Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Exercise-induced muscle damage (EIMD) is a frequent form of skeletal muscle microdamage that occurs after high-intensity, prolonged, or unaccustomed exercise, especially exercise dominated by eccentric contractions. It is commonly characterized by delayed-onset muscle soreness, transient loss of muscle strength, local inflammation, structural disruption of myofibers, and delayed functional recovery. Although mild EIMD may serve as a stimulus for training adaptation, excessive or insufficiently recovered muscle damage can impair exercise performance, disturb training continuity, and reduce participation in physical activity. Therefore, clarifying the molecular mechanisms that underlie the initiation, amplification, and resolution of EIMD is important for optimizing athletic training, improving post-exercise recovery, and guiding evidence-based public fitness practice. Necroptosis is a regulated form of programmed cell death mediated primarily by the receptor-interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling axis. Recent studies have shown that necroptosis is closely involved in tissue injury, sterile inflammation, and repair remodeling. However, whether necroptosis acts as an initiating driver, a secondary damage amplifier, or an adaptive signal required for repair after EIMD remains unclear. This review aimed to summarize the potential role of necroptosis in EIMD and to establish a mechanistic framework linking regulated cell death, inflammatory amplification, immune regulation, and skeletal muscle repair. Relevant studies concerning EIMD, necroptosis, RIPK1/RIPK3/MLKL signaling, damage-associated molecular patterns (DAMPs), inflammatory responses, immune cell recruitment, extracellular matrix remodeling, and muscle regeneration were reviewed and integrated. On this basis, the possible temporal and functional involvement of necroptosis in different phases of EIMD was analyzed. The main evidence summarized in this review suggests that EIMD is not merely a consequence of primary mechanical disruption. Instead, it develops through a dynamic sequence that includes sarcolemmal instability, calcium overload, mitochondrial dysfunction, oxidative stress, inflammatory mediator production, immune cell infiltration, necrotic tissue clearance, and regeneration-associated remodeling. Necroptosis may participate in this process through at least two interconnected mechanisms. First, in the early or progressive phase of EIMD, activation of the RIPK1/RIPK3/MLKL signaling axis may promote MLKL phosphorylation and plasma membrane permeabilization, leading to the release of DAMPs such as high-mobility group box 1, ATP, mitochondrial DNA, and other intracellular components. These signals may activate innate immune pathways, amplify inflammatory cytokine production, and enhance the recruitment of neutrophils and macrophages, thereby aggravating secondary inflammation and extending muscle fiber injury. Second, during the resolution and repair phases, necroptosis-related signaling may also contribute indirectly to the formation of a regenerative microenvironment. By influencing the clearance of necrotic debris, the recruitment and phenotypic transition of immune cells, and the remodeling of extracellular matrix components, necroptosis may affect satellite cell activation, myogenic repair, and the eventual structural and functional recovery of injured skeletal muscle. Thus, the biological effect of necroptosis in EIMD may be context dependent rather than uniformly harmful. Its outcome may depend on exercise intensity, the extent of tissue damage, the timing of pathway activation, the involved cell types, inflammatory status, training background, age, and metabolic condition. In conclusion, necroptosis may represent an important molecular link between skeletal muscle injury, sterile inflammation, and tissue repair after damaging exercise. It may exert a dual role in EIMD by amplifying secondary damage while also contributing to repair coordination under appropriate temporal and microenvironmental conditions. Future studies should determine the activation pattern of RIPK1/RIPK3/MLKL signaling after different exercise protocols, identify the major cell populations undergoing necroptosis in injured skeletal muscle, and examine whether targeted modulation of necroptosis can reduce excessive inflammation without impairing necessary regenerative responses. This review provides a theoretical basis for understanding the pathogenesis of EIMD and for developing targeted strategies to improve skeletal muscle recovery after exercise-induced injury.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Objective To explore the accumulated effects of physical activity,sedentary behavior,and sleep on cardiorespiratory fitness(CRF)among college students and provide effective measures for enhancing their CRF. Methods From May to June in 2023,223 college students aged 18 to 24 years old were recruited from Tianjin University of Science and Technology for a 24 hours activity behavior survey and CRF testing.Compositional analysis was employed to investigate the relationships of physical activity,sedentary behavior,and sleep with CRF.Isotemporal substitution models were established to predict the effects of substituting various activity behaviors on CRF.Results The proportion of time spent on moderate-to-vigorous physical activity(MVPA)was positively correlated with CRF of college students(β=6.40,P=0.002),while the proportion of time spent on sedentary behavior was negatively correlated with CRF(β=-3.02,P=0.004).Light physical activity(LPA)and sleep were not correlated with CRF(β=-1.06,P=0.504).Isotemporal substitution results for 15-min increments showed that replacing other activity behaviors with MVPA significantly increased the CRF of college students[SB:1.72 mL/(kg·min),95% CI=0.94-2.51;LPA:1.82 mL/(kg·min),95% CI=0.95-2.68;sleep:1.64 mL/(kg·min),95% CI=0.84-2.45].In the dose-response relationship from -30 min to 30 min,reallocating time from other behaviors to MVPA had greater adverse effect on CRF than reallocating time from MVPA to other behaviors.Among all the substitutions,replacing LPA with MVPA had the most beneficial effect on improving CRF.Additionally,a 5-min increment was considered the optimal tipping point for MVPA replacing other activities.Conclusions This study underscores the importance of participating in MVPA for improving the CRF of college students.The isotemporal substitution model provides clear goals for the allocation of time for these behaviors,aiding in future intervention measure development and policy-making.
Humans ; Sedentary Behavior ; Sleep ; Students ; Cardiorespiratory Fitness ; Exercise ; Young Adult ; Adolescent ; Universities ; Male ; Female

Objective To explore the effects of time reallocation among moderate-to-vigorous physical activity(MVPA),light physical activity(LPA),sedentary behavior(SB),and sleep on a body shape index(ABSI),body roundness index(BRI),conicity index(CI),and relative fat mass(RFM)of college students by the compositional isotemporal substitution method,thus providing measures for alleviating the obesity problem of college students. Methods Two hundred and ten college students(111 males and 99 females)aged 18-22 years old were recruited from Tianjin University of Science and Technology from April to June in 2023.Three-dimensional acceleration sensors were used to collect data of MVPA,LPA,SB,and sleep of college students.The body height,body weight,and waist circumference were measured,and four novel obesity indicators(ABSI,BRI,CI,and RFM)were calculated.The effects of substituting each activity behavior for 15 min on the obesity indicators were predicted,and the dose-effect relationship was explored at intervals of 5 min from -30 to 30 min.Results MVPA was negatively correlated with ABSI(β=-0.03,P=0.001),BRI(β=-0.27,P=0.049),CI(β=-0.10,P=0.001),and RFM(β=-9.95,P=0.004).LPA was negatively correlated with CI(β=-0.05,P=0.011)and RFM(β=-8.74,P=0.007).Neither SB nor sleep had correlations with ABSI,BRI,CI,and RFM.The results of 15 min isotemporal substitutions showed that increasing the MVPA time decreased the ABSI,BRI,CI,and RFM by 0.006-0.008,0.306-0.393,0.162-0.205,and 2.468-2.897,respectively.Decreasing the MVPA time increased the ABSI,BRI,CI,and RFM by 0.012-0.014,0.548-0.632,0.286-0.328,and 4.358-4.748,respectively.In the dose-effect relationship from -30 min to 30 min,MVPA was irreplaceable,and the negative benefits from substituting MVPA for other activity behaviors were much greater than the positive benefits from substituting MVPA for other activity behaviors.Conclusions Future research should take 24 hours activity behaviors as a whole.Increasing the time spent on MVPA and LPA and decreasing the time spent on SB is one of the effective ways to alleviate the obesity problem among college students.
Humans ; Male ; Students ; Female ; Young Adult ; Obesity ; Sleep ; Adolescent ; Exercise ; Universities ; Sedentary Behavior ; Body Mass Index ; Body Weight

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

Fracture healing is a complex process that necessitates the synergistic action of various cells and molecules. Macrophages play an indispensable and crucial regulatory role in the process of fracture repair, influencing stages such as inflammatory modulation, angiogenesis, and tissue remodeling. This article delves into the functional characteristics of macrophages and their roles at different stages of fracture healing. Additionally, it explores the impact of aging macrophages on the healing process. Furthermore, the potential of emerging therapies, such as hydrogel-based treatments and exosomes, in modulating macrophage responses is analyzed. This study provides a theoretical foundation for the development of innovative therapies aimed at enhancing the efficacy of fracture healing.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

To compare and analyze the clinical manifestations,laboratory characteristics,imaging findings,and treatment outcomes of patients with acute and chronic brucellosis,a retrospective analysis was conducted on 258 patients with brucellosis(202 in the acute group and 56 in the chronic group)hospitalized in Xinkang Hospital in Dalad Banner,Ordos City,Inner Mongolia Autonomous Region,from November 2023 to November 2024.General data,epidemiological characteristics,clinical presentations,laboratory test results,imaging findings,treatment outcomes,and prognosis were collected.The incidences of fever(51.5%vs 7.1%),fatigue(30.2%vs 12.5%),joint pain(42.9%vs 16.1%),and muscle pain(9.9%vs.1.8%)were significantly higher in the acute phase group(all P<0.05).The incidence of osteoarthritis complications was higher in the chronic brucellosis group(51.8%vs 8.9%,χ2=75.697,P<0.01).Univariate ANOVA analysisshowed that the Serum Agglutination Tests(SAT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CRE),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and bone destructionexhibited statistically significant differences between the acute and chronic phases of brucellosis(all P<0.05).Multivariate logistic regression analysis indicated that abnormal ALT(OR=14.18,95%CI:1.11-181.72;P=0.041)and bone destruction(OR=0.16,95%CI:0.04-0.63;P=0.009)were associated with chronic brucellosis.After treatment,all patients experienced have symptom relief in varying degrees,with 157 patients(60.9%)cured and 101 patients(39.1%)symptomatic improved(P<0.01).In conclusion,the incidences of fever,fatigue,and joint pain in patients during the acute phase is significantly higher than that those in patients during the chronic phase,while the incidence of osteoarthritis complications is higher in chronic phase patients.The incidences of abnormal SAT,ALT,AST,TBIL,CRE,CRP,and ESR,and bone destruction varies at different stages of brucellosis.Of those,abnormal ALT and bone destruction show a stronger association with,which can assist the clinical staging of brucellosis.

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged