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.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

To perform the phylogenetic characterization of an isolated porcine rotavirus(PoRV)and investigate its pathogenicity in suckling mice and piglets.A G4P[23]genotype PoRV strain JSJR2023 was successfully isolated from the diarrheic piglet feces through propagation in MA104 cells.The viral proliferation kinetics were analyzed using TCID50 assays,followed by complete genome sequencing through Sanger sequencing platforms.Comprehensive genotyping and phylogenetic reconstruction were conducted using MEGA7.0 with maximum likelihood algorithms.Pathogenicity was assessed in the following animal models:5-day-old C57BL/6 mice and 3-day-old piglets.Multidimensional evaluation included clinical monitoring(diarrhea scoring,growth parameters),virological detection,and histopathological analysis of intestinal tissues.The virus strain JSJR2023 could replicate efficiently in MA104 cells,achieving peak titers of 107.5 TCID50/mL.Whole genome genotype analysis showed that the strain belonged to G4-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1.Phylogenetic analysis indicated that the VP3 and NSP4 genes of JSJR2023 strain were most closedrelated to human species rotaviruses,suggesting genetic reassortment between human and porcine RV strains.The animal experiments in suckling mice showed that the JSJR2023 strain infection caused diarrhea symptoms,intestinal edema and congestion,and shedding of intestinal villus epithelial cells.The pathogenicity experiments in piglets showed that compared with the control group,the challenged group of pig-lets had severe diarrhea symptoms,accompanied by reduced appetite and listlessness.Post-mortem examination revealed that the intes-tines were significantly thinner,congested,and filled with yellow watery contents.The challenged piglets showed typical pathological changes such as thinning of the intestinal wall and shortening and shedding of intestinal villi.In conclusion,this study successfully iso-lated a human-porcine recombinant G4P[23]PoRV strain and established the infection models in suckling mice and piglets,providing important tools for investigating the pathogenic mechanism of PoRV,evaluating vaccines and developing antiviral drug.

Objective:To explore the clinical characteristics and prognostic risk factors of Mycoplasma pneumoniae pneumonia(MPP)in adults across different age groups,providing evidence for age-stratified management strategies.Methods:A retrospective analysis was conducted on 80 MPP patients admitted to the Respiratory Department of a hospital between January 2023 and December 2024.Patients were divided into three groups based on age:young adults(18-40 years),middle-aged adults(41-60 years),and elderly adults(≥ 61 years).Demographic features,clinical indicators,and mixed infections were analyzed.Univariate and multivariate Logistic regression were used to identify risk factors for disease severity.Results:The severity rate was significantly higher in the elderly group(41.2％)compared to the young adult group(7.1％)and middle-aged group(20.0％)(P=0.022).Elderly patients also exhibited significantly higher rates of underlying diseases(chronic lung disease:35.3％vs.3.6％in young adults),elevated inflammatory markers(C-reactive protein:68.3±19.5 mg/L vs.32.5±8.4 mg/L in young adults),mixed infections(52.9％vs.14.3％),and prolonged hospital stays(8.61±2.22 days vs.5.01±1.11 days)(P＜0.05).Multivariate analysis identified age(OR=1.79 per 10 years),chronic lung disease(OR=3.25),blood urea nitrogen ≥6 mmol/L(OR=2.44),and mixed infections(OR=4.26)as independent risk factors for severe MPP(P＜0.05).Conclusion:Clinical manifestations and prognoses of MPP in adults vary significantly across age groups.Elderly patients are characterized by high mixed infection rates,intense inflammatory responses,and renal function impairment,necessitating individualized monitoring and intervention strategies.

Aim To explore the MST1 knockdown at-tenuates the inhibitory effect of salvianolic acid B(Sal B)on pERK anti-renal fibrosis.Methods In vitro experiments stimulated human renal cortical proximal tubular epithelial cells(HK-2)with XMU-XP-1(10μmol·L-1)inhibitor;in vivo experiments induced wild-type(WT)and MST1 systemic knockout mouse(MST1-/-)renal fibrosis models with DEN/CCl4/C2H5OH(DCC)and interfered with Sal B(15 mg·kg-1·d-1,ig)intervention.Renal histopathology was observed by HE and Masson staining;α-SMA and pERK protein expression was detected by Western blot;and pERK protein expression was detected by im-munofluorescence.Results In vitro results showed that Sal B could inhibit pERK protein expression.In vivo results showed that Sal B could improve DCC-in-duced renal tissue pathological injury and inhibit α-SMA and pERK protein expression;MST1-/-aggrava-ted pathological injury and significantly up-regulated α-SMA and pERK protein expression.Conclusion Sal B reduces the stimulatory effect of XMU-MP-1 on HK-2 cells by inhibiting the phosphorylation of ERK protein;Sal B exerts its anti-renal fibrosis effect by inhibiting the phosphorylation of α-SMA protein and ERK pro-tein;and MST1-/-,aggravating the pathological inju-ry of renal tissue,significantly up-regulated the expres-sion of α-SMA and pERK protein,which in turn atten-uated the antirenal fibrosis effect of Sal B.