Low-load resistance training [≤50% one-repetition maximum (1-RM)] produces modest hypertrophic adaptations in untrained individuals. Blood flow restriction (BFR) training, combining low mechanical loads (30-40% 1-RM) with proximal limb occlusion, may augment these adaptations by inducing metabolic stress comparable to higher-load exercise. However, evidence comparing low-load multi-component training with and without BFR in physically inactive young adults remains limited. This study examined whether adding BFR to a standardized low-load training program enhances muscle thickness and functional performance outcomes compared with the same program performed without BFR. In this single-blind randomized controlled trial conducted at Chongqing Medical University from November 2024 to November 2025, we enrolled 48 physically inactive physically inactive university-aged adults (25 males; mean age 18.98 ± 0.64 years). Participants were randomly assigned (1:1) to receive either low-load multi-component with BFR (n=24) or low-load multi-component without BFR) (n=24) training for 6 weeks (4 sessions/week). The BFR group trained at 30% (weeks 1-3) to 40% (weeks 4-6) 1-RM, with pneumatic cuffs inflated to 50% of individual arterial occlusion pressure. Outcomes were muscle thickness (ultrasound), and physical fitness tests. All 48 participants (mean age 19.0 ± 0.6 years) completed the 6-week intervention with ≥85% session attendance. The BFR group demonstrated significantly greater muscle thickness increases compared with without-BFR group in bilateral biceps brachii (right: +0.45 cm vs +0.11 cm, P = 0.001, ηp2=0.20; left: +0.37 cm vs +0.10 cm, P = 0.001, ηp2=0.21) and right rectus femoris (+0.13 cm vs +0.02 cm, P = 0.001, ηp2=0.17). Functional performance improvements favoring BFR included left-hand grip strength (+3.63 kg vs +1.09 kg, P = 0.001, ηp2=0.28), bilateral thigh circumference (P = 0.001, ηp2=0.12), and exercise-specific core training (males: pull-ups +5.92 vs +2.08 repetitions; females: abdominal curls +11.18 vs +3.33 repetitions). Between-group differences reached significance for 10 of 18 primary and secondary outcomes (56%). Seven BFR participants (29%) reported minor, transient discomfort during week 1; no serious adverse events occurred. Adding BFR to low-load multi-component training produced greater improvements in limb muscle thickness and functional performance compared with the same training performed without BFR in physically inactive young adults over 6 weeks. Benefits were most evident in upper extremity hypertrophy and task-specific functional capacity, with 56% of outcomes demonstrating significant between-group differences favoring BFR. The intervention was well-tolerated with no serious adverse events. These findings support BFR-enhanced low-load training as a potential alternative for individuals unable or unwilling to engage in high-load resistance training, though generalizability to other populations and longer-term sustainability require further investigation. https://www.thaiclinicaltrials.org/, identifier TCTR20241110003.
Histamine commonly accumulates in animal-derived feed ingredients and is detrimental to aquaculture species, but the adverse consequences of dietary histamine remain inadequately characterized. Here, we explored the physiological influences of different dietary histamine levels on the growth performance, as well as the intestinal and hepatic health, of American eels, a fish species intolerant to histamine. Five diets were prepared with total histamine levels of 48.94, 198.19, 355.31, 492.44, and 641.37 mg kg-1, respectively. Following a 10-week feeding trial, growth performance, intestinal and hepatic morphology, antioxidant capacity, intestinal microbiota composition, and hepatic metabolites were analyzed. American eels receiving diets with histamine levels exceeding 355.31 mg kg⁻¹ exhibited reduced growth performance, feed utilization, immune competence, intestinal mucosal and hepatocellular integrity, intestinal and hepatic antioxidant capacity, and intestinal digestive enzymes activities, along with elevated intestinal and hepatic malondialdehyde contents, compared to those fed the diet containing 48.94 mg kg-1 histamine. Omics profiling further indicated that, relative to the dietary histamine level of 48.94 mg kg-1, the 641.37 mg kg-1 dietary histamine restructured intestinal microbiota composition by reducing the abundance Enterococcus and Rhodococcus while increasing the levels of Haliangium, Stenotrophomonas, and Blastomonas; and affected hepatic aminoacyl-tRNA biosynthesis, glycine/serine/threonine metabolism, nicotinate/nicotinamide metabolism, and valine/leucine/isoleucine biosynthesis in American eels. Broken-line regression analysis of weight gain rate identified 260.11 mg kg-1 as the maximum tolerable dietary histamine level for American eels. These findings provide crucial insights regarding dietary histamine levels and underscore the importance of restricting histamine content in American eel diets.
Danshen injection, derived from the traditional Chinese medicine Salvia miltiorrhiza Bunge, has been clinically validated for its safety and efficacy in treating various gynecological diseases, including endometrial fibrosis caused by Intrauterine Adhesion (IUA). However, its molecular mechanism in regulating the Laminin Subunit Gamma 2 (LAMC2)-CD44-TGF-β1-SMAD2/3 signaling pathway remains unclear. An IUA rat model was established and treated with low-, medium-, or high-dose Danshen injection via tail vein injection. Endometrial injury and fibrosis were assessed by H&E and Masson's staining, and epithelial/mesenchymal markers were evaluated by immunohistochemistry and Western blot. Single-cell RNA sequencing (scRNA-seq) was performed to characterize cellular composition, pathway enrichment, and predicted intercellular communication. In vitro, Lipopolysaccharide (LPS)-stimulated uterine fibroblasts were used to examine LAMC2 expression, Epithelial-Mesenchymal Transition (EMT)-related marker changes, and TGF-β1/Smad signaling, with pathway interrogation using a CD44 blocker. Simultaneously, corresponding verification was conducted in vivo. Danshen injection improved uterine histopathology, increased endometrial gland number, and reduced collagen deposition in IUA rats. CK-19 and Vimentin showed changes consistent with epithelial-mesenchymal marker alterations, which were partially reversed after Danshen treatment. scRNA-seq revealed an increased fibroblast proportion in the Model group that decreased after Danshen intervention, with differentially expressed genes enriched in fibrosis-related pathways. Cell-cell communication analysis suggested reduced repair-associated signaling and increased LAMC2-associated interactions in the Model group. In vitro, LPS induced LAMC2 upregulation and activation of TGF-β1/SMAD2/3 signaling, which was attenuated by CD44 blockade; similarly, Danshen injection and CD44 inhibition reduced LAMC2 and TGF-β1/SMAD2/3 activation in vivo. Danshen injection may mitigate endometrial fibrosis in IUA, potentially by modulating fibroblast abundance, reducing EMT-related changes, and dampening LAMC2-CD44-associated TGF-β1/SMAD2/3 signaling.
Whether combining gabapentinoids with other agents yields superior efficacy and safety outcomes compared to gabapentinoid monotherapy in patients with neuropathic pain remains unknown. To compare the efficacy and safety of gabapentinoid combination therapy versus monotherapy in patients with neuropathic pain in head-to-head comparative studies. PubMed, Web of Science, Embase, and Cochrane Library were systematically searched from inception to November 4, 2025. Data abstraction and quality assessment were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline and the Cochrane risk-of-bias tool, respectively. Pain scores (standardized to a 0-10 scale) were the primary outcomes, sleep interference scores, Patient Global Impression of Change (PGIC) and adverse events were the secondary outcomes. Study screening and selection were performed independently by 2 reviewers, with any disagreements resolved by a third adjudicator. Heterogeneity among studies was assessed using the I 2 statistic. Twenty-one clinical trials comprising 2204 patients were included in this meta-analysis. Gabapentinoid combination therapy was superior to monotherapy in reducing pain (MD = - 1.27, 95% CI = - 1.55 to - 0.99; n =18) and sleep interference scores (MD = - 0.92, 95% CI = - 1.40 to - 0.45; n =5) and increasing the PGIC response rate (RR = 1.80, 95% CI = 1.36 to 2.39; n =4). Subgroup analyses demonstrated that gabapentinoids, both gabapentin and pregabalin, achieved statistically significant greater pain reduction when combined with other gabapentinoids or antidepressants, dietary supplements, local anesthetic, non-pharmacological treatment, and opioids, whereas only a non-significant decreasing trend with immunomodulators. Notably, patients with painful diabetic neuropathy (PDN) and postherpetic neuralgia (PHN) may benefit more from combination therapy. Although combination therapy was associated with higher overall discontinuation rates and certain adverse events, these safety concerns were largely driven by opioid-gabapentinoid combinations; most other combinations had a safety profile comparable to monotherapy. Gabapentinoid combination therapy was more effective than monotherapy for neuropathic pain, but the benefit-risk profile of specific combinations warrants careful consideration in clinical decision-making. https://www.crd.york.ac.uk/prospero/, identifier CRD420251275655.
Skin wounds, encompassing acute injuries and chronic refractory ulcers, impose substantial physical and economic burdens globally. While animal models are indispensable for dissecting wound healing pathophysiology and testing therapeutic interventions, the discordance between preclinical findings and clinical outcomes remains a critical challenge. To provide a standardized reference for model selection, we conducted a systematic review in accordance with PRISMA guidelines. We comprehensively searched PubMed, Web of Science, and Scopus for studies published between January 1, 2015, and December 31, 2025. Inclusion criteria focused on in vivo cutaneous wound models in mice, rats, and rabbits that reported quantitative outcomes (e.g., closure kinetics, histology, molecular markers). Studies lacking separate control groups or sufficient methodological detail were excluded. The methodological quality of included studies was assessed using SYRCLE's risk of bias tool. A total of 129 studies met the inclusion criteria and were synthesized. We systematically categorized and evaluated mainstream models: (1) Acute wounds: Rodent incisional/excisional models facilitate high-throughput screening but are limited by contraction-dominant healing, whereas rabbit ear models better approximate human re-epithelialization. (2) Chronic wounds: Streptozotocin (STZ)-induced diabetic models in mice and rats predominate but often lack the macrovascular complications of human ulcers, necessitating novel composite models incorporating ischemia and biofilm infection. (3) Pathological scarring: Tension-induced models (e.g., suture anchoring, mechanical stretching) are identified as critical for studying mechanotransduction pathways (e.g., YAP/TAZ) absent in traditional unstressed models. Furthermore, our review identifies a pervasive male bias in study design. We highlight that sex steroids critically modulate inflammation and angiogenesis-with estrogen typically promoting and androgens delaying repair-necessitating the inclusion of both sexes or specific hormone-depleted models (e.g., ovariectomized females) to improve clinical predictive value. No single animal model perfectly recapitulates human cutaneous repair. Based on the synthesis of 129 studies, we propose a hierarchical translational framework: utilizing genetically tractable mice for mechanistic discovery, rats for longitudinal pharmacological screening, and rabbits or porcine models for the validation of scar quality and epithelial closure prior to clinical trials.
Adipose tissue is an active endocrine organ that secretes adipokines involved in metabolic regulation, inflammation, and cardiovascular homeostasis. Increasing evidence suggests that adipokine imbalance may contribute to the development of hypertension. This study aimed to compare circulating adipokine levels in newly diagnosed untreated hypertensive patients and normaotensive controls and to evaluate their association with blood pressure. This case-control study included 180 participants recruited from outpatient clinics at Dicle University Faculty of Medicine. The study population consisted of 96 newly diagnosed untreated hypertensive patients and 84 normotensive controls. Sociodemographic data and blood pressure measurements were recorded. Serum levels of leptin, intelectin, RBP-1, chemerin, visceral adipokine index, adiponectin, resistin, visfatin, and C-reactive protein were measured using ELISA kits. Statistical analyses included group comparisons, correlation analyses, ANCOVA adjusted for age, sex, and body mass index (BMI), and multivariate logistic regression. Leptin, intelectin, RBP-1, resistin, and visfatin levels were significantly higher in hypertensive patients than in controls (p < 0.001). Adiponectin levels were slightly higher in hypertensive individuals, while chemerin, visceral adipokine index, and CRP showed no significant differences. Logistic regression analysis identified age, BMI, and resistin as independent predictors of hypertension. Several adipokines are elevated in hypertension, suggesting a potential role in blood pressure regulation. Among them, resistin appears to be an independent predictor of hypertension and may represent a potential biomarker for cardiovascular risk assessment.
To evaluate the effects of traditional Chinese mind-body practices on university students' physical health and examine whether training characteristics such as duration and frequency influence these outcomes. This systematic review and meta-analysis followed PRISMA guidelines. Randomized controlled trials (RCTs) were identified from PubMed, Web of Science, Embase, the Cochrane Library, and China National Knowledge Infrastructure (CNKI) based on PICOS criteria. Effect sizes were reported as mean difference (MD) or standardized mean difference (SMD). Data were synthesized using multilevel random-effects models. Heterogeneity was assessed using the I² statistic and Cochran's Q test. Subgroup analyses and two-level random-effects meta-regression were conducted to explore potential moderators, including intervention type, frequency, session duration, intervention cycle, and total training dose. Sensitivity analyses and publication bias assessments were performed, and the certainty of evidence was evaluated using the GRADE framework. Eighteen RCTs were included. Traditional Chinese mind-body practices were associated with improvements in several physical health indicators, including vital capacity (SMD = 0.34, 95% CI: 0.11 to 0.56, P = 0.003, GRADE: Moderate), BMI (MD = -0.77, 95% CI: -1.48 to -0.06, P = 0.034, GRADE: Moderate), resting heart rate (MD = -1.16, 95% CI: -2.29 to -0.04, P = 0.043, GRADE: Moderate), sit-and-reach test (MD = 2.99, 95% CI: 1.59 to 4.38, P = 0.000, GRADE: Moderate), and pull-up/sit-up performance (SMD = 0.40, 95% CI: 0.12 to 0.67, P = 0.005, GRADE: Low). The three-level model suggested improvement in the standing long jump, but this was not robust in the two-level sensitivity analysis. No significant changes were observed in handgrip strength, step test index, 50-m Sprint, or single-leg stance test (SLST). Subgroup analyses indicated that Baduanjin combined with Yijinjing, session durations of 45-60 minutes, training three to seven times per week, and intervention periods of 12-16 weeks were associated with larger improvements, although these findings were exploratory. Traditional Chinese mind-body training may improve several physical health indicators among university students, though effects varied across outcomes and interventions. Further large, well-designed RCTs are needed to confirm the consistency and long-term significance of these findings. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251266434, identifier CRD420251266434.
Glucagon is a key hormone regulating gluconeogenesis and glucose homeostasis in mammals, yet its regulatory mechanisms in glucose metabolism in carnivorous fish remain incompletely understood. To systematically investigate glucagon-mediated glucose metabolism in Japanese flounder (Paralichthys olivaceus), liver samples were collected before glucagon injection (0 h) and at 1 h and 6 h post-injection for transcriptome sequencing (RNA-seq). Transcriptome analysis identified numerous differentially expressed genes involved in glucose and energy metabolism. In total, 507, 1458, and 709 differentially expressed genes were detected in the comparisons of 0 h vs 1 h, 1 h vs 6 h, and 0 h vs 6 h, respectively. KEGG enrichment analysis showed that glucagon activated pathways related to glucagon signaling, insulin resistance, FoxO signaling, and energy metabolism, including AMPK and PPAR pathways, suggesting that glucagon rapidly stimulates gluconeogenesis. At 6 h post-injection, genes involved in glycolysis and glucose transport were upregulated, whereas key gluconeogenic genes were downregulated, indicating attenuation of glucagon-induced metabolic responses. Further analysis showed that glucagon suppressed the insulin-mediated PI3K/AKT signaling pathway. Among the candidate genes, SOCS3 and TRIB3 were upregulated and may serve as key regulators linking glucagon and insulin signaling. Functional experiments further showed that knockdown of TRIB3 reduced glucose levels in hepatocyte culture medium and increased the expression of insulin signaling-related genes. Overall, glucagon regulates glucose metabolism in Japanese flounder by promoting gluconeogenesis while suppressing insulin signaling, providing transcriptomic insights into endocrine regulation in carnivorous fish.
Cisplatin remains a first-line chemotherapeutic agent in the treatment of oral squamous cell carcinoma (OSCC). However, the efficacy of cisplatin is frequently compromised by the development of drug resistance. This review systematically examines the multidimensional mechanisms underlying cisplatin resistance in OSCC and the corresponding strategies to overcome this resistance. Mechanisms of chemoresistance involve complex, multi-layered molecular networks, encompassing dysregulation of key gene expression and signaling pathways, epigenetic remodeling, metabolic reprogramming, evasion of regulated cell death, acquisition of epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties, as well as the formation of an immunosuppressive tumor microenvironment (TME). In response to these challenges, multimodal combinatorial approaches are being developed, including small-molecule inhibitors targeting specific resistance nodes, nanotechnology-based targeted drug delivery systems, combination therapies with immune checkpoint inhibitors, and interventions targeting metabolic vulnerabilities. Furthermore, emerging technologies are enabling more precise strategies: patient-derived organoids provide a platform for individualized drug sensitivity testing; single-cell sequencing allows for dissection of cellular heterogeneity within resistant populations and the interactions of these populations with the microenvironment; and artificial intelligence (AI) aids in predictive model building and drug discovery by integrating multi-omics data. In summary, a comprehensive understanding of the systems biology of cisplatin resistance, integrated with novel research paradigms such as nanotechnology, immunotherapy, metabolic targeting, organoid models, single-cell technologies, and AI, will be pivotal for developing personalized combination therapies to ultimately overcome cisplatin resistance in OSCC.
Overweight and obesity have emerged as global health crises and are increasingly recognized as drivers of central nervous system (CNS) dysfunction. Beyond excess energy storage, white adipose tissue (WAT) functions as an active endocrine and immune organ that, during obesity, undergoes inflammatory remodeling and releases cytokines, lipid mediators, adipokines, and extracellular vesicles that influence brain physiology. These peripheral signals disrupt key brain interfaces, including the blood-brain barrier (BBB), perivascular and glymphatic clearance pathways, promoting endothelial dysfunction, altered astrocyte-pericyte support, impaired amyloid-β clearance, and region-specific glial activation. Obesity-associated neuroinflammation is characterized by microglial priming and astrocyte reactivity across the hypothalamus, hippocampus, and other circuits governing metabolism, cognition, and reward, with growing evidence for sex-dependent vulnerability. We further highlight adipokines as key mediators of adipose-brain communication. In obesity, leptin resistance impairs central energy regulation, reduced adiponectin contributes to neuroinflammation and synaptic dysfunction, and elevated resistin enhances TLR4-dependent inflammatory signaling and BBB permeability, collectively linking metabolic stress to neurodegenerative processes. Finally, we review therapeutic strategies targeting the adipose-brain axis, including exercise and dietary interventions that improve neuroplasticity and barrier integrity, and pharmacological approaches such as orlistat and incretin-based therapies. Emerging multi-incretin agonists, including tirzepatide and retatrutide, raise important questions regarding direct CNS actions beyond metabolic benefits, underscoring the need to integrate barrier biology and neuroimmune mechanisms in future studies.
Sleep quality declines with age in older adults, and pharmacological interventions have multiple limitations. As a safe and accessible mind-body exercise, Tai Chi has preliminary evidence supporting its sleep-improving effects, but objective mechanistic studies based on sleep electroencephalography (EEG) remain scarce. Objective: This study aimed to clarify the effect of Tai Chi intervention on improving sleep quality in older adults and reveal its core mechanism through regulating sleep EEG characteristics, using a combination of questionnaires and sleep EEG monitoring. A randomized controlled trial design was adopted, enrolling 67 older adults aged 65-75 years with mild sleep disturbance, who were randomly divided into the Tai Chi group (n=33) and the control group (n=34). The Tai Chi group received 12 weeks of standardized 24-form Tai Chi training (5 times per week, 60 minutes per session), while the control group maintained daily activities without regular exercise. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and sleep diaries. Meanwhile, polysomnography (PSG) was used to collect sleep EEG data, analyzing sleep structure (proportion of each sleep stage) and EEG activity characteristics (slow-wave power, sleep spindle density). After intervention, the total PSQI score and sleep onset latency in the Tai Chi group were significantly reduced, and sleep efficiency was significantly enhanced (P < 0.001). PSG results showed that the proportion of deep sleep stage (N3) in the Tai Chi group increased by 23.1%, delta wave power (0.5-4Hz) was significantly enhanced (P < 0.01), and sleep spindle density (N2 stage) increased by 6.0% (P = 0.07, marginally significant), while no significant changes were observed in sleep indicators of the control group. Correlation analysis revealed that the reduction in total PSQI score was significantly negatively correlated with the increase in N3 stage proportion (r=-0.464, P = 0.0065) and the enhancement of delta wave power (r=-0.382, P = 0.028) in the Tai Chi group. Twelve-week Tai Chi exercise intervention can significantly improve subjective and objective sleep quality in older adults. Its core mechanism is related to enhancing slow-wave activity during deep sleep and optimizing N2 stage sleep spindle density, providing objective EEG evidence for the non-pharmacological intervention of Tai Chi in sleep disorders of older adults.
Diaphragmatic dysfunction and acute cognitive stress/delirium are serious complications of mechanical ventilation that prolong intensive care unit (ICU) stay and are associated with increased mortality. Although accumulating evidence suggests a potential lung-brain axis linking impaired respiratory muscle function to adverse neurocognitive trajectories, early risk stratification remains challenging because clinically relevant signals are multimodal, temporally dynamic, and often partially observed. We aimed to develop an interpretable multimodal deep learning model to predict diaphragmatic dysfunction and high cognitive stress/delirium in mechanically ventilated patients and to identify shared predictors that may reflect lung-brain crosstalk. We conducted a multicenter retrospective study including 25,751 mechanically ventilated ICU patients. A multimodal long short-term memory (LSTM) network was trained using continuous clinical time-series variables (vital signs, ventilator parameters, and medication dosing trajectories) and diaphragm ultrasound videos from a sub-cohort (n = 4,783). Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC). Post-hoc SHapley Additive exPlanations (SHAP) were applied to quantify feature contributions and explore cross-modal interactions. In the independent test set, the multimodal model outperformed both clinical-only (AUC = 0.811) and video-only (AUC = 0.749) baselines for predicting diaphragmatic dysfunction, achieving an AUC of 0.902 (95% CI, 0.88-0.92) and an AUPRC of 0.594 (both P < 0.001 vs. baselines). For high cognitive stress/delirium prediction, the model achieved an AUC of 0.792. Calibration was acceptable, with close agreement between predicted and observed risks (Brier score = 0.12). SHAP analyses indicated that ultrasound-derived diaphragm thickening fraction (DTF) and cumulative neuromuscular blockade exposure were among the strongest predictors of diaphragmatic dysfunction. Notably, diaphragm excursion and heart rate variability emerged as shared influential predictors for cognitive stress/delirium, consistent with the lung-brain crosstalk hypothesis in mechanically ventilated patients. This study presents a multimodal deep learning framework for early identification of mechanically ventilated patients at elevated risk of diaphragmatic dysfunction and high cognitive stress/delirium. Integrating diaphragm ultrasound with longitudinal bedside physiologic and treatment data improves prediction beyond single-modality models, while post hoc explainability highlights candidate shared predictors relevant to a lung-brain axis. These findings suggest that integrated monitoring of respiratory mechanics and sedation-related physiology may support more proactive ventilator management and neuroprotective ICU care.
Current perioperative monitoring of critical biochemical analytes predominantly relies on intermittent arterial blood gas analysis, which carries inherent risks of invasiveness and discontinuous data acquisition. Emerging evidence suggests that variations in electrocardiogram and photoplethysmogram waveforms may hold significant predictive value for detecting critical biochemical analytes changes. Advances in artificial intelligence analysis technologies have further accelerated the development of non-invasive monitoring tools, including real-time non-invasive blood glucose monitoring for diabetic patients and blood potassium monitoring for renal dialysis patients. This review highlights the urgent clinical need for non-invasive, continuous monitoring of the critical biochemical analytes during the perioperative period. It provides a comprehensive summary of current monitoring technologies and signals related to critical biochemical analytes, with a focus on their potential application in non-invasive blood gas monitoring. Based on existing evidence, key analytes such as serum potassium, serum calcium, lactate, and blood glucose have demonstrated robust research foundations and are the primary focus of this review. However, further clinical validation is urgently required to confirm their reliability and applicability in clinical settings. Integrating artificial intelligence with traditional monitoring systems has the potential to significantly enhance the precision, timeliness, and effectiveness of perioperative care. These findings suggest that AI-enhanced non-invasive monitoring could reduce unnecessary blood sampling while providing earlier detection of critical biochemical analytes disorder. Successful clinical translation requires standardized validation protocols and hardware-software co-development to address current limitations in measurement consistency and clinical workflow integration.
Pacing strategy is a central determinant of endurance running performance. While elevation profile is known to influence pacing in trail and mountain running, its potential role in road races characterized by moderate elevation variability remains insufficiently examined. This longitudinal case report aimed to explore how differences in course elevation characteristics were associated with pacing patterns and performance outcomes in an elite half-marathon runner. Ten official half-marathon performances completed over a four-year period (2014-2017) by a single elite male athlete were retrospectively analyzed. Elevation-related metrics (total ascent, total descent, and elevation range) and split times (0-10 km and 11-21 km) were examined descriptively to characterize pacing patterns, classified as positive or negative split. Five races were classified as positive split and five as negative split. Finishing times ranged from 69.18 to 87.05 min, and elevation range varied between 26.3 and 116.8 m. The fastest performance occurred during a negative split on a near-flat course; however, pacing classification and elevation characteristics were not uniformly aligned with performance outcomes across races. Within comparable elevation ranges, both positive and negative pacing profiles were observed, accompanied by substantial variation in finishing times. These findings indicate that moderate elevation variability may interact with pacing regulation in a context-dependent manner rather than acting as an isolated determinant of performance. The results highlight the multifactorial nature of pacing behavior in elite half-marathon competition and underscore the value of individualized longitudinal analyses for understanding performance execution in real-world racing conditions.
The aim of this study was to assess the predictive value of 256-detector-row helical computed tomographic pulmonary angiography (CTPA) parameters, combined with serum D-dimer levels, for risk stratification and 30-day prognostic assessment in patients diagnosed with acute pulmonary embolism (APE). This retrospective cohort study included clinical data from 77 patients with APE, stratified into low-risk (n = 38), intermediate-low-risk (n = 17), intermediate-high-risk (n = 14), and high-risk (n = 8) groups, as well as 89 control individuals, treated at Baoshan People's Hospital between January 2021 and December 2024. Clinical characteristics, CTPA-derived metrics [pulmonary artery (PA)-to-ascending aorta diameter ratio, right-to-left ventricular diameter ratio (RVD/LVD), and superior vena cava diameter], and D-dimer levels were analyzed and compared across groups. Receiver operating characteristic curve analysis and multivariate logistic regression were used to assess predictive performance. The incidence of bilateral pulmonary embolism increased with escalating risk stratification, from 44.7% in the low-risk group to 87.5% in the high-risk group. Similarly, the frequency of thrombus involvement in the main PA and its branches rose from 28.9% to 100%. The RVD/LVD ratio demonstrated a significant positive correlation with risk stratification (ρ = 0.492;95%CI: 0.30-0.64; p < 0.001) and showed statistically significant differences across groups (H = 26.093, p < 0.001); median values were higher in the intermediate-high-risk (1.55) and high-risk (1.52) groups compared with the low-risk group (0.99). D-dimer concentrations increased progressively with risk stratification (H = 45.593, p < 0.001) and effectively differentiated patients with APE from control individuals (p < 0.001), although no significant differences were observed among APE subgroups. The combined model incorporating RVD/LVD and D-dimer yielded an area under the curve (AUC) of 0.917 (95% CI: 0.852-0.983) for predicting high-risk APE, surpassing the performance of individual indicators (RVD/LVD AUC = 0.874; D-dimer AUC = 0.716). Multivariate logistic regression identified both RVD/LVD (OR = 124.605, p = 0.001) and D-dimer (OR = 1.313, p = 0.032) as independent predictors of poor short-term prognosis. The integration of CTPA-derived imaging parameters with D-dimer levels shows promise for risk stratification and prognostic assessment in APE, with the RVD/LVD ratio emerging as a key imaging biomarker. However, given the single-center retrospective design and limited sample size, these findings should be considered exploratory. The combined model requires external validation in larger, multicenter cohorts before its routine clinical applicability, especially in diverse healthcare settings, can be established.
Hospitalized acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is characterized by heightened systemic inflammation and rapid decline in functional capacity. Although exercise rehabilitation is recommended, the physiological appropriateness of exercise intensity during acute hospitalization remains uncertain, particularly across different levels of disease severity. This prospective, assessor-blinded, randomized controlled trial enrolled 141 hospitalized patients with AECOPD. Participants were stratified by disease severity (Grade I-III) and randomized to either a severity-adapted graded exercise rehabilitation program (Study group, n=70) or conventional exercise rehabilitation (Control group, n=71) for 2 weeks from admission, in addition to standard medical treatment. The severity-adapted program applied an inverse matching strategy to optimize relative physiological load, whereby patients with more severe disease received lower-intensity exercise and those with milder disease received higher-intensity exercise. Primary outcomes were changes in systemic inflammatory biomarkers (interleukin-6 [IL-6], interleukin-8 [IL-8], tumor necrosis factor-α [TNF-α], high-sensitivity C-reactive protein [hs-CRP], and white blood cell count [WBC]). Secondary outcomes included functional capacity and symptom-related measures, assessed using the 6-minute walk test (6MWT), modified Medical Research Council dyspnea scale (mMRC), COPD Assessment Test (CAT), and Hospital Anxiety and Depression Scale (HADS). Compared with conventional rehabilitation, severity-adapted graded exercise resulted in a more favorable inflammatory marker profile and greater improvements in functional capacity and symptom burden. Among the inflammatory outcomes, the most statistically robust between-group differences were observed for IL-8, TNF-α, and WBC, whereas IL-6 and hs-CRP showed directionally consistent but more modest evidence. Within the severity-adapted group, patients with milder disease tended to show larger anti-inflammatory and functional gains under higher, well-tolerated relative exercise intensity, whereas patients with moderate-to-severe disease achieved stable improvements under low-to-moderate intensity training. No consistent severity-dependent response pattern was observed in the control group. Severity-adapted graded exercise rehabilitation initiated during hospitalization for AECOPD was associated with a more favorable inflammatory profile and greater improvements in functional capacity and symptom-related outcomes than conventional exercise rehabilitation. These findings support a severity- and function-informed strategy for individualized exercise prescription in hospitalized patients with AECOPD. https://www.chictr.org.cn, ChiCTR; ChiCTR2300072409.
As two classes of persistent environmental pollutants, microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS) accumulate in the human urogenital system, posing a significant health threat. To elucidate their toxic mechanisms and inform disease prevention, this review systematically examines their individual and combined toxic effects on the urogenital system, with a focus on the kidneys. Evidence indicates that exposure to MPs induces renal injury primarily by triggering oxidative stress, programmed cell death, and disrupting the gut-kidney axis, with toxicity demonstrating size and carrier dependence. As endocrine-disrupting chemicals, PFAS disrupt metabolic and hormonal homeostasis via pathways such as PPAR activation and can induce epigenetic alterations, leading to metabolic disorders, inflammation, and potential carcinogenic risks. Exposure in real environments often occurs as mixtures of pollutants. However, studies on their combined toxicity remain limited and inconsistent. Existing evidence suggests that MPs can act as carriers for PFAS, but their "carrier effect" does not necessarily directly translate to enhanced biological toxicity. Combined exposure may trigger distinct effects including synergistic, additive, or even antagonistic effects through complex mechanisms such as the modulation of bioavailability and the synergistic amplification of cellular stress, with the specific pattern highly dependent on exposure characteristics and the biological system. Overall, research in this field is still in the early stage, and the interaction mechanisms and health risks of combined exposure urgently require systematic elucidation. Future research urgently needs to integrate multidisciplinary approaches from environmental science, toxicology, and epidemiology. Efforts should focus on developing precise internal exposure characterization techniques, dissecting the toxicological mechanisms of interactions in multi-scale models, and conducting systematic population cohort studies. This is essential for advancing the risk assessment paradigm from single-pollutant evaluation to combined-exposure assessment and ultimately formulating effective public health protection strategies.
Inhaled anticholinergics are commonly used in chronic respiratory diseases with the intention of reducing bronchial secretions in addition to their bronchodilatory effects. However, evidence regarding their direct influence on mucus production and clearance remains limited and fragmented. This study aimed to identify, evaluate, and synthesize the available evidence on the effects of inhaled and nebulized anticholinergics on mucus volume, rheological properties, mucociliary clearance, cough, and pulmonary function in adults. A systematic review was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD42024575999). Comprehensive searches were performed in PubMed, OVID, Embase, SciELO, EBSCO, ScienceDirect, and Cochrane Library without date restrictions. Randomized and non-randomized studies assessing inhaled or nebulized anticholinergics were included. Risk of bias was evaluated using the RoB 2 and ROBINS-I tools. Out of 2,449 records identified, eight studies comprising 403 participants met the inclusion criteria. Under stable clinical conditions, inhaled ipratropium and tiotropium showed no significant changes in sputum volume, viscosity, or mucociliary clearance compared with placebo. In acute or procedural settings, such as bronchoscopy, nebulized ipratropium was associated with a reduction in bronchial secretion grade and cough frequency. Tiotropium treatment demonstrated decreases in sputum solid fraction and mucin content (MUC5AC and MUC5B). None of the included studies reported impairment of mucociliary clearance or serious adverse events related to treatment. Current evidence does not demonstrate a consistent effect of inhaled or nebulized anticholinergics on sustained reduction of bronchial secretions. However, their use does not appear to cause adverse changes in mucus production or clearance and may induce transient effects during acute cholinergic stimulation. Overall, the findings support a favorable safety profile of these agents regarding airway secretion management. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024575999.
Knee joint dysfunction, including osteoarthritis, ligament injury, and post-surgical conditions, impairs symptoms, physical function, and quality of life. Aquatic rehabilitation leverages water's buoyancy, resistance, and hydrostatic properties to reduce joint load and facilitate exercise, but evidence on its effectiveness across populations and intervention parameters is inconsistent. We conducted a PRISMA-guided meta-analysis of randomized controlled trials (PROSPERO CRD420251139080) comparing structured aquatic exercise with land-based exercise or conventional treatment. Web of Science, PubMed, Embase, SPORTDiscus, CINAHL, and Cochrane Library were searched to July 2025. Change-score standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random-effects models across symptoms, physical function, and quality of life. Heterogeneity was assessed using the I2 statistic. Pre-specified subgroup analyses examined disease type, age, session length, intervention duration, and training frequency. Risk of bias was assessed with RoB 2.0; evidence certainty was appraised using GRADE. Twenty-nine trials (n = 1,984) were included. Aquatic rehabilitation significantly improved symptoms (SMD = -0.55, 95% CI: -0.73 to -0.38) and physical function (SMD = 0.50, 95% CI: 0.34 to 0.65) versus controls, while quality of life improvements were non-significant (SMD = 0.17, 95% CI: -0.15 to 0.50). Benefits were largest in patients with knee osteoarthritis and those <60 years. Interventions ≥8 weeks yielded greater symptom and functional gains. Functional subdomain analysis revealed pronounced improvements in balance, proprioception, and muscle strength, whereas mobility and flexibility showed smaller effects. Session length and training frequency had a minor influence. QoL improvements were primarily observed in younger participants. Aquatic rehabilitation effectively alleviates symptoms and enhances physical function in individuals with knee joint dysfunction, with the greatest benefits observed in knee osteoarthritis patients and adults younger than 60 years. Programs lasting at least 8 weeks yield optimal outcomes, particularly for balance, proprioception, and muscle strength. While improvements in quality of life are less consistent, younger participants may experience psychosocial gains. These findings support the integration of structured aquatic exercise into knee rehabilitation protocols, with attention to patient characteristics and program duration to maximize therapeutic effects. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251139080, identifier CRD420251139080.
Subacute stroke patients frequently experience significant motor impairment. The supplementary motor area (SMA), a critical hub for motor control and functional brain reorganization, plays a pivotal role in recovery. However, traditional interventions such as drug therapy and conventional physical therapy often lack the spatial precision and causal efficacy required for directly and accurately remodeling specific dysfunctional circuits like the SMA in subacute stroke, which results in key challenges in current rehabilitation practice for correcting specific network imbalances and efficiently inducing task-related plasticity. This narrative review elucidates how two advanced, mechanism-driven strategies address these challenges. Non-invasive neuromodulation provides a precise top-down intervention method that can directly regulate the cortical excitability of SMA and its related networks, correcting pathological network imbalances, which is unmatched by traditional methods. In contrast, motor rehabilitation provides a powerful bottom-up, experience-dependent intervention that drives Hebbian plasticity through intensive, task-oriented training, specifically enhancing SMA activation and functional connectivity. Crucially, the major innovation lies in their strategic combination. Non-invasive neuromodulation primes the brain network for learning, while motor rehabilitation consolidates the induced plasticity, thereby yielding synergistic effects that maximize functional recovery. This review synthesizes current evidence on the efficacy and mechanisms of these interventions in promoting SMA reorganization following subacute stroke, analyzing their impacts on network modulation, neuroimaging correlates, and clinical outcomes. By integrating foundational research and clinical insights, it aims to establish a theoretical framework for refining precision, network-targeted rehabilitation strategies for post-stroke motor deficits in the subacute phase.