Objective To propose a framework for risk assessment and stepwise management of pulmonary nodules based on existing guidelines and key studies, and to clarify the boundaries for triage, workup escalation, and referral in different detection scenarios. Methods A problem-oriented evidence synthesis approach was used, prioritizing Chinese expert consensus, Fleischner Society Guidelines, British Thoracic Society (BTS) Guidelines, and Lung-RADS. This was supplemented by studies on risk models, imaging measurements, liquid biopsy, tissue sampling, and surgical treatments. This paper is not presented as a formal consensus or a validated clinical pathway. Results A three-tiered framework consisting of basic non-invasive assessment, advanced assessment, and invasive diagnosis was established. It specified the applicable populations, boundaries for the use of risk models, imaging review, management of conflicting results, evaluation of histopathological consistency, and post-intervention follow-up. Liquid biopsy, genetic testing, and artificial intelligence were defined as investigational or adjunctive tools. Conclusion This framework can serve as a preliminary reference for multidisciplinary teams in developing local protocols. It cannot replace applicable guidelines, pathological diagnosis, shared decision-making with patients, or real-world validation.

Aim To evaluate the tyrosine nitration modification of specific proteins in vascular endothelial cells and its impact on mitochondria-mediated apoptosis.Methods Human umbilical vein endothelial cells were cultured in vitro and divided into three groups:control group(treatment with dimethyl sulfoxide),3-morphansulam(SIN-1)group,and SIN-1+Fe(Ⅲ)5,10,15,20-(tetraphenyl)porphyrin(FeTPP)group.After 24 h,the levels of hexokinase 1(HK1)nitration modification,mitochondrial membrane potential,reactive oxygen species(ROS)production,and endothelial cell proliferation and apoptosis were assessed.A human umbilical vein endothelial cell line knockout of HK1 was constructed using gene editing technology,and its proliferation and apoptosis levels were detected.Results After treatment of hu-man umbilical vein endothelial cells with peroxynitrite generator SIN-1,the level of HK1 protein nitration modification sig-nificantly increased(P＜0.01),reactive oxygen species production significantly increased,mitochondrial membrane poten-tial significantly decreased,endothelial cell proliferation ability significantly decreased,and endothelial cell apoptosis level significantly increased(all P＜0.01).Peroxynitrite decomposition catalyst FeTPP could reverse the above effect(P＜0.01).In addition,HK1 gene knockout also exhibited similar antioxidant effects,with a significant decrease in endothe-lial cell proliferation ability and a significant increase in apoptosis levels(P＜0.01).Conclusion Peroxynitrite can induce an increase in the level of nitration modification of HK1 in vascular endothelial cells,which may be achieved by pro-moting the production of mitochondrial reactive oxygen species,thereby accelerating the process of endothelial cell apoptosis.

Aim To evaluate the tyrosine nitration modification of specific proteins in vascular endothelial cells and its impact on mitochondria-mediated apoptosis.Methods Human umbilical vein endothelial cells were cultured in vitro and divided into three groups:control group(treatment with dimethyl sulfoxide),3-morphansulam(SIN-1)group,and SIN-1+Fe(Ⅲ)5,10,15,20-(tetraphenyl)porphyrin(FeTPP)group.After 24 h,the levels of hexokinase 1(HK1)nitration modification,mitochondrial membrane potential,reactive oxygen species(ROS)production,and endothelial cell proliferation and apoptosis were assessed.A human umbilical vein endothelial cell line knockout of HK1 was constructed using gene editing technology,and its proliferation and apoptosis levels were detected.Results After treatment of hu-man umbilical vein endothelial cells with peroxynitrite generator SIN-1,the level of HK1 protein nitration modification sig-nificantly increased(P＜0.01),reactive oxygen species production significantly increased,mitochondrial membrane poten-tial significantly decreased,endothelial cell proliferation ability significantly decreased,and endothelial cell apoptosis level significantly increased(all P＜0.01).Peroxynitrite decomposition catalyst FeTPP could reverse the above effect(P＜0.01).In addition,HK1 gene knockout also exhibited similar antioxidant effects,with a significant decrease in endothe-lial cell proliferation ability and a significant increase in apoptosis levels(P＜0.01).Conclusion Peroxynitrite can induce an increase in the level of nitration modification of HK1 in vascular endothelial cells,which may be achieved by pro-moting the production of mitochondrial reactive oxygen species,thereby accelerating the process of endothelial cell apoptosis.

Objective:To explore the relationship between the hypertensive snowbirds′ length of migratory stay and their blood pressure control and blood pressure levels.Methods:This study was a cross-sectional study. A population of snowbirds with hypertension was recruited between October and November 2022, and a structured questionnaire was used to collect their self-measured blood pressure and length of stay in Hainan Province. The blood pressure control status is determined based on self-measured blood pressure. According to the self-measured blood pressure to determine whether the blood pressure was well controlled. The associations between snowbirds′ length of stay and their blood pressure control as well as their self-measured blood pressure were analyzed using restricted cubic splines.Results:A total of 362 research subjects were included, 169(46.7%) of whom were male, and their age was (69.7±7.0) years old. The participants′ self-measured systolic blood pressure and diastolic blood pressure were (129.1±16.2) mmHg (1 mmHg=0.133 kPa) and (78.9±10.1) mmHg, respectively. Overall, 174 (48.1%) participants attained adequate blood pressure control. The median length of stay in Wuzhishan City was 7(6, 7) months. There was an inverted U-shaped association between snowbirds′ length of stay and blood pressure control (overall: P=0.023; nonlinearity: P=0.014), where participants with a length of stay of 7 months had the highest rate of blood pressure control. There is a U-shaped curve relationship between length of stay and systolic blood pressure (overall: P=0.001; nonlinearity: P=0.033), and a linear negative correlation with diastolic blood pressure ( β=-1.19, P=0.003). Conclusions:Compared with hypertensive snowbirds with too long or too short lengths of stay, snowbirds who stayed in Wuzhishan City for seven months have better blood pressure control, and systolic blood pressure is also lower.

Objective:To explore therapeutic effect and safety of cilostazol combined clopidogrel +aspirin on aged pa‐tients after percutaneous coronary intervention (PCI) .Methods :A total of 100 aged patients with coronary heart disease undergoing PCI were randomly divided into routine treatment group (n=52 ,received aspirin and clopidogrel antiplatelet therapy) and cilostazol group (n= 48 ,received cilostazol therapy based on routine treatment group ) . Turbidimetry was used to measure platelet aggregation rate (PAR );PAR and mean platelet volume (MPV ) were compared between two groups before ,one week and one month after PCI .All subjects were followed up for six months ,incidence rates of major adverse cardiovascular events (MACE) and hemorrhage events were compared be‐tween two groups .Results:There were no significant difference in MPV and PAR between two groups before PCI . Compared with routine treatment group ,PAR significantly reduced [one week after PCI :(48.7 ± 6.3)% vs .(43.5 ± 5.7)% ,one month after PCI :(46.8 ± 5.8)% vs .(42.4 ± 5.4)% ] in cilostazol group , P<0.05 both . After six-month follow-up ,there was no significant difference in total incidence rate of MACE (16.7% vs .17.3% ) be‐tween cilostazol group and routine treatment group , P>0.05;incidence rate of hemorrhage in cilostazol group was significantly lower than that of routine treatment group (6.25% vs .19.23% , P< 0.01) .Conclusion:Compared with clopidogrel+aspirin therapy ,cilostazol combined clopidogrel+aspirin can more significantly inhibit platelet ag‐gregation ,and significantly reduce hemorrhage events ,so they are safe and effective in aged patients with coronary heart disease undergoing PCI .

Objective To investigate the effect of tMfn2 gene on inhibiting the proliferation of vascular smooth muscle cells (VSMCs) and related mechanism. Method VSMCs were transfected with adenovirus vector encoding tMfn2 or Mfn2 (Adv-tMfn2, Adv-Mfn2). The abundance of tMfn2 protein and Mfn2 protein were deter-mined by Western blot analysis using Mfn2 N-term antibody. The effect of tMfn2 on the proliferation of VSMCs was explored by cell counting and MTT assay. The cell cycle was analyzed using flow cytometry. Western blot were used to detect the expression of p-ERK1/2 and p-Raf-1. Results The results of cell counting and MTT both indi-cated that tMfn2 gene displayed more remarkable effect on inhibiting the proliferation of VSMCs than Mfn2 (P <0.01). Flow cytometry showed that most of the cells infected with Adv-tMfn2 or Adv-Mfn2 were blocked in the stage of G0/G1 and few entered into the S phase. Western blot indicated that overexpression of tMfn2 gene resulted in downregulation of phosphorylated ERK1/2 and Raf-1 protein (P < 0.01). These results demonstrated tMfn2 had stronger effect than Mfn2 (P < 0.01). Conclusions tMfn2 gene is superior to Mfn2 gene in attenuating the proliferation of VSMCs via the Ras-Raf-ERK1/2 signaling pathway.