Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Background and Aims:Pancreatic cancer(PC)is a highly lethal gastrointestinal malignancy with poorly understood pathogenesis.Previous studies suggest that alterations in plasma metabolomics may be associated with PC development;however,traditional observational studies are prone to confounding and reverse causation,making it difficult to establish causal relationships.This study employed a two-sample Mendelian randomization(MR)approach to systematically evaluate the potential causal relationship between 325 nuclear magnetic resonance(NMR)metabolites and PC risk.Methods:Genome-wide association study(GWAS)data of 325 NMR metabolites from the UK Biobank were integrated with GWAS data of PC from FinnGen.Single nucleotide polymorphisms(SNPs)significantly associated with metabolites were selected as instrumental variables.The inverse variance weighted method served as the primary analysis,supplemented by MR-Egger regression,weighted median,weighted mode,Bayesian weighted Mendelian randomization(BWMR),and constrained maximum likelihood(cML)for validation.Multiple sensitivity analyses were performed to assess the robustness of the results.Results:Four metabolites were identified to have significant causal associations with PC risk.Higher phospholipid-to-total lipid ratios in intermediate-density lipoproteins(IDL)(GCST90445881)and small high density lipoproteins(HDL)(GCST90446027),as well as higher free cholesterol-to-total lipid ratios in extremely large very-low-density lipoproteins(VLDL)(GCST90446151),were inversely associated with PC risk.Conversely,an elevated triglyceride-to-total lipid ratio in chylomicrons and extremely large VLDL(GCST90446157)was positively associated with increased PC risk.The findings were consistently supported by multiple sensitivity analyses.Conclusion:This study provides genetic evidence linking lipid metabolism alterations to PC risk.Elevated phospholipid and free cholesterol ratios appear protective,whereas increased triglyceride levels act as risk factors.These metabolite profiles may serve as promising biomarkers for early diagnosis and intervention in PC,offering novel insights for risk assessment and potential metabolic-targeted therapies.

Background and Aims:Pancreatic cancer(PC)is a highly lethal gastrointestinal malignancy with poorly understood pathogenesis.Previous studies suggest that alterations in plasma metabolomics may be associated with PC development;however,traditional observational studies are prone to confounding and reverse causation,making it difficult to establish causal relationships.This study employed a two-sample Mendelian randomization(MR)approach to systematically evaluate the potential causal relationship between 325 nuclear magnetic resonance(NMR)metabolites and PC risk.Methods:Genome-wide association study(GWAS)data of 325 NMR metabolites from the UK Biobank were integrated with GWAS data of PC from FinnGen.Single nucleotide polymorphisms(SNPs)significantly associated with metabolites were selected as instrumental variables.The inverse variance weighted method served as the primary analysis,supplemented by MR-Egger regression,weighted median,weighted mode,Bayesian weighted Mendelian randomization(BWMR),and constrained maximum likelihood(cML)for validation.Multiple sensitivity analyses were performed to assess the robustness of the results.Results:Four metabolites were identified to have significant causal associations with PC risk.Higher phospholipid-to-total lipid ratios in intermediate-density lipoproteins(IDL)(GCST90445881)and small high density lipoproteins(HDL)(GCST90446027),as well as higher free cholesterol-to-total lipid ratios in extremely large very-low-density lipoproteins(VLDL)(GCST90446151),were inversely associated with PC risk.Conversely,an elevated triglyceride-to-total lipid ratio in chylomicrons and extremely large VLDL(GCST90446157)was positively associated with increased PC risk.The findings were consistently supported by multiple sensitivity analyses.Conclusion:This study provides genetic evidence linking lipid metabolism alterations to PC risk.Elevated phospholipid and free cholesterol ratios appear protective,whereas increased triglyceride levels act as risk factors.These metabolite profiles may serve as promising biomarkers for early diagnosis and intervention in PC,offering novel insights for risk assessment and potential metabolic-targeted therapies.

BACKGROUND:Some studies have shown that the hounsfield units(HU)value based on lumbar CT can be used to screen osteoporosis.At present,the number of patients with pulmonary infection has increased;the number of patients with pulmonary infection and type 2 diabetes is also increasing,which increases the utilization rate of chest CT. OBJECTIVE:To investigate the role of lumbar 1 vertebral body HU value based on chest CT in the screening of type 2 diabetes mellitus osteoporosis. METHODS:The clinical data of 244 patients with type 2 diabetes mellitus treated in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022 were analyzed retrospectively.The bone mineral density was obtained by dual-energy X-ray absorptiometry.According to WHO's diagnostic criteria for osteoporosis,the subjects were divided into the non-osteoporosis group(n=120)and the osteoporosis group(n=124).The general condition,T value and HU value of lumbar 1 vertebra in chest CT were compared,and the relationship between the HU value and T value of each position was analyzed and the accuracy of type 2 diabetes mellitus osteoporosis was evaluated. RESULTS AND CONCLUSION:(1)There was no significant difference in sex,age,body mass index,glycosylated hemoglobin,mean blood glucose,calcium(Ca),phosphorus(P),time of type 2 diabetes mellitus,history of hypertension and history of hyperlipidemia between the two groups(P>0.05).(2)The HU value was positively correlated with the lowest T value of the hip(r=0.619,P<0.01);the HU value was positively correlated with the hip T value(r=0.584,P<0.01),and the HU value was positively correlated with the femoral neck T value(r=0.641,P<0.01).When the HU value was 98,the prediction of type 2 diabetes mellitus osteoporosis had good accuracy,and the sensitivity was 70.8%.(3)It is concluded that the HU value of the lumbar 1 vertebra based on chest CT examination is of good value for osteoporosis screening in patients with type 2 diabetes mellitus,and may be an opportunistic and cost-free supplementary screening method for type 2 diabetes mellitus osteoporosis.

OBJECTIVES: Acute ischemic stroke (AIS) is one of the main causes of disability in middle-aged and elderly people, and early activity plays an important role in functional recovery. This study aims to understand the factors that affect the implementation of early activity in patients with AIS and to provide reference for promoting early activity implementation and developing intervention strategies for AIS patients. METHODS: Using purposive sampling, 19 AIS patients and their caregivers who visited at Stroke Center in the Third Xiangya Hospital of Central South University and the Third Hospital of Changsha from June to December 2021, as well as 19 medical staff, hospital administrators, or community workers providing medical health services to stroke patients, were selected as interviewes. A semi-structured interview was conducted based on the social ecological theory model, and the Colaizzi seven-step method was used to analyze the interview data. RESULTS: According to qualitative interview results, the factors affecting early activity in AIS patients were summarized into 4 themes and 12 sub-themes: medical staff factors (insufficient knowledge and skills, insufficient knowledge of early activity, unclear division of responsibilities), patient factors (severity of the disease, lack of knowledge, psychological pressure, fear of falling), social environmental factors (lack of social support, shortage of human resources and rehabilitation equipment, insufficient medical insurance support), and evidence and norms (the evidence for early activity needs improvement, lack of standardized early activity procedures). CONCLUSIONS Early activity in AIS patients is impacted by factors at multiple levels, including medical staff, patients, social environment, and evidence and norms. Developing comprehensive intervention strategies to address these factors can promote early activity implementation in AIS patients.
Aged ; Middle Aged ; Humans ; Ischemic Stroke ; Accidental Falls ; Fear ; Social Environment ; Stroke

Objective: To explore the diagnosis, treatment and prognosis of autoimmune hemolytic anemia (AIHA) after allo-HSCT in patients with thalassemia major (TM). Methods: A retrospective analysis of AIHA status after allo-HSCT in 291 TM patients from July 2007 to December 2017 was conducted. Results: Five of the 291 TM patients (1.72%) were diagnosed with post-transplant AIHA. The median time of AIHA was 7 (5-12) months after HSCT. All post-transplant AIHA patients were positive in direct and indirect Coombs test, the main clinical manifestations were dizziness, fatigue, pale complexion, skin and sclera yellow, and soy sauce urine. The incidence of AIHA was higher after unrelated donor transplantation (6.36%, 4/63) compared with that of sibling donor transplantation (0.43%, 1/228). One patient who received only prednison was dead. Four patients who received rituximab combined with prednisolone were alive, Coombs test in two of them were negative. Conclusions AIHA after allo-HSCT developed in 1.72% patients with TM. Monitoring of Coombs test was important for diagnosis of post-transplant AIHA. The incidence of post-transplant AIHA was higher in unrelated donors compared with that of sibling donors transplantation. Treatment of rituximab combined glucocorticoid was effective strategy for post-transplant AIHA.

Objective To analyze the outcome and the prognostic factors of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). Methods A total of 797 patients receiving HSCT were analyzed retrospectively. The prophylaxis regimen of HVOD in the First Affiliated Hospital of Guangxi Medical University consisted of low molecular weight heparin and lipoprostaglandin E1 (PGE1). Results Fifty-nine patients (7.4%) developed HVOD at 3-49 days after HSCT (median 12 days). Age younger than 15 years at transplant( HR=6.47, P<0.001), busulphan conditioning ( HR=6.40, P<0.001), thalassemia major ( HR=6.35,P<0.001), allogeneic transplantation ( HR=7.74, P=0.005) were univariate risk factors for HVOD. Multivariate analyses suggested that thalassemia major and busulphan conditioning were independently correlated with the development of HVOD. Conclusion Thalassemia major and busulphan conditioning are independent risk factors for HVOD after HSCT.

Objective To label granulocytes in a state of differentiation in mouse bone marrow (BM) with EdU (5-ethynyl-2′-deoxyuridine) for further understanding the changes in granulocyte produc-tion at different stages of differentiation during inflammation. Methods C57BL/6 mice were intraperitoneal-ly (i.p.) injected with EdU and heat-inactivated Escherichia coli(HI E.coli). BM cells were harvested at different time points after HI E.coli injection and then stained with fluorescent-conjugated antibodies(Abs). Myeloblasts,promyelocytes,myelocytes, metamyelocytes and band and segmented neutrophils were identi-fied by fluorescence-activated cell sorting(FACS). The percentage of EdU-positive cells in each population was recorded. Results The percentage of EdU-positive myeloblasts in mice increased by 10.0% at 24 h af-ter intraperitoneal injection with HI E.coli,but decreased by 75.0% and 23.0% at 48 h and 72 h,respec-tively. The percentage of EdU-positive promyelocytes declined by 23.0%,54.5%,64.3% and 77.8% at 24 h,48 h,72 h and 96 h,respectively. The percentage of EdU-positive myelocytes increased by 60.0% and 10.0% at 24 h and 48 h,but decreased by 80.0% and 90.0% at 72 h and 96 h. The percentage of EdU-positive metamyelocytes increased by 50.0% at 24 h,but decreased by 33.3%,61.5% and 66.7% at 48 h,72 h and 96 h. The percentage of EdU-positive band and segmented cells increased by 14.0% at 24 h,but decreased by 50.0%, 77.8% and 88.0% at 48 h, 72 h and 96 h. Conclusion Emergency granulopoiesis occurred 24 h after the establishment of HI E.coli-induced model of acute peritonitis, which meant that the proliferation of myeloid precursor cells,especially that of myelocytes and metamyelocytes,was accelerated and resulted in increasing number of mature neutrophils immigrating to sites of inflammation.

Objective: To investigate the risk factors of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) . Methods: Clinical data from 111 SAA patients who received allo-HSCT were analyzed retrospectively. Factors including age, gender, interval to transplantation, the level of serum ferritin before transplantation were analyzed by Cox multivariate regression analysis. Results: Among the 111 patients who underwent allo-HSCT, 16 developed PGF (14.4%) . Multivariate analysis showed donor type (HR=2.656, 95%CI 1.204-5.858, P= 0.016) and the level of serum ferritin before tansplantation (HR=3.170, 95%CI 1.400-7.180, P=0.006) were significant risk factors for PGF. Conclusion Unrelated donor transplantation and the high level of serum ferritin before transplantation are risk factors for PGF.

Objective To reveal the role of serum ACE2/Ang (1-7)in the occurrence of atrial fibrillation (AF)and find new targets for the prevention and treatment of AF by analyzing the correlation between the serum concentration of ACE2/Ang (1-7 )in patients with rheumatic valvular heart disease and the occurrence of AF. Methods We collected the basic clinical information and peripheral venous blood of patients with rheumatic heart valve disease (totally 46 patients,including 24 with AF and 22 with SR).ELISA method was used to detect the serum concentration of ACE2,Ang (1-7)and AngⅡ in the serum samples.Then the differences and correlation between the two groups were analyzed.Results In the AF group ① the diameter of the left atrium was significantly greater than that in the SR group [(60.70±3.08 vs.48.15±2.16)mm,P<0.05];② the serum concentration of AngⅡ was significantly higher than that in the SR group [(45.88±2.87 vs.35.78±1.08)pg/mL, P<0.05],AngⅡ and left atrium diameter were positively correlated (Pearson test,P<0.05);③ the serum concentrations of ACE2 [(7.87±0.74 vs.11.65±0.57)U/L,P<0.05]and Ang (1-7)[(146.05±17.61 vs. 321.71±36.50)pg/mL,P<0.05]were significantly lower than those in the SR group,and negatively correlated with left atrium diameter (Pearson test,P<0.05);④ the serum concentration of Ang (1-7)was negatively correlated with AngⅡ concentration (Pearson test,P<0.05).Conclusion For patients with rheumatic valvular heart disease,ACE2/Ang (1-7 )may play a protective role in the occurrence of AF via antagonizing AngⅡ and inhibiting atrial remodeling.