Objective: To explore the differential lipid metabolites in the plasma of mice with idiopathic pulmonary fibrosis(IPF). Methods : Thirty SPF C57BL/6 male mice were randomly divided into 2 groups with 15 mice in each group. The experimental groups were divided into control group and bleomycin(BLM) group. The model of idiopathic pulmonary fibrosis was induced by one-time intratracheal infusion of BLM(1 mg/kg). Hematoxylin-eosin(HE) staining was used to observe the lung histopathology. The collagen fiber deposition in lung tissue was observed by Sirius red staining. The differential lipid metabolites in plasma of IPF mice were screened and enriched by lipidomics. Results : HE staining showed that the pulmonary tissue structure was disordered, alveolar septum was broken and alveolar wall was destroyed in BLM group. Sirius red staining showed a large amount of collagen fiber deposition in the lung interstitium of BLM group. The results of lipidomics analysis showed that the lipid metabolism profile of BLM group changed, 15 differential lipid metabolites were screened out, of which 11 differential lipid metabolites were up-regulated, and 4 differential lipid metabolites were down-regulated, mainly concentrated in glycerophosphoglycerophosphates, glycerophosphocholines, steroid lactones, etc. Conclusion The lipid metabolism profile of BLM group mice changes, differential lipid metabolites such as phosphoglycolate phosphatase(PGP)(18:0/18:0), PGP(i-12:0/i-24:0), PGP(i-13:0/a-25:0), and phosphatidylcholine(PC)(18:0/14:0), PC(18:3/16:0), lysophosphatidylcholine(LPC)(16:1), and LPC(18:3) may play an important role in the progression of IPF. These findings provide a new reference for further study of the molecular mechanism of IPF, and also provide a potential new target for clinical treatment.

Objective:To prepare pullulan-spermine (PS)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated with CD3 antibody, and to investigate their effects on T cell proliferation and cytokine secretion.Methods:Purulan polysaccharide was sperminized to synthesize PS, hydrophobically modified, and then grafted with PLGA to synthesize PS-PLGA. Infrared spectroscopy and nuclear magnetic resonance hydrogen spectrum were used to characterize the structure of PS-PLGA. PS-PLGA NPs were prepared by ultrasonic dialysis method and then coupled with CD3 antibody to prepare PS-PLGA-CD3 NPs. The morphological features of PS-PLGA-CD3 NPs were observed by the transmission electron microscope. The particle sizes, Zeta potential and dispersive coefficient of the NPs were measured using the dynamic laser particle size analyzer. The amount of coupled CD3 antibody on the surface of the NPs was determined using quantitative fluorescence analysis method. The effects of 1, 10, 50, 100, and 200 μg/ml PS-PLGA-CD3 NPs on T-cell proliferation were determined using cell counting kit-8 method. The effects of 1, 10, 50, 100, 200 μg/ml PS-PLGA-CD3 NPs on secretion of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-β (TNF-β) by T cell were determined by enzyme-linked immunosorbent assay. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:Pullulan and PS showed strong absorption at 2 939 cm ?1, and PS had a weaker absorption peak at 3 384 cm ?1 than pullulan. The proton peaks of spermine appeared at chemical shifts of 1.25 to 1.50, 1.63, and 2.25 to 2.75. The characteristic peaks of PLGA appeared at chemical shifts of 1.50, 3.40, and 4.80 to 5.30. Compared to pullulan, the characteristic peaks of both PS and PLGA appeared in the corresponding intervals for PS-PLGA. The morphology of PS-PLGA-CD3 NPs with spermine substitution at 9.7% was all regular and circular, with a mean particle size of (173.3±24.5) nm, a Zeta potential of (?12.78±3.68) mV, the dispersive coefficient of 0.254±0.101, and the CD3 antibody mass fraction of (52.1±9.4) μg/mg. The differences in cell survival were statistically significant for PS-PLGA-CD3 NPs and PS-PLGA NPs, respectively, after co-incubation with T cell after 24, 48, and 72 h at concentrations of 50, 100, and 200 μg/ml, respectively (all P<0.05). The results of the three concentration comparisons after 24 h of co-incubation were [(129.8±23.1)% vs (95.5±8.9)%, (137.5±22.7)% vs (95.1±15.8)%, and (142.3±25.6)% vs (93.2±9.2)%]; and the results after 48 h were [(145.9±23.7)% vs (95.8±10.6)%, (149.3±23.5)% vs (94.9±16.3)%, and (161.2±26.9)% vs (91.5±8.3)%]; and the results after 72 h were [(147.6±20.1)% vs (95.9±17.8)%, (152.4±22.3)% vs (92.7±16.5)%, and (167.7±25.4)% vs (90.8±17.4)%]. The differences in the levels of IFN-γ, IL-2 and TNF-β were statistically significant (all P<0.05 or 0.01) at 50, 100 and 200 μg/ml concentrations for PS-PLGA-CD3 NPs and PS-PLGA NPs, respectively. For IFN-γ, the results of the comparison of the three concentrations were [(35.7±3.1) ng/ml vs (16.4±6.9) ng/ml, (67.3±5.2) ng/ml vs (19.6±2.8) ng/ml, and (79.0±4.2) ng/ml vs (19.3±2.3) ng/ml]; and for IL-2, the results were [(43.5±8.2) ng/ml vs (12.6±1.9) ng/ml, (53.5±7.8) ng/ml vs (15.8±3.3) ng/ml, and (64.0±8.2) ng/ml vs (17.4±3.8) ng/ml]; and for TNF-β, the results were [(108.4±18.9) pg/ml vs (40.8±1.3) pg/ml, (152.3±28.3) pg/ml vs (56.4±3.7) pg/ml and (185.0±33.6) pg/ml vs (81.6±10.2) pg/ml]. Conclusions:PS-PLGA-CD3 NPs are successfully prepared, which have the function of effectively promoting T cell proliferation and cytokine sectetion.

Objective To investigate the effects of Yiqi Wenyang Lishui Formula(derived from Wuling San combined with Astragali Radix and Descurainiae Semen Lepidii Semen)on cardiac function and remodeling in heart failure(HF)patients with yang deficiency and fluid retention syndrome and to analyze risk factors for influencing therapeutic efficacy.Methods A total of 120 HF patients with yang deficiency and fluid retention syndrome admitted to Liaocheng Hospital of Traditional Chinese Medicine from February 2022 to January 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random number table.The control group received conventional western therapy,while the observation group received Yiqi Wenyang Lishui Formula additionally.Both groups were treated for 2 months.Changes in cardiac function indicators and remodeling markers were observed.Clinical efficacy was evaluated,and univariate and binary logistic regression analyses were performed to identify independent risk factors affecting treatment outcomes.Results(1)The total effective rate was 81.67％(49/60)in the observation group versus 70.00％(42/60)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy in the observation group was superior to the control group(P＜0.05).(2)After treatment,both groups showed significant reductions compared to those before treatment in left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(P＜0.01).The reduction in LVEDD,LVESD,and serum NT-proBNP levels in the observation group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(3)Univariate analysis revealed that New York Heart Association(NYHA)functional classification,LVEDD,LVESD,and NT-proBNP levels were significantly associated with the therapeutic efficacy of the Yiqi Wenyang Lishui Formula in heart failure patients with yang deficiency and fluid retention syndrome(P＜0.05).(4)Logistic regression identified NYHA classification,LVEDD,LVESD,and NT-proBNP as independent risk factors(P＜0.05)in affecting therapeutic effect of Yiqi Wenyang Lishui Formula in treating HF with yang deficency and fluid retention syndrome,increasing the risk of ineffective treatment by 4.12-fold,1.21-fold,1.19-fold,and 1.00-fold,respectively.Conclusion Yiqi Wenyang Lishui Formula effectively improves cardiac function and remodeling in HF patients with yang deficiency and fluid retention syndrome.NYHA classification,LVEDD,LVESD,and NT-proBNP are independent risk factors for influencing efficacy,warranting close monitoring for optimized therapeutic adjustments.

Objective:To evaluate the value of CEA, CYFRA21-1 and CA125 tests in opportunistic screening of non-small cell lung cancer (NSCLC) based on meta-analysis.Methods:The original research literatures on the diagnostic value of CEA, CYFRA21-1 and CA125 in Chinese NSCLC patients were searched from databases of PubMed, Embase, The Cochrane Library, CNKI, VIP, Database and Wanfang database from establishment to June 2023. The literature screening, data extraction and quality evaluation were carried out independently by two researchers. The quality evaluation tool of diagnostic accuracy studies was used to evaluate the quality of the literature. A summary receiver operating characteristic (SROC) curve was used to assess the overall effectiveness of the tests. The outcome stability and publication bias were detected by using sensitivity analysis and Deeks′ test.Results:A total of 23 studies met the inclusion and exclusion criteria were included. The results of meta-analysis showed that the overall sensitivity of CEA, CYFRA21-1 and CA125 alone in the diagnosis of NSCLC was relatively low, it was 0.49(95% CI: 0.43-0.55), 0.56(95% CI: 0.49-0.63) and 0.41(95% CI: 0.33-0.49), respectively. The overall sensitivity of the combined detection of the three markers for the diagnosis of NSCLC increased to 0.83(95% CI: 0.69-0.91), but the overall specificity decreased to 0.76(95% CI: 0.69-0.83). Conclusions:The single detection of CEA, CYFRA21-1 and CA125 is not recommended for screening NSCLC in population receiving physical examination. Although the sensitivity of the combined detection of CEA, CYFRA21-1 and CA125 for screening NSCLC is improved, but the specificity is decreased, the misdiagnosis rate is increased, so the screening effect is limited.

ObjectiveTo explore the distribution of pharyngeal microbiota in coal miners exposed to dust. Methods Eight coal miners who had been engaged in occupational dust exposure for more than 20 years were selected as the dust-exposed group, and four coal miners who were not exposed to dust at work were selected as the control group using the judgment sampling method. Pharyngeal secretions of the coal miners were collected with throat swabs, and its pharyngeal microbiota was analyzed. The diversity, abundance and evenness of the microbiota were analyzed by gene sequencing using the 16sRNA gene high-throughput sequencing technology. Results A total of 254 operational taxonomic units of pharyngeal microbiota were detected in the coal miners in the control group, which was 210 more than that in the dust-exposed group. The Chao1 index, Shannon index, PD-tree index and Pielou index of pharyngeal microbiota in the dust-exposed group decreased compared with the control group (all P<0.01). The abundance of Bacteroidetes and Clostridum, at the phylum level, in the pharynx of coal miners in the dust-exposed group was higher than that in the control group (all P<0.05). The abundance of Prevotella, Neisseria, and Monas, at the genus level, in the pharynx of coal miners in the dust-exposed group was higher than that in the control group(all P<0.05), while the abundance of Lactobacillus decreased (P<0.05). The analysis results of the receiver operating characteristic curve showed that Lactobacillus, Fusobacterium and Rothia may play a role for pharyngeal microbiota imbalance prediction in dust-exposed workers, and the area under the curves were all 1.00±0.00. Conclusion The species diversity and evenness of pharyngeal microbiota in coal miners exposed to dust are decreased, which may be related to the continuous inhalation of coal dust that disrupts the microbial environment of the throat.

Objective To screen mitochondria-targeting differential genes in alveolar macrophages of silicosis pa-tients and explore the role of mitochondrial homeostasis in alveolar macrophages of silicosis patients.Methods High-throughput sequencing dataset GSE174725 was downloaded,and differentially expressed genes were screened with R software and P＜0.05,|LogFC|＞1,and then intermixed with mitochondrial gene bank MitoCarta3.0 to obtain mitochondria-targeted differentially expressed genes.Then enrichment analysis was carried out to obtain the biological processes and pathways involved in differential genes,and the protein-protein interaction network was constructed.In addition,alveolar macrophages from silicosis patients and healthy controls were collected,the ex-pression levels of differential genes were detected by RT-qPCR,and the expressions of mitochondria-related factors mitochondrial fusion protein 1(MFN1),optic atrophy 1(OPA1)and dynamin-related protein 1(DRP1)in alveolar macrophages of silicosis patients were investigated by Western blot.Results A total of 204 differentially expressed genes were screened in silicosis patients,among which 62 differentially expressed genes were up-regulated,142 dif-ferentially expressed genes were down-regulated,and 22 differentially expressed genes were mitochondria-targeted.The concentration analysis of differentially expressed genes targeted by mitochondria showed that the cell compo-nents mainly enriched included mitochondrial membrane,endoplasmic membrane side components,etc.The bio-logical processes mainly enriched included mitochondrial electron transfer from NADH to ubiquinone,inflammatory response,immune response,etc.The main molecular functions enriched included the rotation mechanism of proton transport ATP synthase activity,NADH dehydrogenase activity,chemokine activity,etc.KEGG enrichment analy-sis mainly focused on the involvement in chemical carcinogenesis-ROS,IL-17 signaling pathway,toll-like receptor signaling pathway,chemokine signaling pathway,TNF signaling pathway,etc.In addition,RT-qPCR results showed that the expressions of mitochondrial cytochrome coxidase 1,mitochondrial cytochrome coxidase 2,mito-chondrial cytochrome coxidase 3,mitochondrially encoded NADH dehydrogenase 1,mitochondrially encoded NADH dehydrogenase 3,mitochondrially encoded NADH dehydrogenase 5,superoxide dismutase and mitochondri-ally encoded ATP synthase 6 gene were down-regulated in silicosis patients(P＜0.05).Western blot and RT-qPCR results showed that,in silicosis patients,the expression of MFN1 and OPA1 decreased(P＜0.05),while the expression of DRP1 increased(P＜0.05).Conclusion Bioinformatics analysis and validation,eight mito-chondrial targeted differential genes(MT-CO1,MT-C02,MT-CO3,MT-ND1,MT-ND3,MT-ND5,SOD and MT-ATP6)were finally obtained,which were enriched in mitochondrial respiratory chain and oxidative stress pathways and might play an important role in the process of silicosis.

Objective:To investigate the mechanism of Sulfo-N-succinimidyloleate (SSO) regulating lipid metabolism disorder induced by silicon dioxide (SiO 2) . Methods:In March 2023, Rat alveolar macrophages NR8383 were cultured in vitro and randomly divided into control group (C), SSO exposure group (SSO), SiO 2 exposure group (SiO 2) and SiO 2+SSO exposure group (SiO 2+SSO). NR8383 cells were exposure separately or jointly by SSO and SiO 2 for 36 h to construct cell models. Immunofluorescence and BODIPY 493/ 503 staining were used to detect cluster of differentiation (CD36) and intracellular lipid levels, the protein expression levels of CD36, liver X receptors (LXR), P-mammalian target of rapamycin (P-mTOR) and cholinephosphotransferase 1 (CHPT1) were detected by Western blot, respectively, and lipid metabolomics was used to screen for different lipid metabolites and enrichment pathways. Single-factor ANOVA was used for multi-group comparison, and LSD test was used for pair-to-group comparison. Results:SiO 2 caused the expression of CD36 and P-mTOR to increase ( P=0.012, 0.020), the expression of LXR to decrease ( P=0.005), and the intracellular lipid level to increase. After SSO treatment, CD36 expression decreased ( P=0.023) and LXR expression increased ( P=0.000) in SiO 2+SSO exposure group compared with SiO 2 exposure group. Metabolomics identified 87 different metabolites in the C group and SiO 2 exposure group, 19 different metabolites in the SiO 2 exposure group and SiO 2+SSO group, and 5 overlaps of different metabolites in the two comparison groups, they are PS (22∶1/14∶0), DG (O-16∶0/18∶0/0∶0), PGP (i-13∶0/i-20∶0), PC (18∶3/16∶0), and Sphinganine. In addition, the differential metabolites of the two comparison groups were mainly concentrated in the glycerophospholipid metabolism and sphingolipid metabolism pathways. The differential gene CHPT1 in glycerophospholipid metabolic pathway was verified, and the expression of CHPT1 decreased after SiO 2 exposure. Conclusion:SSO may improve SiO 2-induced lipid metabolism disorders by regulating PS (22∶1/14∶0), DG (O-16∶0/18∶0/0∶0), PGP (i-13∶0/i-20∶0), PC (18∶3/16∶0), SPA, glycerophospholipid metabolism and sphingolipid metabolism pathways.

Alzheimer's disease(AD)is a multifactorial degenerative disorder of the central nervous system that mainly manifests as cognitive dysfunction and loss of speech.In recent years,the zebrafish has attracted extensive attention because of its high homology with humans in terms of brain structure and function,nerve conduction,and pathogenic genes of AD.This article reviews the advantages of the zebrafish as an animal model of AD,covering topics in the pathogenesis of AD and the evaluation and screening of drugs for treatment of AD.The overall goal is to provide new insights into the pathogenesis of AD and development of novel drugs.

Objective To investigate sex-related differences in left ventricular systolic dysfunction in heart failure with preserved ejection fraction(HFpEF)and type 2 diabetes mellitus(T2DM).Methods A total of 228 HFpEF patients who were treated in the Department of Endocrinology and Cardiology of the Second Hospital of Shijiazhuang from January 2019 to June 2023 were enrolled.They were divided into HFpEF group[women(n=61),men(n=73)]and HFpEF+T2DM group[women(n=49),men(n=73)]according to whether they had T2DM.Conventional echocardiography and left ventricular global longitudinal strain(GLS)data were measured.Sex-related differences of left ventricular structure and function were compared between the two groups.Multivariable linear regression analysis was performed for the determinants of impaired left ventricular GLS for HFpEF with T2DM patients and HFpEF patients of both sexes.Results LVMI was lower in women than in men in HFpEF group(P<0.05).The left ventricular remodeling rate of women was higher in HFpEF+T2DM group than that of men and women in HFpEF group,and the GLS of women was lower than that of men and women in HFpEF group(P<0.05).The E/E'was higher in women than in men in HFpEF and HFpEF+T2DM groups(P<0.05).Multivariable linear regression analysis showed that age,women,HbA1c and LVMI were the determinants of GLS impairement in HFpEF patients with T2DM.Age,T2DM,NT-proBNP and LVMI were the determinants of GLS impairement in HFpEF women patients,where as age,BMI,CHD,NT-proBNP and LVMI were the determinants of GLS impairement in HFpEF men patients.Conclusions There are sex-related differences in left ventricular systolic dyfunction in HFpEF with T2DM patients.With T2DM exerting a greater adverse effect onleft ventricular systolic dyfunction in women with HFpEF than men.

Objective:To explore the effect of problem-based learning (PBL) combined with case-based learning (CBL) in insulin injection patients with type 2 diabetes mellitus (T2DM) .Methods:From August to October 2022, convenience sampling was used to select 120 patients with T2DM treated with insulin injection from the Endocrinology Department of Yiwu Central Hospital as the study subject. According to the admission time, patients were divided into a control group and an intervention group, with 60 cases each. The 60 patients admitted from August 1st to 31st were in the control group and received routine health education, and 60 patients admitted from October 1st to 31st were included in the intervention group and received PBL combined with CBL. This study analyzed and compared the awareness rate of insulin injection knowledge and assessment scores of insulin injection between two groups of patients, and counted the passing rate and improvement rate of assessment scores after intervention. Before and after three months of intervention, this study evaluated the patient's blood glucose status [fasting blood glucose (FPG), 2-hour postprandial blood glucose (2hPG), and glycated hemoglobin (HbA1c) ], and counted the incidence of insulin injection related complications.Results:After four weeks of intervention, the overall awareness rate of insulin injection knowledge in the intervention group was higher than that in the control group, with a statistically significant difference ( P<0.05). The insulin injection assessment score (90.35±4.68), passing rate of assessment score 91.67%, and improvement rate of assessment score (35.48±6.84) % in the intervention group were higher than those [ (84.69±6.72), 75.00%, and (26.28±5.46) %] in the control group, and the differences were statistical ( P<0.05). After three months of intervention, the FPG, 2hPG, and HbA1c of the intervention group patients were lower than those of the control group, with statistically significant differences ( P<0.05). Within three months after intervention, the total incidence of complications in the intervention group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:PBL combined with CBL for insulin injection patients can help to increase their knowledge and operational level of insulin injection, improve blood glucose control, and reduce insulin injection related complications.