Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2％,synovial sarcoma 3.8％,leiomyosarcoma 40.7％,malignant peripheral nerve sheath tumor 3.8％,myxofibrosarcoma 9.6％,pleomorphic sarcoma 19.9％,P=0.001),tumor necrosis(none 38.8％,focal necrosis 20.8％,moderate necrosis 33.8％,extensive necrosis 6.6％,P=0.010),and tumor metastasis(no metastasis 67％,metastasis 33％,P＜0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P＜0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P＜0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|＞1.0 and adjusted P value＜0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|＞2.0 and adjusted P value＜0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective To explore the early brain microstructural changes in patients with alcohol use disorder(AUD)and the correlations with cognitive function.Methods Totally 81 AUD patients(AUD group)and 75 healthy volunteers(control group)were retrospectively enrolled.Gray matter volume(GMV)and cortical thickness of brain regions were calculated with voxel-based morphometry and surface-based morphometry,and the correlations of the above indexes of brain regions being significantly different between groups and clinical cognitive function scale scores were analyzed.Results In AUD group,GMV of bilateral hippocampus,insula,inferior parietal angular gyrus,straight gyrus,central posterior gyrus and cerebellar angle 1 area,of left medial superior frontal gyrus,precuneus,anterior cingulated cortex,middle temporal gyrus and middle occipital gyrus,as well as of right lingual gyrus reduced significantly compared with those in control group.The cortical thickness of bilateral superior frontal gyrus,middle frontal gyrus,inferior frontal gyrus,supramarginal gyrus,superior parietal lobule,inferior parietal lobule,central posterior gyrus,central anterior gyrus,temporal superior gyrus and middle temporal gyrus reduced in AUD group.In AUD group,GMV of left medial superior frontal gyrus was positively correlated with Pittsburgh sleep quality index score(r=0.301,P=0.006),while of the left and right straight gyrus were positively correlated with Hopkins verbal learning test-revised score(r=0.328,0.326;both P=0.003)but negatively correlated with trail making test-B score(r=-0.295,-0.312;P=0.008,0.005),while the cortical thickness of the left central anterior gyrus and the lower part of the right middle frontal gyrus were positively correlated with Beck anxiety inventory score(r=0.323,0.289;P=0.003,0.009).Conclusion Prefrontal cortex atrophy could be observed in early stage AUD patients,which was correlated with cognitive function impaired.

OBJECTIVE To investigate the inhibitory effect of human β defensin-3(HBD3)on the replication of in-fluenza A virus(IAV)[A/PR/8/34(H1N1)virus strain]in human bronchial epithelial cells(BEAS-2B)via the mitochondrial autophagy pathway.METHODS BAS-2B cells were infected with IAV,and cell condition observa-tion:plaque assay and light microscopy.Drug treatment:HBD3,autophagy agonist rapamycin(Rapa),autoph-agy inhibitor LY294002;The expression levels of TUFM、MAVS、NP、M2 and PB1-F2 genes were detected by real-time fluorescence quantitative polymerase chain reaction(qPCR).Western blot was used to detect the protein expression levels of P62、LC3Ⅱ and LC3Ⅰ.RESULTS Plaque formation experiments showed that the number of plaques increased with the increase of viral titer.With the increase of viral titer or the prolongation of infection time,the expres-sion levels of TUFM,MAVS,NP,M2 and PB1-F2 genes in BEAS-2 B cells gradually increased,the expression levels of P62 protein decreased,and the protein expression levels of LC3Ⅱ/LC3Ⅰ increased(P＜0.05).Forty-eight hpi of BE-AS-2B cells with IAV,the number of cells in the IAV group was significantly lower than that in the IAV+HBD3 group,the intercellular space was enlarged,and the cells shrunk significantly.Compared with the IAV group,the expression lev-els of TUFM,MAVS,NP,M2 and PB1-F2 genes in BEAS-2B cells in the IAV+HBD3 group decreased,the expres-sion levels of P62 protein increased,and the protein levels of LC3Ⅱ/LC3Ⅰ decreased(P＜0.05).Gene expression levels of TUFM,MAVS,NP,M2 and PB1-F2 were in the IAV+Rapa+HBD3 group were lower than those in the IAV+Ra-pa group(P＜0.05).The protein expression level of P62 in the IAV+Rapa+HBD3 group was higher than that in the IAV+Rapa group(P＜0.05).The protein expression levels of LC3Ⅱ/LC3Ⅰ were lower in the IAV+Rapa+HBD3 group than in the IAV+Rapa group(P＜0.05).CONCLUSION With the increase of viral titer or the prolongation of in-fection time,the proliferation of IAV in BEAS-2B cells increases,and the cell damage exacerbates.HBD3 can inhibit the replication of IAV after its entry into the cells;HBD3 can protect host cells and inhibit IAV replication by inhibiting MA-VS,TUFM-mediated mitophagy pathways.

Objective To explore the expression pattern and molecular function of ubiquitin-like containing PHD and RING finger domains 1(UHRF1)gene in soft tissue sarcoma(STS),as well as its correlation with clinical characteristics and prognosis of STS.Methods RNA data and related clinical data of 263 STS tissues were obtained from Cancer Genome Atlas(TCGA).Wilcoxon rank-sum test was used to analyze correlation between two groups of data;Spearman correlation coefficient analyzed the top 35 co-expressed genes positively and negatively correlated with UHRF1 expression in STS database,ggplot2 statistical package displayed co-expressed gene heatmap,Pearson correlation coefficient showed correlation between UHRF1 expression and expression of the top 10 genes in the heatmap;different UHRF1 gene expression groups in STS were analyzed using DESeq2 package,ggplot2 package was used to draw volcano plots,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyzed differentially expressed genes(DEGs)and protein functions,ggplot2 package for visualization,and cluster Profiler package for statistical analysis;STRING web was used to establish PPI network of DEGs,and the MCC algorithm in CytoHubba of Cytoscape was used to analyze hub genes.Results In STS,UHRF1 gene was significantly correlated with its histological type(liposarcoma 22.2％,synovial sarcoma 3.8％,leiomyosarcoma 40.7％,malignant peripheral nerve sheath tumor 3.8％,myxofibrosarcoma 9.6％,pleomorphic sarcoma 19.9％,P=0.001),tumor necrosis(none 38.8％,focal necrosis 20.8％,moderate necrosis 33.8％,extensive necrosis 6.6％,P=0.010),and tumor metastasis(no metastasis 67％,metastasis 33％,P＜0.001).In different clinical subgroups(age,gender,histological type,residual tumor,tumor necrosis,tumor depth,margin status,tumor multifocality,radiotherapy),high expression of UHRF1 led to poor prognosis of overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI);Three prognostic factors above were simultaneously shortened in the following five subgroups:namely residual tumor R0 and R1,tumor necrosis extensive,focal and moderate,tumor depth deep,positive margin status,tumor without multifocality.Analysis of the top 10 co-expressed genes associated with UHRF1 expression revealed that the associated positive genes were PAGE5,LINC01425,LCEP3,SERPINB7,AC074031.1,LCE3A,LCE2A,PAGE2B,MYF5,and AC037486.1(P＜0.05);the associated negative genes were CDH19,CSN1S1,TAC3,AC103563.7,SAA1,CHST8,PRLHR,MIR202HG,IGHV1-24,and ART4(P＜0.05).A total of 3 029 DEGs of UHRF1 in STS were obtained with a threshold of|log2 fold-change(FC)|＞1.0 and adjusted P value＜0.05,in which 1 228 genes were up-regulated and 1 801 genes were down-regulated;GO enrichment analyed primary biological processes(BP),original cellular components(CC),and original molecular functions(MF),and KEGG enrichment analyed signaling pathways.A total of 343 DEGs including 133 up-regulated genes and 210 down-regulated genes,were obtained with a threshold of|log2 fold-change(FC)|＞2.0 and adjusted P value＜0.05.The top 10 hub genes were analyzed.The top 3 hub genes were GCG,SST and SHH,respectively.Conclusion UHRF1 is significantly correlated with histological type,tumor necrosis,metastasis,OS,DSS,and PFI events in STS.In co expressed genes model and molecular functions of related positive and negative genes involved in multiple biological processes;The network of differentially expressed genes and protein product interactions involved in mechanisms of occurrence and development of the disease,and provided new ideas for in-depth researches on STS.

Objective To explore the early brain microstructural changes in patients with alcohol use disorder(AUD)and the correlations with cognitive function.Methods Totally 81 AUD patients(AUD group)and 75 healthy volunteers(control group)were retrospectively enrolled.Gray matter volume(GMV)and cortical thickness of brain regions were calculated with voxel-based morphometry and surface-based morphometry,and the correlations of the above indexes of brain regions being significantly different between groups and clinical cognitive function scale scores were analyzed.Results In AUD group,GMV of bilateral hippocampus,insula,inferior parietal angular gyrus,straight gyrus,central posterior gyrus and cerebellar angle 1 area,of left medial superior frontal gyrus,precuneus,anterior cingulated cortex,middle temporal gyrus and middle occipital gyrus,as well as of right lingual gyrus reduced significantly compared with those in control group.The cortical thickness of bilateral superior frontal gyrus,middle frontal gyrus,inferior frontal gyrus,supramarginal gyrus,superior parietal lobule,inferior parietal lobule,central posterior gyrus,central anterior gyrus,temporal superior gyrus and middle temporal gyrus reduced in AUD group.In AUD group,GMV of left medial superior frontal gyrus was positively correlated with Pittsburgh sleep quality index score(r=0.301,P=0.006),while of the left and right straight gyrus were positively correlated with Hopkins verbal learning test-revised score(r=0.328,0.326;both P=0.003)but negatively correlated with trail making test-B score(r=-0.295,-0.312;P=0.008,0.005),while the cortical thickness of the left central anterior gyrus and the lower part of the right middle frontal gyrus were positively correlated with Beck anxiety inventory score(r=0.323,0.289;P=0.003,0.009).Conclusion Prefrontal cortex atrophy could be observed in early stage AUD patients,which was correlated with cognitive function impaired.

OBJECTIVE To investigate the inhibitory effect of human β defensin-3(HBD3)on the replication of in-fluenza A virus(IAV)[A/PR/8/34(H1N1)virus strain]in human bronchial epithelial cells(BEAS-2B)via the mitochondrial autophagy pathway.METHODS BAS-2B cells were infected with IAV,and cell condition observa-tion:plaque assay and light microscopy.Drug treatment:HBD3,autophagy agonist rapamycin(Rapa),autoph-agy inhibitor LY294002;The expression levels of TUFM、MAVS、NP、M2 and PB1-F2 genes were detected by real-time fluorescence quantitative polymerase chain reaction(qPCR).Western blot was used to detect the protein expression levels of P62、LC3Ⅱ and LC3Ⅰ.RESULTS Plaque formation experiments showed that the number of plaques increased with the increase of viral titer.With the increase of viral titer or the prolongation of infection time,the expres-sion levels of TUFM,MAVS,NP,M2 and PB1-F2 genes in BEAS-2 B cells gradually increased,the expression levels of P62 protein decreased,and the protein expression levels of LC3Ⅱ/LC3Ⅰ increased(P＜0.05).Forty-eight hpi of BE-AS-2B cells with IAV,the number of cells in the IAV group was significantly lower than that in the IAV+HBD3 group,the intercellular space was enlarged,and the cells shrunk significantly.Compared with the IAV group,the expression lev-els of TUFM,MAVS,NP,M2 and PB1-F2 genes in BEAS-2B cells in the IAV+HBD3 group decreased,the expres-sion levels of P62 protein increased,and the protein levels of LC3Ⅱ/LC3Ⅰ decreased(P＜0.05).Gene expression levels of TUFM,MAVS,NP,M2 and PB1-F2 were in the IAV+Rapa+HBD3 group were lower than those in the IAV+Ra-pa group(P＜0.05).The protein expression level of P62 in the IAV+Rapa+HBD3 group was higher than that in the IAV+Rapa group(P＜0.05).The protein expression levels of LC3Ⅱ/LC3Ⅰ were lower in the IAV+Rapa+HBD3 group than in the IAV+Rapa group(P＜0.05).CONCLUSION With the increase of viral titer or the prolongation of in-fection time,the proliferation of IAV in BEAS-2B cells increases,and the cell damage exacerbates.HBD3 can inhibit the replication of IAV after its entry into the cells;HBD3 can protect host cells and inhibit IAV replication by inhibiting MA-VS,TUFM-mediated mitophagy pathways.

Objective To evaluate the outcomes of children with stage Ⅳ malignant extracranial germ cell tumors. Methods Twenty-five patients were enrolled in the retrospective analysis. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier method with SPSS 13.0. Results Of the 25 children, there were 13 males and 12 females. The mean age at diagnosis was 2 years old (ranged 1 to 11). Five patients receiving chemotherapy in another hospital before (n=1), or giving up treatment after confirmed diagnosis (n=1), or giving up effective treatment after received less than 2 cycles (n=3) were excluded from this analysis. Of the 20 patients, 90.0% (18/20) achieved complete remission and 5.0% (1/20) achieved partial remission after treatment. The 5-year EFS rate and 5-year OS rate were 70.0%±10.2% and 82.4%±9.2% respectively. There was no death occurred due to complications. Conclusions The effect of this treatment program is positive. The cumulative dose of the drugs is not high, compared with other schemes such as PEB, but there are more drugs involved. Whether these drugs may cause long-term adverse reactions needs further research.

OBJECTIVETo identify potential mutations of the FLG gene in two Chinese families affected with ichthyosis vulgaris.

METHODSAll coding exons and exon-intron boundary of the FLG gene were amplified by polymerase chain reaction (PCR) and analyzed by direct sequencing. The results were compared with those of 100 unrelated healthy controls.

RESULTSTwo novel missense mutations, c.1360A>G (p.T454A) and c.10363G>T (p.D3455Y), were detected in all affected individuals from family 1 and family 2 respectively but none of the controls.

CONCLUSIONThe c.1360A>G (p.T454A) and c.10363G>T (p.D3455Y) of the FLG gene may lead to alteration of the structure and function of the FLG protein and cause ichthyosis vulgaris in the two families.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; Exons ; genetics ; Family Health ; Female ; Genetic Predisposition to Disease ; ethnology ; genetics ; Humans ; Ichthyosis Vulgaris ; ethnology ; genetics ; Intermediate Filament Proteins ; genetics ; Introns ; genetics ; Male ; Mutation, Missense ; Pedigree