Objective To investigate the association between physical activity levels and blood lipids among college freshmen, and to provide scientific evidence for the health management of college freshmen. Methods An electronic questionnaire survey on physical activity was conducted on freshmen of a university, and fasting blood biochemical indicators were detected. The International Physical Activity Questionnaire (IPAQ) short form was used to evaluate the physical activity levels of the participants. Dyslipidemia was defined as an abnormality in any one of the following serum lipid parameters: total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or non-high-density lipoprotein cholesterol. Binary logistic regression and stratified analyses were employed to explore the relationship between physical activity and blood lipids. Results A total of 3 401 participants were included, with an average age of 18.45 ± 0.92 years, and 60.5% were female. The prevalence of dyslipidemia was 17.7%, with a higher rate among males (22.1%) than females (14.8%). After adjusting for confounding factors related to blood lipids, high-intensity physical activity was negatively associated with the risk of elevated LDL-C among males (OR = 0.36, 95% CI: 0.13–0.99, P = 0.049). Conclusion Among freshmen at a medical college in Hubei Province, high-intensity physical activity is negatively associated with the risk of elevated LDL-C in males, but this association needs to be further confirmed by larger prospective cohort studies.

Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

To investigate the role of the DPP4-nestin axis in liver fibrosis induced by alveolar cyst infection,a murine model was established using C57BL/6 mice via hepatic portal vein injection.Liver histopathological changes were assessed using HE staining,while immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of nestin and DPP4 in infected mouse livers.In vitro,J S1 cell line was stimulated with recombinant DPP4 protein to es-tablish a cellular model,and qPCR,Western blot,and shRNA lentivirus interference techniques were utilized to examine the involvement of the DPP4-nestin axis in hepatic stellate cell activation.The findings demonstrated that compared to the Sham group,liver tissue structure disruption and collagen deposition were evident along with significantly increased expressions of nestin and DPP4(P＜0.050 0),which colocalized with nesin and α-SMA.Furthermore,stimulation with recombi-nant DPP4 protein significantly enhanced JS1 cell activation(P＜0.050 0)as well as upregulated nestin expression(P＜0.050 0)when compared to control group cells.Notably,shRNA lentivirus-mediated inhibition of nestin expression effectively suppressed the activating effects exerted by re-combinant DPP4 protein on JS1 cells(P＜0.050 0).Collectively,these results highlight the crucial regulatory role played by the DPP4-nestin axis in hepatic stellate cell activation triggered by alveo-lar infection;thus,targeting this axis may represent a novel therapeutic strategy for treating alveo-lar infection-induced liver fibrosis.

Objective:To explore the distribution of circadian rhythm types in middle school students and analyze the influencing factors of evening-type circadian rhythms.Methods:A cluster sampling method was used to select 10 classes from the junior or senior middle school departments of a certain school, with a total of 381 valid samples obtained from September 16 to October 24, 2023.Psychological health assessments were conducted by the morning and evening questionnaire 5 (MEQ-5), 24-item Hamilton depression scale(HAMD-24), Hamilton anxiety scale (HAMA), social disability screening schedule (SDSS), international physical activity questionnaire short form(IPAQ-SF), and Pittsburgh sleep quality index (PSQI).Based on the score of MEQ-5, students were categorized into evening-type (≤11, n=140), intermediate-type (12-17, n=166), and morning-type (≥18, n=75).The SPSS 25.0 software was used for data analysis, including χ2 test, Kruskal-Wallis test, Spearman correlation analysis, and multiple Logistic stepwise regression analysis. Results:(1)The evening-type, intermediate-type, and morning-type circadian rhythm accounted for 36.7%, 43.6% and 19.7%, respectively.(2) Comparisons among the three groups revealed that the incidence of depression was higher in the evening-type group (32.1%, 45/140) compared to the morning-type(10.7%, 8/75) ( χ2=13.35, P=0.001), the incidence of anxiety was higher in the evening-type (38.6%, 54/140) than in the other two groups(23.5%, 39/166; 20.0%, 15/75) ( χ2=11.70, P=0.003), the incidence of poor sleep quality was higher in the evening-type (61.4%, 86/140) than in the other two groups(44.6%, 74/166; 29.3%, 22/75) ( χ2=21.36, P<0.001), the incidence of social dysfunction was higher in the evening-type (57.9%, 81/140) than in the morning-type(34.7%, 26/75) ( χ2=10.69, P=0.005), and the evening-type had a lower rate of physical activity compared to the other two types ( χ2=19.73, P=0.001).(3) Spearman correlation analysis found a negative correlation between the total MEQ-5 score and the total PSQI score in the evening-type ( r=-0.19, P<0.05).(4) Multiple Logistic regression analysis showed that, compared to the intermediate-type, the risk factors for the evening-type included introverted mother personality ( B=-2.68, OR=0.07, 95% CI=0.01-0.63, P<0.05), and neutral mother personality ( B=-0.66, OR=0.52, 95% CI=0.28-0.96, P<0.05) compared to extroverted mother personality.Compared to high physical activity, low physical activity ( B=-1.12, OR=0.33, 95% CI=0.19-0.57, P<0.01) and moderate physical activity ( B=-0.71, OR=0.49, 95% CI=0.27-0.91, P<0.05) were risk factors for evening-type.Compared to the morning-type, the introverted personality ( B=1.23, OR=3.41, 95% CI=1.18-9.87, P<0.05) and neutral personality ( B=1.36, OR=3.91, 95% CI=1.52-10.05, P<0.01) were the protective factors of the evening-type relative to the extroverted personality.Low physical activity ( B=-1.33, OR=0.26, 95% CI=0.13-0.55, P<0.01) was a risk factor for the evening-type relative to high physical activity. Conclusion:The evening-type circadian rhythm may be associated with anxiety and depressive emotions, reduced sleep quality, and impaired social function in middle school students.Additionally, low physical activity levels may be a risk factor for the occurrence of evening-type circadian rhythm.

Objective To investigate the effects of Remimazolam combined with Esketamine on cellular immunity,cognitive function,and sleep quality in elderly patients with lung cancer during surgery.Methods A total of 106 elderly lung cancer patients who underwent elective thoracoscopic lobectomy from September 2023 to March 2025 were selected and divided into the control group(n=53)and the research group(n=53)according to random number table method.The control group received Midazolam combined with Esketamine for general anesthesia,while the research group received Remimazolam combined with Esketamine for general anesthesia.The intraoperative and postoperative conditions,hemodynamic parameters[heart rate(HR),mean arterial pressure(MAP)]before anesthesia induction(T0),at tracheal intubation(T1),at 1 min before one-lung ventilation(OLV)(T2),at skin incision(T3),at 1 h after OLV(T4),and immediately after extubation(T5),as well as pain and inflammatory factors[5-hydroxytryptamine(5-HT),prostaglandin E2(PGE2),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α)],cellular immunity[peripheral blood natural killer(NK)cells,CD3+,CD4+,CD4+/CD8+],the levels of serum interleukin(IL)-2,interferon-γ(IFN-γ),cognitive function[Mini-Mental State Examination(MMSE)],sleep quality[Pittsburgh Sleep Quality Index(PSQI)],and recovery quality[Postoperative Quality of Recovery-15(QoR-15)score]were compared between the two groups of patients.The adverse reactions and complications were also compared between the two groups.Results There was no significant difference in duration of surgery,duration of anesthesia,intraoperative blood loss,and time to spontaneous breathing recovery of patients between the two groups(P>0.05).The total dosage of Sufentanil in the research group was less than that in the control group,and time to postoperative eye opening,duration of recovery room stay and length of postoperative hospitalization were shorter than those in the control group(P<0.05).At T0 and T5,there was no significant difference in HR and MAP between the two groups(P>0.05),and at T1-T4,HR and MAP in the research group were higher than those in the control group(P<0.05).At the time of recovery,the levels of serum 5-HT,PGE2,hs-CRP,and TNF-α in the research group were lower than those in the control group(P<0.05),and at the time of recovery,the peripheral blood NK cells,CD3+,CD4+,and CD4+/CD8+ratio,serum IL-2 and IFN-γ levels in the research group were higher than those in the control group(P<0.05).At 1 d after surgery,the MMSE and QoR-15 scores of the research group were higher than those of the control group,while the PSQI score was lower than that of the control group(P<0.05).The incidence of adverse reactions and complications in the research group[5.66%(3/53)and 3.77%(2/53)],was lower than that of the control group[18.87%(10/53)and 15.09%(8/53)](P<0.05).Conclusion The combination of Remimazolam and Esketamine in elderly patients undergoing thoracoscopic lobectomy can better maintain intraoperative hemodynamics,stabilize cellular immune function,reduce serum pain and inflammatory factor levels,improve postoperative cognitive function and sleep quality,reduce adverse reactions and complications,and promote postoperative recovery.

Objective:To develop a scale to measure the sense of gain of the elderly, and to evaluate its reliability and validity.Methods:According to the content of the sense of gain, combined with the literature research method and interview method, the scale entry pool was established.After the expert consistency evaluation and the optimal test assembly method (OTA) analysis, the formal version of the scale was formed.The stratified sampling method was used to select 1 043 community-dwelling elders for the survey, and the reliability and validity of the scale were evaluated by methods based on classical test theory.Results:The scale of elderly sense of gain, which was screened by OTA method, included four dimensions: health status, relationship and communication, social security, and ideal expectation, with a total of 17 items. The Cronbach's α value of the formal version of the scale was 0. 850, and the Cronbach's α coefficients of the four dimensions were 0.721, 0.772, 0.779, and 0.930, respectively. The CR values of the combined reliabilities of each dimension were all above 0.7. In terms of AVE values, except for the health status dimension was acceptable, the other three dimensions were all above 0.36. The correlation coefficient between the sense of health acquisition and life satisfaction of the elderly was 0.531 ( P<0.01). Conclusion:The developed scale for measuring the sense of gain of the elderly has good reliability and validity, which can be used as an effective tool for measuring the sense of gain of the elderly.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Objective::To evaluate the diagnostic efficacy and clinical application of the Obstetrical Chinese Disseminated Intravascular Coagulation (DIC) Scoring System (OCDSS).Methods::This study is a retrospective study that collected 1063 cases from Wuhan Union Hospital, Yichang Central People’s Hospital, and the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture between July 2017 and June 2024. These cases were divided into DIC and non-DIC groups based on score standard. Diagnosis of DIC, the rate of hysterectomy, neonatal mortality, and severe asphyxia are the main outcome measures. All the laboratory indicators are all determined by clinical laboratory department of the hospital. Data were expressed as mean ± standard deviation or median (interquartile range) and frequencies. Independent sample t-test or non-parametric test were used to compare measurement data, while the chi-square test was used for count data. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to test the predictive accuracy. Using univariate and multivariate logistic regression analysis to study the high-risk factors. P < 0.050 indicates a statistical significance. Results::Of 1063 participants in this study, 29 participants (2.73%) were diagnosed with obstetrical DIC by OCDSS score standard, and all the participants were diagnosed as DIC with underlying disease. When the Takao, Clark, and Erez score standard is the "gold standard", the OCDSS score standard always shows good sensitivity and specificity, with all the AUC over 0.75. OCDSS score standard also has better predictive of hysterectomy (68.18%, 91.07%, 0.872), severe neonatal asphyxia and death (79.17%, 75.07%, 0.842) than the other three score standards. All the indicators included in the OCDSS score standard contributed to the DIC diagnosis (all the P < 0.001). The indicators in the DIC group were more abnormal than the non-DIC group (all the P < 0.001). Conclusion::OCDSS is a first score standard, especially for pregnancies, it considers the underlying disease, clinical symptoms, and laboratory results. This score system shared a good diagnosis performance for DIC in the Chinese population and may help clinicians make timely decisions.