Yiqi Kaimi prescription regulates protein phosphorylation to promote intestinal motility in slow transit constipation.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical efficacy of the Yiqi Kaimi prescription has been confirmed in slow transit constipation. However, the effects and biological mechanism of Yiqi Kaimi prescription are still unclear. AIMS OF THE STUDY: To identify the effects of Yiqi Kaimi prescription on intestinal motility; To reveal the potential key targets and pathways of Yiqi Kaimi prescription for the treatment of slow transit constipation. MATERIALS AND METHODS: The effects of Yiqi Kaimi prescription on slow transit constipation were investigated in a mouse model. The terminal ink propulsion experiment and fecal indocyanine green imaging was used to measure the intestinal transit time. Protein phosphorylation changes in colon tissues treated with Yiqi Kaimi prescription were detected using a Phospho Explorer antibody microarray. Bioinformatic analyses were performed using the Database for Annotation Visualization and Integrated Discovery (DAVID) and the Search Tool for the Retrieval of Interacting Genes (STRING). Western blot analysis and immunohistochemistry confirmed the observed changes in phosphorylation. RESULT: s: Yiqi Kaimi prescription significantly increased the intestinal transit rate (P < 0.05 vs. model) and reduced the time to first discharge of feces containing fecal indocyanine green imaging in mice (P < 0.05 vs. model). The administration of Yiqi Kaimi prescription induced phosphorylation changes in 41 proteins, with 9 upregulated proteins and 32 downregulated proteins. Functional classification of the phosphorylated proteins with DAVID revealed that the critical biological processes included tyrosine protein kinases, positive regulation of calcium-mediated signaling and response to muscle stretch. The phosphorylation of the spleen tyrosine kinase (SYK) at Tyr348 increased 2.19-fold, which was the most significant change. The phosphorylation level of the transcription factor p65 (RELA) at Thr505 was decreased 0.57-fold. SYK was a hub protein in the protein-protein interaction network and SYK and RELA formed the core of the secondary subnetwork. The key protein phosphorylation after treatment with Yiqi Kaimi prescription were verified by Western blot analysis and immunohistochemistry. CONCLUSION: Yiqi Kaimi prescription significantly enhanced intestinal motility. This effect was attributed to alterations in the phosphorylation levels of various target proteins. The observed changes in protein phosphorylation, including SYK and RELA, may serve as crucial factors in the treatment of slow transit constipation.

Psyllium husk powder increases defecation frequency and faecal score, bulk and moisture in healthy cats.

OBJECTIVES: Constipation is the infrequent or difficult emission of hard, dry faeces and is a common digestive condition in cats. Psyllium is a low-fermentable fibre, with soluble and insoluble components and water-holding properties. It forms a mucilaginous gel with water and is used for the symptomatic treatment of constipation in various species. This study evaluated the effect of dietary psyllium on faecal characteristics in cats. METHODS: Healthy neutered adult cats (six female and three male, aged 3.3-4.4 years) were consecutively fed a dry extruded diet containing either 6% psyllium (test) or 6% cellulose (control) for 10 days each. During the last 3 days (the collection days) of both feeding periods, bowel movements and faecal scores were recorded, and faeces were collected to measure wet weight and moisture. The statistical analysis used linear mixed models with diet, day and their interaction as fixed effects and animal as a random term. RESULTS: The test diet was associated with significantly more bowel movements per day over 3 days (P = 0.0052) and on collection day 2 (P = 0.0229) than the control diet. The mean faecal score was higher (softer faeces) over all three collection days (P <0.0001) and on collection days 1, 2 and 3 (P = 0.0011, P = 0.0349, P = 0.0003, respectively) for the test diet vs the control diet; the total faecal wet weight (P = 0.0003) and faecal moisture (%) were also higher (P = 0.0426) for the test diet. Faeces associated with the test diet often had a dry shell and soft interior, which increased the faecal score. CONCLUSIONS AND RELEVANCE: Psyllium promoted more bowel movements and higher faecal moisture and faecal score in healthy cats, consistent with a previous uncontrolled clinical trial in constipated cats. Together, the studies support the use of dietary psyllium for managing cats with constipation.

Clinical profile of functional constipation in Saudi children.

BACKGROUND: Functional constipation (FC) is a common condition in children, and information on the clinical characteristics of FC in Saudi children is scarce. OBJECTIVE: Describe the clinical profile of FC in Saudi children. DESIGN: Retrospective. SETTING: Hospital that provides primary, intermediate and tertiary care. PATIENTS AND METHODS: All children diagnosed with FC according to the Rome IV criteria were included and had at least one follow-up clinic visit. Demographic and clinical data collected from medical records included the age at onset, duration of constipation, clinical features, treatment modalities, and factors associated with clinical response. Descriptive statistics and Pearson's chi-squared test were used in the statistical analysis to see how categorical study variables were linked to clinical response. A P value of ≤.05 was used to report statistical significance. MAIN OUTCOME MEASURE: Compliance and clinical response to polyethylene glycol (PEG) compared with lactulose. SAMPLE SIZE: 370 children from 0.1 to 13 years of age. RESULTS: The median (IQR) age of onset was 4 (5) years and less than one year in 14%. The median (IQR) duration of constipation was 4 months (11) and less than two months in 93/370 (25%). Abdominal pain was the most commonly associated feature (44%). Screening for celiac disease and hypothyroidism was negative. A Fleet enema was the most common disimpaction method (54%) and PEG was the most common maintenance medication (63.4%). PEG was significantly better tolerated (P=.0008) and more effective than lactulose (P<.0001). Compliance was the only variable significantly associated with clinical response. CONCLUSIONS: PEG was better tolerated and more effective than lactulose in our study, a finding in agreement with the literature. Therefore, PEG should be the drug of choice in the initial management of FC in Saudi children. Prospective studies on the causes of noncompliance are needed to improve the response to treatment. LIMITATIONS: The limitations of retrospective design are missing data, recall bias, and hospital-based limitation, such as missing milder cases treated at the outpatient level. However, the sample size of 370 may have minimized these limitations.

The chemometrics analysis and integrated pharmacology approach to decipher the effect and mechanism between raw and processed cistanche tubulosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa (CT) is the dried fleshy stem with scaly leaves of Cistanche tubiflora (Schenk) Wight, which has the effects of tonifying the kidney-yang, benefiting the vital essence and blood, and moisturizing the intestines and laxatives. There are differences in the activity of CT before and after processing, but the mechanism of processing is not clear. AIM OF THE STUDY: The study aimed to compare the strength of action of CT before and after yellow-wine processing in the treatment of constipation and kidney yang deficiency and to identify the active ingredients responsible for the differences in activity before and after yellow-wine processing. MATERIALS AND METHODS: This study established the fingerprints of CT and PCT using HPLC to identify their shared components. Then efficacy of KYDS and FC were carried out to compare the differences between CT and PCT in terms of efficacy. Next, this study established the spectrum-effect relationship between the shared chemical components and the medical effects of CT and PCT using the gray correlation analysis and entropy methods. Ultimately, the activity of the analyzed chemical components was verified using the zebrafish model. RESULTS: CT was more effective than PCT in promoting intestinal peristalsis, regulating gastrointestinal hormone levels, and thus treating FC. PCT was more effective than CT in improving the level of hormone indexes of the hypothalamus-pituitary-target gland axis, replenishing blood, and enhancing immunity. Through the analysis of the spectrum-effect relationship, it was finally found that 5, 6, 12 (tubuloside A), and 13 (isoacteoside) might be more closely related to the activity of tonifying kidney yang, and peaks 9, 10, and 11 (acteoside) are more closely associated with the treatment of constipation, and peaks 3 (salidroside), 4, 1, 2 (geniposidic acid), and 8 (echinacoside) were associated with both kidney yang tonic and treatment of constipation. At the same time, an activity verification experiment showed that echinacoside, geniposidic acid, and salidroside were effective in the treatment of FC and KYDS, while acteoside was very effective in the treatment of FC, and tubuloside A was significant in supplementing the blood, which validated the spectrum-effect relationship analysis. CONCLUSION: This study proved that the raw CT had a better laxative effect, while the yellow-wine processed CT had a better kidney-yang tonic effect; moreover, spectrum-effect relationships were established to analyze the chemical components leading to changes in the activity of CT before and after yellow-wine processing.

Symptom burden and relief in palliative care units of German Comprehensive Cancer Center and other hospitals.

PURPOSE: The National Hospice and Palliative Registry contains patient data from German hospice and palliative care facilities about symptoms. The aim of the study at hand is to differentiate symptom burden of patients in palliative care units between Comprehensive Cancer Center (CCC) and other hospitals regarding symptom burden and relief of patients in palliative care units. METHODS: The registry analysis provided data of patients in palliative care units (2014-2018). We analyzed characteristic and symptom-related data on 18 symptoms, with considerable symptom-burdened patients (moderate or severe). We followed a cancer (yes/no) and facility-specific descriptive analysis (f, %, µ, Mdn, SD, V, r) using SPSS. RESULTS: We evaluated 10,447 patient records (CCC: 4234 pts/non CCC 6,213 pts), 82% with a cancer diagnosis. For cancer patients, the mean age in CCC-affiliated palliative care units was 68 (SD 19-99) years, in others 73 (SD 23-104) years (p < 0.05; V = 0.2). The proportion of patients with significant symptom burden is lower in CCC-affiliated than in other palliative care units. The difference between facilities shows a significant weak effect in pain, vomiting and constipation, depressiveness, anxiety, and tension. The proportion of cases which symptom burden could be alleviated is higher in CCC-affiliated palliative care units with significant weak/medium effect in pain, nausea, vomiting, shortness of breath, constipation, wound care problems, depressiveness, anxiety, tension, confusion, and problems in organizing care. CONCLUSION: We found differences in symptom burden and symptom relief between CCC-affiliated and other palliative care units. CCCs should continue to feel responsible for sharing knowledge about symptom relief, such as through standard operating procedures and education.

Daily versus three times weekly dosing for treatment of iron deficiency nonanemia in NCAA Division 1 female athletes.

OBJECTIVE: To compare the effectiveness, compliance, and side effect profile between daily or three times weekly (TIW) oral iron supplementation regimens in treating iron deficiency nonanemia (IDNA) in National Collegiate Athletic Association (NCAA) Division 1 female track and field or soccer athletes. DESIGN: Prospective cohort study. SETTING: Division 1 collegiate athletics. PARTICIPANTS: Thirty-three NCAA Division 1 female athletes (18 track and field, 15 soccer). INTERVENTIONS: Daily or TIW dosing of ferrous bisglycinate. MAIN OUTCOME MEASURES: Serum ferritin (µg/L) was measured before and after 8 weeks of supplementation. Self-reported compliance and side effect profile was assessed by electronic survey every 2 weeks. RESULTS: The average main effect for the TIW regimen was a significant increase of 5.17 µg/L (95% CI: 0.86-9.47) in serum ferritin (p = .02). The average main effect for the daily regimen was a significant increase of 12.88 µg/L (95% CI: 4.84-20.93) in serum ferritin (p = .003). The estimated average effect of the treatment on the treated between regimens was a nonsignificant decrease of -7.17 µg/L (95% CI: -19.02 - 3.59) in serum ferritin (p = .17). Thus, the TIW regimen increased serum ferritin 7.17 units less than the daily regimen on average after 8 weeks of supplementation. The athletes following the daily regimen experienced significantly more nausea (p = .04) and constipation (p = .002) compared to the TIW regimen. There was no statistical difference in compliance between the two groups (p = .14). CONCLUSIONS: Both the daily and TIW regimens increased serum ferritin. Compared to the daily regimen, the TIW regimen produced a smaller increase in serum ferritin but less nausea and constipation.

Surgery for chronic idiopathic constipation: pediatric and adult patients - a systematic review.

BACKGROUND: Chronic idiopathic constipation (CIC) is a substantial problem in pediatric and adult patients with similar symptoms and workup; however, surgical management of these populations differs. We systematically reviewed the trends and outcomes in the surgical management of CIC in pediatric and adult populations. METHODS: A literature search was performed using Ovid MEDLINE, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov between January 1, 1995 and June 26, 2020. Clinical trials and retrospective and prospective studies of patients of any age with a diagnosis of CIC with data of at least 1 outcome of interest were selected. The interventions included surgical resection for constipation or antegrade continence enema (ACE) procedures. The outcome measures included bowel movement frequency, abdominal pain, laxative use, satisfaction, complications, and reinterventions. RESULTS: Adult patients were most likely to undergo resection (94%), whereas pediatric patients were more likely to undergo ACE procedures (96%) as their primary surgery. Both ACE procedures and resections were noted to improve symptoms of CIC; however, ACE procedures were associated with higher complication and reintervention rates. CONCLUSION: Surgical management of CIC in pediatric and adult patients differs with pediatric patients receiving ACE procedures and adults undergoing resections. The evaluation of resections and long-term ACE data in pediatric patients should be performed to inform patients and physicians whether an ACE is an appropriate procedure despite high complication and reintervention rates or whether resections should be considered as an initial approach for CIC.

Idiopathic mesenteric phlebosclerosis occurring in a patient with liver cirrhosis: A case report.

BACKGROUND: Idiopathic mesenteric phlebosclerosis (IMP) is a rare gastrointestinal disease with unclear etiology and pathogenesis. IMP occurring in a patient with liver cirrhosis is more scarcely reported than independent IMP. In this study, we reported a case of IMP occurring in a patient with liver cirrhosis, so as to provide a reference for understanding liver cirrhosis with IMP. METHOD: A 63-year-old man with liver cirrhosis was admitted in the hospital's department of infectious disease because of fatigue and constipation for 1 month. The patient had an irregular medical history of antivirus drug and Chinese herbal medicine intake because of the hepatitis B virus infection. No other abnormalities were found in the functions of the liver, coagulation, renal, or complete blood count. Fecal occult blood tests were all positive in 5 detections. Contrast-enhanced computed tomography revealed liver cirrhosis and showed thickening of the wall of the right hemicolon and multiple calcifications of the mesenteric veins. Mesenteric vein computed tomography venography displayed diffuse colon mural thickening of the right colon and tortuous linear calcification line in the right colic veins. Colonoscopy revealed a purple-blue, swollen, rough, and vanished vascular texture mucosa. He was finically diagnosed as liver cirrhosis with IMP by a series of examinations during hospitalization. RESULTS: His symptoms of fatigue and constipation subsided after conservative treatment and withdraw from Chinese herbal medicine. The patient experienced no obvious discomfort during the follow-up period. CONCLUSION: A comprehensive medical diagnosis is necessary for the discovery of IMP, especially IMP with liver cirrhosis. Liver cirrhosis maybe play a key role in the development of IMP. The regulatory mechanism of liver cirrhosis contributing to IMP needs to be further studied based on more clinical cases.

Sacral neuromodulation for constipation and fecal incontinence in children and adolescents - study protocol of a prospective, randomized trial on the application of invasive vs. non-invasive technique.

BACKGROUND: A therapeutic effect of sacral neuromodulation (SNM) on fecal incontinence (FI) and quality of life has been proven in adults. SNM is, however, rarely used in pediatric cases. The aim of the study is to investigate effects of SNM in pediatric constipation in a prospective parallel-group trial. METHODS: A monocentric, randomized, unblinded, parallel-group trial is conducted. SNM is conducted in the invasive variant and in an innovative, external approach with adhesive electrodes (enteral neuromodulation, ENM). We include patients with constipation according to the ROME IV criteria and refractory to conventional options. Patients with functional constipation and Hirschsprung's disease are able to participate. Participants are allocated in a 1:1 ratio to either SNM or ENM group. Clinical data and quality of life is evaluated in regular check-ups. Neuromodulation is applied continuously for 3 months (end point of the study) with follow-up-points at 6 and 12 months. Findings are analyzed statistically considering a 5% significance level (p ≤ 0.05). Outcome variables are defined as change in (1) episodes of abdominal pain, (2) episodes of FI, (3) defecation frequency, (4) stool consistency. Improvement of proprioception, influence on urinary incontinence, quality of life and safety of treatment are assessed as secondary outcome variables. We expect a relevant improvement in both study groups. DISCUSSION: This is the first trial, evaluating effects of neuromodulation for constipation in children and adolescents and comparing effects of the invasive and non-invasive application (SNM vs. ENM). TRIAL REGISTRATION: The study is registered with clinicaltrials.gov, Identifier NCT04713085 (date of registration 01/14/2021).

Effectiveness of Acupressure on Post-Cesarean Bowel Function: A Randomized Controlled Trial.

Background: In cesarean delivery, factors such as general anesthesia affect bowel function, leading postpartum women to experience abdominal tenderness, gas, and constipation. Objective: This study aims to assess the impact of acupressure on bowel function after cesarean delivery. Design: A randomized-controlled experimental study was conducted. Participants: The study population comprised postpartum women who underwent cesarean delivery at Ondokuz Mayis University Health Practice and Research Hospital between July 2021 and January 2022. The sample consisted of 61 postpartum women (acupressure group: 31, control group: 30). Intervention: Participants were divided into two groups: the acupressure group and the control group. Women in the acupressure group received 14 minutes of acupressure application to the LI4 and TH6 points twice, once within the first postoperative hour and again three hours later. The control group received no acupressure intervention. Outcome Measures: Data were collected using a Postpartum Information Form and a Post-cesarean Follow-up Form. Statistical analyses included the Mann-Whitney U test, Student's t test, and chi-squared analysis. Results: The mean age of postpartum women in the acupressure group was 27.61±4.39, while in the control group, it was 28.50±3.85. The mean times for bowel sounds, flatulence, and bowel movements in the acupressure group (9.98±2.77, 19.43±10.25, and 27.13±10.77 hours, respectively) were significantly shorter than those in the control group (14.41±5.07, 23.33±4.20, and 46.16±17.95 hours, respectively) (P < .05). Conclusions: Acupressure was found to be effective in improving bowel function after cesarean delivery, significantly reducing the time taken for participants to experience bowel sounds, flatulence, and bowel movements.

Placebo response to sham electroacupuncture in patients with chronic functional constipation: A secondary analysis.

BACKGROUND: Chronic severe functional constipation is a common disease that requires novel and effective treatment strategies. Acupuncture might constitute a promising therapeutic approach for chronic constipation, but it reportedly engenders an enhanced placebo response. Herein, we aimed to determine the magnitude of the placebo responses to electroacupuncture for constipation and identify its influencing factors. METHODS: In this secondary analysis of a multicenter randomized trial, patients were randomized to a sham electroacupuncture group, which was administered for 8 weeks in 24 sessions of superficial needling at nonacupoints. The placebo response rates were assessed using three responder criteria: ≥3 complete spontaneous bowel movements per week (CSBMs/week), overall CSBM, and sustained CSBM. Logistic regression with backward selection method was employed to identify the potential factors that affected the placebo response. KEY RESULTS: Overall, 539 patients were included in the study. The placebo response rate was 10.58%, 9.46%, and 9.09% according to the three aforementioned criteria, respectively. Those who exhibited more CSBMs/week at baseline were more likely to respond to sham electroacupuncture. Among patients with more than one CSBM per week at baseline, the response rates for achieving the criteria of ≥3 CSBMs per week, overall CSBM, and sustained CSBM were 25.40%, 30.16%, and 22.22%. CONCLUSIONS AND INFERENCE: Electroacupuncture did not demonstrate a large placebo response in functional constipation treatment. The number of CSBMs at baseline may be a moderator of the placebo response to sham electroacupuncture. Thus, superficial needling sham acupuncture may be considered an ideal sham control for clinical trials of chronic constipation.

Strategies used for childhood chronic functional constipation: the SUCCESS evidence synthesis.

Background: Up to 30% of children have constipation at some stage in their life. Although often short-lived, in one-third of children it progresses to chronic functional constipation, potentially with overflow incontinence. Optimal management strategies remain unclear. Objective: To determine the most effective interventions, and combinations and sequences of interventions, for childhood chronic functional constipation, and understand how they can best be implemented. Methods: Key stakeholders, comprising two parents of children with chronic functional constipation, two adults who experienced childhood chronic functional constipation and four health professional/continence experts, contributed throughout the research. We conducted pragmatic mixed-method reviews. For all reviews, included studies focused on any interventions/strategies, delivered in any setting, to improve any outcomes in children (0-18 years) with a clinical diagnosis of chronic functional constipation (excluding studies of diagnosis/assessment) included. Dual reviewers applied inclusion criteria and assessed risk of bias. One reviewer extracted data, checked by a second reviewer. Scoping review: We systematically searched electronic databases (including Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature) (January 2011 to March 2020) and grey literature, including studies (any design) reporting any intervention/strategy. Data were coded, tabulated and mapped. Research quality was not evaluated. Systematic reviews of the evidence of effectiveness: For each different intervention, we included existing systematic reviews judged to be low risk of bias (using the Risk of Bias Assessment Tool for Systematic Reviews), updating any meta-analyses with new randomised controlled trials. Where there was no existing low risk of bias systematic reviews, we included randomised controlled trials and other primary studies. The risk of bias was judged using design-specific tools. Evidence was synthesised narratively, and a process of considered judgement was used to judge certainty in the evidence as high, moderate, low, very low or insufficient evidence. Economic synthesis: Included studies (any design, English-language) detailed intervention-related costs. Studies were categorised as cost-consequence, cost-effectiveness, cost-utility or cost-benefit, and reporting quality evaluated using the consensus health economic criteria checklist. Systematic review of implementation factors: Included studies reported data relating to implementation barriers or facilitators. Using a best-fit framework synthesis approach, factors were synthesised around the consolidated framework for implementation research domains. Results: Stakeholders prioritised outcomes, developed a model which informed evidence synthesis and identified evidence gaps. Scoping review: 651 studies, including 190 randomised controlled trials and 236 primary studies, conservatively reported 48 interventions/intervention combinations. Effectiveness systematic reviews: studies explored service delivery models (n = 15); interventions delivered by families/carers (n = 32), wider children's workforce (n = 21), continence teams (n = 31) and specialist consultant-led teams (n = 42); complementary therapies (n = 15); and psychosocial interventions (n = 4). One intervention (probiotics) had moderate-quality evidence; all others had low to very-low-quality evidence. Thirty-one studies reported evidence relating to cost or resource use; data were insufficient to support generalisable conclusions. One hundred and six studies described implementation barriers and facilitators. Conclusions: Management of childhood chronic functional constipation is complex. The available evidence remains limited, with small, poorly conducted and reported studies. Many evidence gaps were identified. Treatment recommendations within current clinical guidelines remain largely unchanged, but there is a need for research to move away from considering effectiveness of single interventions. Clinical care and future studies must consider the individual characteristics of children. Study registration: This study is registered as PROSPERO CRD42019159008. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 128470) and is published in full in Health Technology Assessment; Vol. 28, No. 5. See the NIHR Funding and Awards website for further award information.

Between 5% and 30% of children experience constipation at some stage. In one-third of these children, this progresses to chronic functional constipation. Chronic functional constipation affects more children with additional needs. We aimed to find and bring together published information about treatments for chronic functional constipation, to help establish best treatments and treatment combinations. We did not cover assessment or diagnosis of chronic functional constipation. This project was guided by a 'stakeholder group', including parents of children with constipation, people who experienced constipation as children, and healthcare professionals/continence experts. We carried out a 'scoping review' and a series of 'systematic reviews'. Our 'scoping review' provides an overall picture of research about treatments, with 651 studies describing 48 treatments. This helps identify important evidence gaps. 'Systematic reviews' are robust methods of bringing together and interpreting research evidence. Our stakeholder group decided to structure our systematic reviews to reflect who delivered the interventions. We brought together evidence about how well treatments worked when delivered by families/carers (32 studies), the wider children's workforce (e.g. general practitioner, health visitor) (21 studies), continence teams (31 studies) or specialist consultant-led teams (42 studies). We also considered complementary therapies (15 studies) and behavioural strategies (4 studies). Care is affected by what is done and how it is done. We brought together evidence about different models of delivering care (15 studies), barriers and facilitators to implementation of treatments (106 studies) and costs (31 studies). Quality of evidence was mainly low to very low. Despite numerous studies, there was often insufficient information to support generalisable conclusions. Our findings generally agreed with current clinical guidelines. Management of childhood chronic functional constipation should be child-centred, multifaceted and adapted according to the individual child, their needs, the situation in which they live and the health-care setting in which they are looked after. Research is needed to address our identified evidence gaps.

Ameliorating effects of transcutaneous auricular vagus nerve stimulation on a mouse model of constipation-predominant irritable bowel syndrome.

Limited treatment options have been shown to alter the natural course of constipation-predominant irritable bowel syndrome (IBS-C). Therefore, safer and more effective approaches are urgently needed. We investigated the effects of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of IBS-C. In the current study, C57BL/6 mice were randomly divided into normal control, IBS-C model control, sham-electrostimulation (sham-ES), taVNS, and drug treatment groups. The effects of taVNS on fecal pellet number, fecal water content, and gastrointestinal transit were evaluated in IBS-C model mice. We assessed the effect of taVNS on visceral hypersensitivity using the colorectal distention test. 16S rRNA sequencing was used to analyze the fecal microbiota of the experimental groups. First, we found that taVNS increased fecal pellet number, fecal water content, and gastrointestinal transit in IBS-C model mice compared with the sham-ES group. Second, taVNS significantly decreased the abdominal withdrawal reflex (AWR) score compared with the sham-ES group, thus relieving visceral hyperalgesia. Third, the gut microbiota outcomes showed that taVNS restored Lactobacillus abundance while increasing Bifidobacterium probiotic abundance at the genus level. Notably, taVNS increased the number of c-kit-positive interstitial cells of Cajal (ICC) in the myenteric plexus region in IBS-C mice compared with the sham-ES group. Therefore, our study indicated that taVNS effectively ameliorated IBS-C in the gut microbiota and ICC.

Nobiletin, an active component of Wenyang Yiqi formula, alleviates constipation associated depression through targeting MAPT to inhibit the MAPK signaling pathway.

BACKGROUND: Slow transit constipation (STC) is a common gastrointestinal disorder that is often accompanied by depression. Nobiletin is a natural compound that has been shown to have anti-inflammatory and anti-depressant effects. PURPOSE: To study the effects of nobiletin extracted from Wenyang Yiqi Formula 19 (WYF) on STC accompanied by depression and the related mechanism in STC mouse models. METHODS: In this study, the effects of nobiletin on STC accompanied by depression were investigated in both an STC animal model and an in vitro study. The animal model was induced by loperamide, and the in vitro study used Interstitial cells of Cajal (ICCs) isolated from STC mice. The efficacy of nobiletin was assessed by comparing various parameters, including stool particle counts, moisture content, intestinal propulsive rate, colon histopathology, microtubule-associated protein-tau (MAPT) expression in colon tissue, serum levels of TNF-α, IL-1ß, IL-6, IFN-γ, and the levels of MAPK pathway-related proteins among three experimental groups. RESULTS: Nobiletin treatment significantly improved stool particle counts, moisture content, intestinal propulsive rate, and colon histopathology in the STC animal model. Nobiletin also decreased MAPT expression in colon tissue and serum levels of TNF-α, IL-1ß, IL-6, IFN-γ, and the levels of MAPK pathway-related proteins. In the in vitro study, nobiletin treatment reversed the increased cell proliferation and cell apoptosis observed in ICC isolated from the STC model. CONCLUSION: The findings of this study indicate that nobiletin exhibits promising therapeutic potential in addressing STC accompanied by depression. This potential may be attributed to its ability to regulate the function of ICC by targeting MAPT.

Efficacy and safety of auricular therapy in the treatment of post-stroke constipation: A protocol for systematic review and meta-analysis.

BACKGROUND: Constipation is one of the common gastrointestinal complications after stroke. It not only aggravates the condition of stroke, but also brings huge medical burden to patients, and has a negative impact on the quality of life of patients. Auricular therapy, as a part of Chinese traditional acupuncture and moxibustion, has been found to be effective in the clinical treatment of constipation. However, no systematic review has investigated the efficacy and safety of auricular therapy in the treatment of post-stroke constipation. Therefore, the aim of this systematic review is to assess the effectiveness and safety of auricular therapy for post-stroke constipation. METHODS AND ANALYSIS: Eight electronic databases including PubMed, Cochrane Library/Cochrane Central Register of Controlled Trials, Web of Science, Embase, China National Knowledge Internet, Chinese Biomedical Literature Database, Wanfang, and VIP databases, will be searched for relevant studies published from inception to February 2023. Two reviewers will independently conduct research selection, data extraction, and evaluation of research quality. Only randomized controlled trials (RCTs) that assess the efficacy and safety of auricular therapy for the treatment of post-stroke constipation will be included in this study. We will use the Cochrane risk of bias assessment tool to evaluate the methodological qualities (including bias risk). If possible, a meta-analysis will be performed after screening. RESULTS: This study may provide high-quality evidence for the efficacy and safety of auricular therapy in treating post-stroke constipation. CONCLUSION: The conclusions of our study will provide an evidence to judge whether auricular therapy is an effective and safe intervention for patients with post-stroke constipation. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study was based on a review of published research. This review will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION: Registration number: PROSPERO CRD42023402242.

The synergistic effect of herbal medicine and probiotics in pediatric functional constipation: A systematic review and meta-analysis.

BACKGROUND: Pediatric functional constipation (PFC) is a prevalent and persistent gastrointestinal disorder, that requires various treatments, including alternative approaches. This review assessed the synergistic efficacy of herbal medicine (HM) and probiotics for PFC. METHODS: We conducted a comprehensive search of 11 databases, including English, Chinese, and Korean databases, until June 29, 2023. The inclusion criteria were randomized clinical trials (RCTs) comparing the intervention of HM with probiotics to that of the same probiotics. Statistical analyses included calculation of the mean difference (MD), standardized MD, risk ratio (RR) with a 95% confidence interval (CI), and assessment of risk of bias using Review Manager Version 5.4 software. The Grading of Recommendations Assessment, Development, and Evaluation rating system was used to evaluate evidence quality. Potential publication bias was assessed using funnel plots, Egger test, the fail-safe N test, and Duval and Tweedie trim and fill method. RESULTS: A total of 22 RCTs involving 2228 patients were included in the meta-analysis. The HM and probiotics group exhibited superior outcomes compared to the probiotics alone group in various parameters: total effective rate (RR: 1.24, 95% CI: 1.19-1.29, P < .001), Bristol fecal Score (MD: 0.80, 95% CI: 0.71-0.89, P < .001), gastrointestinal peptide hormone (motilin) (MD: 35.37, 95% CI: 24.64-64.10, P < .001), inflammation indicator (nitrous oxide) (MD: -12.45, 95% CI: -15.12 to -9.77, P < .001), minimal sensitive volume of the rectum (MD: -8.7, 95% CI: -10.91 to -6.49, P < .001), and recurrence rate (RR: 0.30, 95% CI: 0.21-0.43, P < .001). CONCLUSION: The combination of HM and probiotics may exhibit a synergistic effect on PFC. Nevertheless, it is imperative to undertake rigorously planned RCTs to comprehensively evaluate the synergistic efficacy of HM and probiotics.

The Potential Application of Aloe Barbadensis Mill. as Chinese Medicine for Constipation: Mini-Review.

Aloe barbadensis Mill. has a long history of medicinal use in the annals of traditional Chinese medicine, wherein it has garnered considerable renown. Its multifaceted therapeutic properties, characterized by its anti-inflammatory and antibacterial attributes, alongside its established efficacy as a laxative agent, have been extensively documented. This review commences with an exploration of the nomenclature, fundamental characteristics, and principal constituents of Aloe barbadensis Mill. responsible for its laxative effects. Subsequently, we delve into an extensive examination of the molecular mechanisms underlying Aloe barbadensis Mill.'s laxative properties, types of constipation treatments, commercially available preparations, considerations pertaining to toxicity, and its clinical applications. This review aims to serve as a comprehensive reference point for healthcare professionals and researchers, fostering an enhanced understanding of the optimal utilization of Aloe barbadensis Mill. in the treatment of constipation.

Functional Outcomes of Patients Who Underwent Anorectal Malformation Repair Using MRI Guidance.

BACKGROUND: Despite the initiation of minimally invasive laparoscopic techniques, the majority of patients who undergo anorectal malformation repair still experience functional bowel issues in childhood, including constipation and fecal incontinence. In this study, we evaluate the functional outcomes of a procedure in which magnetic resonance imaging guidance is used during initial laparoscopic repair to better locate the epicenter of the sphincter muscle complex and pelvic floor with the goal of more accurate placement of the neoanus and improved functional outcomes. METHODS: A retrospective chart review evaluated demographic, operative, and outcome details for patients who underwent this procedure. A telephone survey was employed to determine levels of social continence using the validated Baylor Continence Scale and to determine what type of bowel management is used. RESULTS: Twenty-six patients were included. Median age at operation was 7 months, and median age at follow-up was 4 years old, with a range of 1-9. Bowel management regimen results revealed that 19 % (n = 5) use no bowel management regimen, 58 % (n = 15) use laxatives only, and 23 % (n = 6) use enemas. Enema use was not associated with different spine or sacral anomalies (p = 0.77). Fifteen patients (58 %) answered the Baylor Continence Scale questions and had a median score of 14. No difference was found in scores when accounting for lesion level (p = 0.43), quality of needle placement (p = 0.46), or quality of sphincter muscles (p = 0.75). CONCLUSIONS: Using MRI guidance in the repair of anorectal malformations shows promise in both the qualitative and quantitative functional outcomes of this complex patient population. LEVEL OF EVIDENCE: Level III.

Complementary and alternative medicine (CAM) is frequently used by parents for the treatment of functional constipation in children.

OBJECTIVES: Complementary and alternative medicine (CAM) has gained increasing attention as a supportive treatment for chronic diseases such as epilepsy, migraine, autism, and cancer in children. This study aimed to determine the frequency, motivation, and outcomes of CAM in children with functional constipation. METHODS: From January 2018 till September 2019, parents of patients (0-18 years) who were treated for functional constipation (ROME IV-criteria) at our colorectal center were asked to complete a questionnaire on the utilization of CAM. Demographic data and clinical assessments were documented and analyzed for patients with and without CAM treatment. RESULTS: A total of 115 patients were included (mean age: 5.1 years; 49% males), of whom 29 (25%) used CAM as an alternative (4/29,14%) or in addition to conventional therapy (CT), including osteopathy (48%), homeopathy (45%), and natural/herbal remedies (17%). The main reason parents reported for the use of CAM was the urge to leave no treatment option unattempted (76%). Multivariate analysis also identified persistent constipation under CT (72%), adverse effects of CT (24%), and parental use of CAM themselves (83%) as independent variables associated with CAM use. Parents reported positive changes in stool frequency (38%) and fecal incontinence (21%) with CAM. The vast majority (93%) plan to use CAM in the future, and even non-CAM users showed high interest (60%). CONCLUSION: One in four children with functional constipation receives CAM. Significant improvement in stool frequency and continence is missing in the majority. However, parental interest in CAM remains high. Physicians should be aware of CAM when counseling families for functional constipation in children.