Background Meteorological factors are among the key extrinsic triggers for the onset and exacerbation of cardiovascular and cerebrovascular diseases (CVD). Against the backdrop of sustained global warming, elucidating the impact of ambient temperature and atmospheric pressure on CVD, especially on pre-hospital CVD emergent events, has become imperative for evidence-based prevention and emergency preparedness. Objective To quantify the temporal trends of daily mean temperature and atmospheric pressure and their associations with pre-hospital CVD emergent events in Yantai, and to explore effect modification by demographic subgroups and geographic areas, thereby providing an empirical basis for the rational allocation of emergency medical resources. Methods Pre-hospital CVD emergency data from January 1, 2016 to December 31, 2022 were selected from the Yantai 120 Emergency Medical Command System. Synchronous meteorological factors and environmental pollutant data were obtained from the websites of the National Oceanic and Atmospheric Administration and the National Centers for Environmental Information of the United States. Time-series analysis combined with distributed lag non-linear model was used to analyze the association between daily temperature, atmospheric pressure, and pre-hospital CVD emergencies. Average annual percentage changes (AAPC) were calculated using Joinpoint (version 5.2.0.0) to reflect temporal trends. Spearman correlation analysis was employed to screen variables with low collinearity for inclusion in the multi-pollutant adjusted models. Results From 2016 to 2022, a total of 268275 pre-hospital CVD emergency cases were recorded in Yantai City, showing an increasing annual trend (AAPC=7.16%, P=0.002). Emergency volume, daily temperature, atmospheric pressure, and PM₁₀ displayed marked seasonal patterns, with summer bottoms and winter peaks for emergencies, daily temperature higher in summer and lower in winter, and the inverse for atmospheric pressure. Correlation analysis showed that both daily temperature and atmospheric pressure were positively correlated with O₃, with correlation coefficients of 0.745 and 0.723, respectively; negatively correlated with PM_2.5, with correlation coefficients of −0.246 and −0.235, respectively; and negatively correlated with PM₁₀, with correlation coefficients of −0.241 and −0.229, respectively (P < 0.05). A U-shaped correlation was revealed between daily temperature and pre-hospital CVD emergency risk. Using 24 °C as the reference, risk was elevated at both low and high daily temperatures, with the strongest cold effect at –11 ℃ (RR=1.53, 95%CI: 1.35, 1.73) and strongest heat effect at 30 ℃ (RR=1.06, 95%CI: 1.01, 1.11); cold effects were prolonged (lag0–14d) compared to heat effects. Atmospheric pressure exhibited a positive association with emergencies; using a median of 1012.2 hPa as the reference, the maximum risk occurred at 1037 hPa (RR=1.25, 95%CI: 1.03, 1.52), with a 0–5 d lag. In the subgroup analysis, the impact of low temperature was more pronounced among females (RR_{−9 ℃}=1.66), people over 60 years (RR_{−9 ℃}=1.91), and rural residents (RR_{−9 ℃}=1.76). High atmospheric pressure significantly increased the risk of pre-hospital CVD emergency among females (RR_{1035 hPa}=1.54), people under 18 years (RR_{1035 hPa}=3.62), and rural residents (RR_{1035 hPa}=1.46). The sensitivity analysis results indicated that, after excluding the impact of pandemic and the degrees of freedom for time variations, the effects of daily average temperature and atmospheric pressure on pre-hospital CVD emergency volume were consistent with the primary analysis findings. Conclusion Both non-optimal temperature and atmospheric pressure significantly increase the pre-hospital CVD emergency volume; therefore, emergency medical services should develop targeted response protocols, optimize resource allocation, and intensify public health education to mitigate the pre-hospital burden attributable to temperature and pressure fluctuations.

ObjectiveTo explore the effect of elbow-wrist functional orthosis on plantar pressure distribution and balance function in stroke patients with hemiplegia. MethodsFrom June, 2024 to April, 2025, 60 patients with post-stroke hemiplegia were recruited from Huashan Hospital, Fudan University, and Shanghai Hebin Rehabilitation Hospital. They were randomly divided into control group (n = 30) and intervention group (n = 30). The control group received routine neurological rehabilitation, while the intervention group received additional training with an elbow-wrist functional orthosis on the affected side, for eight weeks. Before and after intervention, the Modified Ashworth Scale (MAS) of the elbow joint, plantar pressure symmetry index (SI), plantar contact area and mean plantar pressure were recorded, and balance and mobility were assessed using the Berg Balance Scale (BBS), Timed Up & Go Test (TUGT) and 10-Meter Walk Test (10MWT). ResultsTwo cases dropped out in the control group. After treatment, MAS grades of the elbow joint, forefoot SI, affected side plantar pressure area, BBS scores, TUGT and 10MWT of both groups improved (|Z| > 3.969, |t| > 3.528, P < 0.01), while the hindfoot SI and average pressure of the affected foot improved in the intervention group (∣t∣ > 4.264, P < 0.001). Except for TUGT and 10MWT, the intervention group was superior to the control group (∣Z∣ > 2.030, ∣t∣ > 2.096, P < 0.05). ConclusionThe elbow-wrist functional orthosis can enhance balance function in stroke patients with hemiplegia by reducing upper-limb spasticity, optimizing center-of-gravity distribution, and improving postural control.

ObjectiveTo establish the mouse models of psoriasis-like lesions induced by continuous cold exposure or intermittent cold exposure combined with imiquimod （IMQ）， and to evaluate the interventional effects of Kaixuan Jiedu core prescription （KXJD） on the two models. MethodsMale C57BL/6J mice were selected and classified into two experimental batches. The first batch of 36 mice was randomized into a room temperature group， a continuous cold exposure （10 ℃/24 h） group， and an intermittent cold exposure （10 ℃/6 h） group. Each group was further divided into a normal subgroup and a model subgroup （topical application of IMQ to induce skin lesions）， with 6 mice in each subgroup， for modeling and evaluation. The second batch of 54 mice， with 6 in each group， were subjected to the same temperature grouping with an additional KXJD （30.42 g·kg^-1， continuous gavage for 5 days） group. Comprehensive evaluation of model characteristics and KXJD efficacy was conducted through Psoriasis Area and Severity Index （PASI） scoring， skin temperature measurement by infrared thermography， histopathological observation by hematoxylin-eosin （HE） staining， detection of vascular endothelial growth factor （VEGF） and platelet endothelial cell adhesion molecule 1 （CD31） by immunohistochemistry， detection of Claudin-1 and Occludin by immunofluorescence assay， determination of serum levels of tumor necrosis factor-α （TNF-α） and interleukin （IL）-10 by enzyme-linked immunosorbent assay （ELISA）， and quantification of mRNA levels of IL-17A， IL-23， IL-6， and chemokine ligand 20 （CCL20） in skin lesions by quantitative Real-time polymerase chain reaction （Real-time PCR）. ResultsModel mice in all temperature groups exhibited typical psoriasis-like skin lesions. Compared with the normal groups， the model groups showed increased PASI scores， decreased skin temperatures （P<0.05）， obvious epidermal thickening， parakeratosis， and dermal inflammatory cell infiltration， as well as elevated mRNA levels of IL-17A， IL-23， IL-6， and CCL20 （P<0.05）. Cold exposure further aggravated psoriasis. The total PASI score of the intermittent cold exposure model group was higher than that of the room temperature model group （P<0.05）. The serum IL-10 did not show a compensatory elevation， and the blood vessels presented a characteristic of elevated CD31 expression （P<0.05） without a synchronous increase in VEGF. The continuous cold exposure model group exhibited more significant dermal capillary tortuosity and dilation， with the highest mRNA levels of IL-17A， IL-23， IL-6， and CCL20 among all groups. Compared with the respective model groups， KXJD intervention alleviated skin lesions， reduced epidermal thickness and inflammatory cell infiltration， and increased skin temperature， with the temperature increase being particularly significant in the intermittent cold exposure+KXJD group （P<0.05）. Furthermore， KXJD down-regulated the expression of VEGF and CD31， restored the expression of Claudin-1 and Occludin， decreased the mRNA levels of IL-17A and IL-23 （P<0.05）， and reduced the serum TNF-α level. ConclusionThis study successfully established compound psoriasis-like mouse models induced by cold exposure combined with IMQ. It confirms that cold aggravates the severity of psoriasis by exacerbating the closure of Xuanfu （sweat pores）， microcirculation disorders， and immune imbalance. Moreover， different cold exposure patterns have distinct mechanism differences. Continuous cold exposure focuses on enhancing the inflammatory response via the IL-23/IL-17 axis and angiogenesis， simulating chronic aggravation under a long-term cold environment. Intermittent cold exposure tends to impair immune regulation and induce microvascular endothelial stress， corresponding to acute exacerbations caused by sudden temperature drops. KXJD can effectively alleviate psoriasis-like skin lesions under cold conditions by unblocking Xuanfu， regulating vasomotor function， and correcting abnormal immune-inflammatory responses.

ObjectiveTo investigate the ameliorative effect and potential mechanisms of Kaixuan Jiedu core prescription （KXJD） on imiquimod （IMQ）-combined restraint stress-induced psoriasis-like skin lesions in mice. MethodsA total of 36 C57BL/6J mice were randomly assigned to six groups （n=6 per group）： Normal group， restraint stress blank group， model group， restraint stress model group， KXJD group （30.42 g·kg^-1）， and methotrexate group （0.001 g·kg^-1）. Psoriasis-like lesions were induced by topical IMQ application combined with restraint stress. After 5 days of intervention， the severity of skin lesions was evaluated using the Psoriasis Area and Severity Index （PASI）. The following parameters were assessed： Hypothalamic-pituitary-adrenal （HPA） axis-related hormones， including adrenocorticotropic hormone （ACTH）， corticotropin-releasing hormone （CRH）， and corticosterone （CORT）， central neuronal markers， including neuronal nuclei antigen （NeuN）， microtubule-associated protein 2 （MAP2）， and beta Ⅲ-tubulin （β-Ⅲ tubulin）， microglial activation markers， including ionized calcium-binding adapter molecule-1 （Iba-1） and cluster of differentiation 11b （CD11b）， and skin nerve fiber markers， including protein gene product 9.5 （PGP9.5） and serotonin （5-HT）， as well as the expression levels of inflammatory cytokines tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， and interleukin-1 beta （IL-1β）. ResultsCompared with the normal group， both the model group and the restraint stress model group exhibited more severe psoriasis-like skin lesions， with significantly elevated serum levels of ACTH， CRH， and CORT （P<0.01）. The expression of glucocorticoid receptor （GR） and corticotropin-releasing hormone receptor 1 （CRHR1） in the skin was significantly downregulated. The expression of NeuN， MAP2， β-Ⅲ tubulin， Iba-1， and CD11b in the hypothalamus and hippocampus was significantly upregulated， suggesting abnormal changes in neuronal number or structure and aberrant activation of glial cells （P<0.05， P<0.01）. In addition， the expression of PGP9.5 and 5-HT in the skin， as well as the mRNA levels of TNF-α， IL-6， and IL-1β were all markedly elevated （P<0.05， P<0.01）. Compared with the model group， the restraint stress model group showed further exacerbation in most parameters. Compared with the restraint stress model group， the KXJD group exhibited significantly reduced PASI scores （P<0.01）， significantly decreased serum CRH， ACTH， and CORT levels （P<0.05， P<0.01）， upregulated skin GR and CRHR1 expression， inhibited abnormal neuronal changes and microglial activation in the hypothalamus and hippocampus， attenuated skin nerve fiber hyperplasia and amine signaling molecule release， and significantly reduced pro-inflammatory cytokine mRNA expression （P<0.05， P<0.01）. ConclusionKaixuan Jiedu Core prescription can effectively ameliorate IMQ combined with restraint stress-induced psoriasis-like skin lesions in mice by modulating HPA axis function， inhibiting central neuropathological changes， and attenuating skin nerve fiber hyperplasia， amine signaling molecule （5‑HT） release and local inflammatory responses.

Fluorine, as one of the important trace elements, has multiple physiological functions and participates in body metabolism. Moderate intake of fluoride is beneficial for human health, while excessive fluoride can lead to dental fluorosis, skeletal fluorosis, and multi-organ damage. Typical symptoms of skeletal fluorosis include bone sclerosis, osteomalacia, osteoporosis, and degenerative changes in articular cartilage. The pathological basis for skeletal changes in fluorosis involves enhanced osteogenesis and accelerated bone turnover, which are comprehensively regulated by multiple signaling pathways. Although the etiology of skeletal fluorosis has been determined, its pathogenic mechanisms remain inconclusive. In recent years, researchers have extensively investigated the signaling pathways involved in skeletal fluorosis development, including Notch, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), Wnt/β-catenin, Hedgehog, nuclear factor κB (NF-κB), parathyroid hormone (PTH), and insulin signaling pathways, as well as their interactive networks. This article summarizes and reviews the recent research findings, aiming to provide a theoretical foundation for comprehensively understanding the pathogenic mechanisms of skeletal fluorosis and offer insights for scientific prevention of skeletal fluorosis.

The aim of this research was to investigate the mechanism of chelidonine on H2 O2-in-duced inflammatory injury in porcine intestinal epithelial cells(IPEC-J2)through transcriptome sequencing.IPEC-J2 cells in the logarithmic growth phase were divided into the blank group(K group),H2O2 group(S group)and chelidonine group(L group),with three replicates in each group.Total RNA was isolated from each group for the purpose of constructing a sequencing li-brary.The assembled data underwent functional annotation,differential gene analysis,as well as GO and KEGG enrichment analyses.qPCR was used to confirm the expression of key differentially expressed genes(DEGs),and ELISA was utilized to assess the effect of chelidonine on the permea-bility of IPEC-J2 cells.The results indicated that the sequencing data met the necessary criteria and demonstrated a strong correlation between samples.The GO functional annotation results suggest that the intervention effects of chelidonine involve biological processes such as oxidative stress re-sponse and G2/M phase transition regulation of the mitotic cycle,and are closely associated with molecular functions,such as transmembrane transport activity.The KEGG enrichment analysis indicates that following H2 O2 treatment,DEGs in IPEC-J2 cells are predominantly enriched in the p53 signaling pathway,the coagulation cascade,the FoxO signaling pathway,and various other sig-naling pathways.Following pretreatment with chelidonine,the DEGs exhibit significant enrichment in several signaling pathways related to inflammation,including the TNF signaling pathway,syn-aptic vesicle cycle,and IL-17 signaling pathway.The results of qPCR were consistent with the se-quencing results.Chelidonine has also been found to effectively inhibit LDH release,elevate GLN content,and decrease DOA content.In conclusion,it can be seen that chelidonine can reduce cell permeability and alleviate H2 O2-induced inflammatory injury in IPEC-J2 cells by modulating in-flammation-related pathways such as the TNF signaling pathway.

To investigate the prevalence and associated factors of fall risk among Chinese older adults, and to examine the roles of urban-rural differences, regional disparities, physical health status, and psychosocial factors in falls among this population, thereby providing evidence for tailored fall prevention strategies.

Objective To explore the functions of β-glucan-induced extracellular vesicles(EVs)released from J774A.1 cells.Methods EVs were extracted from the culture supernatant of J774A.1 cells,which were cultured with or without β-glucan,using differential centrifugation.The phenotype of extracellular vesicles was identified by transmission electron microscopy(TEM),nano-particle tracking analysis(NTA)and Western blotting(WB).The peritoneal macrophages(PMs)were harvested from C57BL/6J mice,and incubated with the control EVs(C-EVs)and theβ-glucan-induced EVs(G-EVs).Total RNA was extracted from the PMs and reversely transcribed to cDNA.The expression levels of the macrophage polarization-related genes were detected through real-time fluorescence quantitative PCR(qRT-PCR).Meanwhile,the culture supernatant of the PMs was collected and assayed by enzyme-linked immunosorbent assay(ELISA)to detect the expression levels of proinflammatory cytokines tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Results EVs of the control(C-EVs)and those from the β-glucan-induced(G-EVs)were isolated from J774A.1 cell culture medium.The results of TEM analysis showed that EVs had a membrane wrapped structure and the particle diameters ranged from 100 to 1000 nm.The NTA results showed that the average particle sizes were 162.4 and 175.6 nm respectively.The results of WB assay showed the expressions of characterized marker molecules such as CD81,CD9,CD63 and TSG101 were detected.qRT-PCR results showed that the expression levels of M1 polarization related genes such as Tnfa and inos were significantly increased in PM cells of the C-EVs treatment group,but those in the G-EVs treatment group were significantly lower than in the C-EVs treatment group.Meanwhile,the expression levels of M2 polarization indicators Cd206 and Arg-1 in the C-EVs treatment group were significantly decreased,while those in the G-EVs treatment group were significantly higher than those in C-EVs treatment group.Accordingly,the results of ELISA showed that the expression levels of TNF-α and IL-6 in the conditioned medium of the C-EVs treatment group were significantly increased,while those in the G-EVs treatment group were significantly lower than in the C-EVs treatment group.Conclusion Compared with the natural EVs from J774A.1 cells,the ability of β-glucan-induced EVs to drive M1 polarization of macrophages isdramatically compromised,with much fewer proinflammatory cytokines released,suggesting that β-glucan might contribute to immune regulation through EVs.

Fluorine, as one of the important trace elements, has multiple physiological functions and participates in body metabolism. Moderate intake of fluoride is beneficial for human health, while excessive fluoride can lead to dental fluorosis, skeletal fluorosis, and multi-organ damage. Typical symptoms of skeletal fluorosis include bone sclerosis, osteomalacia, osteoporosis, and degenerative changes in articular cartilage. The pathological basis for skeletal changes in fluorosis involves enhanced osteogenesis and accelerated bone turnover, which are comprehensively regulated by multiple signaling pathways. Although the etiology of skeletal fluorosis has been determined, its pathogenic mechanisms remain inconclusive. In recent years, researchers have extensively investigated the signaling pathways involved in skeletal fluorosis development, including Notch, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), Wnt/β-catenin, Hedgehog, nuclear factor κB (NF-κB), parathyroid hormone (PTH), and insulin signaling pathways, as well as their interactive networks. This article summarizes and reviews the recent research findings, aiming to provide a theoretical foundation for comprehensively understanding the pathogenic mechanisms of skeletal fluorosis and offer insights for scientific prevention of skeletal fluorosis.

The aim of this research was to investigate the mechanism of chelidonine on H2 O2-in-duced inflammatory injury in porcine intestinal epithelial cells(IPEC-J2)through transcriptome sequencing.IPEC-J2 cells in the logarithmic growth phase were divided into the blank group(K group),H2O2 group(S group)and chelidonine group(L group),with three replicates in each group.Total RNA was isolated from each group for the purpose of constructing a sequencing li-brary.The assembled data underwent functional annotation,differential gene analysis,as well as GO and KEGG enrichment analyses.qPCR was used to confirm the expression of key differentially expressed genes(DEGs),and ELISA was utilized to assess the effect of chelidonine on the permea-bility of IPEC-J2 cells.The results indicated that the sequencing data met the necessary criteria and demonstrated a strong correlation between samples.The GO functional annotation results suggest that the intervention effects of chelidonine involve biological processes such as oxidative stress re-sponse and G2/M phase transition regulation of the mitotic cycle,and are closely associated with molecular functions,such as transmembrane transport activity.The KEGG enrichment analysis indicates that following H2 O2 treatment,DEGs in IPEC-J2 cells are predominantly enriched in the p53 signaling pathway,the coagulation cascade,the FoxO signaling pathway,and various other sig-naling pathways.Following pretreatment with chelidonine,the DEGs exhibit significant enrichment in several signaling pathways related to inflammation,including the TNF signaling pathway,syn-aptic vesicle cycle,and IL-17 signaling pathway.The results of qPCR were consistent with the se-quencing results.Chelidonine has also been found to effectively inhibit LDH release,elevate GLN content,and decrease DOA content.In conclusion,it can be seen that chelidonine can reduce cell permeability and alleviate H2 O2-induced inflammatory injury in IPEC-J2 cells by modulating in-flammation-related pathways such as the TNF signaling pathway.