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Structured exercise (SE) and physical therapy (PT) are integral components of disease management. Older adults with inflammatory bowel disease (IBD) represent a growing proportion of patients, and are at disproportionate risk of functional decline due to the combined effects of aging, chronic inflammation, malnutrition, and inactivity. Despite the well-established benefits of SE and PT, most gastroenterologists report feeling inadequately equipped to counsel and refer patients with physical function limitations, and thus these therapies remain underutilized. The purpose of this review is to synthesize the existing evidence and provide practical, actionable guidance for gastroenterologists to incorporate SE and PT into IBD care. Initial studies suggest complementary SE and PT may significantly improve IBD-related musculoskeletal extraintestinal manifestations (EIMs), such as joint pain, fatigue, sarcopenia, frailty, and improve exercise confidence as compared with standard care alone. Additionally, multimodal prehabilitation strategies may significantly reduce severe postoperative complications and shorten hospital stays in older patients undergoing IBD-related surgery. SE and PT are low-cost, low-risk interventions with benefits spanning multiple domains of physical function and morbidity in older adults with IBD. This article highlights pertinent SE and PT literature in the aging IBD population, including underlying pathophysiology, interventions, and scope of practice. Gastroenterologists are provided evidence-based, condition-specific assessments and PT referral pathways that can be implemented in routine practice. Integrating this into the multidisciplinary IBD care team may improve patients' physical function and quality of life.

Bronchiectasis is a chronic inflammatory airway disease characterized by impaired mucociliary clearance, persistent mucus retention, recurrent infections, and progressive airway destruction. Airway clearance techniques (ACTs) are central to the management of bronchiectasis, aiming to interrupt the cycle of mucus stasis, infection, and inflammation. High frequency chest wall oscillation (HFCWO) is a noninvasive mechanical ACT increasingly used to facilitate secretion mobilization and improve airway hygiene in patients with bronchiectasis. The objective of the current narrative review is to assess the current evidence regarding the use of HFCWO in patients with bronchiectasis, with emphasis on its physiological rationale, mechanisms of action, clinical applications, effectiveness, practical implementation, safety profile, and limitations. A narrative literature review was conducted using PubMed, Medline, Embase, Scopus, ClinicalTrials.gov, and the Cochrane Library. Relevant studies were analyzed to summarize current evidence regarding the role of HFCWO in bronchiectasis management. The evidence suggests that HFCWO may improve mucus clearance, reduce symptom burden, enhance quality of life, and decrease exacerbation frequency in selected patients with bronchiectasis. HFCWO therapy is particularly useful in patients with chronic productive cough, impaired mucus clearance, frequent exacerbations, or inadequate response to conventional ACT therapies. Practical application requires individual adjustment of treatment frequency, session duration, oscillation frequency, and pressure amplitude according to disease severity and patient tolerance. Despite its benefits, HFCWO use may be limited by high device cost, maintenance requirements, and variable long-term adherence. Reported adverse effects are generally mild and include chest discomfort, dyspnea, transient oxygen desaturation, and fatigue. HFCWO represents a valuable second-line or adjunctive airway clearance therapeutic modality and may be considered in patients with bronchiectasis, particularly those with significant secretion burden and in whom traditional and active self-administered traditional techniques have failed, are poorly tolerated, or when cognitive/physical limitations prevent active patients' participation. Although current evidence supports its physiological and clinical benefits, future high-quality randomized studies are needed to better define patient selection criteria, long-term outcomes, adherence, and comparative effectiveness relative to other airway clearance techniques.

While many insects have evolved mechanisms to ensure the faithful transmission of bacterial symbionts across generations, the majority of insects lack such mechanisms. Instead, many insects must acquire symbionts from their local environments. Without mechanisms for vertical transmission, insects are thought to be at risk of experiencing low fitness by acquiring low-quality symbiont strains. For example, insects dependent on environmental symbiont transmission may acquire nonsymbiotic bacteria or symbionts that are adapted to other co-localized hosts. Yet, insects often appear capable of interacting with a wide variety of symbiont strains, and environmental transmission is prevalent across diverse insect species. Therefore, it remains unclear whether the evolutionary history of a symbiont actually impacts its benefit to hosts. Here, we test whether the recent evolutionary history of a symbiont impacts its quality to an insect host by inoculating Anasa tristis De Geer (Hemiptera: Coreidae) insects with Burkholderiaceae strains isolated from a conspecific host, a distantly related heterospecific host, and from soil. We find that the soil strain offers few fitness benefits. In contrast, both strains with a recent history of host association support insect survival to adulthood, but the greatest benefits emerge from the symbiont isolated from a conspecific host, which also improves insect development rates. Overall, our study demonstrates that the evolutionary history of a symbiont may impact its quality to insect hosts and lays a foundation for future work to further examine whether environmental transmission carries costs for insect hosts.

This study aimed to evaluate the effects of cosupplementation with high-dose vitamin D3 and flaxseed oil on inflammatory markers, oxidative stress, and metabolic health in elderly patients with T2DM. We conducted an 8-week, triple-blind, randomized, placebo-controlled clinical trial in Iran, enrolling 104 elderly patients with T2DM, of whom 102 completed the study. The intervention group received 500&#x2009;mg of flaxseed oil three times daily and 50,000 IU of vitamin D3 orally every two weeks, while the control group received matching placebos. The primary outcome, serum hs-CRP, was significantly reduced in the intervention group compared to controls (MD: -0.98&#x2009;&#x3bc;g/mL, p = 0.034). Exploratory analyses of secondary outcomes suggested additional potential benefits: total antioxidant capacity improved (MD: +0.60&#x2009;mmol/L, p < 0.05), and reductions were observed in weight (MD: -1.73&#x2009;kg, p < 0.001), BMI (MD: -0.67&#x2009;kg/m2, p < 0.001), fasting blood glucose (MD: -22.83&#x2009;mg/dL, p = 0.015), fasting insulin (MD: -0.94&#x2009;&#x3bc;IU/mL, p = 0.008), homeostatic model assessment of insulin resistance (MD: -1.31, p = 0.001), triglycerides (MD: -15.00&#x2009;mg/dL, p = 0.020), and total cholesterol (MD: -2.52&#x2009;mg/dL, p = 0.028). Physical health-related quality of life, including pain scores and physical functioning, also improved significantly (p < 0.05). The intervention was well tolerated with minimal adverse events. Cosupplementation with flaxseed oil and high-dose vitamin D3 significantly reduced systemic inflammation in elderly patients with T2DM. Exploratory findings further suggest potential benefits for oxidative stress, glycemic control, lipid profile, and physical quality of life, warranting confirmation in future trials. Trial Registration: Iranian Clinical Trials Register: IRCT20161022030424N8.

This systematic review and meta-analysis assessed effectiveness of Premature Infant Oral Motor Intervention in improving oral feeding outcomes in preterm infants. A comprehensive search of electronic databases identified randomised controlled trials evaluating Premature Infant Oral Motor Intervention's impact on feeding-related outcomes. Fourteen randomised control trials involving 855 preterm infants were included. Primary outcome was transition time to full oral feeding. Secondary outcomes included hospital stay length, weight at full oral feeding and discharge, milk transfer rate, and gavage feeding duration. Meta-analysis used a fixed-effects model, and evidence certainty was evaluated via Grading of Recommendations, Assessment, Development and Evaluation framework. Premature Infant Oral Motor Intervention significantly reduced transition time to full oral feeding (MD&#x2009;=&#x2009;-3.91&#x2009;days; 95% CI:-4.19 to -3.62) and shortened hospital stay. Effects on weight at full oral feeding were moderate, while discharge weight and milk transfer rate showed inconsistent effects. Subgroup analyses demonstrated greater efficacy in infants with higher gestational age and intervention frequency. Sensitivity analyses confirmed robustness of findings with minimal publication bias. Evidence certainty was moderate for transition time to full oral feeding but low to very low for secondary outcomes due to heterogeneity and study limitations. Premature Infant Oral Motor Intervention may enhance feeding efficiency and reduce hospitalisation in preterm infants. Further high-quality research is needed to confirm long-term benefits and optimise protocols.

Among mammals, spatial organization (home range size and overlap) may be influenced by kinship, and tolerance among kin is believed to play a role in the evolution of sociality. In solitary species, adults-including close kin-are presumed to have home ranges that are distinct and non-overlapping. We characterized spatial organization and behavioral interactions, including the role of kinship in a free-living population of golden-mantled ground squirrels (Callospermophilus lateralis), a presumably asocial and solitary species. We also capitalized on changes in population size over 25&#x2009;years (1995 to 2019) to quantify the influence of density on that spatial organization. We found extensive overlap between female home ranges (30%) and between male and female home ranges (28%) after the breeding season. However, the core areas of adult female home ranges overlapped minimally (7%), suggesting that squirrels were territorial, but only for the inner part of their home range. Contrary to expectation for solitary ground squirrels, kinship played a role in the spatial organization: related females shared space more than unrelated females. We did not find an effect of overall population density on home range or core area size, but increased local density was associated with an increase in home range size. While we did not find an effect of density alone on spatial overlap, there was a density-mediated increase in space-sharing among kin; space-sharing by female kin was expressed primarily at high densities, suggesting that familiarity and inclusive fitness benefits may offset costs of competition and promote philopatry under certain conditions. We also found behavioral evidence to support this interaction: greater spatial overlap of home range core areas reliably increased the number of chases between squirrels, unless those squirrels were highly related. Overall, we provide evidence of a facultative transition in golden-mantled ground squirrels from asociality to the formation of single-family kin clusters at high densities, the first step toward developing sociality. Our study highlights the importance of considering behavioral interactions in asocial species, as well as the interactive effects of environmental conditions and kinship when assessing the spatial and social organization of mammals.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized not only by differences in social communication and restricted or repetitive behaviors, but also by variable profiles of motor function, sleep, cognition, sensory processing, and adaptive participation. Exercise and structured physical activity have emerged as promising non-pharmacological interventions in ASD, with growing evidence supporting benefits across multiple outcome domains, including executive function, stereotyped behaviors, sleep, motor competence, social communication, and quality of life. However, this field is constrained by fragmented concepts, inconsistent dose documentation, lack of mechanistic integration, and inadequate clinical translation. Exercise is often treated as a generic intervention rather than as a well-defined and physiologically meaningful exposure. This narrative review proposes a precision-informed framework in which exercise in ASD is conceptualized as a structured developmental exposure whose potential therapeutic value may depend on dose architecture rather than modality labels alone. Beyond traditional descriptors such as frequency, intensity, time, and type, exercise dose in ASD should be understood as a multidimensional construct that also includes motor complexity, cognitive demand, social embeddedness, sensory load, predictability, progression rate, and adherence burden. We synthesize ASD-specific clinical evidence together with indirect evidence from broader exercise neuroscience and animal models, while explicitly distinguishing established clinical findings from candidate or hypothesis-generating mechanisms. We also examine how exercise responses may differ according to developmental stage, pubertal changes, gender-associated traits, and the lack of female representation in existing evidence. Overall, we investigate how efficacy findings can inform individualized exercise plans, mechanism-linked trials, and scalable interventions in real-world settings. Taken together, this review offers a conceptual and translational framework for future ASD exercise research, emphasizing standardized dose reporting, evidence-level distinctions, developmental stratification, safety monitoring, and clinically meaningful outcomes.

Migraine in children and adolescents not only impacts academic pursuits and family life but also have secondary psychological effects. Determining the role of acute medication for migraine treatment in this population can reduce the burden associated with migraine. This network meta-analysis aimed to identify the relative efficacy and safety of acute migraine drug in children and adolescents migraine populations. The Cochrane Register of Controlled Trials and MEDLINE via PubMed and Embase databases were searched from inception to August 2025, only published studies in English. Double-blind randomized clinical trials evaluating the currently available acute treatments for childhood and adolescent migraines were included. The primary efficacy endpoint was pain freedom at 2&#xa0;hours. Secondary efficacy endpoints included the proportion of participants with pain relief at 2&#xa0;hours, pain freedom from two to 24&#xa0;h, and the proportion using rescue drugs after 2&#xa0;hours and up to 24&#xa0;h. Adverse events (AEs) were also evaluated. The analysis included 30 studies (involving 8,914 participants and 13 pharmacological interventions). All treatments included demonstrated higher odds ratios (ORs) compared with the placebo for pain freedom at 2&#xa0;hours. Dihydroergotamine was associated with the highest ORs, but its confidence interval included null values. Sumatriptan/naproxen sodium, ibuprofen, zolmitriptan nasal spray, sumatriptan nasal spray, and rizatriptan showed statistical significance. Sumatriptan/naproxen sodium yielded the highest odds (OR: 2.91, 95% CI: 1.87-4.53), followed by ibuprofen (OR: 2.88, 95% CI: 1.47-5.64), and rizatriptan showed the lowest (OR: 1.51, 95% CI: 1.23-1.86). Only sumatriptan/naproxen sodium was associated with a significantly higher OR compared with placebo for pain freedom from two to 24&#xa0;h (OR: 2.31, 95% CI: 1.31-4.07). Ibuprofen exhibited the highest effect size for pain relief at 2&#xa0;hours (OR: 3.21, 95% CI: 1.10-9.34). None of the included drugs was found to reduce the use of rescue drugs from two to 24&#xa0;h. Zolmitriptan was associated with the highest risk of AEs among all treatments. Acetaminophen appears to have the lowest risk of adverse events, comparable to that of a placebo. Ibuprofen can effectively relieve symptoms, characterized by a favorable benefit-risk profile. Sumatriptan and zolmitriptan nasal sprays also exhibited robust efficacy, specifically among populations with prominent nausea and vomiting. Sumatriptan/naproxen sodium merits consideration, especially in patients exhibiting an inadequate response to monotherapy. Dihydroergotamine demonstrated potential benefits in refractory and chronic migraine; however, high-quality studies are warranted to validate these findings.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are strongly linked to obesity, insulin resistance, type 2 diabetes, and progressive liver fibrosis. Dual and triple glucagon-like peptide-1 (GLP-1)-based polyagonists may provide complementary hepatic and metabolic benefits, but their overall efficacy and safety have not been fully established. This systematic review and meta-analysis evaluated randomized controlled trials comparing dual or triple GLP-1-based polyagonists with placebo in adults with MASLD or MASH. PubMed, the Cochrane Central Register of Controlled Trials, ScienceDirect, and Google Scholar were searched from inception through May 19, 2026. Dichotomous outcomes were pooled as risk ratios (RRs), and continuous outcomes were analyzed as mean differences (MDs), using random-effects models. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Six randomized controlled trials involving 961 participants were included. The included GLP-1-based polyagonists-tirzepatide, survodutide, pemvidutide, retatrutide, and cotadutide-significantly increased MASH resolution or histological improvement without worsening of fibrosis (RR 3.32, 95% CI 2.28-4.84; I&#xb2; = 20%) and fibrosis improvement without worsening of MASH (RR 1.49, 95% CI 1.15-1.94; I&#xb2; = 0%). Treatment also produced a greater relative reduction in liver fat content (MD -44.60 percentage points, 95% CI -51.17 to -38.04; I&#xb2; = 0%) and increased the likelihood of achieving at least a 30% relative reduction in liver fat by magnetic resonance imaging-proton density fat fraction (RR 4.71, 95% CI 3.04-7.30; I&#xb2; = 22%). Body weight was significantly reduced, although heterogeneity was considerable (MD -9.14 percentage points, 95% CI -17.38 to -0.91; I&#xb2; = 98%). Nausea, diarrhea, and vomiting were more frequent with polyagonists, but no statistically significant differences were observed in serious adverse events or adverse events leading to treatment discontinuation. In conclusion, dual and triple GLP-1-based polyagonists improve histological and imaging-based hepatic outcomes in MASLD and MASH and may simultaneously address underlying metabolic dysfunction. However, gastrointestinal intolerance, pharmacological heterogeneity, the small number of trials, and limited follow-up warrant cautious interpretation. Larger phase 3 trials are needed to clarify drug-specific efficacy, long-term safety, and effects on liver-related and cardiovascular outcomes.

Microwave therapy has emerged as a minimally invasive treatment option, but long-term real-world data, particularly from Southeast Asian populations, remain limited. To evaluate the effectiveness of microwave therapy and its impact on quality of life (QoL) in patients with axillary hyperhidrosis and bromhidrosis. A longitudinal ambispective case series study was conducted on 52 adult patients with axillary hyperhidrosis and bromhidrosis treated with microwave therapy. Treatment efficacy and QoL improvement were assessed at 1&#xa0;week and at 3, 6, 9, and 12 months post-intervention using the Minor test, Hyperhidrosis Disease Severity Scale (HDSS), Visual Analog Scale (VAS), and Dermatology Life Quality Index (DLQI). Repeated measures were analyzed using mixed-effects models. At 1&#xa0;week, the mean area of discoloration decreased markedly from 49.1 cm2 to 0.3 cm2 in the left axilla, with similar improvement observed in the right axilla. At 12 months, compared with baseline, the model-predicted probability of HDSS grade 4 decreased from 68.2% to 5.7%, while the mean odor score and DLQI score decreased from 6.8 to 3.0 and from 19.5 to 6.5, respectively. Overall satisfaction at 12 months was 66.6%. Statistically significant improvements were observed across the majority of efficacy outcomes (p < 0.05). The most common adverse events were pain and swelling, which were mild and self-limiting, with no serious complications reported. Microwave therapy demonstrated a favorable safety profile and sustained clinical benefits in patients with axillary hyperhidrosis and bromhidrosis over 12 months of follow-up. Although patient satisfaction declined modestly at 12 months, overall treatment outcomes remained favorable.

Dietary intervention is central to the management of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as metabolic-associated fatty liver disease (MAFLD). Although vegetarian dietary patterns are widely considered hepatoprotective, emerging evidence indicates that certain individuals following non-standardized vegetarian diets may fail to obtain the expected hepatic benefits-a phenomenon termed the "vegetarian hepatoprotection paradox." This critical narrative examines the putative mechanisms underlying this paradox. Excessive intake of high-glycemic carbohydrates and fructose, which is common in some vegetarian diets, may activate hepatic de novo lipogenesis. Furthermore, incomplete plant proteins may contribute to impaired very low-density lipoprotein (VLDL)-mediated lipid export, while an imbalanced n-6:n-3 fatty acid ratio may promote hepatic inflammation. These dietary factors may interact with genetic susceptibility, including patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M and transmembrane 6 superfamily member 2 (TM6SF2) E167K variants, disrupting hepatic lipid homeostasis. Additionally, gut dysbiosis may propagate metabolic disturbance through chronic inflammation. Accordingly, a shift from the categorical vegetarian labeling toward an emphasis on plant-based dietary quality-reflecting the principle that dietary quality matters more than the vegetarian label itself-may be warranted. This review discusses evidence-based dietary patterns, including the Mediterranean diet, the Green Mediterranean diet, and the Dietary Approaches to Stop Hypertension (DASH) diet, together with chrononutrition strategies. A precision nutrition approach integrating genetic, metabolic, and microbiome characteristics may represent an emerging but still investigational framework for individualized MASLD/MAFLD interventions.

Cardiac fibrosis, a major pathological hallmark of aging that leads to heart failure, is characterized by excessive collagen deposition. Our knowledge of what sustains collagen synthesis in the aging heart is still very preliminary. Here, we uncover a central role for chaperone-mediated autophagy (CMA), a selective lysosomal degradation pathway, in this process. We demonstrate that CMA is suppressed in the aging heart, which promotes collagen overproduction in fibroblasts, whereas enhancing CMA activity ameliorates fibrosis and diastolic dysfunction. Mechanistically, we identify SHMT2 (serine hydroxymethyltransferase 2) as a CMA substrate whose accumulation with aging drives collagen synthesis by increasing glycine availability. Integrative omics revealed a systemic downregulation of the ketone body &#x3b2;-hydroxybutyrate (BHB) in aged mice. BHB supplementation - via a cyclic ketogenic diet - restored CMA, attenuated fibrosis, and improved cardiac function. This recovery was mediated through BHB-induced activation of the HCAR2 receptor and subsequent phosphorylation of HSPA8/HSC70, which systemically reactivates the CMA machinery. Furthermore, we show that Lycium barbarum polysaccharide (LBP) rejuvenates hepatic ketogenesis and mimics the benefits of BHB. Our findings establish a BHB-HCAR2-CMA-SHMT2 regulatory axis as a critical mechanism driving aging-related cardiac fibrosis and highlight nutritional strategies that target CMA as promising therapies against cardiac aging.

Participation in low-dose computed tomography (LDCT) lung cancer screening remains suboptimal, and evidence on participation determinants is heterogeneous. This scoping review mapped participation factors using the Capability-Opportunity-Motivation-Behavior (COM-B) framework to guide intervention development. We conducted an international scoping review of studies published between January 2013 and June 2025. PubMed, Embase, CINAHL, PsycINFO, Web of Science, and the Cochrane Library were searched. Quantitative, qualitative, and mixed-methods studies examining participation among adults eligible for LDCT screening were included. Factors were coded inductively and mapped to framework domains. Overall, 3229 unique records were screened. Thirty-nine studies were included: 22 quantitative, 13 qualitative, and four mixed-methods studies. Determinants spanned all framework domains. Factors most often associated with higher participation included risk awareness (n&#xa0;=&#xa0;15), perceived benefits (n&#xa0;=&#xa0;13), and clinician recommendation (n&#xa0;=&#xa0;12). Factors most often associated with lower participation included misconceptions (n&#xa0;=&#xa0;13), competing priorities (n&#xa0;=&#xa0;12) and fear of results (n&#xa0;=&#xa0;11). Participation reflects interacting factors. Health literacy barriers, misconceptions, and practical constraints may prevent favorable intentions from translating into uptake. Interventions should combine tailored communication, clinician engagement, improved access, and support addressing risk perception, fear, stigma, and trust.

Declining ophthalmology teaching hours necessitate efficient instructional tools. While generative AI frequently produces structural deviations, these variations can be strategically repurposed as valuable stimuli for comparative learning. This study evaluated the effects of an AI-assisted comparative exercise versus conventional anatomical labeling on knowledge acquisition, learner satisfaction, and cognitive workload. We conducted a quasi-experimental 2&#x202f;&#xd7;&#x202f;2 study with 121 sophomores from two universities in Shanghai, China. Following a standardized 20-min ophthalmic anatomy lecture, intact classes were assigned to either a conventional diagram-labeling task or an AI-assisted comparative exercise. The AI condition included three anatomically correct reference images paired with three expert-curated AI-generated anatomical variants, produced through a systematic expert-in-the-loop approach using Gemini 3.0 Pro. Outcomes comprised baseline and post-intervention knowledge tests, a 5-item satisfaction questionnaire, and the NASA Task Load Index. After baseline adjustment and correction for planned comparisons, no statistically significant AI-versus-conventional difference in post-test knowledge scores was detected (all p&#x202f;>&#x202f;0.05). Among non-medical students, the AI-assisted comparative exercise was associated with higher composite satisfaction (9.17 vs. 7.52; Holm-adjusted p&#x202f;<&#x202f;0.001; r&#x202f;=&#x202f;0.60) and better self-assessed performance (7.76 vs. 6.03; Holm-adjusted p&#x202f;=&#x202f;0.003; r&#x202f;=&#x202f;0.47), whereas composite NASA-TLX scores did not differ between AI and conventional conditions within either background group. These satisfaction and self-assessed performance benefits were not observed among medical students (all p&#x202f;>&#x202f;0.05). A brief AI-assisted comparative exercise did not demonstrate a statistically conclusive advantage in immediate knowledge outcomes, but was associated with higher satisfaction and better self-assessed performance among non-medical students without increasing composite NASA-TLX scores. Carefully curated AI-generated anatomical variants may therefore serve as a structured adjunct for novice ophthalmic anatomy learning.

Since the introduction of the hallmarks of cancer framework over 25 years ago, treatment approaches have evolved into personalized medicine, offering benefits to select patient populations. However, three major components of heterotypic interactions in cancer-mutational evolution of cancer stem cells, epithelial-mesenchymal plasticity (EMP), and cancer-remodeled extracellular matrix (ECM)-remain critical barriers to therapy, particularly in patients who have failed treatment. EMP encompasses a spectrum of to-and-fro transitions between mesenchymal and epithelial states, yielding hybrid phenotypes of evolutionary heterogeneity. These are embedded in the vascular, metabolic, mutational, and immune-suppressive reprogramming of the tumor microenvironment (TME), induced and advanced by the hypoxia-reactive oxygen species (ROS)-hypoxia-inducible factor-1&#x3b1; (HIF-1&#x3b1;)-transforming growth factor-&#x3b2; (TGF-&#x3b2;) signaling axis. This review systematically examines the molecular mechanisms underlying EMP, tumor heterogeneity, and the hallmarks of cancer. It explores pharmacological strategies to target tumor burden, epigenetically revert transitional states, and restore immune-editing functions. Based on this analysis, we propose a phased anti-hallmark Combinations, Timing, and Sequencing (CTS) protocol. The methodology integrates vascular normalization, epigenetic modifiers, trimodal radiotherapy or stereotactic body radiotherapy (SBRT), chemotherapy (CT), and immunotherapy optimization, aiming to improve outcomes while minimizing toxicities. Also, mechanistically, by reverting mesenchymal phenotypes and normalizing the vasculature, the CTS protocol is designed to rescue the immune-suppressive tumor microenvironment-curtailing the recruitment of myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells. This restores cytotoxic T-cell homing, thereby converting immunologically "cold" tumors into "hot," immunotherapy-responsive lesions.

This study employed a network meta-analysis (NMA) to compare the intervention effects of different TCMQE practices on primary outcome measures in PD patients and to rank their efficacy, aiming to provide guidance for clinical practice. A systematic search was conducted in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database to identify randomized controlled trials (RCTs) evaluating traditional Chinese Qigong (QG) exercise interventions for Parkinson's disease patients. The search covered the inception of each database up to April 29, 2026. A Bayesian network meta-analysis was conducted using R software to compare the relative effects of different interventions on primary outcome measures and rank them. Two researchers independently performed literature screening and data extraction. The risk of bias in included studies was assessed using the ROB 2.0 tool. A total of 59 RCTs (3,743 patients) were included. Compared with conventional treatment, Baduanjin (BDJ), QG, and Tai Chi (TC) were associated with improvements in motor symptoms (UPDRS-III). BDJ, TC, and WQX improved balance (BBS), while BDJ, liuzijue (LZJ), QG, TC, and wuqinxi (WQX) showed benefits in gait performance (TUGT). WQX and Yijingjin (YJJ) were associated with improvements in quality of life (PDQ-39), and TC and BDJ with reductions in depressive symptoms (HAMD). This network meta-analysis suggests that different traditional QG interventions may be associated with improvements in motor and non-motor symptoms in Parkinson's disease. However, most pairwise comparisons showed overlapping confidence intervals, and no statistically significant differences were observed between most QG interventions. https://www.crd.york.ac.uk/prospero/, identifier: CRD420251243598.

Recurrent retroperitoneal sarcoma remains a significant therapeutic challenge. Recurrence does not always indicate treatment failure but reflects different tumor biologies with diverse implications for local and systemic management. This review proposes a biology-based framework for recurrent RPS that incorporates histology, disease-free interval, tumor growth kinetics, multifocality, resectability, functional reserve, and therapeutic proportionality. Histological subtype significantly influences recurrence patterns. Well-differentiated liposarcoma often follows a chronic local-regional course, where multiple surgeries can offer long-term control. In contrast, leiomyosarcoma more commonly shows early systemic spread, which diminishes the benefit of repeated local treatments. Disease-free interval and tumor growth rate are important dynamic indicators that improve prognosis and assist in timing treatment. Complete resection is essential for a meaningful survival benefit, but resectability alone does not justify surgery. Radiotherapy and systemic therapy serve complementary roles, mainly in local control, biological modulation, and palliation. Prognostic tools and nomograms aid in initial risk assessment, but are most valuable when combined with dynamic factors that reflect tumor behavior. Future advancements will rely on clinically relevant biomarkers, adaptive predictive models, personalized surveillance, recurrence-focused clinical trials, and shared decision-making based on meaningful patient benefits.

This study demonstrated the clinical application of static guided surgery (SGS) combined with piezoelectric technology for endodontic microsurgery. The research objective was to evaluate the benefits of integrating advanced technologies to achieve atraumatic, accurate osteotomy while preserving natural bone for grafting. Two female patients (ages 38 and 27) with symptomatic apical periodontitis of previously treated mandibular first molars were treated using this innovative approach. The methodology involved comprehensive clinical and radiographic examinations, including CBCT scans and digital oral scans. Virtual surgical planning was performed to design 3D-printed surgical templates that predetermine osteotomy size and apical resection levels. The surgical procedure utilized (Altaqi kit) piezoelectric instruments specially designed for endodontic microsurgery for precise bone and root-tip cutting and root-end preparation under microscopic guidance. The key work in these cases was the ability to precisely and conservatively cut and reposition the bone window as an autogenous bone graft, secured with platelet-rich fibrin plugs. This approach minimized surgical trauma by selectively cutting hard tissues while preserving soft tissues and reducing thermal damage. Both cases demonstrated successful clinical outcomes at 12-18-month follow-up, with patients remaining asymptomatic and showing routine healing without complications. The integration of piezoelectric technology with static surgical guides promoted early healing through bone-preserving techniques. The study concludes that this combined approach offers significant advantages for endodontic microsurgery, particularly in complex anatomical scenarios near critical structures, despite preparation time and equipment costs.

Multidimensional Correlation Magnetic Resonance Imaging (McMRI) represents a promising advancement in medical imaging, offering enhanced diagnostic accuracy through the integration of multiple MRI parameters into unified datasets. In low- and middle-income countries (LMICs), McMRI could significantly improve early disease detection and treatment planning, particularly for complex conditions such as cancer and neurological disorders. Benefits include richer data acquisition, improved tissue characterization, and the potential for cost-effective, non-invasive diagnostics. However, practical barriers remain: limited infrastructure, scarcity of trained personnel, high implementation costs, unstable power supply, and data governance challenges hinder widespread adoption. Addressing these issues requires efficient computational workflows, sustainable technology investment, and capacity-building initiatives tailored to LMIC contexts. This review highlights both the transformative potential and the practical obstacles of deploying McMRI in resource-constrained settings, underscoring the need for collaborative strategies that align technological innovation with healthcare equity.