Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

OBJECTIVES: To analyze sex and age distribution of global disease burden of calcific aortic valve disease (CAVD) from 1990 to 2021. METHODS: CAVD data during 1990-2021 were obtained from the IHME website for Global Burden of Disease (GBD). The prevalence, mortality, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed by gender and age groups. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC). RESULTS: In 2021, there were 13.32 million CAVD patients and 142 000 deaths caused by CAVD globally. Age-standardized prevalence was higher in males (193.2/10⁵) than that in females (128.9/10⁵). Patients in 65-<85 age group accounted for 64.0% of total cases, while those ≥85 years old accounted for 16.1%. From 1990 to 2021, prevalence increased in both sexes with an AAPC of 0.72% for males and 0.57% for females, respectively. Prevalence grew fastest from 2000 to 2010, slowed thereafter, and declined from 2015 to 2021. In <65 years old, the mortality of males was 2.4 times higher than that of females, while in ≥85 years old, mortality of females (117.3/10⁵) exceeded that of males (99.1/10⁵). YLD rates increased with age, and were higher in males for all age groups. DALY rates decreased overall but increased in ≥85 years old, with a greater increase in females. CONCLUSIONS There are significant gender and age disparities in global disease burden of CAVD, with the elderly, especially super-elderly females deserving particular attention. It is recommended to develop personalized intervention strategies for these populations.
Humans ; Male ; Female ; Aged ; Calcinosis/mortality* ; Prevalence ; Global Burden of Disease ; Aged, 80 and over ; Middle Aged ; Aortic Valve/pathology* ; Aortic Valve Stenosis/epidemiology* ; Age Distribution ; Adult ; Disability-Adjusted Life Years ; Sex Distribution ; Global Health ; Aortic Valve Disease/epidemiology* ; Sex Factors

Stroke is a global disease that seriously threatens human life. The pathological mechanisms of ischemic stroke include neuroinflammation, oxidative stress, and the destruction of blood vessels at the lesion site. Here, a biocompatible in situ hydrogel platform was designed to target multiple pathogenic mechanisms post-stroke, including anti-inflammation, anti-oxidant, and promotion of angiogenesis. Double-crosslinked responsive multifunctional hydrogels could quickly respond to the pathological microenvironment of the ischemic damage site and mediate the delivery of nitric oxide (NO) and ISO-1 (inhibitor of macrophage migration inhibitory factor, MIF). The hydrogel demonstrated good biocompatibility and could scavenge reactive oxygen species (ROS) and inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-10 (IL-10), and MIF. In a mouse stroke model, hydrogels, when situated within the microenvironment of cerebral infarction characterized by weak acidity and elevated ROS release, would release anti-inflammatory nanoparticles rapidly that exert an anti-inflammatory effect. Concurrently, NO was sustained release to facilitate angiogenesis and provide neuroprotective effects. Neurological function was significantly improved in treated mice as assessed by the modified neurological severity score, rotarod test, and open field test. These findings indicate that the designed hydrogel held promise for sustained delivery of NO and ISO-1 to alleviate cerebral ischemic injury by responding to the brain's pathological microenvironment.

Objective To investigate the factors influencing poor prognosis in patients with persistent atrial fibrillation combined with heart failure undergoing catheter ablation.Methods The clinical data of 166 patients with persistent atrial fibrillation who underwent elective radiofrequency ablation in the Department of Cardiology of our hospital from January 2023 to June 2024 were retrospectively analyzed.Patients who under-went radiofrequency ablation and developed persistent atrial fibrillation were placed in the poor prognosis group(n=89),and those who did not develop heart failure were placed in the control group(n=77).Logistic regression analysis was used to identify factors influencing poor prognosis in patients with persistent atrial fi-brillation after catheter ablation;latent class analysis(LCA)was used to compare differences in the distribu-tion characteristics of influencing factors between the high-risk group for poor prognosis[B-type natriuretic peptide(BNP)>200 pg/mL]and the low-risk group(BNP≤200 pg/mL).Results There were statistically significant differences between the two groups of patients in terms of age,use of ACEI/ARB medications,dis-ease course,postoperative NYHA cardiac function classification,use of ivabradine,preoperative TG,preopera-tive TC,preoperative HDL-C,preoperative serum cholinesterase,preoperative galectin-3,preoperative LVEF,preoperative NT-proBNP,preoperative cTnI,and preoperative BNP(P<0.05).A disease course≥3.2 years,postoperative NYHA cardiac function classification score≥2 points,preoperative HDL-C<1.05 mmol/L,preoperative NT-proBNP≥12.5 μg/L,and preoperative BNP≥200.00 pg/mL were independent factors in-fluencing adverse outcomes in patients with persistent atrial fibrillation(P<0.05).LCA results showed that the"high-risk type distribution"accounted for a higher proportion in the high-risk group,while the"low-risk type distribution"accounted for a higher proportion in the low-risk group.The incidence of clinical endpoint e-vents in the poor prognosis group was 38.20%,higher than 9.09%in the control group(P<0.05).Conclu-sion Heart failure has an adverse effect on the prognosis of patients with persistent atrial fibrillation after catheter ablation,and there are differences in the incidence of adverse outcomes as well as the distribution characteristics of influencing factors between high-and low-risk groups.

Objective To systematically evaluate the changes in axial length and treatment zone diameter among my-opic patients wearing orthokeratology lenses with different back optic zone diameters.Methods A comprehensive litera-ture search was conducted on PubMed,Embase,the Cochrane Library,Web of Science,Wangfang Med Online and CNKI databases in both Chinese and English to identify randomized controlled trials or controlled trials investigating orthokeratol-ogy lenses with varying back optical zone diameters.The literature was thoroughly reviewed by two researchers,who ex-tracted relevant data and conducted a methodological quality evaluation.Finally,meta-analysis was performed using Rev-Man 5.3 software.In all the included studies,orthokeratology lenses with a conventional back optic zone diameter were taken as the control group,while orthokeratology lenses with a reduced back optic zone diameter were utilized as the ex-perimental group.Results Eight studies involving 437 patients(459 eyes)with myopia were included.The results of me-ta-analysis showed that the axial length changes in the experimental group were significantly lower than those of the control group after wearing orthokeratology lenses for 6 months and 12 months(6 months:MD=-0.09,95％CI:-0.10 to-0.07,Z=10.50,P＜0.05;12 months:MD=-0.11,95％CI:-0.13 to-0.09,Z=12.19,P＜0.05);significant differ-ences in treatment zone diameter were observed between the experimental and control groups at various time points follow-ing orthokeratology lens wearing(MD=-0.82,95％CI:-1.04 to-0.59,Z=7.03,P＜0.05).Conclusion Orthoker-atology lenses designed with smaller back optical zone diameters can effectively delay axial length growth in myopic pa-tients,but their long-term efficacy needs to be confirmed.

Objective To observe the effects of electroacupuncture on the motor function and expressions of Irisin,Decorin and Myostatin in skeletal muscle of SAMP8 mice;To explore the mechanism of electroacupuncture in the treatment of the motor dysfunction of Alzheimer disease(AD).Methods Totally 247-month-old male SAMP8 mice were randomly divided into model group and electroacupuncture group,with 12 mice in each group,and the 12 male SAMR1 mice with the same age were set as the control group."Baihui","Dazhui"and"Shenshu"were selected in the electroacupuncture group,once a day,8 days as one course of treatment,with an interval of 2 days,for a total of 3 courses.The control group and the model group were not intervened.The motor function of mice was tested by grip strength test,pole climbing test and open field test,the mRNA expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by RT-qPCR,and the protein expressions of Irisin,Decorin and Myostatin in quadriceps muscle were detected by immunohistochemistry and Western blot.Results Compared with the control group,the grip peak and duration of the mice in the model group decreased,head turning time and pole climbing time were prolonged(P<0.01),the mRNA and protein expressions of Irisin and Decorin decreased(P<0.05,P<0.01),and the expressions of Myostatin mRNA and protein increased(P<0.05).Compared with the model group,the grip peak and duration of the mice in the electroacupuncture group increased,head turning time and pole climbing time were decreased(P<0.05),the mRNA and protein expressions of Irisin and Decorin increased(P<0.05),and the expressions of Myostatin mRNA and protein decreased(P<0.05).Conclusion Electroacupuncture can improve the motor dysfunction of SAMP8 mice,and its mechanism may be related to regulating the expressions of Irisin,Decorin and Myostatin in skeletal muscle.

Objective:To explore the relationship between body composition and the risk of gestational diabe-tes mellitus(GDM)in pregnant women.Methods:90 pregnant women with spontaneous pregnancy of singleton who underwent routine prenatal examination in our hospital were selected as GDM group,and 219 pregnant women with normal singleton in the same period as control group(NGT).The body composition was determined by bioimpedance method at 24-28 weeks of gestation.The relationship between body mass index(BMI),per-centage of body fat(FMP),percentage of fat-free body weight(FFMP),extracellular/intracellular fluid(ECW/ICW),body fat index(FMI)and GDM were analyzed.The levels of circulating adiponectin,fatty acid binding pro-tein 4(FABP4),leptin and fasting insulin(FINS)were measured by enzyme linked immunosorbent assay(ELISA)method,and their relationship with various indicators of human body composition was analyzed.Results:①Adi-ponectin in GDM group was lower than that in NGT group,while leptin was higher than that in control group(P＜0.05).②The FMP,ECW/ICW and FMI in GDM group were significantly higher than those in control group(P＜0.05).Univariate regression analysis showed that BMI,FMP,FMI and ECW/ICW before pregnancy were the risk factorsof GDM(OR＞1,P＜0.05),FFMP,MP,PP and M/F was the protective factor of GDM(OR＜1,P＜0.05).Multivariate analysis showed that only FMP was significantly correlated with the risk of GDM,which was an independent risk factor(OR＞1,P＜0.05).③In GDM group,HOMA-IR was positively correlated with FMI(r＞1,P＜0.05)and negatively correlated with PP(r＜1,P＜0.05).④The ROC curve showed that the diagnostic value of pre-pregnancy BMI、FMP、ECW/ICW and FMI in GDM was similar.There was no significant difference in pre-pregnancy BMI,FMP and FMI(P＞0.05),but they were slightly better than ECW/ICW(P＜0.001).Conclu-sions:Body composition during pregnancy is related to the risk of gestational diabetes.The increase in FMP is associated with an increased risk of developing GDM.The higher the FMP,the higher the risk of GDM.The diag nostic efficacy of BMI,FMP and FMI in GDM is Similar.

Objective:To investigate the potential biomarkers associated with immune cells in retinal ischemia-reperfusion injury (RIRI).Methods:The RIRI gene expression profile dataset GSE20521 was obtained from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) were screened.The GSE20521 gene set was subjected to Gene Set Enrichment Analysis (GSEA) and Immune Cell Abundance Identifier (ImmuCellAI), yielding information pertaining to enriched pathways and immune cell infiltration.The Weighted Correlation Network Analysis (WGCNA) and Pearson correlation analysis were employed to identify the hub modules and candidate genes exhibiting the strongest correlation with immune infiltration.Subsequently, the protein-protein interaction (PPI) network of candidate genes was constructed, and key genes were screened using CytoHubba plugin.Results:The significant GSEA enrichment pathways in the RIRI group including the interferon-γ (IFN-γ), apoptosis, tumor necrosis factor-α/nuclear factor-κB, IFN-α, complement pathway, interleukin-6 (IL-6)-(signal transducer and activator of transcription 3)(STAT3) and IL2-STAT5 signaling pathways, as well as inflammatory response.Compared with the normal control group, the results of ImmuCellAI evaluation revealed significant increases in the proportions of cDC2 cells, monocyte-derived DC cells, M2 macrophages, and CD8_Tc cells and decreases in the proportions of pDC cells, CD4_T cells, CD4_Tm cells, helper T cells, regulatory T cells, follicular B cells, and eosinophils in the RIRI group (all at P<0.05).A total of 144 DEGs were obtained between the two groups of samples.Taking the intersection of DEGs and hub module genes, 140 candidate genes were obtained.GO analysis showed significant enrichment of positive regulation of cytokine production, leukocyte mediated immunity, wound healing, adaptive immune response, niacinamide adenine dinucleotide phosphate oxidase complex, and chemokine binding, etc.KEGG analysis enriched 50 pathways, including phagosome, pertussis, leishmaniasis tuberculosis, and complement and coagulation cascades.Three key genes were finally obtained, namely Cd68, Tlr2 and Hmox1, which were screened by PPI and different CytoHubba algorithms. Conclusions:The bioinformatics analysis reveals a distinct immune microenvironment in the retina of the RIRI group and normal control group, suggesting a correlation between RIRI and infiltration of multiple immune cell types.

Objective:To investigate the treatment and prognosis of acute carotid artery occlusion during perioperative period of carotid endarterectomy (CEA).Methods:The clinical data of 112 carotid artery stenosis patients who underwent CEA from January 2017 to December 2021 in Lianyungang Hospital Affiliated to Xuzhou Medical University were retrospectively analyzed. The patients were followed up at 6 to 9 months after surgery, the clinical prognosis was evaluated by Glasgow outcome score (GOS), and the head and neck CT angiography (CTA) was performed.Results:Among the 112 patients, 5 patients underwent acute carotid artery occlusion during the perioperative period, including 1 case of intraoperative acute occlusion of internal carotid artery and 1 case of intraoperative internal carotid artery combined with external carotid artery cute occlusion, both of them were re-sutured, and multi-mode monitoring showed that each carotid artery was unobstructed; 2 cases of intraoperative external carotid artery occlusion, no re-suture was performed during the operation; 1 case of intraoperative monitoring showed no obvious abnormality, and the contralateral limb hemiplegia was observed after surgery, and the muscle strength was grade 1, the carotid color Doppler ultrasound showed the occlusion of the internal carotid artery on the operation side. The CT and CTA examination showed focal infarction and common carotid artery on the operation side, and drugs and conservative treatment were given. The follow-up result: GOS 5 scores was in 4 cases, and 4 scores in 1 case; the muscle strength of hemiplegia patient recovered to grade 4; head and neck CTA examination, except for 1 case of common arterial occlusion, the other 4 cases showed no special abnormality.Conclusions:Intraoperative acute carotid artery occlusion can be detected timely by intraoperative multi-mode hemodynamic monitoring during CEA. Vascular recanalization after acute occlusion is possible by adopting active and effective treatment methods, the occurrence of postoperative ischemic stroke can be effectively prevented and the prognosis of patients can be improved.

ObjectiveTo observe the effects of Wendantang on the expression of inflammatory cytokines， autophagy markers， and key molecules of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway in the adipocytes of the rat model of obesity （syndrome of phlegm-dampness） and to explore the material basis of inflammation in obesity （syndrome of phlegm-dampness） and the underlying mechanism of Wendantang intervention. MethodA total of 126 SD rats were randomized into 2 groups： 16 rats in the blank group and 110 rats in the modeling group. The blank group was fed with a basic diet while the modeling group with a high-fat diet to establish the animal model of obesity （syndrome of phlegm-dampness） for 8 weeks. After successful modeling， 48 obese rats were selected according to their body mass and randomized into a model control group， an orlistat （ORLI， 32.40 mg·kg^-1） group， a rapamycin （RAPA， 2 mg·kg^-1） group， and low-， medium-， and high-dose （4.45， 8.90， 17.80 g·kg^-1， respectively） Wendantang groups， with 8 rats in each group. In addition， 8 rats were randomly selected from the blank group to be set as the normal control group. The corresponding agents in each group were administrated by gavage and the model and control groups were administrated with equal amounts of distilled water once daily for 6 weeks. The body mass， Lee's index， body fat ratio， and obesity rate were measured or calculated. The expression of UNC51-like kinase-1 （ULK1）， Beclin1， human autophagy-related protein 5 （Atg5）， p62， and microtubule-associated protein 1 light chain 3 （LC3） Ⅰ/Ⅱ （markers of autophagy in adipocytes） was detected by the immunohistochemical two-step method. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， IL-1β， monocyte chemotactic protein-1 （MCP-1）， IL-4， IL-10， IL-13， and transforming growth factor （TGF）-β in adipocytes. Western blot was employed to measure the protein levels of classⅠ-PI3K， phosphatidylinositol triphosphate （PIP3）， Akt， mTORC1， ULK1， TSC1， and TSC2 in adipocytes. ResultCompared with the blank group， the modeling group showed increased body mass and Lee's index （P<0.01）， the obesity rate >20%， and phlegm-dampness syndrome manifestations such as physical obesity， decreased mobility， decreased appetite， lusterless and tight fur， loose stools， decreased responsiveness to the outside world， and decreased water intake. Compared with the normal control group， the model control group showed increased body mass， Lee's index， body fat ratio， adipocyte autophagy marker expression， pro- and anti-inflammatory cytokine levels （P<0.05， P<0.01）， down-regulated protein levels of classⅠ-PI3K， PIP3， Akt， mTORC1， TSC1， and TSC2 （P<0.01）， and up-regulated protein level of ULK1 （P<0.01）. The intervention groups showed lower body mass， body fat ratio， adipocyte autophagy marker protein expression， and protein levels of TNF-α， IL-6， IL-1β， MCP-1， IL-4， and IL-13 than the model control group （P<0.05， P<0.01）. Moreover， the RAPA and Wendantang （medium and high dose） groups showed lowered levels of IL-10 and TGF-β （P<0.01）， and the ORLI group showed down-regulated expression of TGF-β （P<0.01）. The expression of key molecules of the signaling pathway was up-regulated （P<0.05， P<0.01） while that of ULK1 was down-regulated （P<0.01） in all the intervention groups. Compared with the RAPA group， the Wendantang groups showed up-regulated expression of all autophagy marker proteins in adipocytes （P<0.01）. In addition， the low-dose Wendantang group showed elevated levels of inflammatory cytokines （except TNF-α） （P<0.05， P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.05， P<0.01）. The levels of inflammatory cytokines （except IL-16， MCP-1， and IL-10） were elevated in the medium-dose Wendantang group （P<0.05， P<0.01）. The expression of key molecules except PI3K of the signaling pathway was down-regulated in the medium- and high-dose Wendantang groups （P<0.05， P<0.01）. Compared with the ORLI group， low- and medium-dose Wendantang groups showed up-regulated expression of autophagy markers in adipocytes （P<0.01）， and the low-dose group showed elevated levels of inflammatory cytokines （IL-6， IL-4， and TGF-β） （P<0.01） and down-regulated expression of all key molecules of the signaling pathway （P<0.01）. The medium-dose Wendantang group showed up-regulated expression of IL-4 （P<0.01） and down-regulated expression of key molecules except PI3K of the signaling pathway （P<0.05， P<0.01）. The high-dose Wendantang group showed increased body mass， up-regulated expression levels of autophagy markers （ULK1， LC3 Ⅰ/Ⅱ） （P<0.05， P<0.01）， down-regulated expression of PIP3， mTORC1， and TSC1 （P<0.05， P<0.01）， and lowered levels of Beclin1， Atg5， TNF-α， and IL-13 （P<0.05， P<0.01）. ConclusionThe inflammation in obesity （syndrome of phlegm-dampness） is closely associated with the PI3K/Akt/mTOR pathway-mediated adipocyte autophagy. Wendantang can treat the chronic inflammation in obese rats with the syndrome of phlegm-dampness by regulating this signaling pathway and thus improve adipocyte autophagy.