury of the gastric mucosa was found, e.g. inflammatory reaction and edema in the rats of each group. Compared with the normal group, the gastric emptying rate was decreased (P<0.01), 5-HT level was increased (P<0.01), the protein expression of MTL and ghrelin was reduced (P<0.01) and that of VIP was elevated (P<0.01) in the rats of the model group. The gastric emptying rate was increased (P<0.01), 5-HT level was decreased (P<0.01), and the protein expression of MTL and ghrelin was elevated (P<0.05, P<0.01) in the rats of the EA group when compared with those in the model group.@*CONCLUSIONS@#Electroacupuncture at "Neiguan" (PC 6) and "Zusanli"(ST 36) may effectively relieve gastric dysfunction, strengthen gastric motility and promote gastric emptying so as to alleviate the symptoms of dyspepsia in FD rats, and its mechanism may be related to the regulation of gastrointestinal hormones in the antral tissue.

Effects and mechanisms of traditional Chinese medicines on functional dyspepsia: A review / 中草药·英文版

Functional dyspepsia (FD) is a common and frequently occurring disease in clinic. With the influence of environmental factors, social factors and dietary factors, the incidence rate of FD in the general population is yearly increasing. Traditional Chinese medicine has a long history and far-reaching influence in the treatment of FD. It can prevent and treat FD in the form of multiple-components, targets and channels, with obvious effect and prominent advantages. This article starts with the common syndrome types of FD, and discusses the research progress of single Chinese medicine, effective ingredients and the mechanism of traditional Chinese medicines in treating FD, in order to provide a theoretical basis for the treatment of FD with traditional Chinese medicines.

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.

Research progress in signaling pathways related to treatment of functional dyspepsia with traditional Chinese medicine / 中国中药杂志

Functional dyspepsia(FD) is a prevalent functional gastrointestinal disease characterized by recurrent and long-lasting symptoms that significantly impact the quality of life of patients. Currently, western medicine treatment has not made breakthrough progress and mainly relies on symptomatic therapies such as gastrointestinal motility agents, acid suppressants, antidepressants/anxiolytics, and psychotherapy. However, these treatments have limitations in terms of insufficient effectiveness and safety. Traditional Chinese medicine(TCM) possesses unique advantages in the treatment of FD. Through literature search in China and abroad, it has been found that the mechanisms of TCM in treating FD is associated with various signaling pathways, and research on these signaling pathways and molecular mechanisms has gradually become a focus. The main signaling pathways include the SCF/c-Kit signaling pathway, 5-HT signaling pathway, CRF signaling pathway, AMPK signaling pathway, TRPV1 signaling pathway, NF-κB signaling pathway, and RhoA/ROCK2/MYPT1 signaling pathway. This series of signaling pathways can promote gastrointestinal motility, alleviate anxiety, accelerate gastric emptying, reduce visceral hypersensitivity, and improve duodenal micro-inflammation in the treatment of FD. This article reviewed the research on TCM's regulation of relevant signaling pathways in the treatment of FD, offering references and support for further targeted TCM research in the treatment of FD.

Mechanism of Xiangsha Liujunzi Tang in Regulation of RhoA/ROCK2/MYPT1 Pathway to Improve Gastric Motility in Rats with Functional Dyspepsia / 中国实验方剂学杂志

ObjectiveTo explore the intervention mechanism of Xiangsha Liujunzi Tang in rats with functional dyspepsia （FD） based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 2 （ROCK2）/Myosin phosphatase target Subunit 1 （MYPT1） pathway. MethodSixty male SD suckling rats in SPF grades were randomly divided into blank group （n=10） and model group （n=50）. The comprehensive modeling method （gavage administration of iodoacetamide+exhaustion of swimming+disturbance of hunger and satiety） was used to replicate the rat model of FD. After successful replication of the model， the rats in the model group were randomly divided into model group， mosapride group， and high， middle， and low-dose Xiangsha Liujunzi Tang groups， with 10 rats in each group. Rats in the blank group and model group were given 10 mL kg-1·d-1 normal saline， those in the mosapride group were given 1.35 mg·kg-1·d-1 mosapride， and those in the high， middle， and low-dose Xiangsha Liujunzi Tang groups were given 12， 6， and 3 g·kg-1·d-1 Xiangsha Liujunzi Tang， respectively. The intervention lasted 14 days. The general living conditions of rats were observed before and after modeling and administration， and the 3-hour food intake and body mass of rats were measured. After intervention， the intestinal propulsion rate of rats was measured， and the pathological changes in the gastric tissue were observed by hematoxylin-eosin （HE） staining. The content of choline acetyl transferase （ChAT） and vasoactive intestinal peptide （VIP） in the medulla oblongata and gastric tissue homogenate was determined by enzyme-linked immunosorbent assay （ELISA）， the distribution of adenosine triphosphate （ATP） enzyme in gastric antrum smooth muscle was observed by frozen section staining， and the protein expression levels of RhoA， ROCK2， and phosphorylated-myosin phosphatase target subunit 1 （p-MYPT1） in the gastric tissue were detected by Western blot. ResultCompared with the blank group， the model group had withered hair， lazy movement， slow action， poor general living condition， lower 3-hour food intake， body mass， and lower intestinal propulsion rate （P<0.05）， whereas no obvious abnormality in gastric histopathology. In the model group， the content of ChAT in the medulla oblongata and gastric tissue decreased， the content of VIP in gastric tissue increased， the distribution of ATP enzyme in gastric antrum smooth muscle decreased significantly， and the protein expression levels of RhoA， ROCK2， and p-MYPT1 in the gastric tissue decreased significantly （P<0.05）. As compared with the model group， the general living condition of rats in each intervention group was significantly improved， and the 3-hour food intake， body mass， and intestinal propulsion rate were significantly increased （P<0.05）. There was no significant difference in gastric pathology in the intervention groups. The content of ChAT in the medulla oblongata and gastric tissue increased significantly， the content of VIP in the gastric tissue decreased， the distribution of ATP enzyme in gastric antrum smooth muscle increased significantly， and the protein expression levels of RhoA， ROCK2， and p-MYPT1 in the gastric tissue increased significantly （P<0.05）. The intervention effect of Xiangsha Liujunzi Tang group on the above indexes was dose-dependent. ConclusionXiangsha Liujunzi Tang can effectively improve the general living condition and gastric motility of rats with FD， and its specific mechanism may be related to the activation of the RhoA/ROCK2/MYPT1 pathway in the gastric tissue to regulate smooth muscle relaxation and contraction and promote gastric motility.