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.

Objective To analyze the spatiotemporal distribution characteristics of and trends in the disease burden of dengue fever in China from 2005 to 2024, so as to provide insights into formulation of dengue fever control strategies. Methods Data pertaining to dengue fever cases in China from 2005 to 2024 were retrieved from the Infectious Disease Reporting Information System of Chinese Center for Disease Control and Prevention, and city population, gross domestic product (GDP), GDP per capita, and consumer price index in China were captured from the China Statistical Yearbook, National Bureau of Statistics of China, the China City Statistical Yearbook, and bureaus of statistics in each city. The disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to dengue fever were calculated in China from 2005 to 2024. The direct and indirect economic burdens of dengue fever were estimated to calculate the total economic burden. The trends in the disease burden of dengue fever were estimated in China from 2005 to 2024 using a Joinpoint regression model with the software Joinpoint 4.9.0.0, and the average annual percent change (AAPC) and its 95% confidence interval (CI) were calculated. In addition, the DALYs rate and economic burden of dengue fever in China were subjected to global and local spatial autocorrelation analyses using the software ArcGIS 10.8. Results The gross DALYs due to dengue fever were 5 558 person-years in China from 2005 to 2024, and the DALYs of dengue fever increased from 36 person-years in 2005 to 899 person-years in 2024, with an increase of 23.97 folds. The average annual DALYs rate of dengue fever was 0.02 person-years/10⁵ in China during the 20-year study period from 2005 to 2024, and the DALYs rate peaked in 2014 (0.13 person-years/10⁵) and reduced during the COVID-19 pandemic from 2020 to 2022. YLDs were the main contributor of DALYs due to dengue fever in China from 2005 to 2024, with a total of 5 354 person-years, accounting for 96.33% (5 354 person-years/5 558 person-years) of the gross DALYs. The gross DALYs of dengue fever were 2 982 person-years among men (53.66%) and 2 575 person-years among women (46.34%) in China from 2005 to 2024, and high DALYs of dengue fever were measured among residents at ages of 15 to 30 years (1 639 person-years), 30 to 45 years (1 857 person-years), and 45 to 60 years (1 204 person-years), respectively, accounting for 84.56% (4 700 person-years/5 558 person-years) of total DALYs due to dengue fever in China. The total economic burden of dengue fever was estimated to be 612 million Yuan in China from 2005 to 2024, with an average annual economic burden of 30.584 million Yuan. The economic burden of dengue fever increased from 196 000 Yuan in 2005 to 121 million Yuan in 2024 in China, with an increase of 616.35 folds, and the per capita economic burden increased from 3 322.21 Yuan in 2005 to 4 940.01 Yuan in 2024, with an increase of 48.70%. Dengue fever cases were reported in 274 cities (counties) across 31 provinces (autonomous regions, municipalities) in China from 2005 to 2024, with relatively higher DALYs in Guangdong Province and Yunnan Province. Spatial autocorrelation analysis revealed that the disease burden of dengue fever appeared positive aggregation in Chinese cities (counties) from 2005 to 2024 (global Moran’s I = 0.045, Z = 2.24, P < 0.05), with high-high clusters mainly concentrated in the Pearl River Delta region in Guangdong Province and Xishuangbanna Dai Autonomous Prefecture and Pu’er City in Yunnan Province, and the total economic burden (global Moran’s I = 0.032, Z = 9.55, P < 0.001), per capita economic burden (global Moran’s I = 0.208, Z = 27.34, P < 0.001), and the proportion of total economic burdens in GDP in 2024 (global Moran’s I = 0.017, Z = 5.91, P < 0.001) all presented positive aggregation, with relatively higher total economic burdens mainly concentrated in Guangdong Province and Yunnan Province. Joinpoint regression analysis showed that the gross DALYs rates of dengue fever appeared an overall tendency towards a rise in China from 2005 to 2024 (AAPC = 16.24%, P = 0.029), and the DALYs rate presented an overall tendency towards a rise among both men (AAPC = 14.75%, P = 0.028) and women (AAPC = 14.93%, P = 0.037) during the study period. The per capita direct economic burden appeared an overall tendency towards a rise among dengue fever patients in China from 2005 to 2024 (AAPC = 2.16%, P = 0.012); however, there was no significant difference in the trends in the per capita indirect economic burden (AAPC = 0.46%, P = 0.470). In addition, the DALYs rate of dengue fever appeared a tendency towards a rise in 84.67% (232/274) of cities (counties) in China from 2005 to 2024, and the per capita economic burden appeared a tendency towards a rise in 85.40% (234/274) of cities (counties), while the DALYs rate and per capita economic burden of dengue fever appeared a tendency towards a rise in 77.01% (211/274) of cities (counties). Conclusions The disease burden of dengue fever significantly increased in China from 2005 to 2024. It is recommended to reinforce integrated dengue fever control in high-risk areas and among high-risk populations, and to improve the surveillance of imported dengue fever cases and vector control.

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.

Objective To investigate the radiological features of intracranial white epidermoid cysts(WECs).Methods A retro-spective analysis was conducted on the CT and MRI findings of 7 patients pathologically confirmed with WECs.All patients under-went plain CT and MRI scans,and six patients underwent enhanced MRI scans.Results All cases were solitary lesions,located in the right middle cranial fossa(2 cases),suprasellar area(2 cases),left cerebellopontine angle(1 case),right cerebellar vermis(1 case),and cerebellomedullary cistern(1 case),respectively.The lesions appeared oval or irregular in shape with clear boundaries and no perile-sional edema.The CT scans predominantly showed high density in 7 cases,with calcification in 1 case.On T1WI,7 cases exhibited high signal with mixed signals in some areas;6 cases showed primarily low signal on T2WI and fluid attenuated inversion recovery(FLAIR),with 1 case predominantly showed high signal;all 7 cases demonstrated low signal on diffusion weighted imaging(DWI).The margins of 1 lesion appeared"curly",and another exhibited a"swirl"pattern.5 cases had no enhancement,while 1 case had mild marginal enhancement.Conclusion Intracranial WECs has certain imaging characteristics.When a cystic lesion shows high density on CT,predominantly high signal on T1WI,and mostly no enhancement,considering the possibility of WECs.

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.

OBJECTIVES: To investigate the characteristics of immune cell infiltration in tumor samples from Chinese patients with clear cell renal cell carcinoma (ccRCC) and the correlation of immune cell infiltration with tumor stage and response to immunotherapy. METHODS: Tumor samples and clinicopathological data were collected from 154 ccRCC patients treated in Nanfang Hospital, Southern Medical University from October, 2020 to October, 2023. The immune cell types infiltrating the tumor tissues were identified using immunohistochemistry and immunofluorescence staining, and their correlations with the patients' clinicopathological characteristics were analyzed. Patient-derived tumor tissue fragment models (PDTF) models, constructed using tumor tissues from 22 patients, were treated with PD-1 monoclonal antibody, and T cell activation was detected using flow cytometry to assess the patients' responses to immunotherapy. RESULTS: In Chinese ccRCC patients included in this study, CD8⁺ T cells, CD4⁺ T cells, and CD3⁺ T cells were the most abundant in the tumor tissues. Higher infiltration levels of CD3⁺ T cells (P=0.004), PD-1⁺ T cells (P=0.020), CD68⁺ T cells (P=0.049), CD79⁺ T cells (P=0.049), and Tryptase⁺ cells (P=0.049) were all positively correlated with a larger tumor size (≥5 cm). A higher infiltration level of CD4⁺ T cells was associated with a lower tumor stage. Patients with higher International Society of Urological Pathology (ISUP) grades had higher infiltration levels of CD3⁺ T cells (P=0.023), CD8⁺ T cells (P=0.045), PD-1⁺ T cells (P=0.014), CD20⁺ B cells (P=0.020) and CD79⁺ B cells (P=0.049), and lower levels of Tryptase⁺ cells (P=0.001). Patients with abundant infiltrating immune cells tended to have better responses to immunotherapy. CONCLUSIONS The infiltrating immune cells are heterogeneous in Chinese ccRCC patients, and immune cell infiltration characteristics are closely correlated with clinicopathological parameters of the patients.
Humans ; Carcinoma, Renal Cell/pathology* ; Kidney Neoplasms/pathology* ; Immunotherapy ; Male ; Lymphocytes, Tumor-Infiltrating/immunology* ; Female ; Middle Aged ; CD8-Positive T-Lymphocytes/immunology* ; Aged ; T-Lymphocytes/immunology* ; Programmed Cell Death 1 Receptor/immunology* ; Adult ; CD4-Positive T-Lymphocytes/immunology* ; Neoplasm Staging

Purpose To investigate the expression of semaphorin 5 A(SEMA5A)and programmed death ligand-1(PD-L1)and their clinicopathological significance in gastric cancer.Methods Clinical data of 41 cases of gastric cancer tissues and paired adjacent tissues were collected.Immunohistochemical staining and RT-qPCR were used to de-tect the expression levels of SEMA5A and PD-L1,and analysed the correlation between SEMA5A and PD-L1 and clini-copathological features.In addition,we used lentivirus to construct SEMA5A stable low-expression cell lines.RT-qPCR and Western blot were used to analyse the correlation between the expression of SEMA5A and PD-L1 in gastric cancer tissues.Results The high expression rate of SEMA5A was 65.9％(27/41)in gastric cancer tissues and 39.0％(16/41)in paracancerous tissues,respectively.The positive rates of PD-L1 were 58.5％(24/41)and 14.6％(6/41),respectively.RT-qPCR showed that the relative expression levels of SEMA5A mRNA in gastric cancer and paracancerous tissues were 1.30±0.50 and 0.81±0.48,respectively,while the relative expression levels of PD-L1 mRNA were 0.70±0.42 and 0.12±0.09,respectively.SEMA5A expression was correlated with histological typ-ing of gastric cancer and lymph node metastasis(P＜0.05).PD-L1 expression was correlated with tumour size,T stage,and pathological stage of gastric cancer(P＜0.05).Pearson correlation analysis showed a positive correlation between the expression of SEMA5A and PD-L1 mRNA in gastric cancer tissues,and spearman correlation analysis showed that there was no correlation between the expression of the two in paracancerous tissues.Knockdown of SE-MA5A gene in human gastric adenocarcinoma cell lines resulted in down-regulation of PD-L1 expression.Conclusion Both SEMA5A and PD-L1 are highly expressed in gastric cancer tissues,and there is a correlation between the ex-pressions of SEMA5A and PD-L1.They can serve as potential molecular markers for prognostic evaluation and combi-nation therapy of gastric cancer.

Objective:To develop a Protection Motivation Questionnaire(PMQ)for frailty management in the elderly based on the Protection Motivation Theory(PMT), and test its reliability and validity.Methods:Guided by PMT, the initial questionnaire items were formulated through literature review, semi-structured interviews, and Delphi expert consultation.A total of 551 elderly patients with frailty from a tertiary hospital in Changsha were investigated.Item screening was conducted via critical ratio method, Cronbach's α coefficient, correlation analysis, and factor analysis.The reliability was assessed through internal consistency and test-retest reliability, while validity was evaluated via content validity and structural validity.Results:The final PMQ comprised 25 items across five dimensions: severity, susceptibility, response efficacy, response cost, and self-efficacy.The overall Cronbach's α coefficient was 0.818, with subscale coefficients ranging from 0.701 to 0.821.The split-half reliability was 0.811, test-retest reliability was 0.929, and content validity indexwas 0.86.Exploratory factor analysis extracted five factors, accounting for 52.0% of the cumulative variance.Confirmatory factor analysis demonstrated good model fit( χ2/df=1.626, RMSEA=0.05, CFI =0.914). Conclusions:The developed questionnaire exhibits strong reliability and validity, serving as an effective tool to assess protection motivation for frailty management in the elderly.

Objective Develop a risk prediction model for patients with bacterial liver abscess complicated by sepsis, and validate its predictive performance. Methods Clinical data were collected from 233 patients with bacterial liver abscesses admitted to our hospital between January 2019 and October 2024. Based on the occurrence of sepsis, the patients were categorized into a sepsis group (n=29) and a non-sepsis group (n=204). After conducting univariate analysis and subsequently multivariate Logistic regression analysis, the influencing factors were identified for the construction of a nomogram prediction model. The discrimination of the model was evaluated by the AUC of the ROC curve. The calibration of the model was assessed using the calibration curve and the Hosmer-Lemeshow test. The clinical utility of the model was evaluated through decision curve analysis. Results Age, history of hepatobiliary invasive procedures within three months, coexistence of malignancy, abscess location, blood culture results, and PCT levels are independent factors influencing the development of sepsis in patients with PLA (P < 0.05). The AUC of the model was 0.942, with a sensitivity of 92.6% and a specificity of 89.7%. Both calibration curves and the Hosmer-Lemeshow goodness-of-fit test for the model indicate good model calibration. The decision curves for model indicate that the model yields a favorable net benefit when applied to patients falling within the specified range of predicted probabilities. Conclusion The nomogram prediction model constructed in this study for sepsis in patients with PLA demonstrates good predictive value and can provide a reference for early identification of sepsis in PLA patients.

Objective:To investigate the anti-inflammatory action and mechanism of action of rosmarinic acid(RA),a Chi-nese monomeric herbal compound based on the NF-κB/NLRP3 pathway in a rat model of acute gouty arthritis(AGA).Methods:Forty healthy male SD rats were randomly assigned to five groups,and the model and drug administration groups were established a rat model of AGA by injecting a suspension of sodium urate crystals(MSU)into the joint cavity of the right paw of the rats.The degree of ankle joint swelling was measured using vernier calipers and stained with hematoxylin-eosin(HE).The inflammatory infiltration of the ankle joint and chondrocyte shedding was observed by staining with Safranine O-fast green(SOFG)and Mankin's score.The levels of IL-6,IL-1β and TNF-α in the right ankle joint of rats were determined by ELISA and the expression of NF-κB/NLRP3 pathway-associated proteins in the ankle joint were measured by Western blot.Results:Injection of MSU suspension into the ankle successfully induced AGA in rats.Compared with control group,the rats in model group showed significantly increased ankle swelling(P<0.01),greater in-flammatory infiltration,significant chondrocyte detachment,significantly increased secretion of IL-1β,IL-6 and TNF-α(P<0.01)and increased expressions of NF-κB/NLRP3 pathway-related proteins.Compared with model group,RA showed greater anti-inflamma-tory effects,dose-dependently inhibiting the development of ankle swelling in rats(P<0.01,P<0.001)and inhibited inflammatory cy-tokine infiltration.RA inhibited the secretion of inflammatory cytokines IL-6,IL-1β,TNF-α(P<0.01)and inhibited the expressions of proteins associated with the NF-κB/NLRP3 pathway(P<0.01).Conclusion:RA shows potent anti-inflammatory effects in a mouse model of AGA,and the mechanism is associated with regulation of the NF-κB/NLRP3 pathway.