Objective To investigate the effects and underlying mechanisms of a spray prepared from exosomes derived from M2 macrophages induced by interleukin-4 （IL-4） and tantalum particles （Ta） on the healing of pressure ulcers. Methods Bone marrow-derived macrophages were polarized into M2 macrophages using IL-4 or Ta, and exosomes （Exo-IL-4/Exo-Ta） were extracted. The regulatory effects of Exo-IL-4/Exo-Ta on M1 macrophage phenotypes and fibroblast matrix secretion were evaluated in vitro. Proteomic analysis was conducted to explore the biological processes and regulatory networks associated with Exo-Ta. A rat pressure ulcer model was used to assess the effects of Exo-IL-4/Exo-Ta spray on wound healing rate, inflammatory cell infiltration, and collagen deposition. Results In vitro, Exo-IL-4/Exo-Ta induced the polarization of M1 macrophages to M2 macrophages, reduced the secretion of pro-inflammatory factors, and promoted the expression of anti-inflammatory substances. Additionally, Exo-IL-4/Exo-Ta enhanced the production of collagen and fibronectin in fibroblasts. Proteomic analysis revealed that Exo-Ta primarily participated in biological processes such as energy metabolism and macromolecule biosynthesis. In vivo, Exo-IL-4/Exo-Ta spray accelerated wound healing, reduced inflammatory infiltration, and improved tissue remodeling in the rat pressure ulcer model. Conclusion Exosome sprays derived from M2 macrophages could accelerate pressure ulcer healing by modulating inflammation and promoting tissue regeneration, which demonstrated excellent clinical application potential.

Objective To analyze the serum high-density lipoprotein 3 subtype cholesterol(HDL3-C)levels in patients with ischemic stroke(IS)and explore its clinical value in evaluating the condition and prognosis.Methods A total of 124 patients with IS and 47 healthy controls admitted to the Department of Neurology of the General Hospital of the Eastern Theater Command were continuously se-lected from January to June 2023.The serum samples of IS patients at admission and healthy controls were collected respectively,and the levels of HDL3-C,total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipopro-tein cholesterol(LDL-C),blood glucose(Glu),albumin(Alb),interleukin 6(IL-6)and procalcitonin(PCT)were measured.The National Institutes of Health Stroke Scale(NIHSS)score at admission,modified Rankin Scale(MRS)score at discharge,and Barthel index of the IS patients were calculated.All the IS patients were followed up for 1 year.The time of sequelae caused by stroke,and re-currence of acute cerebrovascular events were recorded in detail.Spearman's correlation analysis was used to explore the correlation be-tween HDL3-C levels and other clinical events and biochemical parameters in the IS patients.Logistic regression analysis was used to analyze the clinical value of serum HDL3-C levels in evaluating the presence of IS.Cox regression analysis was used to analyze the clin-ical value of serum HDL3-C levels in assessing the prognosis of patients with IS.Results Compared with controls,the levels of HDL3-C,HDL-C and Alb of the patients with IS decreased significantly,but the levels of TG and Glu of the IS patients increased sig-nificantly(all P＜0.05).The level of serum HDL3-C in patients with IS was significantly positively correlated with TC(r=0.231,P=0.003),HDL-C(r=0.831,P＜0.001),Alb(r=0.451,P＜0.001)and Barthel index at discharge(r=0.216,P=0.018),while it was significantly negatively correlated with the levels of TG(r=-0.396,P＜0.001),IL-6(r=-0.290,P=0.013),NIHSS at admis-sion(r=-0.187,P=0.041)and MRS at discharge(r=-0.227,P=0.012).Multivariate Logistic regression analyses showed that the decreased level of serum HDL3-C was still independently related to the presence of IS(OR=0.853,95％CI=0.740-0.984,P=0.030)after adjusting for the fectors of age,sex,TC,TG,HDL-C and LDL-C.Multivariate Cox regression analyses demonstrates that the de-creased level of serum HDL3-C was still independently related to the poor prognosis of IS patients(HR=0.710,95％CI=0.517-0.976,P=0.035)after adjusting for the fectors of age,sex,TC,TG,HDL-C and LDL-C.Conclusion The level of serum HDL3-C in pa-tients with IS decreased significantly,and it is independently correlated with poor prognosis.The level of HDL3-C has reference value in evaluating the condition and prognosis of the patients with IS.

Dyslipidemia is the core pathological basis of atherosclerotic cardiovascular diseases (ASCVD). Lipid management strategy undergoes the innovation from "single target" to "multi-dimensional precision" now. The application of apolipoprotein B in the risk management of ASCVD is explored in this paper, and it is highlighted that non-high-density lipoprotein cholesterol is a more reliable risk stratification indicator instead of high triglyceride level. Meanwhile, it is revealed that with the use of multi-omics technologies, the potential of epigenetic modifications and core molecules of lipid metabolism might serve as new indicators for ASCVD risk assessment. This paper also expands the cross-disciplinary multi-dimensional collaborative mechanisms of "heart-eye lipid metabolism association" and "gut-heart axis association", which is conducive to exploring new approaches for lipid management and intervention in ASCVD.

Objective:To assess the clinical value of global RNA N6-methyladenosine (m 6A) and perilipin 2 (PLIN2) mRNA site-specific (chr9:19116312) m 6A modification in peripheral blood as novel molecular biomarkers of coronary artery disease (CAD). Methods:Seventy-four patients with coronary artery disease diagnosed at the Eastern Theater General Hospital from June to December 2023, and 60 age-and sex-matched healthy controls during the same period were selected for a retrospective case-control study. The global RNA m 6A modification level in peripheral blood was detected by RNA methylation quantitative detection kit as a preliminary validation, and PLIN2 site-specific (chr9:19116312) m 6A modification level was further detected using the qPCR quantification technique with single-base elongation and ligation as a rescreening validation. Lipid indicators such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), routine blood indicators such as neutrophil count and platelet count were detected, and the coronary lesion characteristics were further evaluated by using the Gensini score and SYNTAX score systems in conjunction with coronary arteriography results.The CAD group was divided into a single-branch (25 cases) and a multi-branch lesion subgroup (49 cases) according to the number of vascular lesion branches on coronary angiography. The potential value of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood of patients for the adjunctive diagnosis and assessment of coronary artery disease was explored using Spearman correlation analysis, subject operating characteristic (ROC) curves, and logistic regression analysis. Results:Compared with the control group, the levels of global RNA m 6A modification and PLIN2 site-specific (chr9∶19116312) m 6A modification in peripheral blood were significantly decreased in the CAD group (both P<0.05). The levels of global RNA m 6A modification in peripheral blood was also significantly decreased in the single-branch and multi-branch lesion subgroups ( P<0.05), and PLIN2 site-specific (chr9:19116312) m 6A modification in peripheral blood was significantly decreased in the multi-branch lesion subgroup only ( P<0.05). Spearman correlation analysis showed that in both the CAD group and the multi-branch lesion subgroup, global RNA m 6A modification level in peripheral blood was positively correlated with HDL-C ( r=0.246, 0.289, P<0.05) and negatively correlated with SYNTAX score ( r=-0.261, -0.322, P<0.05) and neutrophil count ( r=-0.246, -0.466, P<0.05). In the single-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with Gensini score ( r=-0.566, P<0.05). In the multi-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with platelet count ( r=-0.313, P<0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood for distinguishing CAD and coronary artery multi-branch lesions were 0.915 and 0.918, with specificity of 83.3% and 95.0%, and sensitivity of 85.1% and 75.5%, respectively. The multivariate logistic regression analysis showed that after adjusting confounding factors such as age, sex, proportion of diabetes and hypertension, and TC, the levels of global RNA m 6A modification ( OR=0.691, P<0.001; OR=0.694, P<0.01), and PLIN2 site-specific (chr9:19116312) m 6A modification levels ( OR=0.345, P<0.05; OR=0.143, P<0.01) in peripheral blood remained independently associated with CAD and coronary artery multi-branch lesions, respectively. Conclusions:The analysis of global RNA m 6A in combination with PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood is valuable for the adjunctive diagnosis and assessment of patients with CAD and coronary artery multi-branch lesions.

Objective To analyze the serum high-density lipoprotein 3 subtype cholesterol(HDL3-C)levels in patients with ischemic stroke(IS)and explore its clinical value in evaluating the condition and prognosis.Methods A total of 124 patients with IS and 47 healthy controls admitted to the Department of Neurology of the General Hospital of the Eastern Theater Command were continuously se-lected from January to June 2023.The serum samples of IS patients at admission and healthy controls were collected respectively,and the levels of HDL3-C,total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipopro-tein cholesterol(LDL-C),blood glucose(Glu),albumin(Alb),interleukin 6(IL-6)and procalcitonin(PCT)were measured.The National Institutes of Health Stroke Scale(NIHSS)score at admission,modified Rankin Scale(MRS)score at discharge,and Barthel index of the IS patients were calculated.All the IS patients were followed up for 1 year.The time of sequelae caused by stroke,and re-currence of acute cerebrovascular events were recorded in detail.Spearman's correlation analysis was used to explore the correlation be-tween HDL3-C levels and other clinical events and biochemical parameters in the IS patients.Logistic regression analysis was used to analyze the clinical value of serum HDL3-C levels in evaluating the presence of IS.Cox regression analysis was used to analyze the clin-ical value of serum HDL3-C levels in assessing the prognosis of patients with IS.Results Compared with controls,the levels of HDL3-C,HDL-C and Alb of the patients with IS decreased significantly,but the levels of TG and Glu of the IS patients increased sig-nificantly(all P＜0.05).The level of serum HDL3-C in patients with IS was significantly positively correlated with TC(r=0.231,P=0.003),HDL-C(r=0.831,P＜0.001),Alb(r=0.451,P＜0.001)and Barthel index at discharge(r=0.216,P=0.018),while it was significantly negatively correlated with the levels of TG(r=-0.396,P＜0.001),IL-6(r=-0.290,P=0.013),NIHSS at admis-sion(r=-0.187,P=0.041)and MRS at discharge(r=-0.227,P=0.012).Multivariate Logistic regression analyses showed that the decreased level of serum HDL3-C was still independently related to the presence of IS(OR=0.853,95％CI=0.740-0.984,P=0.030)after adjusting for the fectors of age,sex,TC,TG,HDL-C and LDL-C.Multivariate Cox regression analyses demonstrates that the de-creased level of serum HDL3-C was still independently related to the poor prognosis of IS patients(HR=0.710,95％CI=0.517-0.976,P=0.035)after adjusting for the fectors of age,sex,TC,TG,HDL-C and LDL-C.Conclusion The level of serum HDL3-C in pa-tients with IS decreased significantly,and it is independently correlated with poor prognosis.The level of HDL3-C has reference value in evaluating the condition and prognosis of the patients with IS.

Dyslipidemia is the core pathological basis of atherosclerotic cardiovascular diseases (ASCVD). Lipid management strategy undergoes the innovation from "single target" to "multi-dimensional precision" now. The application of apolipoprotein B in the risk management of ASCVD is explored in this paper, and it is highlighted that non-high-density lipoprotein cholesterol is a more reliable risk stratification indicator instead of high triglyceride level. Meanwhile, it is revealed that with the use of multi-omics technologies, the potential of epigenetic modifications and core molecules of lipid metabolism might serve as new indicators for ASCVD risk assessment. This paper also expands the cross-disciplinary multi-dimensional collaborative mechanisms of "heart-eye lipid metabolism association" and "gut-heart axis association", which is conducive to exploring new approaches for lipid management and intervention in ASCVD.

Objective:To assess the clinical value of global RNA N6-methyladenosine (m 6A) and perilipin 2 (PLIN2) mRNA site-specific (chr9:19116312) m 6A modification in peripheral blood as novel molecular biomarkers of coronary artery disease (CAD). Methods:Seventy-four patients with coronary artery disease diagnosed at the Eastern Theater General Hospital from June to December 2023, and 60 age-and sex-matched healthy controls during the same period were selected for a retrospective case-control study. The global RNA m 6A modification level in peripheral blood was detected by RNA methylation quantitative detection kit as a preliminary validation, and PLIN2 site-specific (chr9:19116312) m 6A modification level was further detected using the qPCR quantification technique with single-base elongation and ligation as a rescreening validation. Lipid indicators such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), routine blood indicators such as neutrophil count and platelet count were detected, and the coronary lesion characteristics were further evaluated by using the Gensini score and SYNTAX score systems in conjunction with coronary arteriography results.The CAD group was divided into a single-branch (25 cases) and a multi-branch lesion subgroup (49 cases) according to the number of vascular lesion branches on coronary angiography. The potential value of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood of patients for the adjunctive diagnosis and assessment of coronary artery disease was explored using Spearman correlation analysis, subject operating characteristic (ROC) curves, and logistic regression analysis. Results:Compared with the control group, the levels of global RNA m 6A modification and PLIN2 site-specific (chr9∶19116312) m 6A modification in peripheral blood were significantly decreased in the CAD group (both P<0.05). The levels of global RNA m 6A modification in peripheral blood was also significantly decreased in the single-branch and multi-branch lesion subgroups ( P<0.05), and PLIN2 site-specific (chr9:19116312) m 6A modification in peripheral blood was significantly decreased in the multi-branch lesion subgroup only ( P<0.05). Spearman correlation analysis showed that in both the CAD group and the multi-branch lesion subgroup, global RNA m 6A modification level in peripheral blood was positively correlated with HDL-C ( r=0.246, 0.289, P<0.05) and negatively correlated with SYNTAX score ( r=-0.261, -0.322, P<0.05) and neutrophil count ( r=-0.246, -0.466, P<0.05). In the single-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with Gensini score ( r=-0.566, P<0.05). In the multi-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with platelet count ( r=-0.313, P<0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood for distinguishing CAD and coronary artery multi-branch lesions were 0.915 and 0.918, with specificity of 83.3% and 95.0%, and sensitivity of 85.1% and 75.5%, respectively. The multivariate logistic regression analysis showed that after adjusting confounding factors such as age, sex, proportion of diabetes and hypertension, and TC, the levels of global RNA m 6A modification ( OR=0.691, P<0.001; OR=0.694, P<0.01), and PLIN2 site-specific (chr9:19116312) m 6A modification levels ( OR=0.345, P<0.05; OR=0.143, P<0.01) in peripheral blood remained independently associated with CAD and coronary artery multi-branch lesions, respectively. Conclusions:The analysis of global RNA m 6A in combination with PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood is valuable for the adjunctive diagnosis and assessment of patients with CAD and coronary artery multi-branch lesions.

Objective:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR), and to explore the risk factors leading to poor prognosis.Methods:The clinical data of 95 patients with ECPR admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to May 2023 were retrospectively analyzed. According to the survival status at the time of discharge, the patients were divided into the survival group and death group. The difference of clinical data between the two groups was compared to explore the risk factors related to death and poor prognosis. Risk factors associated with death were identified by Binary Logistic regression analysis. Results:A total of 95 patients with ECPR were included in this study, 62 (65.3%) died and 33 (34.7%) survived at discharge. Patients in the death group had longer low blood flow time [40 (30, 52.5) min vs. 30 (24.5, 40) min ] and total cardiac arrest time[40 (30, 52.5) min vs. 30(24.5, 40) min], shorter total hospital stay [3 (2, 7.25) d vs. 19 (13.5, 31) d] and extracorporeal membrane oxygenation (ECMO) assisted time [26.5 (17, 50) h vs. 62 (44, 80.5) h], and more IHCA patients (56.5% vs. 33.3%) and less had spontaneous rhythm recovery before ECMO (37.1% vs. 84.8%). Initial lactate value [(14.008 ± 5.188) mmol/L vs.(11.23 ± 4.718) mmol/L], APACHEⅡ score [(30.10 ± 7.45) vs. (25.88 ± 7.68)] and SOFA score [12 (10.75, 16) vs. 10 (9.5, 13)] were higher ( P< 0.05). Conclusions:No spontaneous rhythm recovery before ECMO, high initial lactic acid and high SOFA score are independent risk factors for poor prognosis in ECPR patients.

Objective:To detect the 3′-terminal 2′- O-methylation (2′Ome) modified microRNA-486-5p (miR-486-5p) levels in the serum of patients with coronary heart disease (CHD), and evaluate its clinical application value as a biomarker to assist the diagnosis of CHD. Methods:Seventy patients with CHD diagnosed at the Eastern Theater General Hospital from January 2021 to December 2022 and 60 age-and sex-matched healthy people undergoing health examination during the same period were selected for this retrospective case-control study. The Gensini score was calculated based on coronary angiography results, and patients in the coronary artery disease group was categorized into mild-to-moderate stenosis (40 cases) and severe stenosis subgroups (30 cases); Serum biochemical indexes, miR-486-5p and 2′Ome-miR-486-5p expression levels were compared between the CHD group and the healthy control group; correlation of biochemical indices, Gensini score and serum miR-486-5p and 2′Ome-miR-486-5p levels was assessed by using Spearman correlation analysis; and multifactorial logistic regression was used to analyze the impact of serum miR-486-5p and 2′Ome-miR-486-5p levels on CHD and the degree of coronary artery stenosis; evaluation of the diagnostic value of 2′Ome-miR-486-5p levels on the degree of coronary artery disease and coronary artery stenosis was achieved by using ROC curve.Results:Serum miR-486-5p and 2′Ome-miR-486-5p levels were significantly higher in CHD group than in the healthy control group [0.31 (0.17, 0.84) vs 0.21 (0.11, 0.49), Z=2.055, P<0.05; 2.30 (1.32, 5.40) vs 0.86 (0.55, 1.72), Z=5.840, P<0.05]; Serum 2′Ome-miR-486-5p expression levels were higher in both mild-moderate and severe stenosis subgroups than in healthy controls ( P<0.05), and serum 2′Ome-miR-486-5p levels were higher in the severe stenosis subgroup than in the mild-moderate stenosis subgroup [3.54(1.78, 5.44) vs 1.63(1.25, 4.07), Z=-2.053, P<0.05]. Both serum miR-486-5p and 2′Ome-miR-486-5p levels were positively correlated with the Gensini score ( r=0.277 and 0.479, respectively, P<0.05); multifactorial logistic regression analysis showed that serum 2′Ome-miR-486-5p level was an independent influence factor of the degree of coronary stenosis after adjustig for the effects of confounding factors such as age and sex ( OR=1.025, 95% CI 1.002-1.049, P<0.05). ROC curve analysis showed that the area under the ROC curve of serum 2′Ome-miR-486-5p levels for the diagnosis of CHD patients, mild to moderate and severe stenosis were 0.798, 0.752 and 0.859, with sensitivities of 91.4%, 92.5%, and 73.3%, and specificities of 56.7%, 51.7% and 81.7%, respectively, at the optimal cut-off (0.912, 0.863, 2.209). Conclusion:Serum 2′Ome-miR-486-5p level is increased in CHD patients and is an independent predictor of the severity of coronary artery stenosis, which can be used as a biomarker for the diagnosis of patients with CHD.

Objective:To detect the changes in the levels of miR-21-5p and miR-125a-5p modified with 3′-terminal 2′-O-methylation (3′t-2′Ome) in serum extracellular vesicles (EV) of non-small cell lung cancer (NSCLC) patients, and evaluate their value as auxiliary screening molecular markers for NSCLC patients.Method:A retrospective analysis was conducted on the data of 69 NSCLC patients diagnosed at the Eastern Theater Command General Hospital from May 1st to October 31st,2023, as well as 65 age and gender matched healthy controls during the same period. Two real-time fluorescence quantitative PCR (RT-qPCR) techniques, namely stem-loop method and poly (A) tailed method, were used to detect the levels of 3′t-2′Ome-miR-21-5p and 3′t-2′-Ome miR-125a-5p in serum EV of NSCLC patients and controls.Analyze the correlation between the levels of two types of 3′t-2 ′Ome miRNAs and the differences in clinical stage, pathological classification, and other tumor indicators in patients. Receiver operating characteristic (receiveroperating curve, ROC) curves were used to analyze the efficacy of 3′t-2 ′Ome miR-21-5p and 3′t-2′ Ome miR-125a-5p in serum EV, as well as their combination, in diagnosing NSCLC.Result:Compared with the control group, the levels of 3′t-2′Ome-miR-21-5p in serum EV of NSCLC patients increased [(0.30±0.05) vs (0.35±0.09), t=3.32, P=0.001], while the levels of 3′t-2′Ome-miR-125a-5p decreased [(0.33±0.06 vs 0.25±0.06, t=7.45, P<0.001]. The differences were statistically significant. The expression levels of 2′Ome-miR-21-5p in EV were also significantly elevated in the NSCLC patients at 0-Ⅱ stage, adenocarcinoma patients, and squamous cell carcinoma patients, respectively. Notably, the levels of EV 3′t-2′Ome-miR-21-5p was also statistically significant between the adenocarcinoma patients and squamous cell carcinoma patients [(0.34±0.85) vs (0.40±0.12), P<0.05]. ROC curve analysis showed that the levels of 3′t-2 ′Ome miR-21-5p and 3′t-2′ Ome miR-125a-5p in serum EV, as well as their combined AUC for discriminating NSCLC patients, were 0.647(95% CI 0.550-0.743), 0.825(95% CI 0.756-0.894) and 0.860(95% CI 0.797-0.923), respectively. The sensitivity was 92.3%, 80.0%, 89.2%, and the specificity was 46.4%, 73.9%, and 78.3%, respectively. Conclusion:There are changes in the levels of 2 ′Ome miR-21-5p and 2′ Ome miR-125a-5p in the serum EV of NSCLC patients, and the combined detaction has the potential as an auxiliary screening molecular marker of NSCLC patients.