ObjectiveTo investigate the effects of lectin-like oxidized low-density lipoprotein receptor-1 （LOX-1） gene G501C on brain structure and cognitive function in patients with white matter hyperintensities （WMH）. MethodsA total of 118 patients with WMH were enrolled. All participants underwent T1-weighted and T2-fluid-attenuated inversion recovery （T2-FLAIR） MRI to assess gray matter structure and WMH burden， and completed the mini-mental state examination （MMSE） and Montreal cognitive assessment （MoCA）. Partial correlation and mediation analyses were performed to explore the impact of LOX-1 polymorphism on cognitive function. ResultsParticipants were divided into GG+GC group （n = 35） and CC group （n = 83）. The GG+GC group showed lower MMSE and MoCA scores （MMSE： P=0.003； MOCA： P=0.015）， as well as greater WMH burden （all P0.001）， compared with the CC group. Voxel-based morphometry （VBM） analysis revealed reduced left thalamic volume in the GG+GC group， which was correlated with cognitive scores （all P0.05）. Subregional thalamic analysis further showed volume reductions in the lateral， ventral， medial， and pulvinar thalamic regions （all P0.05） in the GG+GC group， all positively associated with cognitive performance （all P0.05）. Mediation analyses indicated that volumes of the medial and pulvinar thalamic regions mediated the association between genotype and cognitive function （MMSE， MoCA）， and that WMH volume mediated the effect on MoCA scores. ConclusionThe LOX-1 G501C polymorphism may indirectly affect cognitive function by influencing specific thalamic subregional volumes and white matter damage， suggesting a potential mediating role of thalamic structures between genetic background and cognitive impairment.

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 explore the prognosis-related genes of lung adenocarcinoma(LUAD)and establish a prognostic prediction model for LUAD.Methods The differentially expressed genes of LUAD tissues and adjacent normal tissues in the GSE43458,GSE7670,and GSE140797 datasets were screened.The protein-protein interaction(PPI)network analysis,gene ontology(GO)function,Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses,least absolute shrinkage and selection operator for prognosis coefficient screening,disease-specific survival analysis,Cox regression analysis,and gene correlation analysis were performed.Independent prognostic genes of LUAD were screened from the differential genes,and a prognostic prediction model of LUAD was established.The expression of independent prognostic genes was analyzed,and the predictive model was evaluated by receiver operating characteristic(ROC)curve.The GSE68465 data set was used as an external validation set to verify the predictive model.Results There were 197 up-regulated differential genes and 77 down-regulated differential genes in LUAD and adjacent normal tissues common to the three datasets.Through stepwise screening,two genes,IL7R and SLC2A1,were identified as independent prognostic factors for LUAD.IL7R was an independent protective factor,while the SLC2A1 was an independent risk factor.A prediction model for curve was built with IL7R and SLC2A1.The prediction model for LUAD constructed with IL7R and SLC2A1 is as follows:Risk score=(-0.694)×expression level of IL7R+0.763×expression level of SLC2A1.Conclusion This study screened out IL7R as an independent prognostic protective factor for LUDA,and SLC2A1 as an independent prognostic risk factor for LUAD.The LUDA prediction model constructed based on these two genes has good predictive ability and generalization ability,which can provide references for the research and clinical individualized treatment of LUAD.

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 clinical-epidemiological characteristics of connective tissue diseases (CTD) complicated with pulmonary hypertension in Shanxi province from 2018 to 2021.Methods:This was a cross-sectional study. Data of CTD patients with pulmonary hypertension from 2018 to 2021 were collected from the Shanxi Provincial Health Statistics Direct Reporting System based on inpatient medical records. The demographic and clinical data of patients with different CTD types were analyzed.Results:A total of 1 697 CTD patients with pulmonary hypertension were included, among whom there were 451 cases (26.58%) of Sj?gren′s syndrome, 392 cases (23.10%) of systemic lupus erythematosus, 289 cases(17.03%) of systemic sclerosis, 109 cases (6.42%) of mixed CTD, 69 cases (4.07%) of Takayasu arteritis, and 387 cases (22.80%) of other CTD. The majority of patients were female (1 410 (83.09%)), and 783 cases (46.14%) were aged between 41 and 65 years, and 6 cases (0.35%) were performed right heart catheterization. The prevalence of CTD with pulmonary hypertension increased from 0.06/10 4 in 2018 to 0.20/10 4 in 2021. There were significant differences in the severity of pulmonary hypertension, New York Heart Association (NYHA) functional class, length of hospital stay, medical costs, and clinical outcomes among patients with different CTD subtypes (all P<0.001). Patients with systemic sclerosis had the highest proportion of NYHA functional class Ⅲ/Ⅳ(65.1%(188/289)), the longest length of hospital stays (13 (9, 18) days), the highest average medical costs (13 622.67 (8 636.38, 20 597.75) ￥(RMB)), and the lowest rate of improvement and discharge (51.90%(150/289)). Conclusions:Between 2018 and 2021, Shanxi province, where CTD is more common in Sj?gren′s syndrome, has a high proportion of women, a high proportion of people aged 41-65 years, and a low prevalence of right ventricular catheterization in patients with CTD complicated with pulmonary hypertension. The prevalence of CTD complicated with pulmonary hypertension shows a rising trend in Shanxi province from 2018 to 2021, while patients with systemic sclerosis exhibit the most severe cardiac impairment and poorer clinical outcomes compared to other subtypes.

Intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has become the primary treatment for macular edema associated with retinal vascular disease such as diabetic retinopathy and retinal vein occlusion, but there are limitations such as variable treatment efficacy and insufficient durability of therapeutic effects. As the first bispecific antibody applied in ophthalmic treatment, Faricimab achieves favorable outcomes by simultaneously targeting both VEGF-A and angiopoietin-2(Ang-2)pathways. Based on evidence from recent clinical trials and real-world studies, this article reviews the research progress on Faricimab for the treatment of diabetic macular edema(DME), retinal vein occlusion-associated macular edema(RVO-ME)and refractory macular edema compared to the therapeutic effects of other agents. Additionally, based on Faricimab's safety characteristics and future potential, its therapeutic prospects for macular edema associated with retinal vascular diseases are discussed. This review aims to provide evidence-based references for optimizing clinical treatment strategies, thereby contributing to mitigating the risk of vision loss due to macular edema.

•A strategy for in situ metabolically synthesized active drug-based probes was proposed.•The potential purgative targets of SA were successfully hooked and identified.•The work provided a new insight for studying the direct targets of unstable active drugs.

Objective To investigate the clinical characteristics and outcomes of Coronavirus Dis-ease 2019 in immunocompromised hosts.Methods A retrospective analysis was conducted on the clinical data of 230 hospitalized patients diagnosed with Coronavirus Disease 2019 at Nanjing Yimin Hospital from December 2022 to November 2023.The patients were divided into three groups based on their immune status:immunocompromised group(n=59),relatively immunocompromised group(n=129),and immunocompetent group(n=42).The clinical characteristics(such as clinical manifesta-tions,imaging features,and laboratory examinations)and outcomes(such as length of hospital stay and in-hospital mortality)were compared among three groups.Results Compared with there latively immunocompromised and immunocompetent groups,the immunocompromised group showed no obvious specific clinical manifestations.However,the proportions of patients with symptoms such as cough and expectoration were lower,and the occurrences of symptoms such as myalgia and fatigue were less fre-quent in the immunocompromised group(P＜0.05).The chest CT findings in the immunocompro-mised group also lacked specific changes,mainly presenting as subpleural ground-glass opacities and consolidations with multilobar distribution,but fibrotic changes were more common(P＜0.05).The proportion of patients with decreased absolute lymphocyte counts in the immunocompromised group was higher than that in the immunocompetent group,and the proportion of patients with elevated procalcitonin levels was higher than that in the other two groups(P＜0.05).The proportion of severe case sand the length of hospital stay in the immunocompromised group were higher and longer than those in the relatively immunocompromised and immunocompetent groups(P＜0.05).The in-hospital mortality rates in the immunocompromised,relatively immunocompromised,and immunocompetent groups were 10.17％,6.98％,and 2.38％,respectively,with no statistically significant difference(P＞0.05).Conclusion After Coronavirus Disease 2019,immunocompromised hosts do not show obvi-ous clinical and imaging features.However,they have a prolonged length of hospital stay,a signifi-cantly higher proportion of severe cases,and a tendency towards increased in-hospital mortality,which should be given high clinical attention.

Objective To observe the clinical efficacy of scalp acupuncture combined with repetitive transcranial magnetic stimulation in the treatment of patients with mild to moderate vascular dementia and to explore its potential mechanism of action.Methods A total of 102 patients diagnosed with mild to moderate vascular dementia who were treated in the outpatient and inpatient departments of Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from July 2021 to May 2023 were selected as the study subjects.The patients were randomly divided into an observation group and a control group using a random number table,with 51 patients in each group.The control group received repetitive transcranial magnetic stimulation treatment,while the observation group received scalp acupuncture therapy in addition to the treatment given to the control group.The treatment lasted for 16 weeks.After treatment,the clinical efficacy of the two groups was evaluated.Changes in the Mini-Mental State Examination(MMSE)scores,Montreal Cognitive Assessment(MoCA)scores,and traditional Chinese medicine(TCM)syndrome scores were observed before and after treatment.Additionally,serum levels of brain-derived neurotrophic factor(BDNF),vascular endothelial growth factor(VEGF),and homocysteine(Hcy)were measured.The cerebral blood flow velocities in the anterior,middle,and posterior arteries,as well as the levels of lipid peroxide(LPO),malondialdehyde(MDA),and superoxide dismutase(SOD),were compared between the two groups before and after treatment.The safety and incidence of adverse reactions in both groups were also evaluated.Results(1)After treatment,the MMSE and MoCA scores of both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in MMSE and MoCA scores compared to the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the serum levels of BDNF,VEGF,and Hcy in both groups were significantly improved(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the cerebral blood flow velocities in the posterior,middle,and anterior arteries were significantly improved in both groups(P＜0.05),and the observation group showed significantly better improvement in these velocities compared to the control group,with a statistically significant difference(P＜0.05).(4)After treatment,the levels of LPO,MDA,and SOD were significantly improved in both groups(P＜0.05),and the observation group showed significantly better improvement in these levels compared to the control group,with a statistically significant difference(P＜0.05).(5)After treatment,the TCM syndrome scores improved significantly in both groups(P＜0.05),and the observation group showed significantly better improvement in these scores compared to the control group,with a statistically significant difference(P＜0.05).(6)The total effective rate in the observation group was 88.24%(45/51),while it was 70.59%(36/51)in the control group.The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(7)The incidence of adverse reactions in the observation group was 3.92%(2/51),while it was 1.96%(1/51)in the control group.There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Scalp acupuncture combined with repetitive transcranial magnetic stimulation in the treatment of mild to moderate vascular dementia helps regulate cerebral hemodynamics and neurotrophic factor expression,improves cognitive function,and demonstrates significant efficacy with good safety.

Objective To explore the insomnia of naval officers and soldiers under long-term high-intensity tactical training,and to analyze the mediation effect of ruminative thinking in the impact of occupational stress on insomnia.Methods The insomnia severity index,effort-reward imbalance,and ruminative responses scale were used to assess the sleep quality of 585 naval officers and soldiers under long-term high-intensity tactical training in September 2023.Results The detection rate of insomnia in these soldiers under long-term high-intensity tactical training was 20.17%.Insomnia was positively correlated with occupational stress and rumination.Bootstrap mediation effect test showed that rumination played a partial mediating role in the effect of occupational stress on insomnia(95%CI:1.344-3.157),and the mediation effect accounted for 46.47%of the total effect.Conclusion There is a high incidence of insomnia in naval officers and soldiers under long-term high-intensity tactical training.Rumination plays a partial mediating role in the effect of occupational stress on insomnia.