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 study the five-year survival status and influencing factors of elderly patients with lung cancer complicated with chronic obstructive pulmonary disease (COPD). Methods A cohort study was conducted to follow up 450 patients with lung cancer and chronic obstructive pulmonary disease who were hospitalized in our hospital from January 2018 to December 2023. The endpoint of the follow-up was the end of a five-year period or death. The Life Tables method was used to calculate survival rates and plot survival curves. The Cox proportional hazards model was used to analyze the influencing factors of five-year survival. Results The results indicated that the overall five-year survival rate of patients was 4.89%, and it decreased year by year. Cox regression analysis showed that age, gender, family functioning, and psychological status significantly influenced patient survival rate (all P<0.05). Stratified analysis found that the smoking status, family functioning, and psychological status of male patients all had an impact on survival rate (all P<0.05), while the psychological status of female patients had a more significant impact on survival (P=0.008). Conclusion This study provides a scientific basis for comprehensive intervention of elderly lung cancer patients with COPD. It is recommended that clinical attention should be paid to psychological and family factors to improve patient prognosis.

BACKGROUND:Neutrophil extracellular traps and activated platelets are involved in the invasion,metastasis,growth,and angiogenesis of lung cancer,and are closely related to the development and prognosis of lung cancer.OBJECTIVE:To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis,prognosis,and treatment of lung cancer.METHODS:"Platelet activation,lung neoplasms,extracellular traps,treatment"for English search terms and"lung cancer,neutrophil-extracellular traps,platelet activation,P-selectin,treatment"for Chinese search terms were searched in PubMed and CNKI databases.After reading the title and abstract of the literature,according to the inclusion and exclusion criteria,63 articles with high relevance were finally included.RESULTS AND CONCLUSION:(1)Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor.(2)Neutrophil extracellular traps and activated platelets jointly promote the proliferation,growth and metastasis of lung cancer.(3)Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis,prognosis and progression of lung cancer.(4)Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

BACKGROUND:Neutrophil extracellular traps and activated platelets are involved in the invasion,metastasis,growth,and angiogenesis of lung cancer,and are closely related to the development and prognosis of lung cancer.OBJECTIVE:To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis,prognosis,and treatment of lung cancer.METHODS:"Platelet activation,lung neoplasms,extracellular traps,treatment"for English search terms and"lung cancer,neutrophil-extracellular traps,platelet activation,P-selectin,treatment"for Chinese search terms were searched in PubMed and CNKI databases.After reading the title and abstract of the literature,according to the inclusion and exclusion criteria,63 articles with high relevance were finally included.RESULTS AND CONCLUSION:(1)Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor.(2)Neutrophil extracellular traps and activated platelets jointly promote the proliferation,growth and metastasis of lung cancer.(3)Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis,prognosis and progression of lung cancer.(4)Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

ObjectiveTo reveal the molecular mechanism by which the traditional Chinese medicine compound prescription Qiangjing tablets regulate the aging of the testicular tissue and Leydig cells in rats through the cyclin-dependent kinase 4 （CDK4）-early 2 factor （E2F） signaling pathway. MethodsFor the cell experiment， 2-month-old SPF-grade SD male rats were selected and randomly assigned into a blank control group （administrated with an equal volume of 0.9% sodium chloride injection） and a Qiangjing tablets group （20 rats in each group） according to body weight. The Leydig cell model of aging was established by treatment of TM3 cells with 100 μmol·L^-1 H₂O₂， and the modeling performance was evaluated based on the levels of p16 and p21 determined by Western blot. The antioxidant NAC （1 mmol·L^-1） was used as the positive control for eliminating reactive oxygen species （ROS）. Cells were intervened with Qiangjing tablets-containing serum at low （2.5%）， medium （5%）， and high （10%） concentrations. The testosterone level in the cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）， and the protein levels of CDK4， E2F1， and E2F2 were analyzed by Western blot. In the animal experiment， 19-month-old naturally aging rats were used as the model group， and 2-month-old rats as the young control group. The positive control group was subcutaneously injected with 5.21 mg·kg^-1·d^-1 testosterone propionate. Qiangjing tablets were administered by gavage at low， medium， and high doses of 0.72， 1.44， 2.88 g·kg^-1·d^-1， respectively. The general conditions of rats were observed， and the protein levels of CDK4， E2F1， and E2F2 in the testicular tissue were determined by Western blot. ResultsIn the cell experiment， compared with the blank control group， the model group showed upregulated expression of CDK4 and E2F1 （P<0.05） and slightly downregulated expression of E2F2. Compared with that in the model group， the expression of CDK4 was upregulated in the NAC group and the low-dose Qiangjing tablets group （P<0.05）， slightly upregulated in the medium-dose Qiangjing tablets group， and downregulated in the high-dose Qiangjing tablets group （P<0.05）. The NAC group showed downregulated expression of E2F1 （P<0.05） and E2F2， and the low-， medium-， and high-dose Qiangjing tablets groups showed downregulated expression of both E2F1 and E2F2 （P<0.05）. Compared with that in the NAC group， the expression of CDK4 was upregulated in the low-dose Qiangjing tablets group and downregulated in the medium-dose and high dose （P<0.05） groups. The expression of E2F1 was down-regulated in all the three dose groups， with statistically significance in the high dose group （P<0.05）， and that of E2F2 were downregulated in all the three dose groups （P<0.05）. In the animal experiment， compared with the young control group， the model group exhibited downregulated expression of CDK4 （P<0.05） and slightly upregulated expression of E2F1 and E2F2. Compared with that in the model group， the expression of CDK4 decreased in the testosterone propionate group and the low-dose Qiangjing tablets group （P<0.05） but increased in the medium-dose （P<0.05） and high-dose groups. In addition， the expression of E2F1 decreased （P<0.05）， and that of E2F2 was slightly elevated. Compared with that in the NAC group， CDK4 expression was elevated in the Qiangjing tablets groups， with statistical significance in the medium- and high-dose groups （P<0.05）. Similarly， the E2F1 expression was also upregulated in the Qiangjing tablets groups， with statistical significance in the medium-dose group （P<0.05）. The expression of E2F2 was downregulated in all the Qiangjing tablets groups. ConclusionQiangjing tablets delay the aging process of Leydig cells and testicular tissue by up-regulating the expression of CDK4 and lowering the levels of E2F1 and E2F2.

ObjectiveBased on the multidimensional correlation analysis framework of "disease， syndrome， formula， and medicine"， this study aims to systematically elucidate the regulatory effects of effective components in Qiangjing tablet on testosterone synthesis pathways in testicular Leydig cells under oxidative stress， providing a theoretical basis for the treatment of male infertility with traditional Chinese medicine and modern research on compounds. MethodsDisease targets for male infertility were obtained from The Human Gene Database （GeneCards， score ≥20）， the Comparative Toxicogenomics Database （CTD， score ≥150）， DrugBank （score ≥0.2）， and DisGeNET （score ≥0.2）. Targets related to the syndrome of kidney deficiency and blood stasis were acquired from the traditional Chinese medicine syndrome association database SymMap. Components of Qiangjing tablet were retrieved based on The Encyclopedia of Traditional Chinese Medicine （ETCM） database and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）， and they were screened according to a quantitative estimate of drug-likeness （QED ≥ 0.49） and a target confidence index>0.8. Intersecting targets were taken to construct a protein-protein interaction （PPI） network using the STRING database. The network was visualized with Cytoscape software and subjected to the functional annotation of gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis. Quality markers （Q-markers） were predicted via the ADMETlab 2.0 platform based on Lipinski's rule， Pfizer's rule， GSK's rule， and the Golden Triangle. For experimental validation， rats' testicular Leydig cells were used. Exosomes were extracted and loaded with active components via the ultrasonic method. Exosome concentration was determined using a BCA protein quantification kit. Morphology was observed using a transmission electron microscope. The particle size was analyzed with a particle size analyzer. The surface marker proteins such as cluster of differentiation 9 （CD9）， cluster of differentiation 63 （CD63）， and cluster of differentiation 81 （CD81） were identified by Western blot， and drug loading capacity was measured by high-performance liquid chromatography （HPLC）. An oxidative stress model was induced by alpha， alpha'-azodiisobutyramidine dihydrochloride （AAPH）， and Leydig cells were divided into the following groups： A control group， an AAPH group， a quercetin group （Que group）， an exosome group （Exo group）， and a QUE-loaded Exo group （Que-Exo group）. The cell viability was detected using the 3-（4，5-dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide （MTT） thiazolyl blue assay. The reactive oxygen species （ROS） levels and mitochondrial membrane potential were measured by flow cytometry. The levels of oxidative indicators， including malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， catalase （CAT）， and testosterone （T）， were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of steroidogenic enzymes such as cytochrome p450 family 11 subfamily a member 1 （CYP11A1）， hydroxy-delta-5-steroid dehydrogenase， 3 beta- and steroid delta-isomerase 1 （HSD3B1）， and hydroxysteroid 17-beta dehydrogenase 3 （HSD17B3）， regulatory factors such as steroidogenic factor 1 （SF-1） and steroidogenic acute regulatory protein （StAR）， and miR-145-5p content， were detected by Western blot and real-time polymerse chain reaction （Real-time PCR）. ResultsNetwork pharmacology analysis reveals that the main active components of Qiangjing tablet for intervening in male infertility with kidney deficiency and blood stasis syndrome were Que， luteolin， etc.， with the core mechanism involving pathways such as steroid hormone biosynthesis. Experimental results show that compared with the control group， the AAPH group exhibits significantly reduced cell viability （P<0.01）， decreased mitochondrial membrane potential （P<0.01）， significantly elevated levels of ROS， MDA， and miR-145-5p （P<0.01）， significantly reduced activities of SOD， GSH-Px， and CAT， as well as reduced testosterone content （P<0.01）， and significantly downregulated protein and mRNA expressions of steroidogenic enzymes， SF-1， and StAR （P<0.01）. The above indicators were reversed in the Que and Que-Exo groups （P<0.05）. Compared with the Que group， the Que-Exo group showed more significant effects in enhancing cell viability， mitochondrial membrane potential， testosterone level， antioxidant enzyme activities， and expressions of key molecules in the steroidogenic pathway （P<0.05）. ConclusionThis study demonstrates that Que， an active component of Qiangjing tablet， inhibits oxidative stress reaction， improves mitochondrial function in Leydig cells， upregulates steroidogenic enzyme expression， and restores testosterone production. As a carrier for Que， Exo enhance its stability， delivery efficiency， and biological effect. Additionally， miR-145-5p may be closely associated with testosterone synthesis， though its precise molecular mechanism requires further exploration. By integrating traditional Chinese medicine compounds with modern scientific technology， this research expands the paths for the modernized research of traditional Chinese medicine and opens a novel therapeutic direction with translational potential for clinical intervention of male infertility.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

The incidence of chronic venous disease(CVD)is significantly higher in the elderly population compared to non-elderly individuals,with more severe disease manifestations.Additionally,elderly CVD patients often have comorbid conditions such as cardiovascular diseases,making the evaluation process more complex and increasing treatment difficulty.Currently,there are no established recommendations in China for the diagnosis and treatment of CVD in individuals aged 60 and above.Against this backdrop,the Peripheral Vascular Disease Management Branch of the Chinese Geriatric Society has developed the Chinese Expert Consensus on the Diagnosis and Treatment of Chronic Venous Disease in the Elderly based on domestic and international guidelines,relevant evidence-based medical research,and the physiological and clinical characteristics of the elderly population in China.This consensus aims to provide an important reference for improving the diagnosis and treatment of CVD in elderly patients in China.

Objective:To investigate the application value of dual-layer detector spectral CT in the precise outlining of gross tumor volume (GTV) in lung cancer patients.Methods:Imaging data of 39 patients with pathologically confirmed lung cancer on dual-energy enhanced CT scans in Hebei Medical University Third Hospital were retrospectively analyzed. Among them, 13 patients were not complicated with lung atelectasis and 26 cases were complicated with lung atelectasis and 9 of them received positron emission computed tomography (PET-CT) scan. The virtual single-energy images of arterial and venous dual-phase 40 keV images were reconstructed with the spectral base images of Iqon dual-energy CT, and the GTV of the primary foci was outlined using the reconstructed images and conventional enhanced CT images. The GTV outlined by conventional enhanced CT image, 40 keV virtual monoenergetic (VM) CT image, 40 keV VM-iodine density (VM-ID) fusion image in the arterial phase, conventional enhanced CT image, 40 keV VM image and 40 keV VM-ID image in the venous phase and PET-CT image was defined as GTV ACT, GTV A40VM, GTV A40VMID, GTV VCT, GTV V40VM, GTV V40VMID and GTV PET-CT, respectively. The consistency of target area outlining was assessed by calculating the GTV volume, the Dice similarity coefficient (DSC), and the 95 th percentile of the Hausdorff distance (HD95). Pairwise comparison among groups was conducted by Friedman test and corrected by Bonferroni correction. Results:In GTV comparisons, the differences in GTV ACT, GTV VCT, GTV A40VM and GTV V40VM in patients without pulmonary atelectasis were not statistically significant ( χ2=1.89, P=0.595). The DSC and HD95 of GTV ACTvs. GTV A40VM were 0.96 and 3.00, and the DSC and HD95 of GTV VCTvs. GTV V40VM were 0.94 and 2.93, respectively. The differences in GTV ACT, GTV A40VM, GTV A40VMID, GTV VCT, GTV V40VM, GTV V40VMID and GTV PET-CT in patients complicated with pulmonary atelectasis were statistically significant (all P<0.001). Pairwise comparison of Bonferroni correction showed that there was no statistically significant difference in GTV A40VM, GTV A40VMID, GTV V40VM, GTV V40VMID and GTV PET-CT (all P=1.000), all of which were significantly smaller than those of GTV ACT and GTV VCT (both P=0.001), and there was no statistically significant difference between GTV ACT and GTV VCT (both P=1.000). Based on the tumor extent shown by PET-CT (standardized uptake value =2.5), DSC were slightly higher and HD95 were slightly lower than conventional enhanced CT of GTV A40VM, GTV V40VM, GTV A40VMID, GTV V40VMIDvs. GTV PET-CT, respectively. When the arterial phase sequences were compared with PET-CT, pairwise comparison of Bonferroni correction showed that the DSC and HD95 of GTV A40VMvs. GTV PET-CT and GTV ACTvs. GTV PET-CT were statistically significant (both P<0.01), and the differences were not statistically significant among the remaining groups (all P>0.05). When intravenous phase sequences were compared with PET-CT, pairwise comparison of Bonferroni correction revealed that the DSC and HD95 of GTV V40VMIDvs. GTV PET-CT and GTV VCTvs. GTV PET-CT were statistically significant (both P<0.01), and the differences were not statistically significant among the remaining groups (all P>0.05). Conclusions:The use of 40 keV VMI-ID fusion images to outline the target area of the primary tumor lesions is closer to that of PET-CT, which provides a novel option for the precise outlining of the target area of clinical radiotherapy.

The aim of this study was to understand the internal genetic diversity and population history dynamics of ticks in Inner Mongolia,to provide data for designing effective vector control programs and revealing ticks'transmission mechanisms.From 2022 to 2023,the manual collection method was used to collect samples in Inner Mongolia.The 16S rDNA and COI gene sequences of ticks were used to identify Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus,and analyze the sequence characteristics and genetic diversity within the populations.Base composition analysis indicated that the average A+T content of the 16S rDNA gene and CO I gene in the three ticks was significantly higher than that of C+G.Moreover,22 haplotypes of the COI gene and 12 haplotypes of the 16S rDNA sequence were identified in Hyalomma marginatum.Eleven haplotypes were identified according to the COI gene,and nine haplotypes were identified according to the16S rDNA sequence of Haemaphysalis concinna.Two haplotypes were identified on the basis of the COI gene,and six haplotypes were identified on the basis of the 16S rDNA sequence of Ar gas persicus.The minimum 16S rDNA haplotype diversity was 0.264 for Ar gas persicus and 0.579 for the other two species.The nucleotide diversity of the three tick species was less than 0.05.Tajima's val-ue and Fu's Fs value of the neutrality test were negative.Base saturation substitution analysis indicated that neither of the two genes in the three tick species reached saturation.The phylogenetic tree revealed that Hyalomma marginatum,Haema physalis concinna,and Ar gas persicus in Inner Mongolia independently aggregated into branches.In conclusion,the base content of Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus genes in Inner Mongolia was consist-ent with the characteristics of insect mitochondrial DNA content.Furthermore,the three tick populations showed rapid evolu-tionary population expansion,and the phylogeny of three tick species showed independent aggregation into clades,with no pop-ulation isolation.