Search Results (821)

Background: Insomnia requires long-term self-management, prompting many patients to turn to Traditional Chinese Medicine-based lifestyle (TCM-L) practices for health preservation. However, a consensus-based TCM-L content framework is lacking. This study aims to develop a consensus-based TCM-L content framework using a modified Delphi method. Methods: A modified Delphi study was conducted in two phases. In phase 1, a preliminary content framework was developed based on a systematic review, TCM textbooks, and clinical guidelines, consisting of 10 initial domains and 82 subordinate items. In phase 2, 18 local Chinese medicine practitioners were purposively recruited to evaluate the framework over four iterative rounds. Items were rated on a 5-point Likert scale, with consensus defined as a mean ≥ 4.0, a coefficient of variation < 0.25, and a consensus level of agreement ≥ 80%. Iterative modifications, deletions, and additions were informed by both these numerical thresholds and qualitative expert feedback. Kendall’s W was calculated to assess the coordination of consensus. Results: All 18 experts completed four rounds (100% response rate) with high authority (Cr = 0.864–0.883). The initial 10 domains and 82 subordinate items were refined to six domains and 49 subordinate items. Expert consensus was statistically significant across rounds (p < 0.01), with Kendall’s W demonstrating a high concordance of 0.717 for domain importance in the final round. The prioritized sequence of the six domains in the final TCM-L framework was: (1) Domain 1: introduction to TCM-L, (2) Domain 4: sleep–wake routines, (3) Domain 3: dietary regulation, (4) Domain 2: emotional regulation, and tied at (5) Domain 5: mind–body exercise and Domain 6: acupoint massage. Conclusions: This study established a consensus-based TCM-L content framework for insomnia, providing a culturally relevant foundational structure for future lifestyle interventions, clinical education, and self-management support. Full article

Infertility affects approximately one in six individuals worldwide and is a highly heterogeneous disorder resulting from the complex interplay of genetic, epigenetic, endocrine, environmental and lifestyle factors. Although numerous genes and molecular pathways involved in female and male infertility have been identified, elucidating the functional consequences of disease-associated variants remains challenging due to the lack of relevant human experimental models. In recent years, reproductive organoids have emerged as powerful three-dimensional systems that recapitulate key structural, cellular and functional characteristics of the ovary, fallopian tube, endometrium, testis and early embryo. Here, we review the current landscape of reproductive organoid models based on a focused analysis of the literature, with particular emphasis on original studies describing their generation, characterization and applications. Beyond modeling tissue development and reproductive physiology, these models provide unique opportunities to investigate infertility-associated mechanisms, gene regulatory networks, cell–cell communication and tissue-specific responses to environmental and pharmacological stimuli. Single-cell and spatial transcriptomics, multi-omics, CRISPR/Cas9 genome editing, artificial intelligence and bioengineering technologies, including organ-on-chip systems, are expanding their potential as next-generation platforms for functional genomics, disease modeling, biomarker discovery and therapeutic screening. However, current reproductive organoids remain simplified representations of native tissues, with limitations in physiological maturity, reproducibility and standardization, while their clinical predictive value remains to be established. Overall, by linking genomic variation with molecular regulation, cellular phenotypes and tissue organization, reproductive organoids represent promising preclinical platforms for understanding human infertility and may ultimately contribute to the development of precision reproductive medicine. Full article

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has become the most common chronic liver disease in childhood, paralleling the global increase in pediatric obesity and metabolic dysfunction. Once considered a benign condition, pediatric MASLD is now recognized as a heterogeneous and potentially progressive disease that may advance from simple steatosis to steatohepatitis, fibrosis, and, rarely, cirrhosis, with lifelong hepatic and cardiometabolic consequences. Its pathogenesis is multifactorial, involving insulin resistance, adipose tissue dysfunction, chronic low-grade inflammation, genetic and epigenetic susceptibility, environmental factors, and alterations in the gut microbiome. Most affected children are asymptomatic, and diagnosis is often prompted by elevated liver enzymes or incidental imaging findings. Noninvasive tools, including ultrasonography, elastography, serum biomarkers, and emerging multi-omics approaches, are improving disease detection and risk stratification, although liver biopsy remains the reference standard in selected cases. Lifestyle modification, including dietary optimization, increased physical activity, and gradual weight reduction, remains the cornerstone of management, while pharmacological therapies are still under investigation in pediatric populations. The marked variability in disease susceptibility; progression; and treatment response underscores the need for a personalized medicine approach. Integrating clinical characteristics with genomic, epigenomic, metabolomic, and microbiome data may enable early identification of high-risk children, more accurate prognostic assessment, and individualized preventive and therapeutic strategies. Early detection and multidisciplinary care involving pediatricians, hepatologists, endocrinologists, dietitians, and families may help reduce disease progression and the risk of long-term hepatic and cardiometabolic complications. This review summarizes current evidence on the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of pediatric MASLD, with a particular emphasis on precision diagnostics, biomarker discovery, and personalized therapeutic approaches. It also discusses current challenges and future directions for implementing personalized medicine to improve outcomes and reduce the lifelong burden of pediatric MASLD. Full article

Background: The Mediterranean diet (MD) has well-established health benefits, yet modern food systems are driving a nutrition transition. Quantifying how Mediterranean countries have shifted relative to global trends is essential for evidence-based public health. Aim: Dietary changes between 1990 and 2018 were examined in Mediterranean coastline countries (MED) in comparison with high-income non-Mediterranean countries (HIC non-MED) and middle-/low-income non-Mediterranean countries (MLIC non-MED). Methods: Using the Global Dietary Database, within-country changes (1990 vs. 2018) for 13 food categories were analysed across 185 nations in three groups: MED countries (n = 21), HIC non-MED (n = 18), and MLIC non-MED (n = 146). MED countries were further grouped into Southern Europe (SE), Western Asia (WA), and North Africa (NA). Paired unweighted country-level analyses were the primary analyses; population-weighted analyses were sensitivity checks. Benjamini–Hochberg’s false-discovery-rate correction and centred log-ratio compositional analysis were applied. Results: MED seafood intake rose from 20.5 to 33.8 g/day (Δ = +13.3 g/day; 95% CI: +6.2 to +18.4; q = 0.003), and non-starchy vegetables increased from 135.5 to 173.6 g/day (Δ = +38.0 g/day; q = 0.626). Refined/starchy carbohydrate intake rose by 63.3 g/day in MED countries while declining by 33.6 g/day in HIC non-MED countries (between-group divergence +96.9 g/day; q = 0.006). Nuts and seeds rose across all groups; legumes declined modestly in MED countries. Saturated fatty acids + omega-6 polyunsaturated fatty acids (% kcal) rose by +0.6 percentage points in MED countries but fell in HIC non-MED countries. Monounsaturated fatty acids were stable. MED-WA showed the greatest overall divergence from the SE 1990 pattern. Conclusions: These findings highlight a public health paradox: the MD is globally promoted as a model of healthy eating, yet adherence within its region of origin is declining. Targeted, region-specific strategies are urgently needed to preserve beneficial MD elements while addressing emerging diet-related risks. Full article

Background/Objectives: Sleep-related problems are common among university students and are linked to adverse academic and health outcomes. This study evaluated the association between lifestyle medicine adherence and sleep-related problems among first-year Ecuadorian university students. Methods: A cross-sectional study was conducted in Quito, Ecuador, during the 2024–2025 academic year. First-year undergraduate students aged 16–35 years were recruited through a census-based, non-probability strategy (N = 2007). Lifestyle medicine adherence was assessed using the Short Multidimensional Inventory Lifestyle Evaluation for University Students (U-SMILE), and sleep-related problems were defined using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Level 1 Cross-Cutting Symptom Measure sleep domain (score ≥ 2), a symptom screen that is conceptually related to, but not identical with, the U-SMILE sleep quality domain. Multivariable binary logistic regression models were used and adjusted for sociodemographic and health-related covariates. A post-hoc sensitivity analysis recomputed the global U-SMILE score after excluding the sleep quality domain. Results: The median age was 18.0 years, and 51.0% were female. Among participants with Level 1 sleep data (n = 1906), 47.8% were classified as having sleep-related problems. In the fully adjusted model (n = 1893), higher overall U-SMILE scores were associated with lower odds of sleep-related problems (odds ratio (OR) per 1 point = 0.93, 95% Confidence Interval (CI): 0.91–0.94; OR per 1 SD = 0.56, 95% CI: 0.50–0.62). In a post-hoc sensitivity analysis, this association persisted after excluding the sleep quality domain from the global score (OR per 1 point = 0.94, 95% CI: 0.93–0.95; OR per 1 SD = 0.66, 95% CI: 0.60–0.73). Among non-sleep domains, the strongest associations were avoidance of substance use (OR = 0.87), social relationships (OR = 0.90), and nutrition (OR = 0.90); physical activity, nature engagement, and stress management were also significant. Conclusions: Higher lifestyle medicine adherence was associated with lower odds of sleep-related problems, including in post-hoc analyses when the sleep domain was omitted from the U-SMILE total. These findings support multidimensional lifestyle medicine approaches for sleep health promotion in university settings. Full article

Background/Objectives: Excess adipose tissue is associated with adverse changes in muscle metabolism and body composition. GLP-1 receptor agonists (GLP-1 RA) have transformed the treatment of obesity; however, concerns remain regarding the potential impact of treatment-associated weight loss on lean mass. This study aimed to evaluate the effects of GLP-1 RA on body composition in adults with obesity without type II diabetes mellitus (T2DM), with a particular focus on changes in lean mass. Methods: A database search of Medline Ultimate, Scopus, Web of Science, PubMed, and Embase was conducted to identify studies published up to December 30, 2024. Randomized controlled trials involving adults with obesity and without T2DM who received GLP-1 RA and reported changes in body composition were included. The protocol was registered with PROSPERO (CRD42025645378). Random-effects meta-analysis was performed using inverse-variance weighting. Results: A total of 2776 articles were identified, of which three trials comprising 171 participants met the inclusion criteria. Compared with controls, participants receiving GLP-1 RA treatment experienced greater reductions in lean mass (MD = −0.78 kg, 95% CI: [−1.37 to −0.16], I² = 63.2%). GLP-1 RA treatment was also associated with a significant reduction in fat mass (MD = −3.43 kg, 95% CI: [−5.94 to −0.93], I² = 78.2%). Conclusions: The loss of lean mass was greater in patients treated with GLP-1 RA than in the control group. These results highlight the importance for clinicians to incorporate lifestyle interventions, including physical activity and nutritional support, alongside therapy with GLP-1 RA. Full article

Background/Objectives: Diabetes mellitus is a chronic metabolic disorder characterized by impaired regulation of blood glucose due to defects in insulin secretion, insulin action, or both. Physiological and lifestyle factors vary among individuals. General medicine is not applicable to all patients. In this scenario, personalized medicine for each individual becomes costly. Effective management of continuous glucose levels with accurate insulin dosage is challenging. To overcome this, a digital twin (DT)-based insulin dosage simulator with an individual’s metabolic system is proposed in this work. Methods: Various machine learning techniques, mathematical models of physiology, and risk assessment using probability are used to predict the dynamics of patient-specific glucose–insulin. Parameters such as carbohydrate intake, sleep patterns, medications, and physical activity were incorporated into this model to capture real-world variations in daily life. For glucose–insulin interactions, the Bergman Minimal Model (BMM) is used; for time-of-day variability, a circadian insulin sensitivity model is used; and for predicting metabolic risks, Bayesian risk estimation (BRE) is used, which includes hyperglycemia risk. To enhance transparency and interpret model predictions, explainable artificial intelligence (XAI) methods are employed. Results: The simulation results showed improved glucose prediction accuracy, enhanced detection of hypoglycemia risk, and optimized insulin dosing strategies compared with traditional approaches. Conclusions: Overall, the proposed digital twin model offers a scalable solution using the latest techniques A “Prescriptive Analytical Framework” is provided using the BMM and BRE for personalized diabetes management and decision support for clinicians. Full article

Liver fibrosis is the common pathway through which chronic liver injury progresses to cirrhosis, portal hypertension, liver failure, hepatocellular carcinoma, and systemic complications. Its burden is increasing worldwide, driven mainly by metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, viral hepatitis, and cardiometabolic comorbidity. Current evidence supports a clinically practical approach centered on early risk recognition, non-invasive fibrosis assessment, etiologic treatment, lifestyle and metabolic risk reduction, and timely referral of patients with suspected advanced fibrosis. Although advanced cirrhosis may remain only partly reversible, fibrosis can regress when the injurious stimulus is controlled, making prevention of progression a realistic therapeutic goal. This review provides a clinically actionable framework for the assessment, management, and prevention of liver fibrosis, integrating current insights into epidemiological trends, etiopathogenesis, non-invasive and portal-hypertension assessment, sex-specific effects, hepatic and extrahepatic outcomes, and treatment strategies. It highlights the potential for fibrosis regression when the underlying etiologic factor is controlled and emphasizes the stages (F0–F2) at which reversibility is most achievable. Additionally, the paper outlines key research priorities to address current knowledge gaps in biomarker discovery, precision medicine, and artificial intelligence-assisted risk stratification, while defining priorities for personalized screening, multidisciplinary care, and combination antifibrotic research. Full article

Arterial stiffness is increasingly recognized as an important marker of vascular aging and an independent predictor of cardiovascular disease. Among the available methods for assessing arterial stiffness, brachial-ankle pulse wave velocity (baPWV) has gained widespread clinical acceptance because it is simple, noninvasive, highly reproducible, and suitable for routine practice and large-scale population screening. Accumulating evidence has demonstrated that baPWV is associated with hypertension-mediated target organ damage, coronary artery disease, cardiovascular events, and mortality. Beyond its prognostic value, baPWV has been investigated as a potential marker of vascular responses to pharmacological and lifestyle interventions. Emerging evidence also suggests that serial assessment and visit-to-visit variability of baPWV may provide additional prognostic information, although their clinical applicability requires further validation. Another advantage of baPWV is its simultaneous measurement of the ankle-brachial index, enabling comprehensive assessment of both arterial stiffness and peripheral artery disease without additional examination time. This review summarizes the physiological basis, measurement principles, strengths and limitations, and current clinical applications of baPWV, with particular emphasis on cardiovascular risk stratification, target organ damage, therapeutic monitoring, serial assessment, and combined ankle-brachial index evaluation. Finally, future perspectives for integrating baPWV into precision cardiovascular medicine are discussed. Full article

Background: Statins are among the most frequently prescribed medications worldwide, with proven benefits in reducing all-cause and cardiovascular mortality, preventing major adverse cardiovascular events (MACEs), and lowering healthcare costs. Despite their well-established safety and effectiveness, discontinuation of statin therapy remains a common problem in both primary and secondary prevention. Methods: A systematic literature review was conducted in accordance with PRISMA guidelines and registered in the PROSPERO database (CRD420261295172). Original studies published since 1 January 2014 were identified through searches of PubMed (MEDLINE) and Google Scholar using predefined keywords. Methodological quality and risk of bias of the included observational studies were evaluated using the Newcastle-–Ottawa Scale (NOS) and Joanna Briggs Institute (JBI) Critical Appraisal Tools. Results: Synthesized data from 29 included studies indicate that up to half of patients discontinue statin therapy within the first year (discontinuation rates ranging from 27.1% to 47.0% in primary prevention and 18.5% to 32.4% in secondary prevention), with rates increasing over time. Major factors contributing to non-adherence include fear of side effects, particularly statin-associated muscle symptoms (SAMSs), misinformation, limited patient–physician communication, socioeconomic barriers, and polypharmacy. Discontinuation is associated with significantly higher all-cause and cardiovascular mortality (Hazard Ratios ranging from 1.30 to 4.65), higher rates of cardiovascular and cerebrovascular events, worsening metabolic outcomes, reduced quality of life, and greater healthcare expenditures. Conclusions: Improving adherence requires better patient education, addressing misconceptions, strengthening patient–physician relationships, and optimising treatment regimens. A multidisciplinary approach is needed to prevent unjustified discontinuation and improve long-term clinical outcomes. Full article

Endothelial dysfunction is a key mechanism linking obesity, metabolic disturbances, and cardiovascular disease, contributing to the development and progression of atherosclerosis and other vascular complications. This review provides a comprehensive overview of the molecular mechanisms underlying endothelial dysfunction in obesity and discusses current diagnostic approaches and therapeutic strategies aimed at restoring vascular homeostasis. The available evidence indicates that chronic inflammation, oxidative stress, insulin resistance, reduced nitric oxide bioavailability, increased reactive oxygen species production, and dysregulated adipokine signaling play central roles in endothelial impairment. Recent advances in functional vascular assessment, circulating biomarkers, and imaging techniques have improved the early identification of endothelial dysfunction and cardiovascular risk. Current therapeutic strategies include pharmacological agents, such as glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter 2 inhibitors, metformin, and dipeptidyl peptidase-4 inhibitors, together with lifestyle interventions based on healthy dietary patterns and regular aerobic and resistance exercise. These approaches improve glycemic control, reduce inflammation and oxidative stress, enhance endothelial function, and contribute to cardiovascular protection. Overall, the evidence supports an integrated and personalized management strategy targeting both metabolic and vascular abnormalities to reduce cardiovascular risk and improve long-term clinical outcomes in individuals with obesity. Full article

Background/Objectives: Obesity is a chronic, progressive, and relapsing disease that requires long-term, multidisciplinary management rather than episodic weight-loss treatment. Although novel incretin-based anti-obesity pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have markedly improved the clinical management of obesity, weight reduction alone does not fully capture treatment success. Body composition, lean mass preservation, physical function, nutritional adequacy, psychological well-being, adherence, and long-term weight-loss maintenance are increasingly recognized as essential therapeutic outcomes. This narrative review critically examines the role of lifestyle medicine as a co-therapeutic strategy during modern anti-obesity pharmacotherapy, with particular attention to physical activity, nutrition, behavioral support, and individualized monitoring. Methods: A narrative literature search was conducted in PubMed up to June 2026. The review included studies addressing adults with overweight or obesity and evidence related to anti-obesity pharmacotherapy, physical activity, nutrition, body composition, functional outcomes, eating behavior, quality of life, treatment tolerability, adherence, weight regain, and long-term maintenance. Results: Current evidence indicates that incretin-based therapies produce substantial and clinically meaningful weight loss, but pharmacological efficacy may be limited by reductions in lean mass, gastrointestinal adverse events, inadequate nutritional intake, treatment discontinuation, and weight regain after drug withdrawal. Physical activity should be considered a therapeutic component rather than only a tool for increasing energy expenditure, as aerobic exercise supports cardiometabolic health and cardiorespiratory fitness, while resistance training helps preserve muscle strength, bone health, and functional capacity. Nutritional strategies are equally important, particularly during appetite suppression, to maintain adequate protein, fiber, fluids, micronutrients, and diet quality. Behavioral factors, including sleep, stress, mood, stigma, self-regulation, and the food environment, may influence adherence and long-term outcomes. Conclusions: Novel anti-obesity drugs should not be viewed as replacements for lifestyle medicine but as powerful tools within an integrated chronic-care model. The goal of treatment should move beyond maximal body-weight reduction to durable improvements in body composition, metabolic health, physical function, nutritional status, quality of life, and weight-loss maintenance. Full article

Glutathione is an abundant intracellular low-molecular-weight thiol that contributes importantly to cellular redox homeostasis. Besides its well-established role in the antioxidant defense of the cell, glutathione regulates mitochondrial function, metabolism of toxicants, protein thiol oxidation/reduction, redox signaling, and immunity. Disturbances in glutathione metabolism have been shown to play a role in various diseases; however, it has become clear that changes in glutathione metabolism are a part of a complex, multifactorial process. In this review, we summarize current knowledge of the molecular mechanisms governing glutathione synthesis, recycling, compartmentalization, and biological functions, with particular emphasis on redox signaling, the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway, and reversible protein S-glutathionylation. We further examine how disturbances in glutathione homeostasis interact with mitochondrial dysfunction, chronic inflammation, metabolic stress, and impaired cellular signaling in Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, Wilson’s disease, type 2 diabetes, and nonalcoholic fatty liver disease. We also evaluate current translational interventions targeting restoration of glutathione balance through glutathione supplementation, precursor supplementation, pharmacological modulation of endogenous antioxidant mechanisms, dietary interventions, and changes in lifestyle. Despite the fact that many interventions have been promising at the mechanistic and experimental level, there are still insufficient clinical data because of the problems associated with glutathione availability, tissue specificity, disease variability, and a lack of sufficiently powered clinical trials. The conclusion of this review is that glutathione should not be viewed as a universal therapeutic target; instead, glutathione should be perceived as an important factor contributing to cellular resilience and able to help other disease-specific interventions. Future progress in glutathione-based interventions will likely depend on integrating redox biomarkers, patient stratification, and precision medicine strategies to identify individuals most likely to benefit from targeted modulation of glutathione homeostasis. Full article

Background/Objectives: Recurrent pregnancy loss (RPL) has traditionally been investigated predominantly through maternal factors, while the clinical role of paternal assessment remains inconsistently defined. Current guidelines differ substantially regarding semen analysis, sperm DNA fragmentation (SDF), genetic testing, and referral for andrological evaluation. This review aimed to compare contemporary guideline recommendations, critically appraise the directness, prognostic value, and clinical utility of the supporting evidence, and classify paternal assessment strategies as routine, selective, or investigational. Methods: A structured narrative review was conducted using PubMed and Scopus searches through June 2026. International RPL, obstetric, reproductive medicine, and andrology guidelines were compared. Evidence from systematic reviews, meta-analyses, clinical studies, and clinically relevant molecular investigations was evaluated according to its directness to RPL populations, diagnostic and prognostic value, and evidence that test-guided interventions improve miscarriage or live-birth outcomes. Results: Routine paternal assessment should include age, reproductive and medical history, body weight, lifestyle, medication exposure, and relevant environmental or occupational risks. Conventional semen analysis is appropriate primarily when RPL coexists with infertility or suspected male reproductive disease. SDF is the most extensively studied advanced paternal biomarker and is frequently elevated in RPL cohorts, but findings vary by assay and comparator population, while prospective prediction of subsequent live birth and benefit from SDF-directed treatment remain unproven. Parental karyotyping has established counselling value but should be risk-stratified. Sperm aneuploidy testing, oxidative stress assays, seminal microbiome profiling, epigenetic biomarkers, and biomarker-directed interventions remain investigational. Conclusions: Paternal assessment in RPL should be couple-based, clinically targeted, and evidence-informed. Current evidence supports routine clinical evaluation, selective use of semen analysis, SDF testing, genetic assessment, and reproductive urology referral, and restriction of unvalidated biomarkers and treatments to research settings. Full article

Cancer remains one of the leading causes of global mortality, with its incidence continuing to rise due to population growth, aging, lifestyle factors, and environmental exposures. Despite significant advances in early diagnosis and therapeutic strategies, the clinical management of cancer is still hindered by drug resistance, limited selectivity, and treatment-related toxicity. Consequently, increasing attention has been directed toward natural products as sources of novel anticancer agents with improved efficacy and reduced adverse effects. Pogostemon cablin (patchouli), a medicinal plant widely used in traditional medicine, has emerged as a promising candidate owing to its diverse bioactive constituents and broad pharmacological properties. This review systematically summarizes and critically evaluates current evidence on the anticancer potential of patchouli leaves, with particular emphasis on molecular mechanisms and translational relevance. Based on available experimental and preclinical studies, patchouli and its major phytochemicals exhibit notable anticancer activity against a wide range of malignancies, including endometrial, ovarian, liver, skin, nasopharyngeal, prostate, hematological, colorectal, and lung cancers. Mechanistically, these effects are primarily associated with the modulation of apoptosis, cell cycle regulation, oxidative stress, and key oncogenic signaling pathways, as well as potential synergistic interactions with conventional chemotherapeutic agents. Overall, this review highlights the therapeutic promise of patchouli leaves as a source of anticancer agents, identifies current knowledge gaps, and outlines future research directions to facilitate their development and clinical translation. Full article