Biofeedback combined with percutaneous electrical pudendal nerve stimulation for the treatment of low anterior rectal resection syndrome: a study protocol for a randomized controlled trial.

BACKGROUND: Low anterior resection syndrome (LARS) is a distressing condition that affects approximately 25-80% of patients following surgery for rectal cancer. LARS is characterized by debilitating bowel dysfunction symptoms, including fecal incontinence, urgent bowel movements, and increased frequency of bowel movements. Although biofeedback therapy has demonstrated effectiveness in improving postoperative rectal control, the research results have not fulfilled expectations. Recent research has highlighted that stimulating the pudendal perineal nerves has a superior impact on enhancing pelvic floor muscle function than biofeedback alone. Hence, this study aims to evaluate the efficacy of a combined approach integrating biofeedback with percutaneous electrical pudendal nerve stimulation (B-PEPNS) in patients with LARS through a randomized controlled trial (RCT). METHODS AND ANALYSIS: In this two-armed multicenter RCT, 242 participants with LARS after rectal surgery will be randomly assigned to undergo B-PEPNS (intervention group) or biofeedback (control group). Over 4 weeks, each participant will undergo 20 treatment sessions. The primary outcome will be the LARS score. The secondary outcomes will be anorectal manometry and pelvic floor muscle electromyography findings and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29) scores. Data will be collected at baseline, post-intervention (1 month), and follow-up (6 months). DISCUSSION: We anticipate that this study will contribute further evidence regarding the efficacy of B-PEPNS in alleviating LARS symptoms and enhancing the quality of life for patients following rectal cancer surgery. TRIAL REGISTRATION: Chinese Clincal Trials Register ChiCTR2300078101. Registered 28 November 2023.

The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer.

GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for therapeutic interventions, including monoclonal antibodies, CAR-T cells, and T-cell engagers. Despite its therapeutic potential, the insufficient understanding regarding of the receptor's structure and antibody recognition mechanism has impeded the progress of effective therapeutic development. Here, we present the structure of GPRC5D in complex with a preclinical-stage single-chain antibody (scFv). Our structural analysis reveals that the GPRC5D presents a close resemblance to the typical Class C GPCRs in the transmembrane region. We identify a distinct head-to-head homodimer arrangement and interface mainly involving TM4, setting it apart from other Class C homo- or hetero-dimers. Furthermore, we elucidate the binding site engaging a sizable extracellular domain on GPRC5D for scFv recognition. These insights not only unveil the distinctive dimer organization of this unconventional Class C GPCR but also hold the potential to advance drug development targeting GPRC5D for the treatment of multiple myeloma.

Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway.

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.

Bitter taste TAS2R14 activation by intracellular tastants and cholesterol.

Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1,2. TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications3. Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and Gi1 proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery.

Ammonia stripping by in situ biogas self-circulation to upgrade continuous thermophilic and mesophilic digestion of hydrothermal high-solid sludge.

High-solid anaerobic digestion of hydrothermal sewage sludge has been developed. In order to upgrade the process by focusing on ammonia inhibition, a simply-equipped stripping system without additional alkali or heat supply was introduced by in situ biogas self-circulation. As the determined limit of total ammonia nitrogen at 1500 mg/L and 1000 mg/L for the mesophilic (MAD) and thermophilic anaerobic digestion (TAD) respectively and stripping rate at 5 L/min, continuous MAD and TAD was conducted in parallel. The stripping system successfully polished up the ammonia inhibition, and methanogenic capability of the TAD was promoted to approximately 90.0 % of the potential. Intermittent stripping mode proved usable. More frequent stripping was inevitable for the TAD as compared to the MAD. Hydraulic retention time below 20 d resulted in failure of the stripping mode due to rapid ammonia generation. Overall, this technology was practical in upgrading high-solid sludge digestion by effective ammonia control.

Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring.

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.

Growth Process of Fe-O Nanoclusters with Different Sizes Biosynthesized by Protein Nanocages.

All protein-directed syntheses of metal nanoclusters (NCs) and nanoparticles (NPs) have attracted considerable attention because protein scaffolds provide a unique metal coordination environment and can adjust the shape and morphology of NCs and NPs. However, the detailed formation mechanisms of NCs or NPs directed by protein templates remain unclear. In this study, by taking advantage of the ferritin nanocage as a biotemplate to monitor the growth of Fe-O NCs as a function of time, we synthesized a series of iron NCs with different sizes and shapes and subsequently solved their corresponding three-dimensional atomic-scale structures by X-ray protein crystallography and cryo-electron microscopy. The time-dependent structure analyses revealed the growth process of these Fe-O NCs with the 4-fold channel of ferritin as nucleation sites. To our knowledge, the newly biosynthesized Fe35O23Glu12 represents the largest Fe-O NCs with a definite atomic structure. This study contributes to our understanding of the formation mechanism of iron NCs and provides an effective method for metal NC synthesis.

Research Progress on Anti-Inflammatory Effects and Related Mechanisms of Astragalin.

Chronic inflammation is a significant contributor to the development of cancer, cardiovascular disease, diabetes, obesity, autoimmune disease, inflammatory bowel disease, and other illnesses. In the academic field, there is a constant demand for effective methods to alleviate inflammation. Astragalin (AST), a type of flavonoid glycoside that is the primary component in several widely used traditional Chinese anti-inflammatory medications in clinical practice, has garnered attention from numerous experts and scholars. This article focuses on the anti-inflammatory effects of AST and conducts research on relevant literature from 2003 to 2023. The findings indicate that AST demonstrates promising anti-inflammatory potential in various models of inflammatory diseases. Specifically, AST is believed to possess inhibitory effects on inflammation-related factors and protein levels in various in vitro cell models, such as macrophages, microglia, and epithelial cells. In vivo studies have shown that AST effectively alleviates neuroinflammation and brain damage while also exhibiting potential for treating moderate diseases such as depression and stroke; it also demonstrates significant anti-inflammatory effects on both large and small intestinal epithelial cells. Animal experiments have further demonstrated that AST exerts therapeutic effects on colitis mice. Molecular biology studies have revealed that AST regulates complex signaling networks, including NF-κB, MAPK, JAK/STAT pathways, etc. In conclusion, this review will provide insights and references for the development of AST as an anti-inflammatory agent as well as for related drug development.

Potential Anti-Inflammatory Constituents from Aesculus wilsonii Seeds.

A chemical study of Aesculus wilsonii Rehd. (also called Suo Luo Zi) and the in vitro anti-inflammatory effects of the obtained compounds was conducted. Retrieving results through SciFinder showed that there were four unreported compounds, aeswilosides I-IV (1-4), along with fourteen known isolates (5-18). Their structures were elucidated by extensive spectroscopic methods such as UV, IR, NMR, [α]D, and MS spectra, as well as acid hydrolysis. Among the known ones, compounds 5, 6, 8-10, and 12-16 were obtained from the Aesculus genus for the first time; compounds 7, 11, 17, and 18 were first identified from this plant. The NMR data of 5 and 18 were reported first. The effects of 1-18 on the release of nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW264.7 cells were determined. The results showed that at concentrations of 10, 25, and 50 µM, the novel compounds, aeswilosides I (1) and IV (4), along with the known ones, 1-(2-methylbutyryl)phloroglucinyl-glucopyranoside (10) and pisuminic acid (15), displayed significant inhibitory effects on NO production in a concentration-dependent manner. It is worth mentioning that compound 10 showed the best NO inhibitory effect with a relative NO production of 88.1%, which was close to that of the positive drug dexamethasone. The Elisa experiment suggested that compounds 1, 4, 10, and 15 suppressed the release of TNF-α and IL-1ß as well. In conclusion, this study enriches the spectra of compounds with potential anti-inflammatory effects in A. wilsonii and provides new references for the discovery of anti-inflammatory lead compounds, but further mechanistic research is still needed.

Yigansan ameliorates maternal immune activation-induced autism-like behaviours by regulating the IL-17A/TRAF6/MMP9 pathway: Network analysis and experimental validation.

BACKGROUND: Maternal immune activation (MIA) is a significant factor inducing to autism spectrum disorder (ASD) in offspring. The fundamental principle underlying MIA is that inflammation during pregnancy impedes fetal brain development and triggers behavioural alterations in offspring. The intricate pathogenesis of ASD renders drug treatment effects unsatisfactory. Traditional Chinese medicine has strong potential due to its multiple therapeutic targets. Yigansan, composed of seven herbs, is one of the few that has been proven to be effective in treating neuro-psychiatric disorders among numerous traditional Chinese medicine compounds, but its therapeutic effect on ASD remains unknown. HYPOTHESIS: Yigansan improves MIA-induced ASD-like behaviours in offspring by regulating the IL-17 signalling pathway. METHODS: Pregnant C57BL/6J mice were intraperitoneally injected with poly(I:C) to construct MIA models and offspring ASD models. Network analysis identified that the IL-17A/TRAF6/MMP9 pathway is a crucial pathway, and molecular docking confirmed the binding affinity between the monomer of Yigansan and target proteins. qRT-PCR and Western blot were used to detect the expression levels of inflammatory factors and pathway proteins, immunofluorescence was used to detect the distribution of IL-17A, and behavioural tests were used to evaluate the ASD-like behaviours of offspring. RESULTS: We demonstrated that Yigansan can effectively alleviate MIA-induced neuroinflammation of adult offspring by regulating the IL-17A/TRAF6/MMP9 pathway, and the expression of IL-17A was reduced in the prefrontal cortex. Importantly, ASD-like behaviours have been significantly improved. Moreover, we identified that quercetin is the effective monomer for Yigansan to exert therapeutic effects. CONCLUSION: Overall, this study was firstly to corroborate the positive therapeutic effect of Yigansan in the treatment of ASD. We elucidated the relevant molecular mechanism and regulatory pathway involved, determined the optimal therapeutic dose and effective monomer, providing new solutions for the challenges of drug therapy for ASD.

Untargeted urine metabolomics and machine learning provide potential metabolic signatures in children with autism spectrum disorder.

Background: Complementary to traditional biostatistics, the integration of untargeted urine metabolomic profiling with Machine Learning (ML) has the potential to unveil metabolic profiles crucial for understanding diseases. However, the application of this approach in autism remains underexplored. Our objective was to delve into the metabolic profiles of autism utilizing a comprehensive untargeted metabolomics platform coupled with ML. Methods: Untargeted metabolomics quantification (UHPLC/Q-TOF-MS) was performed for urine analysis. Feature selection was conducted using Lasso regression, and logistic regression, support vector machine, random forest, and extreme gradient boosting were utilized for significance stratification. Pathway enrichment analysis was performed to identify metabolic pathways associated with autism. Results: A total of 52 autistic children and 40 typically developing children were enrolled. Lasso regression identified ninety-two urinary metabolites that significantly differed between the two groups. Distinct metabolites, such as prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, were revealed to be associated with autism through the application of four different ML methods (p<0.05). The alterations observed in the phosphatidylinositol and inositol phosphate metabolism pathways were linked to the pathophysiology of autism (p<0.05). Conclusion: Significant urinary metabolites, including prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, exhibit associations with autism. Additionally, the involvement of the phosphatidylinositol and inositol phosphate pathways suggests their potential role in the pathophysiology of autism.

Predicting autism spectrum disorder using maternal risk factors: A multi-center machine learning study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex environmental etiology involving maternal risk factors, which have been combined with machine learning to predict ASD. However, limited studies have considered the factors throughout preconception, perinatal, and postnatal periods, and even fewer have been conducted in multi-center. In this study, five predictive models were developed using 57 maternal risk factors from a cohort across ten cities (ASD:1232, typically developing[TD]: 1090). The extreme gradient boosting model performed best, achieving an accuracy of 66.2 % on the external cohort from three cities (ASD:266, TD:353). The most important risk factors were identified as unstable emotions and lack of multivitamin supplementation using Shapley values. ASD risk scores were calculated based on predicted probabilities from the optimal model and divided into low, medium, and high-risk groups. The logistic analysis indicated that the high-risk group had a significantly increased risk of ASD compared to the low-risk group. Our study demonstrated the potential of machine learning models in predicting the risk for ASD based on maternal factors. The developed model provided insights into the maternal emotion and nutrition factors associated with ASD and highlighted the potential clinical applicability of the developed model in identifying high-risk populations.

Variability of ambient air ammonia in urban Europe (Finland, France, Italy, Spain, and the UK).

This study addressed the scarcity of NH3 measurements in urban Europe and the diverse monitoring protocols, hindering direct data comparison. Sixty-nine datasets from Finland, France, Italy, Spain, and the UK across various site types, including industrial (IND, 8), traffic (TR, 12), urban (UB, 22), suburban (SUB, 12), and regional background (RB, 15), are analyzed to this study. Among these, 26 sites provided 5, or more, years of data for time series analysis. Despite varied protocols, necessitating future harmonization, the average NH3 concentration across sites reached 8.0 ± 8.9 µg/m3. Excluding farming/agricultural hotspots (FAHs), IND and TR sites had the highest concentrations (4.7 ± 3.2 and 4.5 ± 1.0 µg/m3), followed by UB, SUB, and RB sites (3.3 ± 1.5, 2.7 ± 1.3, and 1.0 ± 0.3 µg/m3, respectively) indicating that industrial, traffic, and other urban sources were primary contributors to NH3 outside FAH regions. When referring exclusively to the FAHs, concentrations ranged from 10.0 ± 2.3 to 15.6 ± 17.2 µg/m3, with the highest concentrations being reached in RB sites close to the farming and agricultural sources, and that, on average for FAHs there is a decreasing NH3 concentration gradient towards the city. Time trends showed that over half of the sites (18/26) observed statistically significant trends. Approximately 50 % of UB and TR sites showed a decreasing trend, while 30 % an increasing one. Meta-analysis revealed a small insignificant decreasing trend for non-FAH RB sites. In FAHs, there was a significant upward trend at a rate of 3.51[0.45,6.57]%/yr. Seasonal patterns of NH3 concentrations varied, with urban areas experiencing fluctuations influenced by surrounding emissions, particularly in FAHs. Diel variation showed differing patterns at urban monitoring sites, all with higher daytime concentrations, but with variations in peak times depending on major emission sources and meteorological patterns. These results offer valuable insights into the spatio-temporal patterns of gas-phase NH3 concentrations in urban Europe, contributing to future efforts in benchmarking NH3 pollution control in urban areas.

Economic Evaluation of an Enhanced Post-Discharge Home-Based Care Program for Stroke Survivors.

OBJECTIVES: To examine the cost-effectiveness of an enhanced postdischarge home-based care program for stroke survivors compared with usual care. METHODS: This was a trial-based economic evaluation study. One hundred and sixteen patients with ischemic stroke were recruited from neurology units in a Chinese hospital and randomized into intervention (n = 58) or usual care groups (n = 58). The intervention commenced with predischarge planning and transitioned to home follow-up postdischarge. Trained nurse case managers supported by an interdisciplinary team provided comprehensive assessment, individualized goal setting, and skill training to support home-based rehabilitation for intervention group participants. Standard care was provided to usual care group participants. Total cost and quality-adjusted life-years gained at 3-month (T1), 6-month (T2), and 12-month (T3) follow-ups were calculated. The incremental cost-effectiveness ratios between the groups were obtained. RESULTS: The intervention group showed a significant increase in utility compared with the usual care group at T1 (P = .003), T2 (P = .007), and T3 (P < .001). The average total QALY gain from baseline for the intervention group was higher than for the usual care group at all time points. The likelihood of being cost-effective ranged from 61.9% to 67.2% from the provider perspective, and from 59.7% to 66.8% from the societal perspective. CONCLUSIONS: The results showed that the intervention program was cost-effective with significantly higher quality-adjusted life-years for stroke survivors when compared with usual care. It provides economic evidence to support the development of home-based stroke rehabilitation program, especially in the low- and middle-income countries.

Novel Cocrystal Structures of Peptide Antagonists Bound to the Human Melanocortin Receptor 4 Unveil Unexplored Grounds for Structure-Based Drug Design.

Melanocortin 4 receptor (MC4-R) antagonists are actively sought for treating cancer cachexia. We determined the structures of complexes with PG-934 and SBL-MC-31. These peptides differ from SHU9119 by substituting His6 with Pro6 and inserting Gly10 or Arg10. The structures revealed two subpockets at the TM7-TM1-TM2 domains, separated by N2857.36. Two peptide series based on the complexed peptides led to an antagonist activity and selectivity SAR study. Most ligands retained the SHU9119 potency, but several SBL-MC-31-derived peptides significantly enhanced MC4-R selectivity over MC1-R by 60- to 132-fold. We also investigated MC4-R coupling to the K+ channel, Kir7.1. Some peptides activated the channel, whereas others induced channel closure independently of G protein coupling. In cell culture studies, channel activation correlated with increased feeding, while a peptide with Kir7.1 inhibitory activity reduced eating. These results highlight the potential for targeting the MC4-R:Kir7.1 complex for treating positive and restrictive eating disorders.

Unveiling the structural mechanisms of nonpeptide ligand recognition and activation in human chemokine receptor CCR8.

The human CC chemokine receptor 8 (CCR8) is an emerging therapeutic target for cancer immunotherapy and autoimmune diseases. Understanding the molecular recognition of CCR8, particularly with nonpeptide ligands, is valuable for drug development. Here, we report three cryo-electron microscopy structures of human CCR8 complexed with Gi trimers in the ligand-free state or activated by nonpeptide agonists LMD-009 and ZK 756326. A conserved Y1.39Y3.32E7.39 motif in the orthosteric binding pocket is shown to play a crucial role in the chemokine and nonpeptide ligand recognition. Structural and functional analyses indicate that the lack of conservation in Y1143.33 and Y1724.64 among the CC chemokine receptors could potentially contribute to the selectivity of the nonpeptide ligand binding to CCR8. These findings present the characterization of the molecular interaction between a nonpeptide agonist and a chemokine receptor, aiding the development of therapeutics targeting related diseases through a structure-based approach.

A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways.

The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts.

A potent neutralizing nanobody targeting a unique epitope on the receptor-binding domain of SARS-CoV-2 spike protein.

SARS-CoV-2 and its variants continue to threaten public health. Nanobodies that block the attachment of the RBD to host cell angiotensin-converting enzyme 2 (ACE2) represent promising drug candidates. In this study, we reported the identification and structural biological characterization of a nanobody from a RBD-immunized alpaca. The nanobody, termed as 2S-1-19, shows outstanding neutralizing activity against both pseudotyped and authentic SARS-CoV-2 viruses. The crystal structure of 2S-1-19 bound to SARS-CoV-2 RBD reveals an epitope that overlaps with the binding site for ACE2. We also showed that 2S-1-19 reserves promising, though compromised, neutralizing activity against the Delta variant and that the trivalent form of 2S-1-19 remarkably increases its neutralizing capacity. Despite this, neither the monomeric or trimeric 2S-1-19 could neutralize the Omicron BA.1.1 variant, possibility due to the E484A and Q493K mutations found within this virus variant. These data provide insights into immune evasion caused by SARS-CoV-2 variants.

Intestinal Symptoms Among Children aged 2-7 Years with Autism Spectrum Disorder in 13 Cities of China.

BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. METHODS: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. RESULTS: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. CONCLUSION: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.