To investigate the causal relevance of melatonin metabolism, which provides the biological basis for circulating melatonin levels, to specific depression symptom subtypes, we performed a targeted systematic review of melatonin metabolism pathways in the human brain and liver. Using two-sample Mendelian randomization (MR), we assessed the causal effects of metabolism pathways and/or individual genes on major depressive disorder (MDD) and nine symptom subtypes derived from Patient Health Questionnaire-9 (PHQ-9). Instrumental variables (IVs) were expression quantitative trait loci (eQTL) for eight individual genes, one synthesis route, and three degradation routes. Results were assessed using Bayesian colocalization and phenome-wide association analyses. At the pathway-level, the genetically proxied synthesis-route signal was associated with PHQ-9 Assessment 5 (PHQ9A5, OR: 0.89, 95% CI: 0.85-0.93), but sensitivity analyses suggested this association was primarily driven by TPH1 and may reflect serotonin-related biology. In contrast, higher brain melatonin degradation raised the risk of both PHQ9A1 (OR: 1.03, 95% CI: 1.02-1.04) and PHQ9A7 (OR: 1.03, 95% CI: 1.02-1.03). Within degradation, up-regulation of the kynurenine sub-pathway increased the odds of PHQ9A3 (OR: 1.05, 95% CI: 1.02-1.07), PHQ9A4 (OR = 1.04, 95% CI: 1.02-1.06) and PHQ9A7 (OR: 1.05, 95% CI: 1.02-1.07). Gene-level analyses were largely concordant, except for SULT1A1, whose higher expression was genetically protective for PHQ9A3 but risk-increased for PHQ9A1 and PHQ9A4. Overall, these results demonstrate that melatonin metabolism exerts symptom-specific and pathway-specific causal effects on depression. A stratified view of melatonin's role may help optimize the application of exogenous melatonin supplementation.

Nigeria's rapidly expanding older adult population, mirroring a global demographic shift, is driving a surge in dementia cases. Currently 4.9% of Nigerian older adults have dementia and this figure is set to increase. Fragmented care delivery, weak institutional infrastructure, and pervasive social stigma severely hinder effective diagnosis, treatment, and structural support. This paper proposes a Modern Service Framework for Dementia Care in Nigeria; a proactive, evidence-based national strategy designed to overhaul Nigerian healthcare delivery through six critical, intersecting pillars. The proposed framework establishes a coordinated intervention pathway by: (1). Creating integrated, communicative health systems, (2). Promoting healthy ageing and life-course prevention, (3). Driving diagnostic innovation and primary-care screening, (4). Raising targeted community, traditional, and religious awareness, (5). Scaling workforce capacity alongside sustainable funding mechanisms, and (6). Fostering cross-sectoral partnerships to safeguard vulnerable individuals. Rapid, formal adoption of this comprehensive framework is vital to mitigate the immense economic and caregiving burdens placed on families and the broader healthcare system, ultimately ensuring that every Nigerian living with dementia receives equitable, dignified, and rights-based support.

Traditional epidemiological surveillance methods are often limited by delays in reporting and fragmented data systems. Saudi Arabia faces additional public health challenges from mass gatherings during Hajj and Umrah, an increasing burden of noncommunicable diseases and rapid urbanization, highlighting the need for investing in digital epidemiology.

Saudi Arabia has accelerated digital transformation in health care through Vision 2030 initiatives. The strategies include health information exchange platforms, analytics driven by artificial intelligence, telemedicine services and digital monitoring systems used during Hajj. We review current initiatives to invest in digital epidemiology in Saudi Arabia, implementation challenges and policy priorities.

Saudi Arabia's health system operates under a predominantly public model. The health ministry is the main provider, regulator and finance provider of most health-care services. Health-care coverage is nearly universal, with citizens receiving services free of charge through the public system. Ongoing reforms aim to gradually decentralize certain functions.

The initiatives under Vision 2030 have supported disease surveillance, data integration and public health response capacities. Existing digital health reforms have created a foundation for integrating digital epidemiology into routine public health practice. However, challenges remain, including fragmented interoperability between institutions, workforce shortages, unequal digital access, and concerns about data governance, privacy and algorithmic bias.

Saudi Arabia's experience suggests that digital epidemiology is more effective when integrated within broader digital health reforms. Successful implementation requires not only digital infrastructure, but also workforce development, ethical governance, transparency and mechanisms for integrating digital data into public health decision-making.

Purpose: Most children with autism live in resource-limited settings with limited access to timely interventions. To address this gap, the World Health Organization developed Caregiver Skills Training (CST) to support caregivers and expand intervention access globally. This study examined the feasibility and preliminary outcomes of a modified CST in mainland China. Methods: Using the ecological validity model and qualitative interviews, the CST materials were culturally adapted and modified for the Chinese context. A pre- and post-test controlled trial was conducted with caregivers of children with autism aged 2-9 years, who were assigned to either the CST intervention group (N = 15) or a caregiver education control group (N = 15). Clinical outcomes for caregivers and children were evaluated at baseline and after a 10-week intervention period. Results: Cultural adaptation and modifications focused on language adjustments, localization of case examples and demonstrations, and optimization of teaching methods and training schedules. Supplementary within-group analyses indicated pre-post changes in caregiver knowledge and skills, parenting stress, and selected child outcomes, including speech/language/communication, sensory/cognitive awareness, and overall autism symptoms. However, most between-group differences were not statistically significant after baseline adjustment. Conclusions: The findings provide preliminary evidence for the feasibility of culturally adapted and modified CST in mainland China. Given the pilot nature of the study and the absence of statistically significant between-group effects for most outcomes, the outcome findings should be interpreted as exploratory and hypothesis-generating rather than evidence of efficacy. Further large-scale studies with greater statistical power and objective outcome measures are needed to evaluate effectiveness and implementation feasibility.

The intricate balance between angiotensin-converting enzyme 1 (ACE1) and 2 (ACE2) in the pulmonary vasculature is pivotal for the pathogenesis of pulmonary arterial hypertension (PAH). Catalysing the K48-linked deubiquitination, ubiquitin carboxyl-terminal hydrolase 10 (USP10) is involved in tumour suppression, autophagy, and cell proliferation. This study aims to determine whether a positive feedback loop of USP10 and AMP-activated protein kinase (AMPK) in pulmonary endothelium is protective against PAH.

In silico data analyses and in vitro culture cell experiments were used to investigate the role of USP10 in human idiopathic PAH (IPAH) and rodent pulmonary hypertension (PH) as well as the underlying mechanism involving a positive feedback loop of AMPK and USP10 in lung endothelium. Endothelial cell (EC)-specific USP10 transgenic (Tg) mice and mice administered liraglutide were used to explore the efficacy of the AMPK/USP10 loop in mitigating PH in rodents.

USP10 level was decreased in the lung endothelium of human IPAH and rodent PH. AMPK/USP10 loop activation increased ACE2 Ser-680 phosphorylation and Lys-788 deubiquitination, thus contributing to the homeostatic level of ACE2 and lung vascular patency. Mice with liraglutide administration phenocopied the mitigated PH in EC-specific USP10 Tg mice, in part because of the activated AMPK/USP10 loop in the pulmonary endothelium.

Genetic or pharmacologic [via glucagon-like peptide-1 receptor agonists (GLP-1 RAs)] interventions in the AMPK/USP10 loop can augment ACE2 level in lung endothelium. This type of ACE2 enhancement garners protection against PAH in humans and PH in rodents, which provides a rationale for using GLP-1 RAs to alleviate PAH.

Fragmented primary health care in China fails to tackle the growing burden of noncommunicable diseases. Despite substantial investment, fewer than half of patients with diabetes achieve glycaemic control.

Tianjin's 2020-2023 reform established a public-private partnership model where WeDoctor managed community health centres under a capitation scheme. This strategy integrated: (i) monthly prepaid capitation covering all diabetes-related outpatient services; (ii) claims auditing and clinical decision support using artificial intelligence (AI); (iii) dedicated health managers for care coordination; and (iv) redesigned services incorporating complication screening and digital medication management. A pilot study including 494 945 patients with diabetes compared three care models from 2022 to 2023: WeDoctor-community health centre care, hospital care and usual care.

Tianjin city serves 15 million residents through 177 hospitals and 266 community health centres. Chronic disease management is fragmented: the Health Commission regulates care standards, while the Insurance Bureau controls funding.

Visits for diabetes at WeDoctor health centres increased 2.6% (0.7/26.6) but declined 10.6% (-3.8/35.7) for hospital-based care and 2.3% (-0.8/34.1) for usual care. All groups reduced outpatient expenditure. The WeDoctor model generated a 37.62 million United States dollars (US$) surplus, boosted health centre diabetes revenue by 65% (US$ 154 577/237 805) and raised physician annual salaries by 30% (US$ 5172/17 241). More than three quarters of patients expressed satisfaction with and trust in the WeDoctor model.

Integrating capitation financing with third-party governance and AI support can strengthen primary health care, contain costs and enhance patient-centred care.

Background/Objectives: Bilateral thoracoscopic sympathectomy (BTS) is the definitive treatment for primary focal hyperhidrosis, yet postoperative pain remains an undertreated consequence with no established analgesic consensus. This study compared three analgesic regimens on pain trajectory, opioid consumption, and functional recovery following BTS. Methods: In this prospective observational cohort study, 300 patients undergoing BTS were allocated in a non-randomized manner reflecting institutional practice to three parallel cohorts (n = 100 each): Group 1 received systemic opioids alone; Group 2 received opioids plus pre-emptive local anesthetic wound infiltration; and Group 3 received opioids plus thoracoscopic-guided intercostal nerve block (ICNB). Primary outcomes included pain intensity on the Numerical Rating Scale and total opioid consumption. Results: ICNB patients reported significantly lower mean peak pain scores (3.8 ± 1.7) versus local infiltration (4.6 ± 1.9) and opioid-only groups (5.2 ± 2.1; p < 0.001). Total opioid consumption was reduced by 38% in the ICNB group (12.4 ± 4.8 mg vs. 20.1 ± 6.3 mg; p < 0.001). Moderate-to-severe pain occurred in 42.0% of ICNB patients versus 74.0% of controls (p < 0.001). ICNB was independently associated with reduced moderate-to-severe pain (adjusted odds ratio (AOR) 0.31; 95% confidence interval (CI) 0.17-0.56; p < 0.001). ICNB patients returned to normal activities faster (median 3 vs. 5 days; p = 0.008) with higher satisfaction (91.0% vs. 78.0%; p = 0.044). Conclusions: In this observational cohort, ICNB was associated with significantly lower postoperative pain scores, reduced opioid consumption, and faster functional recovery following BTS. These findings suggest that ICNB may be an effective adjunct analgesic strategy for ambulatory BTS, pending confirmation in randomized controlled trials.

Objective: We aimed to quantify the prognostic value of glucose monitoring-derived time in range (TIR), including continuous glucose monitoring (CGM), flash glucose monitoring (FGM), and fingertip capillary glucose monitoring (FCGM), for predicting adverse clinical outcomes in patients with type 2 diabetes mellitus (T2DM). Research Design and Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL, via OVID) were systematically searched from 2017 to November 2025 for studies evaluating the risk of all clinically relevant outcomes associated with different TIRs in T2DM. Extracted data were standardized to evaluate the effect of a 10% increment in TIR. Pooled estimates were calculated using inverse-variance random-effects models incorporating dose-response analysis. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Results: Twenty-four observational studies involving 20 distinct associations and 35,916 participants were included. Dose-response meta-analyses were conducted for nine associations. The results showed that each 10% increment in TIR was significantly associated with a reduced risk of multiple adverse complications, including all-cause mortality (odd ratio [OR] = 0.88, 95% confidence interval [CI]: 0.82-0.93), vision-threatening diabetic retinopathy (OR = 0.93, 95% CI: 0.87-0.98), diabetic retinopathy (OR = 0.92, 95% CI: 0.89-0.95), lower extremity atherosclerotic disease (OR = 0.86, 95% CI: 0.82-0.91), diabetic peripheral neuropathy (OR = 0.77, 95% CI: 0.71-0.84), and cardiovascular autonomic neuropathy (OR = 0.81, 95% CI: 0.68-0.97). In contrast, the associations for albuminuria (KDIGO [Kidney Disease: Improving Global Outcomes] A2 and A3) and amputation did not reach statistical significance in the primary meta-analysis. Conclusions: In conclusion, each 10% increment in TIR is consistently associated with a reduced risk of mortality and various micro- and macrovascular complications in T2DM. These findings suggest TIR as a robust prognostic indicator and actionable therapeutic target in diabetes management.

Background: Cardiovascular disease (CVD) remains the leading cause of mortality across the European Union (EU), with a fourfold to fivefold east-west gradient in standardized circulatory-disease mortality. Romania ranks second highest in the EU (787 per 100,000 inhabitants in 2023). Primary-prevention practice is organized around two quantitative frameworks-the 2021 European Society of Cardiology (ESC) SCORE2/SCORE2-OP system and the 2018/2019 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equations (PCE)-which converge on therapy but diverge on patient selection. Methods: We conducted a structured narrative review (SANRA-compliant) of contemporary primary-prevention guidelines, validation studies, key trials of risk-modifier interventions, and Romanian epidemiological data through April 2026. On this basis, we developed ROMA-CV (Risk Of Multifactorial Atherosclerosis-CardioVascular) as a conceptual, country-specific risk-stratification framework anchored to existing Class I/IIa recommendations or Level A/B evidence, rather than as a fully developed, ready-to-use clinical tool Results: Four structural limitations of SCORE2 are clinically consequential in Romania: (i) an age floor of 40 years that excludes the population in which premature myocardial infarction is most preventable; (ii) a country-level calibration coefficient applied to individuals; (iii) permissive treatment of lipoprotein(a) [Lp(a)]; and (iv) an under-emphasis of subclinical-atherosclerosis imaging. We propose ROMA-CV (Risk Of Multifactorial Atherosclerosis-Cardiovascular), a four-step algorithm retaining SCORE2 as the quantitative spine while embedding once-in-a-lifetime Lp(a) measurement, a mandatory amplifier checklist, and selective coronary artery calcium (CAC) or carotid/femoral ultrasound imaging. Conclusions: ROMA-CV is a hypothesis-generating proposal that operationalizes existing evidence-based recommendations into a deterministic Romanian pathway aligned with the 2025-2030 Romanian National Plan for Non-Communicable Diseases and the EU Cardiovascular Health Plan. The algorithm is not a validated clinical decision tool and requires prospective external validation in Romanian cohorts-alongside feasibility, cost-effectiveness, and implementation studies-before any consideration of routine clinical adoption.

Since organ donation after citizen death became the sole legal source in 2015, lung transplantation (LTx) in China has undergone a systematic transformation, shifting from numerical scarcity to scale expansion and from technical exploration to sustained improvement in quality. From a management perspective, this article provides a comprehensive review of the development of LTx in China between 2015 and 2024, demonstrating that its central achievement has been the establishment of an integrated management system that combines national top-level policy design, standardized and homogeneous training, multidisciplinary collaboration, standardized clinical pathways, and rigorous quality assessment. Supported by a mechanism based on data-driven decision making, standard-guided implementation, and closed-loop management, this system has effectively ensured quality homogeneity and controllable risk during the dissemination of advanced transplantation techniques. Over the past decade, the number of hospitals performing LTx increased from 9 to 45, annual procedure volume rose from 118 to 925 cases, and the cumulative total of completed LTx was 5483. During the same period, 30-day survival improved from 78.5% to 85.3%. This system-oriented management model provides an important reference for the global community, particularly for developing countries facing challenges related to resource imbalance, by demonstrating how institutional innovation can facilitate the safe and efficient dissemination of highly complex medical technologies.