OBJECTIVE: To explore the efficacy of acupuncture based on "gut-brain axis" combined with sensory integration training in children with autism spectrum disorder (autism) and its effect on gastrointestinal symptoms. METHODS: A total of 96 children with autism were randomized into an observation group and a control group, 48 cases in each group, with 3 cases dropped out. Children in the control group received sensory integration training. On the basis of the treatment in the control group, children in the observation group received acupuncture therapy based on "gut-brain axis", and the point selection of scalp acupuncture was forehead five needles, i.e. bilateral Touwei (ST8), Toulinqi (GB15), Shenting (GV24) and Sishencong (EX-HN1), the point selection of body acupuncture was Zhongshu (GV7) and bilateral Tianshu (ST25), Pishu (BL20), Xinshu (BL15), Zusanli (ST36), Hegu (LI4), Taichong (LR3). Acupuncture was delivered once every other day, 3 times a week. Both groups were treated for 12 weeks. Before and after treatment, the scores of autism behavior checklist (ABC), childhood autism rating scale (CARS), autism treatment evaluation checklist (ATEC) and gastrointestinal TCM symptoms, as well as the relative abundance of intestinal flora were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the ABC and CARS scores were decreased compared with those before treatment in the two groups (P<0.001, P<0.05), and the ABC and CARS scores in the observation group were lower than those in the control group (P<0.01). After treatment, the item scores of language, sensory perception, sociability, behavior, and the total score of ATEC in the observation group were decreased compared with those before treatment (P<0.001, P<0.01), the item scores of language, sociability, behavior, and the total score of ATEC in the control group were decreased compared with those before treatment (P<0.01, P<0.001, P<0.05); the each-item and total scores in the observation group were lower than those in the control group (P<0.05). After treatment, the scores of loose stool, stomach duct pain, stomach duct stuffiness, decreased appetite, and the total scores of gastrointestinal TCM symptoms were reduced compared with those before treatment in the two groups (P<0.001), and the above scores in the observation group were lower than those in the control group (P<0.001). After treatment, the relative abundance of Escherichia coli and Enterococcus was decreased compared with that before treatment in the two groups (P<0.001), and the above relative abundance in the observation group was lower than that in the control group (P<0.001); the relative abundance of Bifidobacterium and Lactobacillus was increased compared with that before treatment in the two groups (P<0.001), and the above relative abundance in the observation group was higher than that in the control group (P<0.001). The total effective rate was 88.9% (40/45) in the observation group, which was higher than 66.7% (30/45) in the control group (P<0.05). CONCLUSION On the basis of sensory integration training, acupuncture based on "gut-brain axis" can improve the behavioral status and gastrointestinal symptoms, and correct the imbalance of intestinal flora in children with autism.
Humans ; Acupuncture Therapy ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child, Preschool ; Child ; Acupuncture Points ; Treatment Outcome ; Brain-Gut Axis ; Gastrointestinal Diseases/physiopathology*

Acupuncture-moxibustion therapy has been known to ameliorate the symptoms of functional gastrointestinal disorders (FGIDs), although its mechanism remains unclear. The paper reviews the articles on acupuncture-moxibustion therapy for FGIDs in recent 5 years, and it is revealed that acupuncture-moxibustion therapy can alleviate FGIDs symptoms through regulating gastrointestinal motility, modulating visceral hypersensitivity, improving the impaired gastric-duodenal mucosal barrier and inflammation, balancing intestinal microbiota, and adjusting the gut-brain axis. Currently, the molecular mechanism of acupuncture-moxibustion therapy remains unknown for FGIDs, the specific disease target is not identified, and the interaction among various molecules is not elucidated adequately. The researches in the future should employ advanced technologies and methodologies to comprehensively and deeply explore and clarify the mechanism of acupuncture- moxibustion therapy for FGIDs.
Humans ; Moxibustion ; Acupuncture Therapy ; Gastrointestinal Diseases/microbiology* ; Animals

OBJECTIVE: To evaluate the advantages and limitations of transcutaneous electrical acupoint stimulation (TEAS) in the treatment of patients with severe gastrointestinal function injury in intensive care unit (ICU) by analyzing dynamic changes of intestinal fatty acid binding protein (I-FABP), D-lactic acid and citrulline. METHODS: A prospective single-center randomized controlled trial was conducted. Patients with severe gastrointestinal function injury admitted to the ICU from February 2021 to January 2024 were enrolled [age > 18 years old, acute gastrointestinal injury (AGI) grade 2 to 3, stable hemodynamics]. Patients with different AGI grades were randomly assigned in a 1:1 ratio to the TEAS group and the control group using simple randomization. Both groups received conventional treatment and enteral nutrition (EN). In addition, the TEAS group underwent TEAS at the Neiguan and Zusanli points for 30 minutes per session, twice daily for 7 days. Baseline data, including age, gender, underlying diseases, and primary diagnoses, were recorded. Three intestinal biomarkers, such as I-FABP, D-lactic acid, and citrulline were measured before and after 7 days of treatment. EN tolerance indicators and 28 days survival status were documented. The differences in various indicators were compared between the two groups, subgroup analyses were conducted based on AGI grading, and interaction between AGI grade and TEAS were analyzed. The 28-day Kaplan-Meier survival curves were generated for both groups. RESULTS: Finally, 133 patients were included, with 68 in the TEAS group and 65 in the control group. Baseline characteristics were comparable between the two groups. A comparison of the dynamic changes in intestinal biomarkers revealed that the I-FABP level in both groups decreased after treatment compared to pre-treatment, with a more pronounced reduction in the TEAS group. The least square mean difference (LS Mean difference) for the corrected I-FABP level between the two groups during the observation period was -0.23 μg/L [95% confidence interval (95%CI) was -0.45 to -0.01], which was statistically significant (P = 0.041). Additionally, a significant interaction with AGI was observed (P = 0.004). Post-treatment, D-lactic acid level decreased in both groups compared to pre-treatment, with a more significant reduction in the TEAS group. The LS Mean difference for the corrected D-lactic acid level was -0.08 mmol/L (95%CI was -0.11 to -0.05), which was statistically significant (P < 0.001), and the interaction with AGI was also significant (P = 0.005). There was no significant change in citrulline levels between the two groups before and after treatment. The LS Mean difference for the corrected citrulline level was -0.17 μmol/L (95%CI was -1.87 to 1.53), which was not statistically significant (P = 0.845), and no significant interaction with AGI was observed (P = 0.913). Comparison of EN tolerance parameters between the two groups revealed that the TEAS group had a longer total EN time (hours: 72±31 vs. 60±28) and higher total EN calories (kJ: 11 469.23±7 237.34 vs. 6 638.76±5 098.37), as well as a higher 70% target caloric attainment rate (52.9% vs. 32.3%) compared to the control group (all P < 0.05). The incidence of abdominal distension after EN was lower in the TEAS group than that in the control group (23.5% vs. 43.1%, P < 0.05), while the incidence of diarrhea after EN was higher in the TEAS group (22.1% vs. 7.7%, P < 0.05). There were no significantly differences in AGI grade reduction rate, post-EN vomiting/gastric retention rate, incidence of feeding interruption, and 28-day survival rate between the two groups. Furthermore, there were no significantly interaction between these observation measures and AGI. Kaplan-Meier survival analysis showed that there was no significantly difference in 28-day cumulative survival rate between the TEAS group and the control group [Log-Rank test: P = 0.501, hazard ratio (HR) = 0.81, 95%CI was 0.43-1.51), and there was no significantly interaction with AGI (P = 0.702). CONCLUSIONS The advantage of TEAS in the treatment of ICU patients with severe gastrointestinal function injury lies in its ability to reverse intestinal cell necrosis and promote the reconstruction of intestinal barrier function. Additionally, gastrointestinal tolerance is significantly improved, and both the duration and total calories of EN are increased. However, the limitation of TEAS therapy is that it does not promote the recovery of intestinal cell absorption and synthesis function in the target patients. Moreover, it may lead to nutrient solution overload due to improved gastrointestinal tolerance. Furthermore, TEAS does not appear to improve 28-day cumulative survival rate in the target patients.
Humans ; Prospective Studies ; Intensive Care Units ; Acupuncture Points ; Fatty Acid-Binding Proteins/metabolism* ; Transcutaneous Electric Nerve Stimulation ; Male ; Female ; Citrulline/metabolism* ; Lactic Acid/metabolism* ; Gastrointestinal Diseases/therapy* ; Middle Aged ; Enteral Nutrition ; Adult

OBJECTIVE: Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved. METHODS: Transgenic mice were used to trace Nestin⁺/nerve growth factor receptor (Ngfr)⁺ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms. RESULTS: EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein⁺ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice. CONCLUSION EA facilitates ENS repair by promoting Nestin⁺/Ngfr⁺ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin⁺/Ngfr⁺ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals ; Electroacupuncture ; Enteric Nervous System/physiology* ; Gastrointestinal Motility/physiology* ; Glial Cell Line-Derived Neurotrophic Factor/metabolism* ; Diabetes Mellitus, Experimental/therapy* ; Signal Transduction ; Mice ; Gastrointestinal Diseases/physiopathology* ; Proto-Oncogene Proteins c-ret/metabolism* ; Mice, Transgenic ; Male ; Nerve Regeneration ; Neural Stem Cells ; Mice, Inbred C57BL ; Acupuncture Points

Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
Humans ; Flavonoids/pharmacokinetics* ; Tablets ; Animals ; Gastrointestinal Diseases/drug therapy* ; Liver Diseases/drug therapy* ; Drug Development ; Clinical Trials as Topic ; Scutellaria baicalensis/chemistry*

Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and other gastrointestinal diseases. The World Health Organization has classified H. pylori as a group Ⅰ carcinogen. Antibiotics are the primary clinical approach for eradicating H. pylori. However, incomplete eradication of H. pylori by antibiotics can lead to persistent infection, which is a major risk factor for the high incidence of gastric cancer. The widespread use of antibiotics has led to the emergence of multidrug resistance in H. pylori, contributing to treatment failures of chronic gastric diseases and increasing the risk of spreading resistant strains. Multidrug-resistant H. pylori has become a serious challenge in the diagnosis and treatment of gastrointestinal diseases. This paper reviews the global trends in the development of multidrug resistance in H. pylori, the underlying mechanisms, the challenges it poses to clinical diagnosis, and its impact on drug development, drawing on relevant literature and the research findings from our group. It proposes using cgt expression as a novel method for determining viable bacteria, identifying intracellularization as a new form of resistance in H. pylori, and exploring the potential of O-glycans as a therapeutic approach against H. pylori to address multidrug resistance. It provides new insights into understanding the mechanisms of H. pylori multidrug resistance and its prevention strategies, offering promising directions for future clinical treatments and antimicrobial drug development.
Helicobacter pylori/genetics* ; Humans ; Drug Resistance, Multiple, Bacterial ; Helicobacter Infections/microbiology* ; Anti-Bacterial Agents/therapeutic use* ; Gastrointestinal Diseases/drug therapy*

OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with gastrointestinal dysfunction. METHODS: A total of 100 patients with AECOPD complicated with gastrointestinal dysfunction were randomly divided into an EA group (50 cases, 2 cases dropped off, 1 case excluded) and a medication group (50 cases). Both groups were treated with symptomatic and supportive treatment such as low flow oxygen, nebulized inhalation of short-acting β2 agonist (SABA) or short-acting muscarinic antagonist (SAMA) combined with inhaled corticosteroid (ICS). The EA group was treated with EA at Zusanli (ST 36), Yinlingquan (SP 9), Zhongwan (CV 12), Shuifen (CV 9), Tianshu (ST 25), Chize (LU 5) and Lieque (LU 7), with discontinuous wave, 2 Hz in frequency, 30 min each time, once a day. In the medication group, oral mosapride citrate tablets were given, 3 times a day, 5 mg each time. Both groups were treated for 5 d. Before and after treatment, the gastrointestinal symptom rating scale (GSRS) score was observe, serum procalcitonin (PCT), C-reactive protein (CRP), and plasma oxygenation index (PaO₂/FiO₂) were detected, and patient satisfaction degree was evaluated in the two groups. RESULTS: Compared with before treatment, except for diarrhea dimension in the medication group, the total scores and each dimension scores of GSRS were decreased (P<0.05), serum PCT and CRP were decreased (P<0.05), plasma PaO₂/FiO₂ was increased (P<0.05) in the two groups after treatment. After treatment, in the EA group, the total score and abdominal pain, dyspepsia, constipation and diarrhea scores of GSRS were lower than those in the medication group (P<0.05), meanwhile serum PCT and CRP were lower and plasma PaO₂/FiO₂ was higher than those in the medication group (P<0.05). The improvement of gastrointestinal symptoms, life quality and overall satisfaction degree in the EA group were superior to those in the medication group (P<0.05). CONCLUSION EA could improve the symptoms of patients with AECOPD complicated with gastrointestinal dysfunction, reduce inflammatory response, improve oxygenation and patient satisfaction degree.
Humans ; Electroacupuncture ; Gastrointestinal Diseases/therapy* ; Pulmonary Disease, Chronic Obstructive/therapy* ; Diarrhea ; Abdominal Pain ; C-Reactive Protein

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

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Humans ; Mice ; Animals ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Colitis/metabolism* ; Inflammatory Bowel Diseases/drug therapy* ; Inflammation ; Anti-Inflammatory Agents/pharmacology* ; Disease Models, Animal

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×10⁹ vs. (11±5)×10⁹/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.
Nephrotic Syndrome/drug therapy* ; Humans ; Child ; Adolescent ; Male ; Female ; Gastrointestinal Diseases/diagnosis* ; Adrenal Cortex Hormones/therapeutic use* ; Nausea/chemically induced* ; Vomiting/chemically induced* ; Abdominal Pain/chemically induced* ; Mental Processes/drug effects* ; China