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Children and young people with intellectual and developmental disability have long been known to suffer from inequities in accessing safe and quality health care. These challenges are most felt within the emergency department due to its busy, crowded, and overstimulating environments with staff that are not trained to provide reasonably adjusted care. The study is an evaluation using qualitative and quantitative methods of a continuing education and quality improvement programme designed to increase the knowledge, skills, and confidence of healthcare staff in providing reasonable adjustments to children and young people with intellectual disability in hospitals. This study evaluated the Motivated for Change programme, which uses Behavioural change, Adult Learning, and Quality Improvement strategies to drive practice change and service improvement. A hundred and thirty-one and 89 staff participated in a pre- and post-intervention survey. Interviews were conducted with parents of children and young people with intellectual and developmental disability attending the emergency department. Observational studies were also conducted in the pre- and post-intervention phase. These were transcribed, categorised, and coded with themes derived. Consensus was reached through meetings with the research team. The Motivated for Change programme has demonstrated significant increases in staff knowledge, skills, and experience in providing safe and quality care for these children and young people. Evidence of change is reflected in the parent and staff interview and observational study themes. In addition, staff were further motivated to undertake quality improvement projects, develop an in-house training programme to provide ongoing training for new staff, and make further improvements in the department. The Motivated for Change programme has demonstrated its efficacy in enabling changes in the practice of reasonable adjustments and the emergence of local champions for sustained efforts for ongoing improvements in safety and quality of care. The development of the research question and outcome measures was informed by data from previous research publications involving parents and staff. We sought input from a parent advisory committee in the design of the study. Parents were not involved in the recruitment and conduct of the study. Results were presented to the parent advisory at the end of the study.

The incidence and mortality of malignant tumors remain persistently high, while current clinical chemotherapeutic agents are often limited by significant drug resistance and adverse reactions. Consequently, small-molecule compounds derived from traditional Chinese medicine(TCM) have emerged as a focus in anti-tumor research owing to their advantages of multi-targeting action and low toxicity. As the core active component of Glycyrrhiza uralensis, glycyrrhizic acid(GA) is an oleanane-type pentacyclic triterpenoid saponin, constituting 5%-11% of the total content of G. uralensis. Its anti-tumor activity has been validated across various tumor systems, with mechanisms of action encompassing key processes such as cell cycle arrest, induction of tumor cell apoptosis, inhibition of tumor angiogenesis, blockage of invasion and metastasis, regulation of the tumor immune microenvironment(TIME), and alleviation of chronic inflammation. In terms of its therapeutic value, the combination of glycyrrhizic acid with other agents, such as tanshinone Ⅱ_A(Chinese medicine) or cisplatin(conventional chemotherapy) can achieve enhanced efficacy, reduced toxicity, targeted delivery, and reversal of drug resistance. This positions GA as possessing dual values, functioning both as a therapeutic agent and as a drug delivery carrier. This review systematically summarized the anti-tumor pharmacological activities, mechanisms, combined medication potential, and safety profiles of GA. It elaborated on the network mechanism of core regulatory hubs, analyzed the limitations of current research, and proposed targeted strategies for clinical translation. This work aims to provide a reference for the transition of GA from fundamental research to clinical application, while also offering a paradigm for the development of anti-tumor small-molecule compounds from TCM.

Protein supplements have gained popularity among gym users in Saudi Arabia. This study aimed to collect data from adults in Saudi Arabia focusing on six components related to protein supplements: demographic characteristics of participants, health and physical activity information, knowledge and attitudes, use, health beliefs, and safety concerns. This study was a cross-sectional, observational online survey targeting adults in Saudi Arabia. Participants included males and females aged 18 and older. Participants who did not complete the survey, as well as pregnant or breastfeeding women, were excluded. Ethical approval was obtained from the Deanship of Scientific Research at Qassim University. Data were analyzed by gender using SPSS version 25, with descriptive statistics and chi-square tests. A total of 358 participants completed the online questionnaire, while two participants did not complete it between March 29, 2024 and December 31, 2024. Regarding knowledge and attitudes, about 68.2% of participants (including both users and non-users of protein supplements) were aware of protein supplements, with males (81.3%) showing significantly higher awareness than females (63.7%). Additionally, 64.8% of participants (both male and female) were unaware of the risks associated with protein supplements. Of all participants, 56% of males and 39.3% of females did not believe that natural protein sources are enough for muscle building, indicating a significant difference. About 127 participants (35.5%) reported using protein supplements either currently or in the past, with no significant difference between males and females. Of those who reported using protein supplements, 11.8% experienced some side effects and were significantly less knowledgeable about the amount of protein they should consume from food and how much protein is enough for their needs. The majority of protein supplement users (48.8%) did not know if protein powders could contain doping agents, with females reporting significantly higher responses than males. Regarding safety concerns, only 43.3% of protein supplement users looked for protein supplements marked with NSF Certified for Sport® on the package, with no significant difference between males and females. Finally, 78% of protein supplement users expressed a need for more information on how to select the best protein supplements, with the highest need found in females and participants who exercise regularly, who showed significantly higher needs for additional guidance. There remains a significant need for increased education about the proper use of protein supplements to minimize potential side effects and increase understanding of their health risks and safety concerns.

We evaluat the efficacy and safety of adeno-associated virus-mediated gene therapy for CNGA3- and CNGB3-associated achromatopsia. Human studies were systematically searched from database inception to March, 2026, and 9 studies were included. Pooled analysis showed modest, but statistically significant, improvement in best-corrected visual acuity, with a mean difference of 2.65 ETDRS letters, and significant improvement in contrast sensitivity. Retinal sensitivity did not improve significantly, whereas color discrimination showed small but significant improvement. Dose-stratified findings suggested a non-linear response, with greater benefit at lower to intermediate doses than at the highest dose. Safety analysis indicated an approximate adverse-event probability of 29%, with events generally mild, transient, and manageable. Current evidence suggests favorable short- to mid-term safety and modest functional benefit, mainly in CNGA3-associated achromatopsia, while efficacy in CNGB3-associated disease remains uncertain.

GNAO1-related disorders (GNAO1-RD), caused by variants in GNAO1 encoding the Gαo protein, comprise a broad phenotypic spectrum including movement disorders (MD) and/or epilepsy and are typically associated with developmental delay and intellectual disability. Currently, only symptomatic treatments are available. Zinc can restore guanosine triphosphate hydrolysis and cellular interactions of dysfunctional Gαo. ZINCGNAO1 evaluated the safety and feasibility of oral zinc supplementation in GNAO1-RD. ZINCGNAO1 was a 6-month, open-label, fixed-dose, single-centre pilot trial in Germany. Eligible participants were aged 6 months to 30 years, had a genetically confirmed GNAO1 variant, at least one hallmark feature of GNAO1-RD (MD, hypotonia, epilepsy, or global developmental delay), and had a Gross Motor Function Measure-66 (GMFM-66) score of 75 or lower. Zinc acetate dihydrate was administered orally in age-dependent dosages. Primary outcomes were safety, assessed by adverse event monitoring and laboratory analyses, and feasibility, defined as treatment adherence of at least 80% of days. Exploratory secondary outcomes included changes in MD severity (Burke-Fahn-Marsden Dystonia Rating Scale-Movement Score, BFMDRS-M, Abnormal involuntary movement scale, AIMS), and related disability (BFMDRS-Disability Score), motor function (GMFM-66), quality of life (Caregiver Priorities and Child Health Index of Life with Disabilities, CPCHILD), occupational performance (Canadian Occupational Performance Measure performance and satisfaction scores, COPM-P/-S), epilepsy, and participant- or caregiver-reported outcomes. This trial was registered at ClinicalTrials.gov (NCT06412653) and the EU Clinical Trials Register (2024-512735-72-00) and is complete. Between Aug 2, 2024, and Jan 27, 2025, 13 participants with 11 different genetic variants were enrolled; 11 completed the follow up of the trial. Mean age at inclusion was 8.0 years (range 0.5-25.1). Overall treatment feasibility was 84.6% (11/13). No treatment-related serious adverse events occurred, and laboratory monitoring did not identify clinically relevant safety concerns during the 6-month treatment period. Exploratory secondary outcomes showed no change in MD severity. The mean BFMDRS Disability Score decreased from 25.5 (SD 2.6) to 23.5 (SD 2.8; nominal p = 0.005). Mean GMFM-66 increased from 33.1 (SD 12.8) to 37.8 (SD 12.8, nominal p = 0.006). COPM-P increased from 2.6 (SD 0.8) to 3.8 (SD 1.3; nominal p = 0.003), and COPM-S from 2.7 (SD 0.9) to 4.1 (SD 1.7; nominal p = 0.002). CPCHILD and seizure occurrence showed no clear treatment-related change; two participants had seizures during the trial. Our preliminary findings show that oral zinc supplementation was safe and feasible in this GNAO1-RD population. Exploratory secondary outcomes suggested possible improvements in motor function and daily activities. Larger controlled trials are needed to assess efficacy. GNAO1-Gemeinsam nicht allein e.V.

Population aging has created an urgent need for innovative and culturally grounded educational strategies to prepare a compassionate and competent elder care workforce. This mixed-methods action research study explored the effects of an 18-week intergenerational, music-based educational intervention on Indigenous university students' aging knowledge, attitudes toward older adults, and caregiving willingness in Taiwan. Guided by contact theory, transformative learning, and cultural safety frameworks, the program combined classroom learning, structured intergenerational music activities at community care centers, and reflective group sessions. Twenty-two Indigenous students participated in the study. Quantitative results indicated significant improvements in aging knowledge, attitudes toward older adults, and caregiving willingness, with large effect sizes across all measures. Qualitative thematic analysis identified three mechanisms of change: challenging stereotypes and fostering emotional connection through intergenerational contact; perspective transformation through critical reflection; and strengthening cultural identity and caregiving intentions within a culturally safe learning environment. These findings highlight the effectiveness of integrating intergenerational and arts-based approaches with cultural safety principles in gerontological education. This low-cost, scalable model provides an innovative pathway for reducing ageism and cultivating a culturally responsive elder care workforce, particularly among Indigenous students and other culturally diverse groups.

To evaluate clinical outcome and safety of procedural conscious sedation and analgesia (PCSA) performed by interventional radiologists (IRs) for patients undergoing percutaneous high-dose-rate brachytherapy (HDR-BT) of the liver. This large-scale, monocentric, retrospective study analyzed the safety-profile of PCSA using fentanyl and midazolam in patients undergoing HDR-BT for liver tumors. Medication was administered by trained IRs exclusively responsible for drug administration and cardiorespiratory monitoring. American Association of Anesthesiologists (ASA) status was recorded for all patients. Peri- and post-interventional complications directly or presumably related to PCSA, were assessed. Between 08/2017 and 12/2023, 1062 minimally invasive tumor ablations were performed in 686 patients with: 29.4% hepatocellular carcinoma, 28.7% metastasized colorectal cancer, 6.4% cholangiocarcinoma, metastases from lung cancer (6.1%), pancreatic cancer (4.1%), neuroendocrine tumors (5.1%) and 15.8% other metastases. PCSA-related complications were low (14/1062 procedures, 1.3%). Peri-interventional arrhythmias occurred during 4 procedures (0.4%). One patient (0.09%) experienced severe hypoxemia requiring brief cardiopulmonary resuscitation with return of spontaneous circulation, intubation and ICU-admission. Multivariable regression showed no significant correlations of PCSA-related complications with age, sex, BMI, ASA, chronic obstructive pulmonary disease (COPD), liver cirrhosis or medication doses but a significant correlation of obstructive sleep apnea syndrome (OSAS). No peri- or post-procedural deaths occurred. PCSA can safely be performed by adequately trained IRs with standardised protocols and support from anesthesiologists for emergencies or high-risk-patients. Careful patient selection, hemodynamic monitoring, structured PCSA documentation and immediate availability of anesthesiological support for severe AEs are essential to minimize risks. PCSA in OSAS should be managed by anesthesiologists.

Understory ecological cultivation of Chinese medicinal herbs is a crucial component of China's national strategy for developing forest-based economies, yet it frequently faces challenges such as low yields and high production costs. This review synthesizes comparative studies on the active constituent content of nine medicinal herbs-Panax ginseng, P. quinquefolius, P. notoginseng, Polygonatum, Dendrobium, Paris polyphylla, Coptis chinensis, Bletilla striata, and Epimedium-between understory cultivation and field cultivation. The findings indicate that Dendrobium in understory cultivation systems generally exhibit higher levels of polysaccharides than greenhouse-grown counterparts. For C. chinensis, alkaloid content shows no significant difference between understory cultivation and shaded field cultivation. Extended growth periods enable P. ginseng and P. quinquefolius to achieve total and rare ginsenoside concentrations surpassing those of short-cycle cultivated counterparts. The quality of Polygonatum, P. notoginseng, P. polyphylla, and B. striata is influenced by forest stand type and shade intensity, with no clear patterns yet established. Flavonoid accumulation in Epimedium is sensitive to canopy closure, exhibiting an optimal light-intensity range. Moreover, understory cultivation enhances soil microbial diversity and reduces the abundance of certain phytopathogens, suggesting potential ecological pest/disease-suppression effects, although direct evidence regarding pest/disease incidence rates and agrochemical residues remains lacking. Overall, the impact of understory cultivation on medicinal herb quality is species-specific and environmentally contingent, with quality advantages likely arising from moderate abiotic stress, extended growth duration, and enhanced biodiversity. Future research should standardize experimental designs, quantify key ecological factors, and deepen mechanism understanding of forest-medicinal herb interactions to support high-quality industry development.

To systematically investigate the Chinese food market for food-grade microbial strains in 2025, clarify the fundamental attributes such as the concept, classification, and efficacy types of these strains, analyze differences in domestic and international policies, standards, and management models, assess the current market development status and core issues. A combination of literature review and field survey was adopted. First, the evolution, definition, classification system, and efficacy types of food-grade microbial strains were systematically reviewed. Second, differences in the policy frameworks and management models for food-grade microbial strains between domestic and international contexts were compared. Finally, based on survey data collected from 470 ordinary food products containing food-grade microbial strains from July to October 2025, quantitative and qualitative analyses of market size, product characteristics, and existing issues were conducted. The food-grade microbial strains have a long history of application, with their concepts and classifications continuously refined as biotechnology advances. In 2022, both domestic and international lists of microbial strains were updated, and the reclassification of lactobacilli had a significant impact on the food industry. The Chinese market for food-grade microbial strains showed sustained growth, reaching a terminal market size of 134.89 billion yuan in 2024. Products were diversifying and becoming more refined, with composite microbial agent-containing products dominating the market. However, issues such as non-standard labeling, unauthorized functional claims for ordinary foods, and insufficient support for food-grade microbial strain testing technology persisted. Additionally, while both domestic and international regulations prioritized safety and emphasized strain-specific characteristics, notable differences existed in regulatory classification, approval process design, and health claim requirements. The Chinese food market for food-grade microbial strains has significant growth potential. However, addressing existing issues requires multifaceted measures, including strengthening full-chain supervision of labeling standards, improving the inspection and testing technology system for food-grade microbial strains, strictly regulating the functional claims of ordinary foods, and enhancing the core competitiveness of domestic enterprises. These efforts will help resolve current market challenges and promote the industry's sustainable development toward standardization and high quality.

Most in vitro chemical safety workflows are performed in ambient air, although many human tissues experience substantially lower physiological oxygen levels. This mismatch can alter redox tone, stress-response signaling, and interpretation of chemical effects. Here, we present R3ACT (Redox & Antioxidant Capacity Tracker), an animal-free, oxygen-controlled live-cell NAM for mechanistic profiling of redox perturbation and antioxidant-response activation. In human HaCaT keratinocytes adapted to 5 kPa O₂, R3ACT combines viability-gated concentration selection, oxygen-controlled plate-reader measurements, high-content microscopy, and deep-learning-assisted single-cell analysis. The workflow integrates cytosolic and mitochondrial HyPer7.2 biosensors for H₂O₂ dynamics with POINTER, an Nrf2 transcriptional reporter, to assess antioxidant-response engagement. As proof of concept, four exposure-relevant materials were profiled in the main screen, with iron formulations assessed as additional pharmaceutical case examples. Zinc oxide produced the strongest reproducible Nrf2 activation across two independent runs, confirmed by single-cell microscopy. Polystyrene nanoplastics likewise showed reproducible, microscopy-confirmed Nrf2 activation, whereas perfluorooctanoic acid showed a borderline response that was not confirmed by microscopy. Salicylic acid induced Nrf2 activation under physiological oxygen and was interpreted as antioxidant-response engagement rather than skin-sensitization classification. HyPer7.2 provided compartment-specific mechanistic context, but often revealed transient fluctuations rather than consistent material-induced H₂O₂ increases. Together, these data position R3ACT as an early-stage, oxygen-controlled NAM that may support animal-free chemical and drug-screening workflows by generating mechanistic redox/Nrf2 response profiles for compound prioritization. Further benchmarking, predefined performance criteria, and inter-laboratory studies are required before regulatory applicability can be assessed.

Acute exacerbation of chronic obstructive pulmonary disease(AECOPD) constitutes the acute deterioration phase of chronic obstructive pulmonary disease(COPD), typified by an abrupt intensification of respiratory symptomatology, encompassing exacerbated dyspnea, heightened cough severity, augmented sputum volume, and pronounced respiratory insufficiency. Systemic inflammatory cascades serve as a cardinal etiological driver of AECOPD, emanating from multifaceted host-pathogen interactions involving viral, bacterial, or polymicrobial infections, superimposed upon environmental modulators that collectively precipitate accelerated pathological progression. These contributory elements markedly escalate the inflammatory milieu within the small airways, surmounting endogenous anti-inflammatory safeguards, thereby precipitating airway epithelial barrier disruption, microvascular dilation, edema, and prolific immune cell infiltration, which in turn perpetuate an inflammatory amplification loop. Such mechanisms converge to synergistically impair pulmonary function and extend durations of inpatient care. Current therapeutic paradigms for AECOPD predominantly incorporate bronchodilators, anti-inflammatory pharmacotherapies, supplemental oxygen administration, and mechanical ventilatory support. Notwithstanding these interventions, persistent limitations include the adverse sequelae of protracted systemic glucocorticoid therapy, escalating antimicrobial resistance profiles, and ventilator-associated morbidities. Ergo, there exists an imperative to investigate novel therapeutic modalities that confer enhanced safety and efficacy. TCM proffers salient therapeutic merits via its multi-target and multi-pathway pharmacodynamics, facilitating regulation of pivotal signaling pathways, including the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB), NF-κB/NOD-like receptor pyrin domain containing 3(NLRP3), phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), Janus kinase(JAK)/signal transducer and activator of transcription(STAT), and neutrophil elastase(NE)/mucin 5AC(MUC5AC) pathways. Through such regulatory interventions, TCM efficaciously attenuates inflammatory response, ameliorates symptomatic burden, and diminishes the incidence of AECOPD. The present investigation endeavors to delineate systematically the extant advancements in TCM-mediated regulation of inflammation-related signaling pathways within the context of AECOPD, thereby furnishing a robust theoretical framework and empirical guidance for optimized clinical interventions and pharmaceutical innovations in AECOPD management.

Neuro-emotional technique (NET) is a structured mind-body intervention used by certified practitioners to identify and address stress-related emotional patterns associated with physiological and behavioural responses. Published NET research has described changes in psychological symptoms, pain, quality of life, brain physiology, inflammatory markers, and blood chemistry, yet the mechanisms underlying these effects remain incompletely defined. This narrative review and conceptual synthesis propose that memory reconsolidation theory and predictive processing provide complementary frameworks for understanding how NET may influence stress-linked somatic-emotional patterns. Reconsolidation research suggests that previously consolidated emotional memories may become temporarily labile following reactivation if a sufficient prediction error occurs, permitting updating before restabilisation. Predictive processing models propose that emotional learning may be expressed as embodied predictions about threat, safety, self, action, and physiological demand, rather than solely as conscious narrative recall. Taken together, these frameworks suggest that the clinically relevant target of NET may be a body-brain prediction pattern rather than a discrete memory or a fixed physiological state. This article introduces somatic-emotional updating to describe the proposed modification of emotionally encoded physiological prediction patterns through concurrent emotional activation and contradictory embodied experience. Within this model, NET may create clinical conditions in which a stress-linked somatic-emotional pattern is reactivated while the patient simultaneously experiences a sense of present-time safety, interoceptive attention, practitioner support, and non-threatening somatosensory input. This combination is proposed to constitute embodied mismatch, the clinical expression of prediction error, which may provide conditions consistent with reconsolidation-relevant updating. The model does not propose that NET has been proven to induce memory reconsolidation. Rather, it identifies structural parallels between the NET clinical sequence and reconsolidation phases and proposes somatic-emotional updating as a theoretically coherent and falsifiable hypothesis for future research. Proposed research priorities include measuring durable changes in target emotional reactivity, autonomic regulation, biological stress markers, and adaptive function following NET, as well as comparing full NET with modified protocols that isolate key procedural elements.

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This paper systematically evaluated the efficacy, safety, and economic profile of oral Chinese patent medicine for the treatment of inflammatory bowel disease(IBD) through rapid health technology assessment. A total of 145 studies(including 110 RCTs) were included, involving 23 kinds of Chinese patent medicines. The results demonstrate that most Chinese patent medicines, used alone or combined with western medicine, exhibit superior outcomes in terms of total clinical efficacy, improvement of TCM syndrome patterns, and disease activity compared to western medicine alone, with a favorable safety. And the adverse reactions are predominantly mild gastrointestinal or neurological symptoms. Average daily costs range from 1.12 to 39.00 yuan. However, economic research is insufficient. There is sufficient evidence showing that Shenling Baizhu San/Pills/Granules and Bupi Yichang Wan for spleen deficiency with Qi stagnation, as well as Guchang Zhixie Wan/Capsules for liver depression with spleen deficiency pattern have notable advantages in efficacy, safety, and recurrence rate reduction. Nevertheless, the methodological quality of current research is generally low, with substantial heterogeneity in outcome indicators, and lack of long-term follow-up and real-world evidence. High-quality clinical research, pharmacoeconomic evaluations are urgently needed to support decision-making and rational drug use.

This study aims to investigate the phototoxic effects of imperatorin(IMO) and its potential mechanisms of inducing skin photodamage and cellular senescence. A phototoxicity model was established on the dorsal skin of SD rats, which were randomly divided into a control group, an IMO group(0.8 mg&#xb7;cm~(-2)), a long-wave ultraviolet A(UVA) group(10 J&#xb7;cm~(-2)), and an IMO + UVA group. The rats were continuously observed for 72 h, and Draize skin scores were assessed. Hematoxylin-eosin(HE) staining was used to observe histopathological changes, and Verhoeff-Van Gieson(VVG) staining was utilized to evaluate changes in dermal elastic and collagen fibers. Human dermal fibroblasts(HDF) were cultured in vitro and divided into control, IMO, UVA(1 J&#xb7;cm~(-2)), and groups of IMO with low, medium, and high doses(1, 2.5, and 5 &#x3bc;g&#xb7;mL~(-1)) + UVA. The CCK-8 assay was used to assess the cell viability. Transcriptomics by RNA-seq was used to analyze the changes in gene expression. Real-time quantitative PCR(RT-qPCR) was used to detect the mRNA expressions of the top 10 senescence-associated genes. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of senescence-associated secretory phenotype(SASP) factors like matrix metalloproteinase-3(MMP-3), interleukin(IL)-6, and IL-8. Immunofluorescence was used to evaluate the senescence-associated heterochromatin foci(SAHF) markers like heterochromatin protein 1&#x3b3;(HP1&#x3b3;) and trimethylation of histone H3 at lysine 9(H3K9me3). Senescence-associated &#x3b2;-galactosidase(SA-&#x3b2;-gal) staining was performed to detect the senescent cells, and Western blot was used to detect the expression and localization of growth arrest and DNA damage-inducible alpha(GADD45A), G_2/M phase-specific cyclin B1(Cyclin B1), and cyclin-dependent kinase 1(CDK1) proteins. Flow cytometry was used to analyze the cell cycle. The siRNA was used to silence GADD45A gene to verify its function. In vivo results show that, compared to the control group, the IMO + UVA group has significantly higher skin damage scores, with stratum corneum loss, inflammatory cell infiltration, reduced collagen fiber density, and abnormal deposition of elastic fibers. In vitro results demonstrate that IMO + UVA significantly inhibits the cell viability of HDF(P<0.05). RNA-seq and RT-qPCR verifications indicate that IMO + UVA significantly upregulate the expressions of senescence-associated genes, with GADD45A gene showing the most significant change. The IMO + UVA group also shows significant increases in SASP factor secretion, SA-&#x3b2;-gal activity, SAHF formation, and the proportion of cells in the G_2/M phase(P<0.05). Western blot results demonstrate that IMO + UVA promote the expression of GADD45A protein and inhibit nuclear translocation of Cyclin B1, thereby reducing the kinase activity of the Cyclin B1-CDK1 complex. Silencing GADD45A gene effectively alleviates G_2/M phase arrest and cellular senescence phenotype. In summary, IMO in combination with UVA can induce photodamage to the skin and accelerate cellular senescence, and the mechanism may involve G_2/M phase arrest mediated by the activation of the GADD45A/Cyclin B1/CDK1 axis.

Sex-based differences in treatment response to neuroprotective strategies during endovascular treatment (EVT) for acute ischemic stroke remain poorly understood. This study aimed to evaluate sex-specific effects of methylprednisolone on outcomes after EVT for acute ischemic stroke due to large vessel occlusion. Secondary analysis of the MARVEL (Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke) randomized controlled trial. We compared outcomes following methylprednisolone versus placebo, stratified by sex. We also compared outcomes between women and men receiving methylprednisolone. The primary outcome was defined as the 90-day modified Rankin Scale score (mRS) ordinal shift. Secondary outcomes included mRS score of 0-4, 0-3, 0-2, 0-1 at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 hours. This study included 1680 patients (49.9% methylprednisolone, 56.7% men). Stratified by sex, among men, the methylprednisolone group was more likely to have a primary outcome compared with placebo [adjusted OR (aOR) 1.26 (1.00-1.59), P = 0.047] and reduce mortality (P < 0.01) and sICH (P = 0.031); among women, the primary outcome was similar between two treatment arms (P = 0.66), with similar findings for the safety outcomes. Additionally, stratified by different treatment arms, no significant difference was found in the primary outcome between men and women treated with methylprednisolone (P = 0.31) and placebo (P = 0.68). In this exploratory analysis, methylprednisolone appeared to be associated with better clinical outcomes in men compared with placebo. Nevertheless, the interaction between treatment and sex was not statistically significant. Furthermore, among patients receiving methylprednisolone, clinical outcomes did not differ significantly between men and women. ChiCTR.org.cn Identifier: ChiCTR2100051729. This study looked at whether an anti-inflammatory drug called methylprednisolone has different effects in men and women who had a severe stroke caused by a large blood clot in a brain artery and underwent a procedure called endovascular treatment to remove the clot. The research was based on data from a large clinical trial that included 1,680 patients. About half received methylprednisolone and the other half received a placebo. The researchers compared outcomes between men and women who received the drug versus placebo, and also directly compared men and women who received the drug. The results showed that among men, those who received methylprednisolone had better recovery of daily functions 90 days after the stroke compared to men who received placebo. They also had lower rates of death and symptomatic bleeding in the brain. Among women, however, there was no significant difference in recovery between those who received methylprednisolone and those who received placebo. When researchers directly compared men and women who both received methylprednisolone, their recovery outcomes were not significantly different. In summary, this study suggests that methylprednisolone may be more helpful for recovery in men with this type of stroke, while the benefit in women was less clear. These findings indicate that sex may be an important factor to consider when using this medication in future stroke treatment.

Genomic research on high-consequence Risk Group 4 (RG4) viruses is significantly hindered by the stringent biosafety level 4 (BSL-4) containment requirements, because virus inactivation prior to removal from containment often compromises nucleic acid integrity. As a focused solution to retain nucleic acid integrity as well as safety compliance, we developed and validated a comprehensive suite of optimized workflows compatible with BSL-4 containment and next-generation sequencing applications. We systematically assessed inactivation, homogenization, and RNA extraction methods to establish robust bulk RNA sequencing workflows for diverse sample types. We also adapted state-of-the-art single-cell RNA sequencing (scRNA-seq) by integrating inactivation steps without compromising data quality. To demonstrate feasibility, we conducted scRNA-seq analysis on cells exposed to Lassa virus. Additionally, we optimized viral genome enrichment strategies for high-depth sequencing of multiple RG4 viruses. These validated workflows enable safe, reproducible, and high-resolution genomic analyses of RG4 pathogens, significantly expanding the experimental toolkit for BSL-4 research.

Total thyroidectomy, a procedure for various thyroid pathologies, is traditionally performed using conventional clamp-and-tie hemostasis (CH). Advanced high-energy devices (HEDs), including the Harmonic Scalpel (HS) and LigaSure (LS), offer energy-based vessel sealing with potential efficiency gains, but safety concerns and cost implications remain. This systematic review and Bayesian network meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety of energy-based hemostasis devices versus CH in total thyroidectomy. This Systematic review included 22 prospective RCTs, published between 2005 and 2022, enrolling 3,824 patients. The primary outcomes included operative time (OT), intraoperative blood loss (IOBL), and transient recurrent laryngeal nerve (RLN) injury and hypocalcemia. Secondary outcomes were postoperative hematoma (POH), postoperative drain output (POD), and length of hospital stay (LOS). Intervention rankings were determined using the Surface Under the Cumulative Ranking Curve (SUCRA), SUCRA values reflect the probability that an intervention ranks higher relative to others for a given outcome and do not indicate a clinical or statistical superiority; therefore, they should be interpreted alongside effect estimates and credible intervals. In comparison with CH, both HS and LS were statistically significantly superior, reducing OT by approximately 22&#xa0;min (HS: SUCRA 0.76, LS: SUCRA 0.73). HS demonstrated further significant superiority over CH, reducing LOS by -0.37 days (SUCRA 0.93) and POD output by -24 mL (SUCRA 0.87). While HS showed a numerical reduction in IOBL, this difference did not reach statistical significance, yet HS ranked highest for this outcome (SUCRA 0.91). Importantly, no significant differences were detected among HS, LS, and CH for key safety outcomes, including transient RLN palsy, transient hypocalcemia, and POH. Energy-based hemostasis devices, particularly HS, were associated with shorter operative time and reduced postoperative fluid output and hospital stay compared with conventional clamp-and-tie hemostasis. However, the certainty of evidence for most outcomes was moderate to low, the analysis was underpowered to establish equivalence for rare safety events, and the modest clinical gains should be weighed against device costs and local operating-room efficiency. These findings support conditional, context-dependent use of HEDs rather than routine preference for any single device.

Clinical settings generate real-world data (RWD), which offers valuable insights into pharmaceutical effectiveness and safety. Agencies, such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA) of Japan, are increasingly using Real-World Evidence (RWE) in their decision-making processes. Registries play a critical role in RWE studies by systematically collecting patient data. Implementing stringent quality control and quality assurance measures is essential to achieve RWD reliability. This study identified the essential quality elements for registry-based RWD and developed a proposed data quality management checklist. A scoping review of peer-reviewed literature and regulatory guidelines published between 2001 and 2026 was conducted using PubMed, Embase, and the websites of major regulatory agencies. Eligible studies included those addressing RWD, RWE, and data quality checklist relevant to registry-based research. In total, 30 sources, comprising 24 publications and 6 institutional guidelines, were included. The analysis identified two core dimensions of data quality: relevance (availability, sufficiency, and representativeness) and reliability (accuracy, completeness, provenance, and timeliness). We developed a quality assessment checklist that addresses the following four key domains: study design, data collection and management, regulatory compliance, and continuous improvement. The proposed checklist offers a structured framework to enhance the reliability of RWD and enable systematic quality assessment. Future studies should assess its applicability across various research settings. This study supports robust data quality management, benefiting researchers, regulatory agencies, pharmaceutical companies, and healthcare institutions.