The Therapeutic Effect of Biling Weitong Granules Combined with Oryz-Aspergillus Enzyme and Pancreatin Tablet on Reflux Esophagitis with Functional Dyspepsia

Objective:To investigate the therapeutic effect of Biling Weitong Granules combined with oryz-aspergillus enzyme and pancreatin tablets on patients with reflux esophagitis with functional dyspepsia.Methods:Sixty patients diagnosed with reflux esophagitis with functional dyspepsia who were admitted to the Affiliated Hospital of Hebei University between June 2020 and June 2023 were selected and divided into two groups:the control group and the observation group,each consisting of 30 cases.The control group received oryz-aspergillus enzyme and pancreatin tablets only,while the observation group received Biling Weitong Granules in addition to the tablets.The clinical efficacy,Chinese medicine syndrome points,esophageal kinetic indexes,gastrointestinal hormone levels,and therapeutic safety of both groups were evaluated.Results:The total efficiency of the observation group reached 93.33%,significantly higher than the 73.33%of the control group(P<0.05).After treatment,patients in the observation group exhibited significantly lower scores for Chinese medicine symptoms such as early satiety,belching,abdominal distension,abdominal pain,and loss of appetite compared to the control group(P<0.05).Furthermore,the observation group showed significantly higher upper esophageal sphincter pressure,lower esophageal sphincter pressure,and distal esophageal contraction scores compared to the control group(P<0.05).Additionally,levels of gastric motility hormone,vasoactive intestinal peptide,and gastrin were significantly higher in the observation group compared to the control group(P<0.05).Throughout the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,indicating comparable safety of the two treatment modalities(P>0.05).Conclusion:The combination of Biling Weitong Granules with oryz-aspergillus enzyme and pancreatin tablets demonstrates significant efficacy in the treatment of reflux esophagitis with functional dyspepsia,with a better safety profile.This finding warrants further clinical promotion.

Study of the potential mechanism of acupuncture treatment for functional dyspepsia based on association rule mining and bioinformatics/network pharmacology approach

Objective:To explore the main acupoint prescription and mechanism of acupuncture in treating Functional dyspepsia(FD)by analyzing the clinical randomized controlled trial literature on acupoints and targets of acupuncture in the treatment of FD combined with association rule mining and bioinformatics/network pharmacology methods.Methods:Search relevant clinical randomized controlled trial literature on acupoints and therapeutic targets of acupuncture in the treatment of FD from eight databases from their inception to June 18th,2022.We obtained acupuncture selection points,meridian,and therapeutic targets and established acupoints database for acupuncture treatment of FD.FD-related targets were collected from GeneCards,DisGeNET,OMIM,and DrugBank databases.We obtained the potential targets of acupuncture on FD by taking the intersection of acupuncture for FD therapeutic targets and FD-related targets.We performed the protein-protein interaction network,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results:In this study,26 Randomized Controlled Trials related to acupuncture treatment of FD were retrieved.We obtained 29 acupoints,17 acupuncture for FD therapeutic targets,and 10 intersection targets.Tumor necrosis factor(TNF),Interleukin(IL)-1,and Neuropeptide Y(NPY)are key targets of acupuncture in the treatment of FD.Conclusion:ST36-CV12-PC6-LR3 is the main acupoint prescription for FD.Acupuncture may affect Neuroactive ligand-receptor interaction,Gastric acid secretion,and IL-17,TNF signaling pathways by regulating related key targets,and play a synergistic role in the treatment of FD by inhibiting gastric acid secretion,alleviating inflammatory response,regulating the brain-gut axis,improving mood and other aspects.

Traditional Chinese medicine compounds for the treatment of functional dyspepsia:an updated meta-analysis of randomized,double-blind,placebo-controlled trials

Objective To evaluate the efficacy and safety of traditional Chinese medicine(TCM)compounds for the treatment of functional dyspepsia(FD).Methods The Pub Med,Embase,Cochrane Library,Web of Science,Chinese Biomedical Database(CBM),Wanfang Data,China National Knowledge Infrastructure(CNKI),and China Science and Technology Journal Database(VIP)were searched to collect randomized,double-blind,and placebo-controlled trials of FD treated with TCM compounds.The search duration was from the establishment of the database to March 2,2021.After two researchers independently screened the literature,extracted the data,and evaluated the bias risk included in the study,they used Rev Man 5.4 software for meta-analysis.Results A total of 23 clinical trials were included,including 2898 patients.Meta-analysis showed that the overall remission rate of FD treated with TCM compounds was significantly higher than that of placebo(73.8%vs.46.2%)[RR=1.50,95%CI(1.29,1.76),P<0.00001].Among the single symptoms,TCM compounds were superior to the placebo in improving epigastric pain[MD=﹣0.99,95%CI(﹣1.37,﹣0.61),P<0.00001],epigastric burning sensation[MD=﹣0.32,95%CI(﹣0.59,﹣0.05),P=0.02],postprandial fullness discomfort[MD=﹣1.59,95%CI(﹣1.96,﹣1.21),P<0.00001],and early satiety symptoms[MD=﹣0.93,95%CI(﹣1.32,﹣0.54),P<0.00001].Compared with the placebo,TCM compounds treatment can obviously improve TCM syndrome in patients with FD[MD=﹣5.58,95%CI(﹣7.55,﹣3.61),P<0.00001],gastric emptying rate[MD=12.22,95%CI(8.90,15.55),P<0.00001],and helped to improve patients’quality of life[MD=11.27,95%CI(0.10,22.43),P=0.05].No severe adverse events were reported between the two groups[RR=1.34,95%CI(0.91,1.96),P=0.14].Conclusion Our results showed that TCM compounds treatment could significantly alleviate FD symptoms,improve gastric emptying in FD patients,and help to improve their quality of life.No severe adverse reactions have been reported in clinical applications.Due to the limitation of the quantity and quality of the included studies,the above conclusions need to be verified by more high-quality studies.

PRESENT SITUATION OF STUDY AND VIEW ON FUNCTIONAL DYSPEPSIA TREATED WITH SPECIFIC ACUPOINTS IN ACUPUNCTURE

Acupuncture plays a dominant role in treating functional dyspepsia （FD）. By reviewing and e- valuating clinical ROT and fundamental research with high quality in the past 17 years, it is found that specific acupoints are the chief in the treatment of FD; additionally, there are differences between specific acupoints and non-specific acupoints in therapeutic effect, explaining that the specificity of meridian points plays an im- portant role in treatment. However, because of inadequate high-quality researches in clinics, the specificity of acupoints can＇t be proved until the researches of clinical effect and mechanism of therapeutic difference are intensified.

Effect of clinician-patient communication on compliance with flupentixol-melitracen in functional dyspepsia patients

AIM: To explore whether clinician-patient communication affects adherence to psychoactive drugs in functional dyspepsia(FD) patients with psychological symptoms. METHODS: A total of 262 FD patients with psychological symptoms were randomly assigned to four groups. The patients in Groups 1-3 were given flupentixol-melitracen(FM) plus omeprazole treatment. Those in Group 1 received explanations of both the psychological and gastrointestinal(GI) mechanisms of the generation of FD symptoms and the effects of FM. In Group 2, only the psychological mechanisms were emphasized. The patients in Group 3 were not given an explanation for the prescription of FM. Those in Group 4 were given omeprazole alone. The primary endpoints of this study were compliance rate and compliance index to FM in Groups 1-3. Survival analyses were also conducted. The secondary end points were dyspepsia and psychological symptom improvement in Groups 1-4. The correlations between the compliance indices and the reductions in dyspepsia and psychological symptom scores were also evaluated in Groups 1-3.RESULTS: After 8 wk of treatment, the compliance rates were 67.7% in Group 1, 42.4% in Group 2 and 47.7% in Group 3(Group 1 vs Group 2, P = 0.006; Group 1 vs Group 3, P = 0.033). The compliance index(Group 1 vs Group 2, P = 0.002; Group 1 vs Group 3, P = 0.024) with the FM regimen was significantly higher in Group 1 than in Groups 2 and 3. The survival analysis revealed that the patients in Group 1 exhibited a significantlyhigher compliance rate than Groups 2 and 3(Group 1 vs Group 2, P = 0.002; Group 1 vs Group 3, P = 0.018). The improvement in dyspepsia(Group 1 vs Group 2, P < 0.05; Group 1 vs Group 3, P < 0.05; Group 1 vs Group 4, P < 0.01) and psychological symptom scores(anxiety: Group 1 vs Group 2, P < 0.01; Group 1 vs Group 3, P < 0.05; Group 1 vs Group 4, P < 0.01; depression: Group 1 vs Group 2, P < 0.01; Group 1 vs Group 3, P < 0.01; Group 1 vs Group 4, P < 0.01) in Group 1 were greater than those in Groups 2-4. The compliance indices were positively correlated with the reduction in symptom scores in Groups 1-3. CONCLUSION: Appropriate clinician-patient communication regarding the reasons for prescribing psychoactive drugs that emphasizes both the psychological and GI mechanisms might improve adherence to FM in patients with FD.

Symptom-based tendencies of Helicobacter pylori eradication in patients with functional dyspepsia

AIM: To investigate whether there were symptom-based tendencies in the Helicobacter pylori (H. pylori) eradication in functional dyspepsia (FD) patients. METHODS: A randomized, single-blind, placebo-controlled study of H. pylori eradication for FD was conduct- ed. A total of 195 FD patients with H. pylori infection were divided into two groups: 98 patients in the treatment group were treated with rabeprazole 10 mg twice daily for 2 wk, amoxicillin 1.0 g and clarithromycin 0.5 g twice daily for 1 wk; 97 patients in the placebo group were given placebos as control. Symptoms of FD, such as postprandial fullness, early satiety, nausea, belching,epigastric pain and epigastric burning, were assessed 3 mo after H. pylori eradication. RESULTS: By per-protocol analysis in patients with successful H. pylori eradication, higher effective rates of 77.2% and 82% were achieved in the patients with epigastric pain and epigastric burning than those in the placebo group (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belching were 46%, 36%, 52.5% and 33.3%, respectively, and there was no significant difference from the placebo group (39.3%, 27.1%, 39.1% and 31.4%) (P > 0.05). In 84 patients who received H. pylori eradication therapy, the effective rates for epigastric pain (73.8%) and epigastric burning (80.7%) were higher than those in the placebo group (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belch- ing were 41.4%, 33.3%, 50% and 31.4%, respective- ly, and did not differ from those in the placebo group (P > 0.05). By intention-to-treat analysis, patients with epigastric pain and epigastric burning in the treatment group achieved higher effective rates of 60.8% and 65.7% than the placebo group (33.3% and 31.8%) (P < 0.05). The effective rates for postprandial fullness, early satiety, nausea and belching were 34.8%, 27.9%, 41.1% and 26.7% respectively in the treatment group, with no significant difference from those in the placebo group (34.8%, 23.9%, 35.3% and 27.1%) (P > 0.05). CONCLUSION: The efficacy of H. pylori eradication has symptom-based tendencies in FD patients. It may be effective in the subgroup of FD patients with epigastric pain syndrome.

Incidence and psychological-behavioral characteristics of refractory functional dyspepsia:A large, multi-center, prospective investigation from China

AIM:To explore the incidence and psychological and behavioral characteristics of refractory functional dyspepsia(RFD)in China.METHODS:The subjects of this study were 1341 new outpatients with functional dyspepsia(FD)who were diagnosed according to the RomeⅢcriteria at four hospitals in Guangdong Province between June and September 2012,and 100 healthy volunteers.All subjects completed questionnaires and scales administered.RESULTS:Three-hundred and twenty-seven of the 1341patients with FD had RFD(24.4%).Patients with RFD had a longer disease duration and a more severe form of the disease than patients with non-refractory FD(NRFD).The prevalence of depression and anxiety symptoms was higher in patients with RFD than in patients with NRFD.The prevalence of unhealthy eating behaviors,lack of physical activity,and sleeping disorders was higher in patients with RFD than in patients with NRFD.Patients with RFD sought medical advice on more occasions and spent more money on treatment than patients with NRFD.Finally,patients with RFD had poorer quality of life than patients with NRFD.CONCLUSION:RFD is not rare in clinical practice and should get attention by patients and doctors because of its long duration,severe symptoms,and associations with abnormal psychology and poor quality of life.

Beneficial effects of antidepressant mirtazapine in functional dyspepsia patients with weight loss

AIM: To explore the effects and mechanism of action of antidepressant mirtazapine in functional dyspepsia(FD) patients with weight loss.METHODS: Sixty depressive FD patients with weight loss were randomly divided into a mirtazapine group(MG), a paroxetine group(PG) or a conventional therapy group(CG) for an 8-wk clinical trial. Adverse effects and treatment response were recorded. The Nepean Dyspepsia Index-symptom(NDSI) checklist and the 17-item Hamilton Rating Scale of Depression(HAMD-17) were used to evaluate dyspepsia and depressive symptoms, respectively. The body composition analyzer was used to measure body weight and fat. Serum hormone levels were measured by ELISA.RESULTS:(1) After 2 wk of treatment, NDSI scores were significantly lower for the MG than for the PG and CG;(2) After 4 or 8 wk of treatment, HAMD-17 scores were significantly lower for the MG and PG than for the CG;(3) After 8 wk of treatment, patients in the MG experienced a weight gain of 3.58 ± 1.57 kg, which was significantly higher than that observed for patients in the PG and CG. Body fat increased by 2.77 ± 0.14kg, the body fat ratio rose by 4%, and the visceral fat area increased by 7.56 ± 2.25 cm2; and(4) For the MG, serum hormone levels of ghrelin, neuropeptide Y(NPY), motilin(MTL) and gastrin(GAS) were significantly upregulated; in contrast, those of leptin, 5-hydroxytryptamine(5-HT) and cholecystokinin(CCK) were significantly downregulated. CONCLUSION: Mirtazapine not only alleviates symptoms associated with dyspepsia and depression linked to FD in patients with weight loss but also significantly increases body weight(mainly the visceral fat in body fat). The likely mechanism of mirtazapine action is regulation of brain-gut or gastrointestinal hormone levels.

Reassessment of functional dyspepsia:From the editor

Dyspepsia refers to group of upper gastrointestinal symptoms that occur commonly in adults. Dyspepsia is known to result from organic causes, but the majority of patients suffer from non-ulcer or functional dyspepsia. Epidemiological data from population-based studies of various geographical locations have been reviewed, as they provide more realistic information. Population-based studies on true functional dyspepsia （FD） are few, due to the logistic difficulties of excluding structural disease in large numbers of people. Globally, the prevalence of uninvestigated dyspepsia （UD） varies between 7%- 45%, depending on definition used and geographical location, whilst the prevalence of FD has been noted to vary between 11%-29.2%. Risk factors for FD have been shown to include females and underlying psychological disturbances, whilst environmental/lifestyle habits such as poor socio-economic status, smoking, increased caffeine intake and ingestion of non-steroidal anti-inflammatory drugs appear to be more relevant to UD. It is clear that dyspepsia and FD in particular are common conditions globally, affecting most populations, regardless of location.

Helicobacter pylori eradication therapy for functional dyspepsia: Systematic review and meta-analysis

AIM: To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD).METHODS: Randomized controlled trials (RCTs) investigating the efficacy and safety of H. pylori eradication therapy for patients with functional dyspepsia published in English (up to May 2015) were identified by searching PubMed, EMBASE, and The Cochrane Library. Pooled estimates were measured using the fixed or random effect model. Overall effect was expressed as a pooled risk ratio (RR) or a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0.RESULTS: This systematic review included 25 RCTs with a total of 5555 patients with FD. Twenty-three of these studies were used to evaluate the benefits of H. pylori eradication therapy for symptom improvement; the pooled RR was 1.23 (95%CI: 1.12-1.36, P &#x0003c; 0.0001). H. pylori eradication therapy demonstrated symptom improvement during long-term follow-up at &#x02265; 1 year (RR = 1.24; 95%CI: 1.12-1.37, P &#x0003c; 0.0001) but not during short-term follow-up at &#x0003c; 1 year (RR = 1.26; 95%CI: 0.83-1.92, P = 0.27). Seven studies showed no benefit of H. pylori eradication therapy on quality of life with an SMD of -0.01 (95%CI: -0.11 to 0.08, P = 0.80). Six studies demonstrated that H. pylori eradication therapy reduced the development of peptic ulcer disease compared to no eradication therapy (RR = 0.35; 95%CI: 0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy increased the likelihood of treatment-related side effects compared to no eradication therapy (RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies demonstrated that patients who received H. pylori eradication therapy were more likely to obtain histologic resolution of chronic gastritis compared to those who did not receive eradication therapy (RR = 7.13; 95%CI: 3.68-13.81, P &#x0003c; 0.00001).CONCLUSION: The decision to eradicate H. pylori in patients with functional dyspepsia requires individual assessment.

Effect of domperidone therapy on nocturnal dyspeptic symptoms of functional dyspepsia patients

AIM:To investigate the incidence of nocturnal dyspeptic symptoms in patients with functional dyspepsia(FD) and whether prokinetic drugs can alleviate them. METHODS:Eighty-five consecutive Chinese patients with FD were included in this study.One week after single-blinded placebo run-in treatment,baseline nocturnal intragastric pH,bile reflux and nocturnal dyspeptic symptoms of eligible patients,including epigastric pain or discomfort,abdominal distention and belching, were investigated with questionnaires.Patients exhibiting nocturnal dyspeptic symptoms were randomly and double-blindly assigned to domperidone group or placebo group.Nocturnal intragastric pH and percentage of duodenogastric bile reflux time were determined after treatment. RESULTS:Of the 85 FD patients,2 females withoutnocturnal symptoms,who responded to placebo run-in treatment,were excluded from the study,30(36.1%) exhibited nocturnal dyspeptic symptoms with increased duodenogastric bile reflux time(intragastric bilirubin absorbance>0.14)and mean gastric pH(confirming the existence of bile reflux)(P=0.021,0.023) at night were included in the study.Of these 30 patients,21(70%)had overt nocturnal duodenogastric bile reflux,which was significantly higher than that of those without nocturnal symptoms(P=0.026).The 30 patients were allocated to domperidone group or placebo group(n=15).The nocturnal duodenogastric bile reflux and gastric pH were significantly decreased after domperidone treatment(P=0.015,0.021).The severity score of nocturnal dyspeptic symptoms was also significantly decreased after domperidone treatment (P=0.010,0.015,0.026),which was positively correlated with the reduced nocturnal bile reflux or gastric pH(r=0.736,0.784,0.753 or r=0.679,0.715,0.697, P=0.039,0.036,0.037 or P=0.043,0.039,0.040). CONCLUSION:A subgroup of Chinese FD patients show overt nocturnal dyspeptic symptoms,which may be correlated with the excessive nocturnal duodenogastric bile reflux.Domperidone therapy can alleviate these symptoms.

Gene polymorphisms associated with functional dyspepsia

Functional dyspepsia(FD) is a constellation of functional upper abdominal complaints with poorly elucidated pathophysiology. However, there is increasing evidence that susceptibility to FD is influenced by hereditary factors. Genetic association studies in FD have examined genotypes related to gastrointestinal motility or sensation, as well as those related to inflammation or immune response. G-protein b3 subunit gene polymorphisms were first reported as being associated with FD. Thereafter, several gene polymorphisms including serotonin transporter promoter, interlukin-17 F, migration inhibitory factor, cholecystocynine-1 intron 1, cyclooxygenase-1, catechol-o-methyltransferase, transient receptor potential vanilloid 1 receptor, regulated upon activation normal T cell expressed and secreted, p22 PHOX, Toll like receptor 2, SCN10 A, CD14 and adrenoreceptors have been investigated in relation to FD; however, the results are contradictory. Several limitations underscore the value of current studies. Among others, inconsistencies in the definitions of FD and controls, subject composition differences regarding FD subtypes, inadequate samples, geographical and ethnical differences, as well as unadjusted environmental factors. Further well-designed studies are necessary to determine how targeted genes polymorphisms, influence the clinical manifestations and potentially the therapeutic response in FD.

Functional dyspepsia:Are psychosocial factors of relevance?

The pathogenesis of Functional Dyspepsia （FD） remains unclear, appears diverse and is thus inadequately understood. Akin to other functional gastrointestinal disorders, research has demonstrated an association between this common diagnosis and psychosocial factors and psychiatric morbidity. Conceptualising the relevance of these factors within the syndrome of FD requires application of the biopsychosocial model of disease. Using this paradigm, dysregulation of the reciprocal communication between the brain and the gut is central to symptom generation, interpretation and exacerbation. Appreciation and understanding of the neurobiological correlates of various psychological states is also relevant. The view that psychosocial factors exert their influence in FD predominantly through motivation of health care seeking also persists. This appears too one-dimensional an assertion in light of the evidence available supporting a more intdnsic aetiological link. Evolving understanding of pathogenic mechanisms and the heterogeneous nature of the syndrome will facilitate effective management. Co-morbid psychiatric illness warrants treatment with conventional therapies. Acknowledging the relevance of psychosocial variables in FD, the degree of which is subject to vadation, has implications for assessment and management. Available evidence suggests psychological therapies may benefit FD patients particularly those with chronic symptoms. The rationale for use of psychotropic medications in FD is apparent but the evidence base to support the use of antidepressant pharmacotherapy is to date limited.

Sonographic evaluation of proximal gastric accommodation in patients with functional dyspepsia

AIM: To assess the value of ultrasonography (US) in evaluation of proximal gastric accommodation disorder in patients with functional dyspepsia (FD). METHODS: Between April 2011 and March 2012, 45 patients with FD and 27 healthy volunteers were enrolled in this study. Two-dimensional ultrasound (2DUS) and 3-dimensional ultrasound (3DUS) were performed sequentially to measure proximal gastric area (PGA), maximal proximal gastric diameter (MPGD), and proximal gastric volume (PGV). These values were measured separately in the two groups every other 5 min for a duration of 25 min after the beginning of ingestion of a test meal. Air pocket grading was done separately for images of 2DUS and blocks of 3DUS obtained at five scanning time points. RESULTS: Both PGA and PGV of patients were significantly smaller than healthy controls (P = 0.000 and 0.002, respectively). Comparing the two parameters between the groups at each time point, the differences were also statistically significant (P = 0.000-0.013), except at 10 min for the PGV (P = 0.077). However, no overall difference was found between the groups in the MPGD measurements (P = 0.114), though it was statistically significant at a 20-minute examination point (P = 0.026). A total of 360 sets or blocks of images were obtained for both 2DUS and 3DUS. For the images analyzed by 2DUS, none were excluded because of gastric gas, and 50 (13.9%) and 310 (86.1%) sets were determined as air pockets grades 1 and 2, respectively. For the images analyzed by 3DUS, 23 (6.4%) blocks were excluded from the measurement due to presence of a large fundus air pocket (grade 3); fifty (13.9%) and 287 (79.7%) blocks were also graded as 1 and 2, respectively. CONCLUSION: Measurement of both PGA and PGV by 2DUS and 3DUS could be useful for assessment of the proximal gastric accommodation.

Diet and functional dyspepsia: Clinical correlates and therapeutic perspectives

Hypervigilance and symptoms anticipation,visceral hypersensitivity and gastroduodenal sensorimotor abnormalities account for the varied clinical presentation of functional dyspepsia(FD)patients.Many patients recognize meals as the main triggering factor;thus,dietary manipulations often represent the first-line management strategy in this cohort of patients.Nonetheless,scarce quality evidence has been produced regarding the relationship between specific foods and/or macronutrients and the onset of FD symptoms,resulting in nonstandardized nutritional approaches.Most dietary advises are indeed empirical and often lead to exclusion diets,reinforcing in patients the perception of“being intolerant”to food and self-perpetuating some of the very mechanisms underlying dyspepsia physiopathology(i.e.,hypervigilance and symptom anticipation).Clinicians are often uncertain regarding the contribution of specific foods to dyspepsia physiopathology and dedicated professionals(i.e.,dietitians)are only available in tertiary referral settings.This in turn,can result in nutritionally unbalanced diets and could even encourage restrictive eating behaviors in severe dyspepsia.In this review,we aim at evaluating the relationship between dietary habits,macronutrients and specific foods in determining FD symptoms.We will provide an overview of the evidence-based nutritional approach that should be pursued in these patients,providing clinicians with a valuable tool in standardizing nutritional advises and discouraging patients from engaging into indiscriminate food exclusions.

Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia

Functional gastrointestinal disorders(FGID) are common clinical syndromes diagnosed in the absence of biochemical,structural,or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age,geography,and culture. Etiology of abdominal pain associated FGIDs,including functional dyspepsia(FD),remains incompletely understood,but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD,with focus on pediatric data when available,and provides a summary of potential therapeutic targets.

Novel mechanisms in functional dyspepsia

Functional dyspepsia （FD） is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mechanisms, the underlying casual pathways associated with FD remain obscure. The currently proposed pathophysiologic mechanisms associated with FD include genetic susceptibility, delayed as well as accelerated gastric emptying, visceral hypersensitivity to acid or mechanical distention, impaired gastric accommodation, abnormal fundic phasic contractions, abnormal antroduodenal motility, acute and chronic infections, and psychosocial comorbidity. A greater understanding of the abnormalities underlying FD may lead to improved management. The aim of this editorial is to provide a critical overview of current pathophysiologic concepts in functional dyspepsia.

Cholecystokinin hyperresponsiveness in functional dyspepsia

Functional dyspepsia （FD） is a common disorder of yet uncertain etiology. Dyspeptic symptoms are usually meal related and suggest an association to gastrointestinal （GI） sensorimotor dysfunction. Cholecystokinin （CCK） is an established brain-gut peptide that plays an important regulatory role in gastrointestinal function. It inhibits gastric motility and emptying via a capsaicin sensitive vagal pathway. The effects on emptying are via its action on the proximal stomach and pylorus. CCK is also involved in the regulation of food intake. It is released in the gut in response to a meal and acts via vagal afferents to induce satiety. Furthermore CCK has also been shown to be involved in the pathogenesis of panic disorder, anxiety and pain. Other neurotransmitters such as serotonin and noradrenaline may be implicated with CCK in the coordination of GI activity. In addition, intravenous administration of CCK has been observed to reproduce the symptoms in FD and this effect can be blocked both by atropine and Ioxiglumide （CCK-A antagonist）. It is possible that an altered response to CCK may be responsible for the commonly observed gastric sensorimotor dysfunction, which may then be associated with the genesis of dyspeptic symptoms.

Efficacy and safety of Xiangsha Liujunzi granules for functional dyspepsia: A multi-center randomized double-blind placebo-controlled clinical study

AIM To assess the efficacy and safety of a Chinese herbal medicine (CHM), Xiangsha Liujunzi granules, in the treatment of patients with functional dyspepsia (FD). METHODS We performed a randomized, double-blind, placebo-controlled trial with patients from three centers. Two hundred and sixteen subjects diagnosed with FD according to ROME. criteria and confirmed by upper gastrointestinal endoscopy and spleen-deficiency and Qi-stagnation syndrome were selected to receive Xiangsha Liujunzi granules or placebo for 4 wk in a 2: 1 ratio by blocked randomization. The subjects also received follow-up after the 4-wk intervention. Herbal or placebo granules were dissolved in 300 mL of water. Participants in both groups were administered 130 mL (45 degrees C) three times a day. Participants were evaluated prior to and following 4 wk of the intervention in terms of changes in the postprandial discomfort severity scale (PDSS) score, clinical global impression (CGI) scale score, hospital anxiety and depression scale (HADS) score, traditional Chinese medicine symptoms score (SS), scores of various domains of the 36-item short form health survey (SF-36), gastric emptying (GE) and any observed adverse effects. RESULTS Compared with the placebo group, patients in the CHM group showed significant improvements in the scores of PDSS, HADS, SS, SF-36 and CGI scale (P < 0.05 or P < 0.01). They also showed the amelioration in the GE rates of the proximal stomach and distal stomach (P < 0.05 or P < 0.01). CONCLUSION Xiangsha Liujunzi granules offered significant symptomatic improvement in patients with FD.

Cerebral mechanism of puncturing at He-Mu point combination for functional dyspepsia: study protocol for a randomized controlled parallel trial

Acupuncture is widely used to treat functional dyspepsia with satisfactory outcomes. Combination of the He and Mu acupoints is commonly used and has a synergistic effect on functional dyspepsia; however, its underlying mechanisms remain unclear. Therefore, a randomized controlled parallel clinical trial is currently underway at Chengdu University of Traditional Chinese Medicine, China. This trial is designed to explore the efficacy of and central responses to the He-Mu point combination in patients with functional dyspepsia using functional magnetic resonance imaging. A total of 105 patients with functional dyspepsia will be allocated into 3 groups： the low-He point group（puncturing at Zusanli（ST36））, Mu point group（puncturing at Zhongwan（CV12））, and He-Mu point combination group（puncturing at ST36 and CV12）. Every participant will receive 20 sessions of manual acupuncture for 4 weeks. The needles will be inserted perpendicularly to a depth of 1 to 2 cun. The angle of rotation and twisting will range from 90 to 180 degrees, while lifting and thrusting will range from 0.3 to 0.5 cm. The various manipulations will be performed 60 to 90 times per minute. The needles will remain in place for 30 minutes, during which manipulation will be applied every 10 minutes. Magnetic resonance imaging will be performed before and after 20 sessions of acupuncture. The primary outcome is symptom improvement according to the Chinese version of the Nepean Dyspepsia Index. Secondary outcomes include the Leeds dyspepsia questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Beck Anxiety Inventory, Beck Depression Inventory, and visual analogue scale scores before and after 10 and 20 sessions of acupuncture. Needle sensation and adverse events will be used to assess the therapeutic effects. This study will promote more widespread awareness of the benefits of acupoint combination in the clinical setting and provide a further explanation of the neuromechanism by which acupuncture at the He-Mu point combination for functional dyspepsia. Registration： Chinese Clinical Trial Registry, Chi CTR-IOR-15006402.