Objective:To evaluate the application potential of the bimodal ultrasound/near-infrared (NIR) composite nanoscale probe Arg-Gly-Asp (RGD)/Ag 2Te/perfluoropentane (PFP) @ mesoporous silica nanoparticles (MSN) in the diagnosis and treatment of microvascular diseases. Methods:Nanoprobes loaded with RGD, PFP and Ag 2Te were prepared by ultrasound sonication and carbodiimide method. The characterization of the nanoprobes was determined. The imaging performance, photothermal response, and target-seeking ability of the nanoprobes under NIR irradiation were verified. The biosafety of the nanoprobes was examined, and the thrombolytic ability of the nanoprobes was evaluated. The mice were observed to visualize microvessels of the abdominal wall under the NIR-Ⅱ imaging, and the microvascular visualization ability of the nanoprobes was evaluated. Results:The particle size of nanoprobes was (205.3±2.9) nm and the potential was (2.05±0.58) mV. The coupling rate of the RGD was (82.27±0.36)%, the encapsulation rate of the quantum dots was (80.80±3.26)%, and the photostability of the quantum dots was good. The fluorescence intensity was enhanced with the increase of the mass concentration of RGD/Ag 2Te/PFP@MSN, and the warming effect was more obvious. After ultrasound and NIR irradiation, the thrombolysis rate was significantly increased. RGD/Ag 2Te/PFP@MSN successfully realized NIR-Ⅱ fluorescence imaging of mice microvessels. The cytotoxicity assay and hemolysis assay showed that the probe had a good biosafety. Conclusion:The RGD/Ag 2Te/PFP@MSN nanoprobe is a potential strategy for targeted therapy of thrombotic diseases, combining dual-modality therapy of ultrasound and NIR to offer new possibilities for non-invasive and visual diagnosis and treatment of microvascular embolism.

Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

Objective To analyze the effect of Roflumilast combined with Budesonide in the treatment of chronic bronchitis complicated with chronic obstructive pulmonary disease(COPD).Methods A total of 98 patients with chronic bronchitis complicated with COPD admitted from February 2023 to February 2025 were selected and divided into group A(n=49)and group B(n=49)by random number table method.Group A was given Budesonide,and group B was given Roflumilast combined with Budesonide.The clinical efficacy,symptom scores[Chronic Obstructive Pulmonary Disease Assessment Test(CAT),modified British medical research council(mMRC)],pulmonary function[forced vital capacity(FVC),peak exploratory flow(PEF),forced exploratory volume in one second(FEV1)],respiratory mechanics indexes[airway resistance(Raw),dynamic compliance(Cdyn),peak inspiratory pressure(PIP)],inflammatory factors[interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP)],oxidative stress markers[8-iso-prostaglandin F2α(8-iso-PGF2α),malondialdehyde(MDA),super oxide dismutase(SOD),glutathione peroxidase(GSH-Px)],adverse reactions and prognosis were compared between the two groups.Results The total effective rate of group B[95.92%(47/49)]was higher than that of group A[83.67%(41/49)](P<0.05).After treatment,CAT,mMRC score,PIP,Raw,8-iso-PGF2α,MDA,hs-CRP,TNF-α and IL-8 in group B were lower than those in group A,while FVC,PEF,FEV1,Cdyn,SOD and GSH-Px were higher than those in group A(P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).The number of acute exacerbation in group B was less than that in group A at 3 and 6 months after treatment(P<0.01).Conclusion The combination therapy of Roflumilast and Budesonide is significantly effective in the treatment of chronic bronchitis complicated with COPD.It can alleviate clinical symptoms,improve patients'pulmonary function and respiratory mechanics,inhibit inflammation and oxidative stress response,and has a favorable safety profile and good prognosis.

Objective To analyze the effect of Roflumilast combined with Budesonide in the treatment of chronic bronchitis complicated with chronic obstructive pulmonary disease(COPD).Methods A total of 98 patients with chronic bronchitis complicated with COPD admitted from February 2023 to February 2025 were selected and divided into group A(n=49)and group B(n=49)by random number table method.Group A was given Budesonide,and group B was given Roflumilast combined with Budesonide.The clinical efficacy,symptom scores[Chronic Obstructive Pulmonary Disease Assessment Test(CAT),modified British medical research council(mMRC)],pulmonary function[forced vital capacity(FVC),peak exploratory flow(PEF),forced exploratory volume in one second(FEV1)],respiratory mechanics indexes[airway resistance(Raw),dynamic compliance(Cdyn),peak inspiratory pressure(PIP)],inflammatory factors[interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP)],oxidative stress markers[8-iso-prostaglandin F2α(8-iso-PGF2α),malondialdehyde(MDA),super oxide dismutase(SOD),glutathione peroxidase(GSH-Px)],adverse reactions and prognosis were compared between the two groups.Results The total effective rate of group B[95.92%(47/49)]was higher than that of group A[83.67%(41/49)](P<0.05).After treatment,CAT,mMRC score,PIP,Raw,8-iso-PGF2α,MDA,hs-CRP,TNF-α and IL-8 in group B were lower than those in group A,while FVC,PEF,FEV1,Cdyn,SOD and GSH-Px were higher than those in group A(P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).The number of acute exacerbation in group B was less than that in group A at 3 and 6 months after treatment(P<0.01).Conclusion The combination therapy of Roflumilast and Budesonide is significantly effective in the treatment of chronic bronchitis complicated with COPD.It can alleviate clinical symptoms,improve patients'pulmonary function and respiratory mechanics,inhibit inflammation and oxidative stress response,and has a favorable safety profile and good prognosis.

Objective:To evaluate the application potential of the bimodal ultrasound/near-infrared (NIR) composite nanoscale probe Arg-Gly-Asp (RGD)/Ag 2Te/perfluoropentane (PFP) @ mesoporous silica nanoparticles (MSN) in the diagnosis and treatment of microvascular diseases. Methods:Nanoprobes loaded with RGD, PFP and Ag 2Te were prepared by ultrasound sonication and carbodiimide method. The characterization of the nanoprobes was determined. The imaging performance, photothermal response, and target-seeking ability of the nanoprobes under NIR irradiation were verified. The biosafety of the nanoprobes was examined, and the thrombolytic ability of the nanoprobes was evaluated. The mice were observed to visualize microvessels of the abdominal wall under the NIR-Ⅱ imaging, and the microvascular visualization ability of the nanoprobes was evaluated. Results:The particle size of nanoprobes was (205.3±2.9) nm and the potential was (2.05±0.58) mV. The coupling rate of the RGD was (82.27±0.36)%, the encapsulation rate of the quantum dots was (80.80±3.26)%, and the photostability of the quantum dots was good. The fluorescence intensity was enhanced with the increase of the mass concentration of RGD/Ag 2Te/PFP@MSN, and the warming effect was more obvious. After ultrasound and NIR irradiation, the thrombolysis rate was significantly increased. RGD/Ag 2Te/PFP@MSN successfully realized NIR-Ⅱ fluorescence imaging of mice microvessels. The cytotoxicity assay and hemolysis assay showed that the probe had a good biosafety. Conclusion:The RGD/Ag 2Te/PFP@MSN nanoprobe is a potential strategy for targeted therapy of thrombotic diseases, combining dual-modality therapy of ultrasound and NIR to offer new possibilities for non-invasive and visual diagnosis and treatment of microvascular embolism.

ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1（SLC8A1） mRNA in the myocardium of healthy organ donors （n=24） and heart failure （HF） patients （n=21） were assessed by real-time quantitative polymerase chain reaction （RT-qPCR） assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts （mCFs） with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay， respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation （RIP） was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 （Idh2） mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients， while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression， and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA （siRNA） could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.

ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.

Objective:To investigate the clinical value of multiparametric myocardial imaging using a dual-layer detector spectral CT in the non-invasive preoperative assessment of patients with coronary atherosclerotic heart disease (CHD) undergoing percutaneous coronary intervention (PCI).Methods:The clinical and imaging data of 90 patients who underwent coronary CT angiography (CCTA) with dual-layer spectral detector CT and invasive coronary angiography (ICA) within 30 days at the Affiliated Changshu Hospital of Nantong University from January 2021 to October 2022 were retrospectively analyzed. A total of 189 coronary arteries were included in the study cohort. The patients were divided into PCI ( n=44) and non-PCI groups ( n=46) according to whether they received PCI after evaluation with ICA. The diameter stenosis rate of the coronary arteries, myocardial iodine concentration (IC) and effective atomic number (Z eff) values were obtained from CCTA conventional and spectral images. The IC values and Z eff values of the myocardium in the areas with abnormal perfusion were compared with those in the areas with normal perfusion. The diagnostic performance of these parameters, as well as their combined model, was evaluated and compared using receiver operating characteristic (ROC) curve and area under the curve (AUC) in the pre-PCI assessment of patients with CHD. Results:Baseline patient data did not show statistically significant differences between the PCI and non-PCI groups (all P>0.05). There were statistically significant differences in IC values [(0.42±0.28) and (2.26±0.48) mg/ml] and Z eff values (7.39±0.33 and 8.50±0.25) between the myocardium areas with abnormal perfusion and the myocardium areas with normal perfusion in all patients (all P<0.001). The AUC for assessing whether patients with CHD need PCI treatment using myocardial IC and Z eff values were 0.865 and 0.853, respectively, which were significantly higher than assessment based only on lumen diameter stenosis rate (AUC=0.726, P<0.001). Conclusions:The IC and Z eff derived from myocardial spectral images can be used to diagnose myocardial perfusion abnormalities in patients with CHD. The spectral myocardial multi-parameters imaging shows promising potentials in pre-PCI assessment of patients with CHD, which can improve the efficiency of evaluation and may help to avoid unnecessarily invasive procedures.

Objective:To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats.Methods:The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor β 1 (TGF-β 1) were detected by Western blotting ( n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results:At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-β 1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group ( t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group ( t=7.21, P<0.05). Conclusions:The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

Objective To explore the dilemma of self-management behavior maintenance in ischemic stroke patients,and to provide references for continuous self-management intervention design for ischemic stroke patients.Methods The descriptive qualitative research method was used to select samples by the purpose sampling method.From November to December 2023,18 patients hospitalised with stroke from the neurology ward of a tertiary general hospital in Luoyang City,Henan Province were selected for semi-structured interviews.Based on the Capability,Opportunity,Motivation-Behavior(COM-B)model,the data were analyzed by directed content analysis.Results A total of 3 themes and 12 sub-themes were identified,namely capability factors(poor level of health literacy,lack of self-control),opportunity factors(lack of medical resources impeding the maintenance of behaviors,social customs inducing the return of undesirable behaviors,difficult to satisfy the need for multiple emotional support,behavior being improved briefly after follow-up),and motivation factors(impulsive thinking,role conflict leading to forgetfulness,difficult to change previous bad habits,acceptance of the aging,weak self-management effect,symptoms inducing behavioral changes).Conclusion The maintenance of self-management behavior in ischemic stroke patients is affected by 3 aspects of obstacles,including capability,opportunity and motivation.On the premise of fully evaluating the specific characteristics of ischemic stroke patients,medical staff should meet the multidimensional needs of patients to promote the maintenance of self-management behaviors to improve their health outcomes.