SEARCH · Search PubMed

Results for “Dysfunctional Elimination Syndrome”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

200 records · Page 3Linked to original sources

PubMed2026

Psychiatric Diagnoses and Psychotropic Medications Among Military-Affiliated Adolescents and Young Adults With Polycystic Ovary Syndrome.

PURPOSE: To study rates of psychiatric diagnoses and psychotropic medication prescription among U.S. military-affiliated adolescents and young adults (AYA) with polycystic ovary syndrome (PCOS). METHODS: This retrospective matched cohort study included U.S. military-affiliated AYA (aged 15-21 years) enrolled in TRICARE Prime for at least 6 months during the surveillance period (January 2016 to October 2023). Military-affiliated AYA were grouped into three categories: individuals diagnosed with PCOS (N = 6,911), age-matched individuals with no diagnosed PCOS symptoms (N = 35,814), and individuals with diagnosed symptoms suggestive of PCOS (N = 2,136). The presence of a psychiatric diagnoses and prescriptions for psychotropic medications were obtained via the International Classification of Diseases, 10th Revision, Clinical Modification codes and National Drug codes, respectively. RESULTS: AYA with diagnosed PCOS had higher odds of having a psychiatric diagnosis and being prescribed a psychotropic medication compared to an age-matched comparison group (psychiatric diagnosis odds ratio [OR] = 2.48 [2.35-2.62], medication OR = 2.14 [2.03-2.25]) and individuals with symptoms suggestive of PCOS (psychiatric diagnosis OR = 1.11 [1.003-1.23], medication OR = 1.16 [1.05-1.28]). DISCUSSION: The odds of psychiatric comorbidities and psychotropic medication prescription were more than twice as high as among U.S. military-affiliated AYA with PCOS. More research is needed to determine whether health-care utilization and military-related factors impact mental health outcomes among AYA with PCOS. Additionally, tailored, multidisciplinary mental health services for AYA with PCOS are needed.

Humans↗

PubMed2026

Predictors of transition readiness in adolescents with neurogenic lower urinary tract dysfunction.

PURPOSE: Adolescents with Neurogenic Lower Urinary Tract Dysfunction (NLUTD) face significant challenges in their quality of life and readiness to transition to adult healthcare services. This study examines the impact of various demographic and clinical factors on transition readiness. METHODS: We performed a retrospective review of prospectively collected data from 75 adolescents with NLUTD managed at a specialized tertiary referral pediatric facility. We employed multivariate linear regression analysis to explore the relationship between transition readiness scores collected from the Good2Go questionnaire, including the total transition readiness score and its sub-domains (self-advocacy, knowledge, self-care, and social support), and predictors such as age, sex, reconstructive surgery status, and clean intermittent catheter (CIC) usage. RESULTS: The mean age of participants was 16.74 years (SD 2.44). Reconstructive surgery had been performed in 32 % of patients, and 77.3 % were on CIC. Multivariate regression analysis indicated that age significantly predicted transition readiness across several domains. Each additional year of age was associated with a 4.40-point increase in the total transition readiness score, a 3.66-point increase in knowledge, a 4.26-point increase in self-advocacy and a 5.41-point increase in self-care. Conversely, CIC significantly negatively impacted the social support domain, with scores decreasing by 9.69 points. Reconstructive surgery was significantly associated with lower self-care scores, with an average decrease of 12.12 points among those who had undergone surgery. CONCLUSION: Age significantly improves transition readiness in adolescents with NLUTD, reflecting cognitive and developmental growth. However, the negative effects of CIC on social support and reconstructive surgery on self-care underscore the need for personalized interventions to optimize health outcomes during the transition to adult care.

Humans↗

PubMed2026

Interventions with a significant mortality difference in acute respiratory distress syndrome: A systematic review and comparison with Guidelines.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has a high mortality rate. European Society of Intensive Care Medicine (ESICM) and American Thoracic Society (ATS) Guidelines are the worldwide reference for clinicians in management of ARDS. Mortality represents one of the most important outcomes in intensive care practice and randomized controlled trials (RCTs) the highest level of evidence. We compared Guidelines recommendations with RCT results to highlight differences and find potential new therapeutic opportunities. METHODS: We performed a systematic review of all RCTs reporting a statistically significant mortality difference in ARDS and a subsequent comparison with ESICM and ATS Guidelines recommendations. RESULTS: We identified 33 RCTs and 23 interventions with mortality difference in ARDS patients. Seven interventions relate to invasive ventilation strategies, two to noninvasive ventilation strategies, one to extracorporeal membrane oxygenation (ECMO), 12 to drugs and one to nutritional support. In 25/33 (76%) RCTs the intervention was associated with mortality reduction and in 8/33 with mortality increase (24%). Multicenter studies were 24/33 (73%) while blinding was adopted in 19/33 (58%) studies. Guidelines recommendations supported by RCTs with mortality impact include: the use of low tidal volume ventilation, prone positioning, venovenous ECMO, steroids and the avoidance of high frequency oscillatory ventilation. Eight of the interventions identified were not mentioned by Guidelines but demonstrated reduced mortality, and five further interventions demonstrated increased mortality. CONCLUSIONS: This systematic review highlights potential gaps between RCTs results and Guidelines that could be used to plan future research or highlight topics to be discussed in future Guidelines.

Humans↗

PubMed2026

Association of ERBB4 and SHBG gene polymorphisms with polycystic ovarian syndrome in South Indian women: a case-control genetic analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a multifactorial endocrinological disorder with a substantial genetic component. However, the role of genes involved in follicular development and androgen regulation remains incompletely understood, particularly in South Indian populations. This study aimed to evaluate how variations in the ERBB4 and SHBG genes affect PCOS risk. METHODOLOGY: A hospital-based case-control study was conducted among 400 South Indian women, comprising 200 women with PCOS and 200 age-matched healthy controls. Genomic DNA was extracted to study SNPs at ERBB4 (rs2178575 and rs1351592) and SHBG (rs1799941 and rs727428) using ARMS-PCR genotyping. The study compared genotype and allele frequencies between cases and controls while assessing their associations with allelic, homozygous, heterozygous, dominant, recessive, and over-dominant genetic models. Genotyping accuracy was confirmed by re-genotyping and Sanger sequencing of a subset of samples. RESULTS: The ERBB4 rs2178575 polymorphism demonstrated a significant association with PCOS, as the AA genotype and A allele combination increased risk across all three genetic models, including homozygous, recessive, and allelic models. The ERBB4 rs1351592 variant was associated with 3-fold higher risk of PCOS in heterozygous and GC carriers. The SHBG rs1799941 polymorphism showed a significant link to PCOS through its effects on heterozygous and allelic states, whereas rs727428 displayed no significant connection due to its monomorphic distribution. CONCLUSION: These findings suggest that polymorphisms in ERBB4 and SHBG may contribute to PCOS susceptibility in South Indian women in a locus- and model-specific manner, revealing the intricate genetic structure that defines this medical condition.

Humans↗

PubMed2026

A validated sensitive LC-MS/MS method and its application in elucidating the unique ocular pharmacokinetic profile of 0.01% atropine underpinning its clinical utility for myopia.

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify atropine in ten rabbit ocular tissues enabling systematic characterization of the ocular pharmacokinetic profile of 0.01% atropine sulfate eye drops after a single topical administration. The method demonstrated excellent linearity (coefficient of determination, R2 ≥ 0.9908) across all matrices, with lower limits of quantification (LLOQ) of 0.05 ng/mL for most tissues and 0.10 ng/mL for retina and lens; intra- and inter-day accuracy, precision, matrix effects, extraction recoveries, and stability all met the acceptance criteria. Following a single bilateral topical dose (50 μL/eye) in New Zealand White rabbits, atropine distributed rapidly into all 12 ocular compartments (the sclera further divided into three anatomical regions) with marked heterogeneity-the highest exposures were found in conjunctiva and cornea, a distinct anterior-to-posterior concentration gradient was observed in the sclera, sustained retention was noted in the retina (mean residence time from zero to the last measurable time point, MRT0-t 3.30 h), while aqueous and vitreous humor eliminated rapidly (elimination half-life, t₁/₂ < 0.7 h), and all tissues except aqueous humor followed a two-compartment model. This validated method and the comprehensive pharmacokinetic data reveal that topically applied 0.01% atropine achieves sustained exposure in key myopia-regulating tissues (retina, choroid, posterior sclera) with low exposure in side-effect target tissues (iris, ciliary body, lens).

Animals↗

PubMed2026

Neoplasms in prune belly syndrome: A novel case of early-onset metastatic bladder carcinoma and systematic review of reported tumors.

PURPOSE: Prune Belly Syndrome (PBS) is a rare congenital malformation complex characterized by cryptorchidism, urinary tract abnormalities and deficiency of the abdominal wall musculature. Although advances in neonatal and reconstructive care have substantially improved survival, the long-term risk of malignancy in this population remains poorly defined. We report a novel case of early-onset metastatic bladder carcinoma in a patient with PBS and perform a systematic review of all tumors described in association with the syndrome. METHODS: A systematic literature review was performed according to PRISMA guidelines and registered in PROSPERO (CRD420251072086). Databases searched through April 2025 included PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane, and SciELO. Reported tumor cases in PBS patients were identified and classified as either PBS-associated or not. We additionally describe a new case of invasive bladder carcinoma. RESULTS: Seventeen studies comprising 20 patients met inclusion criteria. Tumors directly related to the genitourinary tract accounted for half of the cases. Bladder carcinoma was the most frequent neoplasm (35%), followed by hepatoblastoma (25%). Bladder tumors occurred at markedly younger ages and often presented as advanced diseases. Our index case involved a 33-year-old man with PBS who developed metastatic muscle-invasive urothelial carcinoma and died shortly after diagnosis. DISCUSSION: Improved survival in PBS has led to recognition of new late complications, including malignancy. Tumorigenesis may be influenced by chronic urinary stasis, infection, catheterization, cryptorchidism, and underlying genitourinary developmental abnormalities. These findings should be interpreted as hypothesis-generating given the limited number of reported cases. CONCLUSION: Although uncommon, malignancies in PBS may occur earlier and behave more aggressively than in the general population. Given the current level of evidence, careful long-term follow-up with clinical awareness is warranted, rather than routine invasive screening for all patients.

Humans↗

PubMed2026

METTL14-mediated m6A modification of CCNE1 accelerates progression of myelodysplastic syndromes via MAPK-ERK and PI3K-AKT signaling pathways.

BACKGROUND: N6-methyladenosine (m6A) is the most common RNA modification and plays a key role in the initiation, progression, and relapse of multiple cancers, including hematologic malignancies. However, the role of m6A and m6A regulatory genes in myelodysplastic syndromes (MDS) remains unclear. This study aims to elucidate the function and molecular mechanism of methyltransferase METTL14 in MDS. METHODS: RT-qPCR was used to assess the expression of multiple m6A regulators, focusing on METTL14 in MDS patients and cell lines. METTL14 overexpressing and knockdown cell lines were established, and CCK-8, EdU, and flow cytometry assays were performed to explore the biological functions of METTL14.Dot blot, MeRIP-Seq, MeRIP-qPCR, RT-qPCR, and Western blot were employed to investigate the underlying molecular mechanism. RESULTS: Dysregulation of multiple m6A regulators was observed in MDS, among which METTL14 was upregulated. Elevated METTL14 expression increases MDS risk and adverse prognosis, emerging as a biomarker for poor prognosis. METTL14 promoted proliferation and cell-cycle progression of MDS cells while inhibiting apoptosis; corresponding changes were observed in cell cycle and apoptosis markers. METTL14 regulated cellular m6A levels. Downstream targets of METTL14 were enriched in cell cycle-related pathways, with CCNE1 identified as a critical target. Knockdown of METTL14, actinomycin D, or S-adenosylhomocysteine treatment reduced CCNE1 mRNA and protein levels. Furthermore, METTL14 activated MAPK-ERK and PI3K-AKT signaling via CCNE1 in an m6A-dependent manner, thereby promoting proliferative MDS cells' capacity. CONCLUSIONS: This study delineates a METTL14/m6A/CCNE1 signaling axis in MDS progression and suggests that METTL14-mediated m6A modification may be a potential therapeutic target for MDS.

Humans↗

PubMed2026

Changes in hemoglobin levels and cardiometabolic health in adults with metabolic syndrome - a secondary outcome analysis of a six-month randomized controlled trial.

BACKGROUND: Lower hemoglobin (Hb) levels within the normal range have been associated with favorable metabolic traits in cross-sectional studies. This study investigated whether changes in Hb levels correlated with changes in physiological and cardiometabolic parameters during a six-month behavioral intervention in individuals with metabolic syndrome. METHODS: The six-month randomized controlled trial aimed to reduce sedentary behavior in adults with metabolic syndrome (n = 64). Key measurements included fasting blood samples, insulin sensitivity during a hyperinsulinemic-euglycemic clamp, insulin-stimulated liver glucose uptake, liver fat content (LFC), indirect calorimetry, cardiorespiratory fitness, and cardiac function. Correlations between changes in these variables and changes in Hb levels at baseline, three, and six months were examined. RESULTS: Cross-sectionally, higher Hb levels correlated with lower insulin sensitivity (r=-0.35, p = 0.005), higher resting O2 consumption (r = 0.41, p < 0.001), higher resting energy expenditure (r = 0.49, p < 0.001), higher LFC (r = 0.40, p = 0.011), and greater left ventricular wall thickness (r = 0.42, p = 0.001). The intervention did not significantly impact Hb levels, and changes in Hb levels did not correlate with most cardiometabolic changes. However, reduced Hb levels correlated with reduced fasting blood glucose (r = 0.29, p = 0.032), improved insulin sensitivity (r = -0.26, p = 0.045), and increased cardiorespiratory fitness (r = -0.29, p = 0.033). CONCLUSIONS: Changes in Hb levels did not consistently correlate with changes in cardiometabolic markers during the intervention. However, reductions in Hb levels may relate to improved insulin sensitivity and fitness. Along cross-sectional correlations, this may be clinically relevant for individuals with metabolic syndrome. Further studies are merited to clarify the role of Hb levels in this high-risk group.

Humans↗

PubMed2026

Efficacy of dapagliflozin on hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: a pre-specified single-arm analysis from a randomized controlled trial.

AIM: To evaluate the association of dapagliflozin therapy with changes in hepatic steatosis and non-invasive fibrosis surrogate markers in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) over 12 months. METHODS: This is a pre-specified single-arm analysis from a randomised, open-label, parallel-group trial. Of 54 participants randomised to dapagliflozin 10 mg daily, 50 (92.6%) completed the 12-month follow-up and were included in the per-protocol analysis. Assessments at baseline, 3, 6, and 12 months included transient elastography (CAP and LSM), ultrasonography, and biochemical tests. Primary endpoints were changes in hepatic steatosis (CAP) and non-invasive fibrosis surrogates (LSM). RESULTS: Significant reductions were observed in hepatic steatosis (CAP: 316.7 to 245.7 dB/m; mean change - 71.02 dB/m, 95% CI: -63.4 to - 78.6; p < 0.001) and in liver stiffness as a non-invasive fibrosis surrogate (LSM: 8.59 to 7.28 kPa; mean change - 1.31 kPa, 95% CI: -0.92 to - 1.70; p < 0.001). Improvements were also observed in glycaemic control, body weight, lipid profile, liver enzymes, ultrasonographic steatosis grading, and serum fibrosis markers. Genitourinary infections were the most frequently reported adverse events (32%); no serious adverse events were recorded. CONCLUSIONS: Dapagliflozin was associated with significant improvements in hepatic steatosis, non-invasive fibrosis surrogate markers, metabolic parameters, and liver function in T2DM patients with MASLD over 12 months. These findings provide region-specific evidence for an Indian population and support further controlled investigation. However, these findings should be interpreted in light of the pre-specified single-arm design of this analysis, the open-label methodology, relatively small sample size, and the absence of liver biopsy confirmation.

Humans↗

PubMed2026

Efficacy and safety of human albumin combined with furosemide in acute decompensated heart failure with hepatic dysfunction.

BACKGROUND: Congestion is the most common clinical presentation on admission of patients with acute decompensated heart failure (ADHF). Finding effective ways to alleviate congestion has become a pivotal management step. This study sought to investigate the efficacy and safety of intravenous (IV) albumin use in conjunction with furosemide in patients hospitalized for ADHF with hepatic dysfunction in terms of subjective regression of congestion symptoms and worsening renal function. METHODS: This prospective, open-label, randomized-pragmatic trial recruited 241 patients with hepatic dysfunction hospitalized for ADHF. Patients (78 years, 54% female) were assigned to receive IV albumin with furosemide or IV furosemide alone. The coprimary study endpoints were patients' global assessment of symptoms score, quantified as the area under the curve (AUC) of the score on a visual analog scale, and the change in creatinine levels over 72 hours from admission. RESULTS: The experimental treatment group demonstrated a greater improvement in patients' global assessment of symptoms scores (AUCbaseline-72 h 3,767 vs 3,457 points; P < .001) and a milder increase in creatinine levels (0.07 vs 0.18 mg/dL; P = .045) than the IV furosemide group. The length of stay was 1 day shorter (4 vs 5 days; P < .001) and the incidence of worsening renal function was lower (25% vs 38%; P = .037) in the experimental treatment group. CONCLUSIONS: In this hypothesis generating study, among patients with ADHF and hepatic dysfunction, concomitant use of IV albumin and furosemide for the first 72 hours resulted in a significant improvement in subjective perception symptoms of decongestion and a milder increase in creatinine levels than IV furosemide alone.

Aged↗

PubMed2026

Immunohistochemical evaluation of Ki-67 and GLI1 in sporadic and nevoid basal cell carcinoma syndrome-associated odontogenic keratocysts.

INTRODUCTION: Odontogenic keratocyst (OKC) is a developmental odontogenic cyst that may occur sporadically (OKCsp) or in association with nevoid basal cell carcinoma syndrome (NBCCS) (OKC-sy). NBCCS is an autosomal dominant disorder characterised by morphological abnormalities and an increased predisposition to several neoplasms, including basal cell carcinomas. Mutations in the tumour suppressor gene PTCH1 have been reported in patients with OKC and NBCCS. PTCH1 participates in a signalling cascade that culminates in the translocation of GLI transcription factors to the nucleus, thereby activating target genes involved in cell proliferation. Aberrant GLI1 expression has been associated with increased proliferation in lung adenocarcinoma and other cancers. OBJECTIVE: To compare GLI1 and Ki-67 protein expression in OKCs associated with NBCCS versus sporadic OKCs. MATERIALS AND METHODS: We included 13 OKCsp and 9 OKCsy from a children's hospital and university ... Immunohistochemistry was performed using anti-GLI1 and anti-Ki-67 to assess GLI1 expression and cell proliferation. RESULTS: No significant differences were observed in GLI1 or Ki-67 expression in the epithelial component of OKCsy versus OKCsp. A positive correlation between GLI1 and Ki-67 expression was detected in the total sample (r = 0.71, p < 0.05). CONCLUSION: The positive correlation between GLI1 and Ki-67 expression in OKCs suggests an association between SHH pathway activity and cell proliferation in both sporadic and syndromic lesions.

GLI1↗

PubMed2026

Early infantile developmental and epileptic encephalopathy: clinical spectrum, diagnosis, outcomes, and evolving treatment strategies.

Early infantile developmental and epileptic encephalopathy (EIDEE) is among the most severe epilepsy syndromes, with onset before three months of age and an estimated incidence of approximately 10 per 100,000 live births. The 2022 International League Against Epilepsy classification unified the historically distinct Ohtahara syndrome and early myoclonic encephalopathy under a single diagnostic framework defined by frequent drug-resistant tonic and/or myoclonic seizures, an abnormal neurological examination, and an abnormal interictal electroencephalogram-most characteristically a burst-suppression pattern. This narrative review synthesizes the clinical, electrophysiological, neuroimaging, genetic, and therapeutic literature within the EIDEE framework. The clinical phenotype is characterized by central hypotonia, postnatal microcephaly, cortical visual impairment, and age-dependent syndromic evolution toward infantile epileptic spasms syndrome or Lennox-Gastaut syndrome in the majority of patients. Electroencephalography remains essential for syndromic classification, while systematic metabolic screening and early trio whole-exome or whole-genome sequencing are central to the etiologic workup, achieving diagnostic yields of 60-65%. The most commonly identified genetic causes include STXBP1, KCNQ2, and SCN2A variants. Outcomes are poor overall and strongly etiology-dependent: vitamin-responsive disorders carry a substantially more favorable prognosis, whereas mortality reaches 25% in genetic cohorts. Genotype-guided pharmacotherapy is now applicable to a clinically meaningful subset of patients, with sodium channel blockers, potassium channel openers, and emerging antisense oligonucleotide therapies representing important therapeutic advances. Gene therapy trials are underway but have encountered early safety signals, underscoring the vulnerability of this population. Critical unmet needs include earlier molecular diagnosis, precision therapies targeting developmental outcomes beyond seizure control, and prospective international registries to characterize the long-term natural history of EIDEE.

Humans↗

PubMed2026

Chinese herbal medicine Xiangsu Hewei Granules in treating non-erosive gastroesophageal reflux disease with liver stomach stagnation heat syndrome: A multicentre, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiangsu Hewei Granules are an herbal preparation that has shown potential for controlling symptoms of nonerosive gastroesophageal reflux disease (NERD) in preliminary studies. However, high-quality randomized controlled evidence for its use in NERD remains lacking. AIM: To verify the efficacy and safety of Xiangsu Hewei Granules in treating NERD with liver stomach stagnation heat syndrome. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, multicentre phase III trial included 480 patients (aged 18-65 years) with confirmed NERD (GerdQ≥8; negative H. pylori) and traditional Chinese medicine (TCM) liver stomach stagnation heat syndrome. Patients were randomized 3:1 to receive either Xiangsu Hewei Granules or placebo, thrice daily for 8 weeks. The primary outcomes were the effective rate of the response based on visual analog scale (VAS) scores for heartburn and acid regurgitation at week 8. The secondary outcomes included reductions in the TCM syndrome score, etc. RESULTS: 479 participants (mean age 48.5 years, SD10.2; 54.3% female) entered the full analysis set and safety set (360 tests group; 119 control group, 1 participant in the control group withdrawing before medication). At week 8, compared with the control group, the test group demonstrated significantly better effective rate of VAS score response for heartburn(76.39% vs 21.01%, 95% CI 55.38 (45.98, 62.94) %, p < 0.01),acid regurgitation (79.72% vs 23.53%, 95% CI56.39 (46.90, 64.12) %, p < 0.01), and TCM syndrome score (69.23% vs 30.13%, p < 0.01) at week 8. CONCLUSION: In this selected population of NERD patients with liver-stomach stagnation heat syndrome (e.g., negative H. pylori, no pH-impedance phenotype, and low anxiety/depression scores), Xiangsu Hewei Granules demonstrated efficacy and safety in improving heartburn, acid regurgitation, and TCM syndrome scores. However, generalizability to the broader NERD population and its comparative effectiveness against standard proton pump inhibitor therapy require further investigation.

Humans↗

PubMed2026

Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Dietary therapy is central to irritable bowel syndrome (IBS) management, yet the long-term durability of the low-FODMAP diet (LFD), and of microbiome-guided personalization, remains unclear. We assessed the long-term clinical and gut-microbiome effects of a microbiome-guided personalized diet (PD) compared with a standard LFD in adults meeting Rome IV criteria for IBS. In this multicenter, open-label randomized controlled trial with blinded outcome assessment, participants who completed a 6-week dietary intervention (PD or LFD) were followed at 6 and 12 months without further dietary intervention. Outcomes included the IBS Severity Scoring System (IBS-SSS), IBS Quality of Life (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS); gut microbiota were profiled by 16S rRNA sequencing. Longitudinal changes were evaluated using linear mixed-effects models, responder analyses, PERMANOVA, and PERMDISP. Both diets reduced IBS-SSS at 6 weeks. PD maintained symptom improvement at 6 and 12 months (-82.0 and -78.3 points from baseline), whereas LFD benefits regressed by 12 months (+29.3 points; between-group p = 0.001). At 12 months, IBS-SSS responder rates were higher with PD than LFD (62.5% vs 34.5%; absolute risk difference +28.0%, 95% CI 4.2-47.7; Fisher p = 0.029), and IBS-QOL, HADS-anxiety, and HADS-depression showed more favourable trajectories with PD. PD was associated with sustained Shannon alpha-diversity gains (+0.488 at 6 weeks; +0.205 at 12 months; both p < 0.01). A modest between-group beta-diversity difference at 6 months (R2 = 0.035; p = 0.011) was not significant at 12 months. This hypothesis-generating follow-up suggests more durable benefit with PD; larger trials powered for long-term clinical and microbiome outcomes are warranted.

Humans↗

PubMed2026

Clinical efficacy and brain mechanism characteristics of guide chi and regulate spirit tuina therapy in the treatment of post-stroke walking dysfunction: A randomized controlled trial based on fNIRS.

BACKGROUND: This study aims to preliminarily evaluate the role of Guide Chi and Regulate Spirit(GCRS) Tuina in enhancing walking function in post-stroke patients with walking dysfunction; secondly, by using functional near-infrared spectroscopy (fNIRS), it investigates the effect of GCRS Tuina on the restoration of brain function in this patient population. METHODS: Participants in the control group received 4-week rehabilitation treatment, while those in the Combined Tuina Group (CTG) additionally received GCRS Tuina therapy for another 4 weeks on this basis. Functional Ambulation Category (FAC), Fugl - Meyer Assessment Scale for Lower Extremity Motor Function (FMA - LE), and Modified Barthel Index (MBI) were evaluated at the baseline and after 4 treatment weeks. A gait and motion analysis system was used to measure step length, stride, walking speed, and step frequency. FNIRS was used to measure the resting-state functional connectivity(FC) strength, as well as the β - value and HbO2 concentration mean during the walking task. RESULTS: A total of 60 participants completed the randomized, and 53 completed the trial and entered the statistical analysis. Compared with the Single Rehabilitation Group(SRG), the CTG group had higher FAC, FMA-LE, and MBI scores after 4 weeks. After the treatment course, the standardized step length, stride, walking speed, and step frequency of the CTG were higher than SRG. At the Region of Interest(ROI) level, the CTG exhibited 13 inter-ROI FC strengths that were higher than SRG, and the differences could survive the FDR correction (PFDR<0.05). Under the walking task, the CTG group had higher β values in 18 channels and higher Oxyhemoglobin(HbO2) concentrations in 19 channels than the SRG (PFDR <0.05). CONCLUSION: GCRS Tuina therapy can significantly improve patients' walking function, enhance lower limb motor ability and daily living ability. It can improve walking efficiency. Tuina can significantly increase the FC and enhance the activation levels and HbO2 concentrations. The stimulation of Tuina may help reconstruct the brain's motor control network, restore impaired motor function, promote the occurrence of neural plasticity, strengthen the neural circuits in the cognitive-motor-sensory cortex to improve walking function. TRIAL REGISTRATION: This study has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR2024000654).

Humans↗

PubMed2026

Protein sorting and proteostasis mechanisms in CFTR-related exocrine pancreas dysfunction: A systematic narrative review.

The pancreas consists of exocrine and endocrine compartments. In the exocrine pancreas, cystic fibrosis transmembrane conductance regulator (CFTR) functions mainly in ductal epithelial cells as a chloride and bicarbonate channel. Its activity depends on proper protein folding, trafficking, and localization to the apical membrane. This systematic narrative review aims to synthesize the available evidence on the role of protein sorting machinery in CFTR channelopathies and its contribution to exocrine pancreatic dysfunction. A thorough search was conducted using PRISMA criteria on PubMed, Wiley Online Library, and Scopus for studies published in English between January 2000 and November 2025. Twenty studies that met the inclusion criteria were included in this review. Pathogenic CFTR variants impair protein folding, endoplasmic reticulum (ER) exit, and endosomal recycling, resulting in reduced apical membrane expression and stability. These defects disrupt the localization of associated transporters and secretory proteins, impair ductal bicarbonate secretion, alter zymogen handling, and promote acinar injury, although these claims are supported mainly by indirect experimental models and therefore require clinical confirmation. CFTR channelopathies in the exocrine pancreas encompass both ion transport defects and broader disruptions of protein sorting machinery. CFTR may contribute to the assembly, stabilization, or localization of selected apical transport complexes, and its loss can secondarily alter epithelial organization. Therapeutic approaches targeting both channel correction and intracellular trafficking may improve pancreatic function and mitigate disease progression.

Humans↗

PubMed2026

Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Hypermobile Ehlers-Danlos Syndrome (hEDS), characterized by joint hypermobility and multisystem involvement, is the most common type of EDS. Its comorbidities are wide-ranging, reflecting the involvement of connective tissue and its role in a multitude of processes. hEDS has been hypothesized to have hormonal aspects since the disorder is diagnosed more often in women and symptom changes closely correlate with hormonal shifts. To better understand the etiology and biochemical changes in hEDS and its comorbidities, a multiple-omics study was performed in women, controls (n = 45) and those with hEDS (n = 45), alongside the collection of questionnaires related to symptom severity. Metabolomic evaluation was performed on serum samples and RNA isolated from fibroblasts cultured from skin punches was analyzed for transcriptomics. Samples from hEDS patients had statistically significantly lower levels of multiple androgen sulfate metabolites, compared with controls, driven largely by participants aged 30-49. Changes to other classes of steroid hormones (corticosteroids, progestogens, and estrogens) were largely not significant between hEDS and control groups. Transcriptomics of skin fibroblasts from hEDS patients revealed downregulation of multiple enzymes involved in biosynthesis, metabolism, and disposition of androgens, compared with controls. Multiple steroid hormones correlated with symptoms surveyed in 18-29 year old participants with hEDS. Shifts in steroid hormone metabolites in hEDS compared with controls may be due to changes to metabolism and disposition, but more validation is necessary to be conclusive. This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities.

Humans↗

PubMed2026

Differential contributions of mt-Tr and Cs variants to developmental cochlear defects and mitochondrial dysfunction in A/J mice.

A/J mice exhibit early-onset hearing loss linked to Cdh23, mitochondrial tRNA-Arg (mt-Tr), and citrate synthase (Cs) variants. Although developmental cochlear defects have been identified in juvenile A/J mice, the hierarchical contributions of mt-Tr versus Cs remain unclear. Using reciprocal intercross-derived strains to decouple mitochondrial haplotypes from nuclear factors, we demonstrate that the mitochondrial background is the primary determinant of auditory dysfunction. Mice with A/J mtDNA (AXB strains) displayed significantly higher ABR thresholds, accelerated hair cell attrition, and severe stereocilia dysmorphology compared to those with B6 mtDNA (BXA strains), occurring largely independently of the Cs genotype. While the Cs mutation exacerbated hearing loss, its impact was secondary to that of the dominant mitochondrial background. Systemic behavioral assessments and mitochondrial assays confirmed that A/J mitochondria exert a more profound metabolic impact than the Cs mutation. Our findings establish that the mitochondrial genomic background, with the mt-Tr locus as a prominent candidate variant, serves as the principal driver of developmental cochlear defects and early-onset hearing loss in A/J mice, while the nuclear Cs mutation acts as a synergistic modifier. This study underscores the critical role of mitonuclear crosstalk in inner ear maturation and provides new insights into the etiology of hereditary hearing loss.

Animals↗