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 relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

Objective To analyze the predictive value of spermatic vein diameter in diagnosing occult oblique inguinal hernia in children.Methods A total of 93 children of oblique inguinal hernia were admitted to Hangzhou Linping District Maternal &Child Health Care Hospital from August 2021 to August 2023 as research objects,including 15 with 30 sides of bilateral dominant hernia and 78 with 78 sides of unilateral dominant hernia.Among them,21 with 21 sides of contralateral recessive hernia were found by laparoscopic exploration in unilateral dominant hernia.The 108 sides of dominant hernia were used as dominant hernia group and 21 sides of occult hernia group as recessive hernia group.According to different ages,the patients were divided into 1 to 3 years old group 60 cases,4 to 6 years old group 33 cases;Children with oblique inguinal hernia were divided into＜2 years group(68 cases)and ≥2 years group(25 cases).The color ultrasound diagnostic instrument uses a 7.5MHz linear transducer to measure the diameter of the spermatic vein in the inguinal region of the child using blood flow imaging with a signal displayed at 2mm/s.Receiver operating characteristic(ROC)curve analysis of the predictive value of spermatic vein diameter for the diagnosis of occult inguinal hernia in children.Results Compared with occult hernia group,diameter of spermatic cord was increased in dominant hernia group(P＜0.05).Compared with overt hernia group,diameter of spermatic cord in＜2 year group and ≥2 year group was smaller,and difference was statistically significant(P＜0.05).In prediction of disease diagnosis with different age and course of disease,sensitivity of 1 to 3 years old was lower than that of 4 to 6 years old,and specificity was higher.The sensitivity of ≥2 years group was lower than that of＜2 years group.The specificity was higher and difference was statistically significant(P＜0.05).Conclusion diameter of spermatic vein can be used to predict the diagnosis of occult oblique inguinal hernia in children with high sensitivity and specificity.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Objective:To explore the regulatory mechanism of voltage-dependent anion channel 1(VDAC1) on the proliferation, migration and invasion of lung adenocarcinoma(LUAD) cells.Methods:This study employed a combination of bioinformatics and experimental validation methods, conducting bioinformatics analysis and cytological experimental validation in the central laboratory of the School of Medicine, Anhui University of Science and Technology from February 2023 to August 2024.Clinical histological specimen validation was performed using immunohistochemistry, and a retrospective analysis was conducted on 5 cases of lung adenocarcinoma and adjacent samples from Huai′an First People′s Hospital affiliated with Nanjing Medical University. The TCGA network database was analyzed for the expression pattern, prognostic value, and functional enrichment of VDAC1 in LUAD. A549 cells with VDAC1 knockdown and H1650 cells with VDAC1 overexpression were established through lentiviral transfection. The expression difference of VDAC1 protein in LUAD and adjacent tissue specimens was detected by immunohistochemistry.The effects of VDAC1 on the proliferation, migration, and invasion capabilities were explored through CCK8 assay, scratch healing assay, and Transwell assay.The activation levels of epithelial-mesenchymal transition (EMT) marker proteins, cell cycle-dependent kinases, and molecules in the PI3K/AKT/mTOR signaling pathway were detected by Western blot.Results:Bioinformatics analysis revealed that VDAC1 was highly expressed in LUAD cells ( P<0.000 1) and was an independent risk factor for LUAD ( P<0.000 1). Functional enrichment analysis showed significant enrichment of the PI3K/AKT/mTOR, G2M checkpoint, and P53 signaling pathways ( P<0.001). Compared to adjacent control tissues, the expression level of VDAC1 protein is higher in lung adenocarcinoma tissues.Overexpression of VDAC1 promoted the proliferation ( P<0.000 1), migration, and invasion( P<0.01) of H1650 cells, while knockdown of VDAC1 inhibited the proliferation ( P<0.000 1), migration, and invasion ( P<0.05) of A549 cells.Western Blot experiments showed that compared to the control group, the expression levels of vimentin (1.10±0.11 vs 2.39±0.15, P<0.001), N-cadherin (0.94±0.12 vs 2.72±0.06, P<0.001), CDK1 (0.93±0.04 vs 1.53±0.03, P<0.000 1), CDK2 (1.04±0.13 vs 2.29±0.06, P<0.001), CDK4 (0.90±0.03 vs 2.00±0.11, P<0.01), p-PI3K (1.08±0.13 vs 1.85±0.12, P<0.01), and p-AKT (1.03±0.11 vs 1.69±0.06, P<0.001) were increased in H1650 cells overexpressing VDAC1, while E-cadherin expression decreased (2.18±0.14 vs 0.997±0.11, P<0.001).In contrast, in A549 cells with VDAC1 knockdown, the expression levels of vimentin (1.70±0.26 vs 0.97±0.09, P<0.05), N-cadherin (1.98±0.25 vs 1.03±0.06, P<0.05), CDK1 (1.13±0.03 vs 0.95±0.02, P<0.01), CDK2 (2.29±0.12 vs 0.92±0.10, P<0.001), CDK4 (1.71±0.096 vs 1.12±0.11, P<0.01), p-PI3K (1.67±0.09 vs 0.97±0.03, P<0.001), and p-AKT (1.53±0.04 vs 1.02±0.03, P<0.000 1) decreased, while E-cadherin expression increased (1.04±0.04 vs 1.85±0.26, P<0.05). Conclusions:VDAC1 may promote the proliferation, migration, and invasion of LUAD cells by activating EMT and cyclin-dependent kinases through the PI3K/AKT/mTOR pathway.

Objective:To explore the effects of early electroacupuncture(EA)intervention on the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway-related protein expression and oligodendrocytes in mice with amyotrophic lateral sclerosis(ALS),and uncover the potential molecular mechanisms underlying the improvement of motor function in ALS mice by early EA intervention.Methods:ALS mice carrying the SOD1G93A gene were randomly divided into a model group and an EA group,with 10 mice in each group;10 littermate mice with a negative SOD1G93A genotype served as the control group.In the EA group,Baihui(GV20),Tianzhu(BL10),and Tianshu(ST25)were selected with needles retained for 10 min,5 consecutive days per week,with 2 days of rest.One week constituted a course of treatment,and a total of 3 consecutive courses were performed.The other groups were grasped and fixed similarly,but without intervention.Motor function was assessed using the open field test(OFT)and Morris water maze(MWM).Subsequently,hematoxylin-eosin staining was used to observe neuron morphology in the M1 region of the cerebral cortex.Immunofluorescence was performed to detect the positive cell rate of TAR DNA-binding protein 43(TDP-43),and double immunofluorescence staining was used to observe the positive cell rate and cell states of ionized calcium-binding adaptor molecule 1(Iba-1)and myelin basic protein(MBP)in the M1 region of the cerebral cortex.Western blotting was used to detect the relative expression levels of TDP-43,tumor necrosis factor(TNF)-α,HMGB1,and TLR4 proteins.Results:Compared to the control group,the model group exhibited a reduced total movement distance in the OFT,and an increased escape latency,as well as fewer platform crossings in the MWM,with statistically significant differences(P<0.01).In the model group,the number of degenerated and necrotic neurons in the M1 region of the ALS mouse cerebral cortex increased,with significant nuclear shrinkage and cytoplasmic vacuolization;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex increased(P<0.01),and the relative expression level of TDP-43 protein in the cerebral cortex showed a significant increase(P<0.01);the Iba-1 positive cell percentage increased,while the MBP positive cell percentage decreased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins increased(P<0.05).Compared to the model group,the EA group showed an increased total movement distance(P<0.01),and a reduced escape latency,and more platform crossings in the MWM,with statistically significant differences(P<0.05).In the EA group,neurons showed improvement,with reduced degeneration and necrosis,and larger,clearer nuclei;the percentage of TDP-43 immunofluorescence positive cells in the M1 region of the cerebral cortex decreased(P<0.05),and the relative expression level of TDP-43 protein also decreased(P<0.05);the percentage of Iba-1 positive cells in the M1 region of the cerebral cortex decreased,while the percentage of MBP positive cells increased(P<0.01);the relative expression levels of TNF-α,HMGB1,and TLR4 proteins decreased(P<0.05).Conclusion:EA intervention can suppress microglial activation,improve the state of oligodendrocytes,and reduce abnormal TDP-43 aggregation in the M1 region of the cerebral cortex in ALS model mice;its mechanism of action may be related to the HMGB1/TLR4 signaling pathway.

Objective:To explore the evaluation and relationship of hepatitis B virus(HBV)surface antigen(HBsAg)in clinical laboratory in different detection systems,further scientifically and reasonably to explain the test results for serving clinical practices.Methods:During the period from June 2021 to July 2022,100 425 specimens of patients with screened,suspected and confirmed HBV infections were collected from the clinical departments(mainly infectious hepatology)of Nanyang Central Hospital.Detection methodology included quantitative(electrochemiluminescence and chemiluminescence),qualitative(gold standard),semi-quantita-tive(ELISA),and highly sensitive HBV-DNA(RT-PCR)methods,and then analyzed the strengths and weaknesses and closeness be-tween each methodology.The relationship between the two Roche HBsAg detection systems was analyzed by correlation analysis.The HBsAg efficacy analysis was validated using Cut/Off value setting and detection limit,which in turn analyzed the distribution of false-positive and false-negative reporting models.Results:Detection results for low-and medium-concentration HBsAg showed a correla-tion between the electrochemical luminescence semi-quantitative method and ELISA method.ELISA method still had advantages in terms of sensitivity and specificity when detecting HBsAg,and there were no significant differences compared to domestic and interna-tional HBsAg quantitative detection systems.Performance validation conducted in accordance with the CNAS-GL038 document showed that the minimum detection limit for HBsAg calculated using the ELISA method in this laboratory was 0.1 U/ml.When the ROC curve Cut/Off value was set to 0.105,the area under the curve was the largest(AUC=0.986).Based on Roche's semi-quantitative electroche-miluminescence detection and patient medical history,in the common reporting model for hepatitis B five-item detection using ELISA method,HBsAg false positives occurred most frequently when HBsAg was positive alone,and HBsAg occurred most frequently in the false positive range when the OD value was less than 0.5.In ELISA method for detecting HBsAg,as the OD value increased from 0.01 to 0.10,the number of false-negative results also increased.Roche Elecsys HBsAg Ⅱ Quant Ⅱ and Elecsys HBsAg Ⅱ testing systems exhibited good linearity under certain conditions,with a ratio of approximately 1/0.18.In Elecsys HBsAg Ⅱ Quant Ⅱ detection sys-tem,the test results of HBsAg samples diluted 400 times were highly consistent with the original test results with a coefficient of deter-mination R2=0.993 8.Conclusion:There was a certain relationship between various detection systems of HBsAg at a suitable concen-tration.The detection of HBsAg by ELISA can meet the needs of clinical detection.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To screen the optimal machine learning model for predicting the recurrence condition of hepatocellular carcinoma (HCC) at different time points post-surgery, based on the cutoff value of the Ki67 positive proliferation index condition calculated from recurrence-free survival and combined with various clinical features.Methods:retrospective study included initially treated patients with solitary HCC who underwent radical surgery at the Fifth Medical Center of the PLA General Hospital from January 2013 to March 2023. Data included general clinical data, preoperative laboratory parameters, and surgical pathology information about the subjects. The postoperative recurrence status was assessed by querying the medical record system or by telephone follow-up. The Ki67 positive index cutoff value was determined by the X-tile software based on the patient's recurrence-free survival status and time analysis. Survival rates were calculated using the Kaplan-Meier method, and survival curves were plotted. The study population was randomly divided into training and testing groups in a 7:3 ratio using a computer-generated random number method. The minimum redundancy maximum relevance (mRMR) method was used for feature variable selection. Predictive models for postoperative HCC recurrence conditions in patients with HCC were constructed using random forest, support vector machine, logistic regression, and gradient boosting decision tree machine learning algorithms. Inter-group comparisons for continuous data were performed using the t-test or Mann-Whitney U test. Inter-group comparisons of enumeration data were performed using the Pearson χ2 test, continuity-corrected χ2 test, or Fisher's exact test. Results:The cutoff values for the Ki67 positivity index were 0.3 and 0.5 in 510 cases, with a follow-up time ranging from 1.2 to 11.4 years (median: 6.2 years). The recurrence-free survival time was between 1 and 135 months (median: 32 months), with recurrence-free survival rates post-surgery at 1, 2, 3, and 5 years were 87.5%, 77.1%, 61.2%, and 54.5%, respectively. The top five variables predicted HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years, in accordance with information obtained by the mRMR screen out. The Ki67 positivity index screened a successfully constructed machine learning model to predict HCC recurrence and non-recurrence conditions following surgical follow-up at 6 months, 1 year, 2 years, and beyond 2 years. The machine learning model based on the gradient boosting decision tree algorithm had the best prediction performance among them (areas under the receiver operating characteristic curves for predicting HCC recurrence within six months in the training and validation sets were 0.996 and 0.946, and accuracies were 0.972 and 0.935, respectively).Conclusion:A machine learning model was successfully constructed using the Ki67 positivity index combined with four readily available clinical features to predict HCC recurrence. The machine learning model based on the gradient boosting decision tree algorithm demonstrated the best performance in terms of predicting HCC recurrence within six months after surgery.

[Objective]To propose syndrome differentiation and treatment approach of acupuncture for migraine based on the relationship between"spleen and stomach disorders"and the etiology and pathogenesis of migraine,providing theoretical and practical references for the clinical management.[Methods]The connotation of"spleen and stomach disorders"and its association with migraine were systematically reviewed.Based on this perspective,treatment strategies and acupuncture prescriptions for migraine were formulated,and supported by a representative clinical case study.[Results]"Spleen and stomach disorders"serves as a critical pathological foundation for migraine.Its pathogenesis can be summarized into four patterns"impaired spleen transport leading to malnourishment of the brain""phlegm-dampness obstructing the orifices and impairing mental clarity""spleen-stomach disharmony causing Qi stagnation"and"spleen deficiency with blood stasis resulting in orifice obstruction".Acupuncture treatment should prioritize regulating spleen-stomach function,supplemented by dredging local meridians and harmonizing Qi and blood.Key acupoints include Zhongwan(CV12),Xiawan(CV10),Qihai(CV6),and Guanyuan(CV4)for reinforcing primordial Qi,consolidating the foundation,and harmonizing Qi and blood;Zusanli(ST36),Shangjuxu(ST37)and Xiajuxu(ST39)for regulating Qi movement and balancing Yin and Yang;Sizhukong(TE23)and Fengchi(GB20)for clearing the head,improving vision,and relieving pain.In the presented case,the patient was diagnosed as dual deficiency of Qi and blood,acupuncture therapy focusing on replenishing Qi,nourishing blood and unblocking collaterals achieved significant clinical efficacy.[Conclusion]"Spleen and stomach disorders"is a pivotal mechanism underlying recurrent migraine.Acupuncture treatment for migraine should emphasize restoring spleen-stomach function,prioritizing the reinforcement of primordial Qi and harmonization of Qi and blood,thereby addressing the root cause to reduce migraine recurrence.