Objective: To explore the association between the cumulative effect of body mass index (BMI) in childhood and the frequency of elevated blood pressure and cumulative burden of blood pressure, so as to provide a basis for preventing high blood pressure in children. Methods: Data were derived from the "Cardiometabolic Risk Cohort Study" conducted from 2012 to 2018, which included all students from three nine year schools (comprising primary and secondary school) in Zigong City. A total of 1 583 students with normal blood pressure at baseline were included in the study. Questionnaires and physical examinations were administered to collect demographic information, BMI, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Follow up surveys were conducted annually. To measure cumulative effects, the total area under the BMI curve (BMI-AUCt), cumulative burden of SBP (CB-SBP), and cumulative burden of DBP (CB-DBP) were calculated using the trapezoidal rule. Multinomial Logistic regression models were employed to analyze the relationship between BMI-AUCt and the frequency of elevated blood pressure during the follow up period. Additionally, multiple linear regression models combined with restricted cubic splines (RCS) were used to explore the dose response relationships of BMI-AUCt with CB-SBP and CB-DBP, respectively. Results: At baseline, the median ( IQR ) values for BMI, SBP and DBP of the students were 15.0(14.2, 16.1) kg/m 2 ，89.0(87.0, 90.0) mmHg and 58.0(54.0, 60.0 ) mmHg, respectively. During follow up, the median( IQR ) BMI, SBP and DBP for students with 0, 1 and ≥2 occurrences of high blood pressure were: 14.8(14.0, 15.9), 15.2(14.3, 16.3), 15.8(14.9, 17.0) kg/m 2; 89.0(87.0, 90.0),89.0(87.0,90.0), 89.0(87.0, 90.0)mmHg; 58.0(54.0, 60.0), 58.0(54.0, 59.5), 59.0(56.0, 59.0) mmHg. Results from the multinomial Logistic regression model, after adjusting for baseline age, sex, school, overweight/obesity status and number of measurements showed that compared to students with 0 occurrence of high blood pressure during follow up, for every 1 unit increase in BMI-AUCt, the risk of having 1 occurrence and ≥2 occurrences of high blood pressure increased by 4%( OR =1.04) and 6%( OR =1.06), respectively(both P <0.05). Multiple linear regression combined with restricted cubic splines(RCS) revealed non linear dose response relationships between BMI-AUCt and both CB-SBP and CB-DBP(all P trend <0.01, all P non linearity <0.01). Specifically, BMI-AUCt was positively correlated with CB-SBP when BMI-AUCt exceeded 30.08 kg/m 2×year( β =0.13) and with CB-DBP when BMI-AUCt exceeded 48.41 kg/m 2×year( β =0.12)(both P <0.01). Conclusions Children with a higher cumulative BMI may face an increased risk of cumulative blood pressure burden. It is necessary to enhance dynamic monitoring of children s BMI and blood pressure for reducing the risk of elevated blood pressure in childhood.

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.

ObjectiveTo investigate the optimal termination time for acupuncture in treating patients with acute peripheral facial paralysis and its cost-effectiveness. MethodsA total of 120 eligible patients with acute-stage peri-pheral facial paralysis were randomly assigned to either the mild dysfunction termination group and the complete recovery termination group， with 60 patients in each group. Both groups received the standard acupuncture treatment protocol. Treatment in the mild dysfunction termination group was terminated when the Sunnybrook facial grade scale （SFGS） score first reached or exceeded 83 points， while that in the complete recovery termination group was terminated when the SFGS score first reached or exceeded 95 points. Assessments were conducted before treatment， 6 and 12 months after onset. SFGS， facial disability index （FDI） including physical function （FDIp） and social function （FDIs）， self-rating anxiety scale （SAS）， and self-rating depression scale （SDS） scores were assessed before treatment， and 6 and 12 months after onset. Any acupuncture-related adverse events during treatment were recorded for safety evaluation. Treatment sessions and medical costs including direct costs， indirect costs， insurance coverage， total societal costs， and patient out-of-pocket expenses were also recorded， and an economic evaluation was conducted including cost-effectiveness ratio （CER） and incremental cost-effectiveness ratio （ICER）. ResultsUltimately， 56 patients in the mild dysfunction termination group and 55 in the complete recovery termination group completed the follow-up. At 6 and 12 months after onset， SFGS and FDIp scores in both groups improved significantly while FDIs， SAS and SDS scores decreased （P＜0.05）. Comparison of scores between groups 6 months and 12 months after onset showed no statistically significant differences （P＞0.05）. During the trial， the incidence of adverse events was 13.3% （8/60） in the mild dysfunction termination group and 18.3% （11/60） in the complete recovery termination group， with no statistically significant difference （P＞0.05）. The number of treatment sessions， total social costs， and out-of-pocket expenses in the mild dysfunction termination group were significantly lower than those in the complete recovery termination group （P＜0.05）. The CER of the mild dysfunction termination group in SFGS， FDIp， FDIs， SAS， and SDS scores was lower than that of the complete recovery termination group. The ICER analysis showed that continuing treatment until full recovery incurred an additional cost of 573.30 CNY/point in SFGS improvement， whereas 1-point improvement in FDIp， FDIs， SAS， and SDS required 21,355.25 CNY， 1779.60 CNY， 3713.96 CNY， and 2755.52 CNY， respectively. ConclusionFor acupuncture in treating acute peripheral facial palsy， terminating treatment when mild dysfunction is achieved yields long-term efficacy comparable to that of continuing treatment until complete recovery， while significantly reducing medical costs and socioeconomic burden.

ObjectiveTo investigate the role of runt-related transcription factor 3 （RUNX3） in transforming growth factor-β₁ （TGF-β₁）-induced activation of mouse primary pulmonary fibroblasts （PFs）， and its effects on fibroblast activation protein （FAP） expression， cell proliferation， and collagen synthesis. MethodsPFs were isolated from C57BL/6 mice and cultured. A RUNX3 knockdown model was established using small interfering RNA （siRNA）. Cells were assigned to the control group （Control）， TGF-β₁-treated group （TGF-β₁）， negative control group （TGF-β₁+siRNA-NC）， and RUNX3-silenced group （TGF-β₁+si-RUNX3）. In addition， a RUNX3 overexpression rescue experiment was performed based on TGF-β₁ stimulation. Protein and mRNA levels of RUNX3， FAP， and typeⅠcollagen （COL1A1） were measured by Western blot and reverse transcription quantitative real-time PCR （RT-qPCR）. Cell proliferation was assessed using CCK-8 and EdU assays. Co-expression of COL1A1 and FAP was examined by double immunofluorescence staining. ResultsCompared with the Control group， RUNX3， FAP， and COL1A1 expression levels were upregulated in PFs in the TGF-β₁ group （P<0.01）. The CCK-8 assay showed that the absorbance value was reduced in the RUNX3 knockdown group compared with the negative control group （P<0.01）. Consistently， the EdU assay demonstrated a lower proportion of EdU-positive cells in the RUNX3 knockdown group than in the negative control group （P<0.01）. Immunofluorescence double staining revealed decreased fluorescence intensities of COL1A1 and FAP in the RUNX3 knockdown group relative to the negative control. Under RUNX3 overexpression conditions， these fluorescence signals exhibited a partial rebound （P<0.01）. ConclusionRUNX3 in TGF-β1-induced PFs may promote cell proliferation and collagen synthesis by positively regulating FAP expression. Targeting the RUNX3/FAP axis may represent a potential therapeutic strategy for pulmonary fibrosis.

Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

Objective To develop and validate a nomogram incorporating postoperative blood pressure and other multifactorial predictors for the risk of delayed cerebral ischemia(DCI)following surgical clipping in patients with aneurysmal subarachnoid hemorrhage(aSAH).Methods This retrospective cohort study consecutively enrolled 272 aSAH patients who underwent aneurysm clipping at the Department of Neurosurgery,Second Affiliated Hospital of Chongqing Medical University from January 2018 to January 2022.Demographic,clinical,and imaging data were collected.Predictors were screened using LASSO regression,and a multifactorial logistic regression-based nomogram was constructed.The dataset was randomly divided into training(n=190)and validation(n=82)sets at a 7∶3 ratio.Model discrimination,calibration,and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration curves,and decision curve analysis(DCA),respectively.Results Among 272 enrolled patients,98(36%)developed DCI.Multivariate analysis identified age(OR=0.97;95%CI:0.94～0.99;P=0.036),World Federation of Neurological Surgeons(WFNS)grade(OR=1.36;95%CI:1.02～1.82;P=0.038),Fisher grade(OR=1.44;95%CI:1.01～2.05;P=0.048),and mean arterial pressure on postoperative day 2(OR=1.06;95%CI:1.03～1.09;P<0.001)as independent risk factors for DCI.The model achieved C-indices of 0.739(95%CI:0.668～0.810)in the training set and 0.760(95%CI:0.647～0.872)in the validation set.Calibration curves demonstrated high agreement between predicted and observed probabilities(mean absolute error=0.027),while DCA confirmed significant net clinical benefit at threshold probabilities of 15%～65%.Conclusion We successfully developed a predictive model incorporating age,WFNS grade,Fisher grade,and postoperative day 2 mean arterial pressure,with elevated postoperative blood pressure identified as an early critical indicator for DCI development.

Cytokeratin 19 fragment antigen 21-1(CYFRA21-1)is a new biomarker which has received much attention in recent years for cancer screening,and has shown great potentials for screening and diagnosis of various cancers,especially non-small cell lung cancer.CYFRA21-1 level in human serum has important clinical significance in the diagnosis,prognosis and treatment of lung cancer.Recently,a variety of detection techniques have been established to effectively enrich the detection technology system of CYFRA21-1,such as enzyme-linked immunosorbent assay,chemiluminescence,fluorescence,immunochromatography,electrochemical method,and surface enhanced Raman spectroscopy,etc.These techniques provide technical support for early diagnosis of lung cancer.However,the research progress of CYFRA21-1 detection methods is rarely reported.In this paper,CYFRA21-1 and its clinical significance were briefly introduced,and the progress of detection technology in recent ten years was reviewed,which was expected to provide reference for developing more sensitive,accurate,fast and convenient detection methods.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

ObjectiveTo understand the incidence and mortality trends of acute cardiovascular and cerebrovascular events in Yangpu District of Shanghai from 2009 to 2022, and provide a basis for the prevention and control of cardiovascular and cerebrovascular events. MethodsData were obtained from the Shanghai Acute Cardiovascular and Cerebrovascular Events Surveillance Platform. Data on the incidence and mortality of cardiovascular and cerebrovascular events in the population (age group, gender) from 2009 to 2022 were collected, and the Joinpoint Regression Program version 4.9 was used to calculate the average annual percent change (AAPC) in the incidence and mortality rates of acute cardiovascular and cerebrovascular events. ResultsFrom 2009 to 2022, the crude incidence and standardized incidence rate of acute cardiovascular and cerebrovascular events in Yangpu District showed no significant changes (AAPC=1.41%, P=0.569; AAPC=-1.03%, P=0.675), the crude mortality rate of acute cardiovascular and cerebrovascular events in Yangpu District did not change significantly (AAPC=-3.04%, P=0.213), while the standardized mortality rate showed a decreasing trend (AAPC=-6.23% P=0.014). From 2009 to 2022, the crude incidence rates and age-standardized incidence rates for both males and females in Yangpu District showed no significant changes. The crude mortality trends for both genders were not significant, while the age-standardized mortality rates showed a decline (AAPC=-5.33%, P=0.029; AAPC=-7.50%, P=0.006). The incidence rate and age-standardized incidence rate were higher in males than in females. The crude incidence rates in the 30‒, 40‒, and 45‒year-old age groups increased annually (AAPC=9.13%、7.11%、4.67%, all P=0.001), and the crude mortality ratse in the 60‒, 65‒, 70‒, 75‒, 80‒, and 85‒year-old age groups declined annually (AAPC=-4.24%, P=0.044; AAPC=-5.41%, P=0.028; AAPC=-6.73%, P=0.004; AAPC=-7.46%, P=0.002; AAPC=-8.24%, P=0.002; AAPC=-6.16%, P=0.035). ConclusionFrom 2009 to 2022, the crude incidence, standardized incidence rate and crude mortality rate of cardiovascular and cerebrovascular events in Yangpu District tended to be stable, and the standardized mortality rate showed a downward trend. Men, middle-aged and young people were the key groups in the prevention and treatment of cardiovascular and cerebrovascular diseases, and it should be continued to improve the ability of medical emergency and increase the integration of medical and prevention.