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PubMed2026

Divergent responses of the gill, hepatopancreas, and eyestalk to acute alkalinity stress in Penaeus vannamei: Osmoregulatory compromise, metabolic trade-off, and endocrine disruption.

The expansion of aquaculture into inland saline-alkali waters is constrained by high carbonate alkalinity (CA), a severe environmental stressor for crustaceans. However, the systemic molecular mechanisms underlying its lethal toxicity remain poorly understood. In this study, we employed a comparative transcriptomic approach to investigate the tissue-specific responses of Pacific white shrimp, Penaeus vannamei, under acute lethal stress (48 h-LC50). We focused on three functionally distinct organs: the gill, hepatopancreas, and eyestalk. The results revealed a systemic but highly tissue-specific transcriptomic response. The gill, as the primary interface, exhibited severe structural impairment and critical failure of osmoregulation, highlighted by the significant downregulation of delta-1-pyrroline-5-carboxylate synthetase (P5CS). In contrast, the hepatopancreas initiates a profound metabolic trade-off, sacrificing growth-related pathways to bolster a robust antioxidant defense system, as evidenced by the activation of sulfur metabolism and high protein turnover. The eyestalk displayed a striking disconnect between hyperactivated stress signaling pathways (e.g., mTOR/FoxO) and the collapse of its protein secretory machinery, marked by the suppression of the ER translocon component Sec61. Collectively, our findings suggest that lethal alkalinity toxicity in P. vannamei results from systemic collapse driven by a complex interplay of osmoregulatory failure, metabolic trade-offs, and endocrine disruption. This study provides a comprehensive molecular snapshot of an organism at its physiological limit, offering novel insights into the adaptive strategies and ultimate tolerance boundaries of crustaceans in extreme environments.

Animals↗

PubMed2026

Associations of Illness Perception, Resignation Coping, and Social Support With Self-Regulatory Fatigue in Patients With Type 2 Diabetes: A Cross-Sectional Study.

AIMS: To examine the associations among illness perception, resignation coping, social support, and self-regulatory fatigue (SRF) in patients with Type 2 diabetes mellitus. The study specifically explores whether resignation coping and social support exhibit indirect associations with SRF in the context of illness perception. DESIGN: A cross-sectional study. METHODS: From November 2024 to October 2025, a convenience sample of 302 adult patients with T2DM was recruited from a tertiary general hospital in China. Participants completed validated instruments with established psychometric properties, namely the Brief Illness Perception Questionnaire, the Medical Coping Modes Questionnaire, the Perceived Social Support Scale, and the Self-Regulatory Fatigue Scale. Statistical analyses included Spearman correlation and serial mediation analysis using the PROCESS Macro (Model 6) with bias-corrected bootstrapping. RESULTS: SRF was positively correlated with negative illness perception (r = 0.579, p < 0.01) and resignation coping (r = 0.612, p < 0.01), and negatively correlated with social support (r = -0.598, p < 0.01). Serial mediation analysis revealed that illness perception was associated with SRF through indirect pathways involving resignation coping and social support. Resignation coping and social support mediated the association between illness perception and self-regulatory fatigue, both individually and sequentially. CONCLUSIONS: Negative illness perception correlates with higher SRF. This observed correlation is additionally linked to indirect pathways involving resignation coping and lower social support. Collectively, these findings highlight a pattern of interrelated cognitive (illness perception), behavioural (resignation coping), and resource (social support) factors that are associated with self-regulatory fatigue in this cross-sectional study. IMPLICATIONS FOR THE PROFESSION: The findings offer a clear, evidence-based framework for nursing practice. They highlight the potential value of integrated assessment and intervention that simultaneously addresses patients' illness beliefs, maladaptive coping strategies, and social support systems, which are associated with lower SRF and better diabetes self-management. REPORTING METHOD: This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: Patients participated solely as research participants by providing survey data. They were not involved in the study design, implementation, data analysis, interpretation, or manuscript preparation. All patients provided written informed consent prior to questionnaire completion.

Humans↗

PubMed2026

The Childhood Cancer and Leukemia International Consortium (CLIC): Expanding global collaboration in pediatric cancer etiology research.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

Humans↗

PubMed2026

In Vivo Genome Editing Approach to Disrupt Hydroxyacid Oxidase 1 for the Treatment of Primary Hyperoxaluria Type 1.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that leads to kidney and liver failure. PH1 is caused by a mutation in the alanine glyoxylate aminotransferase (AGXT) gene, which encodes a key metabolic enzyme that converts glyoxylate to glycine in the liver. Inability to metabolize glyoxylate leads to oxalate overproduction, yielding insoluble calcium oxalate crystals; accumulation of these crystals leads to progressive organ failure. Here, we used a novel, minimally disruptive genome-editing approach to disrupt the mechanism of action of hydroxyacid oxidase 1 (HAO1), an upstream enzyme in the glyoxylate metabolic pathway. Successful gene editing and disruption of the HAO1 gene is expected to increase levels of glycolate, a harmless intermediate of the glycine metabolic pathway, thereby preventing the formation of calcium oxalate crystals. We intravenously administered an adeno-associated virus (AAV) vector expressing the M1HAO1 meganuclease to both wild-type and Agxt-/- mice, a mouse model of PH1. We observed >30% editing of HAO1 in Agxt-/- mice, correlating with a dose-dependent increase in serum glycolate levels. At the highest dose tested, urine glycolate levels increased by 79%, with a concomitant 75% decrease in urine oxalate levels. We also evaluated in vivo targeting in rhesus macaques injected with AAV expressing two different versions of the HAO1 meganuclease. Dose-dependent editing of hepatic DNA and RNA was achieved, and serum glycolate levels changed in a manner consistent with successful liver editing; additionally, the treatment was well tolerated. Our results indicate that AAV-delivered meganucleases can effectively target HAO1 in mice and nonhuman primates to achieve high levels of HAO1 gene editing. Moreover, increased glycolate levels in serum indicate that this intervention significantly impacts the HAO1-mediated glycolate-to-glyoxylate pathway. These data suggest that this approach may represent an effective treatment for PH1.

Hyperoxaluria, Primary↗

PubMed2026

Mesenchymal Stem Cell-Derived Exosomes Combined With 3-Dimensional Hyaluronan-Based Scaffold Promote Tendon-to-Bone Tunnel Healing.

PURPOSE: Tendon-to-bone healing remains a major clinical challenge due to poor regenerative capacity at the enthesis. This study aimed to evaluate the effects of mesenchymal stem cell-derived exosomes combined with a 3-dimensional hyaluronan-based scaffold on graft healing within bone tunnels. This study was conducted in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines. METHODS: A total of 128 tendon-bone models were created in 64 Sprague-Dawley rats, randomized into four groups: control, exosome-only, scaffold-only, and exosome-loaded scaffold. At weeks 4 and 8 postoperatively, samples were analyzed histologically (hematoxylin-eosin, Masson Trichrome), immunohistochemically (fibroblast growth factor 2, bone morphogenetic protein 2), and biomechanically (maximum failure load). RESULTS: At both time points, the exosome-loaded scaffold group demonstrated significantly enhanced vascularization, cellular activity, and collagen fiber continuity and parallelism compared to all other groups (P < .05). Fibroblast growth factor 2 and bone morphogenetic protein 2 expression levels were highest in the exosome-loaded scaffold group, indicating early activation of proregenerative pathways. Biomechanically, this group also exhibited the greatest maximum failure load (15.64 ± 0.86 N at week 4; 22.97 ± 2.86 N at week 8), suggesting superior tendon-to-bone integration. The exosome-only group showed delayed but comparable improvements by week 8. CONCLUSIONS: Combining mesenchymal stem cell-derived exosomes with a 3-dimensional hyaluronan-based polycaprolactone/tricalcium phosphate scaffold enhances early and sustained healing at the tendon-bone interface. This cell-free, biocompatible strategy significantly improves vascularization, growth factor expression, collagen organization, and mechanical strength. These findings support its potential as a clinically translatable approach for improving tendon-to-bone healing outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Animals↗

PubMed2026

Cognitive behavioural therapy-based interventions on stress outcomes in pregnant women: A systematic review and meta-analysis.

BACKGROUND: Stress symptoms were the most common psychological problem in pregnancy. Cognitive behavioural therapy-based interventions are effective for antenatal depression and anxiety symptoms; but there are fewer studies for stress symptoms. OBJECTIVE: The review aims to (1) examine the effectiveness of cognitive behavioural therapy-based interventions in reducing stress outcomes (pregnancy-specific stress symptoms, generic symptoms, and objective stress) in pregnant women, and (2) identify significant moderators affecting the effectiveness of the intervention. DESIGN: Systematic review, meta-analysis, and meta-regression analysis of randomised controlled trials. METHODS: We conducted a three-step search (12 databases, 4 clinical registries, and citation searches) in English and Chinese up to July 24, 2025, by two independent reviewers. Meta-analysis, subgroup, and meta-regression analyses were performed using the R software. Quality assessment and certainty of the evidence were assessed with the Cochrane risk-of-bias tool version 2 and Grading of Recommendations, Assessment, Development, and Evaluation criteria. Publication bias was assessed using funnel plots and Egger's test. RESULTS: We included 20 randomised controlled trials involving a total of 6966 pregnant women from nine countries. Random-effects meta-analyses found that interventions significantly alleviated pregnancy-specific stress symptoms (Hedges' g = -0.84, 95% Confidence Interval, CI -1.42, -0.26, p < .01, I2 = 92.3%), reduced generic stress symptoms (g = -0.64, 95% CI -1.09, -0.20, p < .01, I2 = 87.4%) with median and large effect sizes at post-intervention. No effect was found in lowering cortisol levels (g = -0.99, 95% CI -2.58, -0.60, p = .12, I2 = 84%) at post-intervention. Subgroup and meta-regression analyses indicated that region, age of participants, use of intention-to-treat, missing data management analyses, frequency, modalities, and approaches of interventions, use of different comparators, and attrition rate were significant factors affecting the effectiveness of interventions. Subgroup analyses suggested that the intensity of intervention should be more than once per week using a blended mode among Asian populations. Multivariate meta-regression analyses indicated that both younger age (β = 0.13, p = .02) and a lower attrition rate (β = 0.03, p = .03) significantly improved the effectiveness of interventions. The overall certainty of the evidence was rated as either very low or low. CONCLUSIONS: Cognitive behavioural therapy-based interventions can supplement antenatal care to alleviate pregnancy-specific stress symptoms and generic stress symptoms, particularly in young Asian women. However, the evidence has some uncertainties. These findings should be interpreted with caution due to substantial heterogeneity. Well-designed trials on a large-scale with long-term follow-ups were needed. REGISTRATION: PROSPERO registration ID: CRD420251115913.

Humans↗

PubMed2026

Integrated Telehealth Rehabilitation and Quality of Life in Mechanically Ventilated Adults: A Randomized Clinical Trial.

IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P = .04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P = .34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P = .03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P < .001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.

Humans↗

PubMed2026

Congenital Laryngomalacia: Pathophysiology, Clinical Spectrum, and Holistic Management.

Congenital laryngomalacia is the most common cause of infant stridor and arises from interacting structural, neuromuscular, and inflammatory mechanisms that produce dynamic supraglottic collapse. Disease severity spans mild stridor to significant obstruction, aspiration, and failure to thrive, often influenced by comorbid medical conditions. Diagnosis relies on flexible laryngoscopy supported by instrumental swallowing studies and microdirect laryngoscopy and bronchoscopy when indicated. Most infants respond to conservative management, particularly targeted feeding modifications, while acid suppression offers benefit in selective cases. Supraglottoplasty provides effective, durable improvement for severe disease and significantly enhances infant outcomes and family quality of life.

Humans↗

PubMed2026

Feasibility and barriers to same-day physical therapy following lumbar fusion surgery.

OBJECTIVE: To evaluate the feasibility of same-day (postoperative day 0; POD0) physical therapy (PT) following lumbar fusion and to identify factors associated with failure to participate. METHODS: This retrospective study analyzed prospectively collected data from patients undergoing single-level posterior spinal fusion (PSF), with or without anterior (ALIF) or lateral (LLIF) interbody fusion, between January and December 2024 at a single institution. A standardized POD0 PT protocol was implemented for eligible patients. Patients were categorized into two groups: successful POD0 PT (ambulatory on POD0) and unable to participate. Demographic and surgical variables were compared between groups. Reasons for inability to participate were recorded and categorized. RESULTS: Among 129 patients in whom POD0 PT was attempted, 84 (65%) successfully participated, while 45 (35%) were unable. There were no significant differences in age, sex, BMI, ASA class, operative time, estimated blood loss, or surgical approach between groups. Patients who successfully completed POD0 PT had a significantly shorter hospital length of stay compared to those who did not (3.4 ± 1.6 vs 5.8 ± 2.9 days, P < 0.001), with no differences in complication rates, discharge disposition, emergency department visits, or reoperation rates. The most common barriers to POD0 PT were postoperative pain, medical issues (e.g., orthostatic hypotension, nausea, dizziness), and anesthesia-related somnolence. Less common factors included postoperative restrictions and logistical issues such as brace availability. CONCLUSIONS: POD0 PT following lumbar fusion is feasible in the majority of patients and is associated with a shorter hospital stay without increased complications. Failure to participate was not associated with the baseline patient or surgical characteristics evaluated in this study. Instead, the most common barriers were postoperative pain, transient medical issues, and anesthesia-related somnolence, suggesting that optimization of modifiable perioperative factors may improve the implementation of POD0 PT.

Humans↗

PubMed2026

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals↗

PubMed2026

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, α-smooth muscle actin (αSMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans↗

PubMed2026

[Clinical efficacy and safety of electroacupuncture at the motor area for Parkinson's disease with musculoskeletal pain: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of electroacupuncture (EA) at the motor area for Parkinson's disease (PD) with musculoskeletal pain. METHODS: Fifty-eight patients with PD accompanied by musculoskeletal pain were randomly assigned to an EA group (29 cases, 1 case dropped out) and a sham EA group (29 cases, 1 case dropped out). The EA group was treated with EA at the motor area contralateral to the painful side (for bilateral pain, the left motor area was selected), using disperse-dense wave (2 Hz/20 Hz), with a current intensity of 1-2 mA, and needles were retained for 30 min. The sham EA group was treated with sham EA at non-acupoint area located 5-20 mm posterior to the motor area contralateral to the painful side. The connection mode was the same as that in the EA group, but no electrical current was delivered, and the needles were retained for 30 min. Both groups were treated once daily for 5 consecutive days. Visual analogue scale (VAS) for pain, unified Parkinson's disease rating scale part Ⅲ (UPDRS-Ⅲ), 24-item Hamilton depression rating scale (HAMD-24), Hamilton anxiety rating scale (HAMA), and 39-item Parkinson's disease questionnaire (PDQ-39) scores were evaluated before treatment, immediately after treatment, and at 2 and 4 weeks after treatment completion in the two groups. Safety was also assessed in the two groups. RESULTS: In both groups, VAS scores for pain after treatment and at 2 and 4 weeks after treatment completion were lower than those before treatment (P<0.01, P<0.05). VAS scores for pain in the EA group were lower than those in the sham EA group after treatment and at 2 and 4 weeks after treatment completion (P<0.05). In the EA group, UPDRS-Ⅲ, HAMD-24, HAMA, and PDQ-39 scores after treatment and at 2 and 4 weeks after treatment completion were lower than those before treatment (P<0.05, P<0.01). In the sham EA group, there were no statistically significant differences in UPDRS-Ⅲ, HAMD-24, HAMA, and PDQ-39 scores at any post-treatment time point compared with those before treatment (P>0.05). There were no statistically significant differences in UPDRS-Ⅲ, HAMD-24, HAMA, and PDQ-39 scores between the two groups at any post-treatment time point (P>0.05). No serious adverse events occurred during the trial. CONCLUSION: EA at the motor area could reduce pain intensity in patients with PD accompanied by musculoskeletal pain, and improve pain-related motor symptoms, emotional status, and quality of life, with a favorable safety profile.

Humans↗

PubMed2026

Contact tracing for hepatitis C: perspectives of people with experience of substance use and hepatitis C on intervention acceptability.

INTRODUCTION: Chronic hepatitis C (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. In the UK, the principal risk factor for HCV is injecting drug use. The introduction of direct acting anti-virals (DAA's) have transformed HCV care, with cure rates of over 95%. However, HCV is often asymptomatic, and reinfection is a concern. Modelling and real-life studies demonstrate the potential effectiveness of a contact tracing approach for finding people who have acquired HCV through injecting drug use. However, it is not used routinely in the UK. This qualitative study was undertaken to assess the acceptability of a contact tracing approach to identify people who have injected drugs with an index patient recently diagnosed with HCV. METHODS: Twelve people with lived or living experience of injecting drug use and an HCV diagnosis were interviewed using semi-structured interview topic guides. Participants were purposefully selected according to the inclusion criteria and to ensure there was an even spread of male and female participants. Sekhon's Theoretical Framework of Acceptability, incorporating seven components (affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness, and self-efficacy) was used to analyse data from interview transcripts. RESULTS: A sample of 12 people who inject drugs in the UK indicated that a contact tracing approach was acceptable across two components of Sekhon's acceptability framework: affective attitude and ethicality. Participants broadly found the idea of tracing people who may be at risk of contracting HCV acceptable, and the approach aligned with their value systems. A contact tracing approach would help alleviate concerns about putting other people's lives at risk through HCV transmission and was seen as a 'sensible' way of finding people at risk. However, there were caveats to this acceptability. Contact tracing approaches delivered by mainstream health, or governmental organisations increased burden, opportunity costs and perceived effectiveness of a contact tracing approach for HCV, particularly within contexts of exclusion and criminalisation of people who inject drugs. Burden and opportunity costs were also affected by individual experiences and risks of violence, sexual violence and abuse. There was a lack of knowledge of contact tracing approaches amongst respondents, leading to a lack of intervention coherence and misunderstandings of what contact tracing was and how it would work. Trusted relationships with NGOs and HCV specialist nurses reduced burden and increased confidence and ability (self-efficacy) to engage with a contact tracing approach. CONCLUSION: People who inject drugs broadly perceive contact tracing as an acceptable method of finding people who are at risk of HCV. However, this acceptability is based on specific modes of delivery through trusted organisations. Findings further highlight the importance of naming and describing contact tracing approaches appropriately, as well as assessing and mitigating against potential risk to index patients, to increase self-efficacy and capacity to engage. Considering these findings, the potential for expanding existing contact tracing approaches should be explored to ensure the UK reaches and maintains its elimination targets.

Humans↗

PubMed2026

Intravenous Nicorandil in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: The CLEAN Randomized Clinical Trial.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium-channel opener with nitrate-like properties, may reduce reperfusion injury and microvascular obstruction in ST-segment elevation myocardial infarction (STEMI), but large-scale randomized evidence on long-term clinical outcomes is inconclusive. OBJECTIVES: The CLEAN trial aimed to assess whether adjunctive intravenous nicorandil improves 12-month clinical outcomes in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial conducted at 49 hospitals in China, patients aged 18 to 80 years with STEMI within 12 hours of symptom onset were randomly assigned (1:1) to receive intravenous nicorandil (6 mg bolus before reperfusion followed by 6 mg/h infusion for 48 h) or matching placebo. Oral nicorandil was prohibited during follow-up. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, or unplanned hospitalization for heart failure within 12 months. RESULTS: Between January 2021 and December 2023, 1,503 patients were enrolled and randomly assigned to nicorandil (n = 748) or placebo (n = 755). The primary composite outcome occurred in 98 patients (13.1%) in the nicorandil group (113 events over 717.2 person-years) and 99 (13.1%) in the placebo group (136 events over 710.3 person-years), with no significant difference between groups (rate ratio: 0.869; 95% CI: 0.650-1.162; P = 0.3429). Among secondary outcomes, nominal reductions were observed in cardiovascular death (1.9% vs 3.6%; HR: 0.515; 95% CI: 0.269-0.983) and target-vessel revascularization (1.1% vs 3.0%; HR: 0.322; 95% CI: 0.143-0.727), whereas rates of nonfatal myocardial infarction and unplanned hospitalization for heart failure were similar between groups. Adverse events did not differ between groups. CONCLUSIONS: In patients with STEMI undergoing primary percutaneous coronary intervention, adjunctive intravenous nicorandil did not significantly reduce the 12-month primary composite outcome. These findings do not support routine use of intravenous nicorandil in unselected patients with STEMI. (Clinical Efficacy and sAfety of Intravenous Nicorandil; NCT04665648).

Humans↗

PubMed2026

Valproate vs levetiracetam in juvenile myoclonic epilepsy: systematic review and meta-analysis.

INTRODUCTION: Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome with onset typically in adolescence and a chronic course requiring long-term antiseizure medications (ASMs). Valproate (VPA) is the most effective treatment for seizure control in JME but use is limited by metabolic, cognitive, and teratogenic adverse effects (AEs). Levetiracetam (LEV) is an alternative ASM when VPA is contraindicated or not tolerated. Comparisons of the efficacy and long-term tolerability of VPA and LEV remain limited. METHODS: We conducted a systematic review and meta-analysis using PRISMA guidelines and the Cochrane Handbook. We searched PubMed, Embase, and the Cochrane Library from inception through January 2026 for studies in JME patients comparing LEV and VPA, and included randomized controlled trials and comparative observational studies with ≥ 6 months of follow-up. Primary outcomes were seizure remission and ASM failure or treatment discontinuation. Secondary outcomes included, memory impairment, weight gain or obesity, dizziness, and overall AEs. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Heterogeneity was assessed using the I2 statistic. RESULTS: Seven studies encompassing 1,009 patients were included. VPA was associated with higher pooled seizure remission rates compared with LEV (344 of 574 vs. 169 of 390; RR 1.44, 95% CI 1.27-1.63); however, substantial heterogeneity (I2 = 88.4%) limits confidence in this finding. VPA was associated with a lower risk of drug failure or treatment discontinuation (RR 0.68, 95% CI 0.54-0.86), with no heterogeneity (I2 = 0.0%). VPA was also associated with a higher risk of memory impairment (RR 5.37, 95% CI 2.05-14.04; I2 = 74.5%) and weight gain or obesity (RR 6.40, 95% CI 3.64-11.26; I2 = 35.9%). No significant differences were observed between treatments regarding dizziness (RR 0.91, 95% CI 0.61-1.37; I2 = 21.2%). Sensitivity analyses confirmed the robustness of the pooled estimates. CONCLUSION: VPA was associated with higher seizure remission rates and lower treatment discontinuation compared with LEV; however, these findings must be interpreted with caution given the substantial heterogeneity, the predominance of observational studies, and the serious risk of bias identified in most included studies VPA also demonstrated lower rates of treatment discontinuation, despite a higher burden of cognitive impairment and weight gain. No relevant differences were observed regarding dizziness. Large-scale randomized trials with standardized outcome definitions and longer follow-up are needed to define the comparative risk-benefit profiles of LEV and VPA in JME.

Humans↗

PubMed2026

All-inside repair is an effective treatment for medial meniscus posterior root tears: a systematic review and meta-analysis of biomechanical and clinical evidence.

BACKGROUND: Medial meniscus posterior root tears (MMPRTs) reproduce the biomechanics of subtotal meniscectomy. Repair is favored, but the role of all-inside repair (AR) remains unclear relative to transtibial pull-out (TP). This study aimed to review the biomechanical and clinical evidence on AR for MMPRTs. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO). MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Outcomes included patient-reported outcome measures (PROMs), magnetic resonance imaging (MRI), and biomechanical performance. When available, random-effects meta-analysis was performed. RESULTS: Thirteen studies were included. AR restored contact mechanics and showed load to failure comparable to TP, with lower stiffness. Meta-analysis showed lower conversion to total knee arthroplasty with AR versus non-repair (RR 0.18, 95% CI 0.05-0.58), and no significant PROM differences between AR and TP. CONCLUSIONS: AR showed favorable biomechanical properties and improved outcomes versus non-repair. Compared with TP, no significant clinical differences were observed. AR may represent a reasonable option in selected scenarios.

Humans↗

PubMed2026

Multi-omic biomarkers in cardiovascular disease: Discovery to clinical translation.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, necessitating improved risk stratification and early detection strategies. Multiomics approaches that integrate genomics, transcriptomics, proteomics, metabolomics, and epigenomics offer unprecedented opportunities for biomarker discovery and precision medicine in cardiovascular care. This narrative review examines the current landscape of multiomics biomarkers for CVD, tracing their evolution from discovery to clinical translation. We synthesize evidence from recent studies evaluating the clinical utility of integrated omics approaches across diverse cardiovascular conditions, including atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation. High-throughput proteomics has identified novel protein signatures that enhance cardiovascular risk prediction beyond traditional risk factors. Metabolomics has revealed pathway-specific biomarkers, including trimethylamine N-oxide and lipid species, associated with atherogenesis. Polygenic risk scores derived from genomic data demonstrate incremental value when combined with clinical risk scores. Multiomics biomarkers represent a transformative approach to cardiovascular risk assessment and disease management.

Humans↗

PubMed2026

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96 h-LC50 of the agent to juvenile M. edulis was 8.84 mg/L, and 10 mg/L of the agent completely inhibited mussel attachment within 24 h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals↗