Differential effects of APOE polymorphism in neurotoxicity-responsive astrocytes induced by inflammatory factor / 吉林大学学报(医学版)

Objective:To discuss the differential effects of apolipoprotein E(APOE)gene polymorphism in the neurotoxicity-reactive astrocytes,and to provide the theoretical basis for the study of the pathogenesis of Alzheimer's disease(AD).Methods:The primary cortical astrocytes from the APOE-knockout mice(APOE-/-)were isolated and cultured in vitro,and the purity of the cells was identified by immunofluorescence staining.The human APOE3 and APOE4 recombinant over-expression plasmids were constructed and separately transfected into the primary APOE-/-astrocytes,and the APOE-/-primary cells were regarded as control.Western blotting method was used to detect the expression levels of APOE and glial fibrillary acidic protein(GFAP)proteins in the cells;enzyme-linked immunosorbent assay(ELISA)method was used to detect the APOE level in the cellular culture supernatant.The inflammatory models were prepared with the primary astrocytes transfected with APOE3 and APOE4 and co-stimulated with interleukin-1α(IL-1α),tumor necrosis factor(TNF),and complement C1q.The cells were divided into APOE3+PBS group,APOE4+PBS group,APOE3+IL-1α+TNF+ C1q group,and APOE4+IL-1α+TNF+C1q group.Cell immunofluorescence staining method was used to observe the morphology of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of glypican 4(Gpc4),glypican 6(Gpc6),thrombospondin 1(Thbs1),thrombospondin 2(Thbs2),SPARC-like protein 1(Sparcl1)and glial cell line derived neurotrophic factor(GDNF),C3,and S100 calcium binding protein B(S100B)mRNA in the cells in various groups;microsphere phagocytosis assay was used to detect the phagocytic capacities of the cells in various groups;Western blotting was used to detect the protein expression levels of B-cell lymphoma 2(Bcl-2),and cysteinyl aspartate specific protease-3(Caspase-3)proteins in the cells in various groups.Results:Compared with APOE-/-group,the expression levels of APOE and GFAP proteins in the cells and the APOE level in the cellular culture supernatant in transfected APOE3 and transfected APOE4 groups were increased(P<0.01).The fluorescence microscope observation results showed that compared with APOE3+PBS and APOE4+PBS groups,the astrocytic processes in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α+TNF+Cq1 group became shorter and the cell bodies became larger;compared with APOE3+IL-1α +TNF+Cq1 group,the astrocytic processes in APOE4+IL-1α +TNF+Cq1 group were even shorter.Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE3+IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression levels of Gpc4,Gpc6,Thbs1,Thbs2,and Sparcl1 mRNA in the cells in APOE4+IL-1α +TNF+Cq1 group were significantly decreased(P<0.05 or P<0.01).Compared with APOE3+PBS and APOE4+PBS groups,the expression levels of GDNF mRNA in the cells in APOE3+IL-1α+TNF+Cq1 group and APOE4+ IL-1α +TNF+Cq1 group were decreased(P<0.01),and the expression levels of C3 and S100B mRNA were increased(P<0.01);compared with APOE3+IL-1α +TNF+Cq1 group,the expression level of GDNF mRNA in the cells in APOE4+IL-1α+TNF+Cq1 group was decreased(P<0.05),and the expression levels of C3 and S100B mRNA were increased(P<0.05).Compared with APOE3+ PBS group and APOE4+PBS group,the numbers of hagocytosis of microspheres in the cells in APOE3+ IL-1α +TNF+Cq1 group and APOE4+IL-1α +TNF+Cq1 group were significantly decreased;compared with APOE3+IL-1α+TNF+Cq1 group,the number of hagocytosis of microspheres in the cells in APOE4+IL-1α+TNF+Cq1 group was significantly decreased.Compared with APOE3+PBS group and APOE4+PBS group,the expression levels of Bcl-2 protein in the cells in APOE3+IL-1α+TNF+ Cq1 group and APOE4+IL-1α +TNF+Cq1 group were decreased(P<0.05 or P<0.01)and the expression levels of Caspase-3 protein were significantly increased(P<0.01);compared with APOE3+ IL-1α+TNF+Cq1 group,the expression level of Bcl-2 protein in the cells in APOE4+IL-1α+TNF+ Cq1 group was decreased(P<0.01),and the expression level of Caspase-3 protein was increased(P<0.05).Conclusion:The APOE4 genotype has a stronger ability to induce the inflammatory factors compared with APOE3;it can lead to a neurotoxicity-reactive astrocyte phenotype,increase the neurotoxicity,affect the astrocyte apoptosis,and aggravate the neuron damage.

Effect of apolipoprotein C1 expression on proliferation and apoptosis of human liver cancer HepG2 cells and its mechanism / 吉林大学学报(医学版)

Objective:To discuss the effect of apolipoprotein C1(APOC1)expression on the proliferation and apoptosis of the hepatocellular carcinoma cells,and to preliminarily clarify the related molecular mechanism.Methods:The expression level of APOC1 mRNA in hepatocellular carcinoma tissue and its relationship with the prognosis of the patient were analyzed by The Cancer Genome Atlas(TCGA)Database;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of APOC1 mRNA in different hepatocellular carcinoma cells;the human liver cancer HepG2 cells with low APOC1 expression were selected as the subjects.The HepG2 cells were transfected with pcDNA3.1-APOC1 plasmid to over-express APOC1(APOC1 over-expression group),and the HepG2 cells transfected with empty vector pcDNA3.1 were regarded as control group.MTS assay and 5-ethynyl-2'-deoxyuridine(EdU)staining were used to detect the proliferative activities and proliferation rates of the cells in two groups;Transwell chamber assay was used to detect the numbers of migration cells in two groups;flow cytometry and TUNEL assay were used to detect the percentages of the cells at different cell cycles and apoptotic rates in two groups;Western blotting method was used to detect the expression levels of extracellular regulated protein kinase(ERK),phosphorylated ERK(p-ERK),protein kinase B(AKT),phosphorylated AKT(p-AKT),B-cell lymphoma-2(Bcl-2),and cleaved cysteinyl aspartate specific proteinase-3(cleaved caspase-3)proteins in the cells in two groups.Results:The TCGA Database results showed that the expression level of APOC1 mRNA in hepatocellular carcinoma tissue was lower than that in normal liver tissue(P<0.05),and the patients with low expression of APOC1 mRNA had poor prognosis.The RT-qPCR results showed that the expression level of APOC1 mRNA in the HepG2 cells was the lowest,and the HepG2 cells were chosen for the subsequent research.Compared with control group,the proliferative activity and proliferation rate of the cells in APOC1 over-expression group were decreased(P<0.05 or P<0.01),the number of migration cells was decreased(P<0.01),and the percentage of the cells at S phase and the apoptotic rate were significantly increased(P<0.01).Compared with control group,the expression levels of p-ERK,p-AKT,and Bcl-2 proteins in the cells in APOC1 over-expression group were significantly decreased(P<0.05),and the expression level of cleaved caspase-3 protein was increased(P<0.01).Conclusion:High expression of APOC1 can inhibit the proliferation of the human liver cancer HepG2 cells and induce the apoptosis,and its mechanism may be related to inhibition of the expressions of p-ERK,p-AKT,Bcl-2 proteins and promotion of the expression of cleaved caspase-3 protein.

Effects of body mass index and serum lipid levels on prostate volume in patients with benign prostatic hyperplasia / 现代泌尿外科杂志

【Objective】 To explore the correlation between body mass index (BMI) and lipid indexes with prostate volume in patients with benign prostatic hyperplasia (BPH) so as to provide reference for the clinical prevention of this disease. 【Methods】 Clinical data of 578 patients admitted to the Department of Urology of Chinese PLA General Hospital during Jan.2014 and Dec.2022 were collected.The patients underwent initial prostate puncture biopsy or prostatectomy and BPH was confirmed pathologically.The patients’ age, time of onset of the disease, BMI, past medical history and biochemical indexes were analyzed.According to the total prostate volume (TPV) grading, the patients were divided into TPV>75 mL and TPV≤75 mL groups.The general data of the two groups were compared, and predictors of TPV were determined with linear regression analysis.The samples were stratified with BMI to observe the differences in the effects of apolipoprotein B (ApoB) on TPV. 【Results】 There were 215 cases in the TPV>75 mL group and 363 cases in the TPV≤75 mL group.The levels of BMI, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) were higher in the TPV>75 mL group (P0.05), and ApoB predicted prostate volume growth in overweight and obese BPH population respectively (β=26.411, P=0.011; β=47.602, P=0.017). 【Conclusion】 Age, ApoB and BMI can be used as predictors of volume growth in BPH patients, which can help further research on the pathogenesis and progression of BPH.

Effects of olfactory three needle on apolipoprotein E and pathological substrates in the hippocampus of mice with Parkinson's disease dementia / 中国康复医学杂志

Objective:To explore the mechanism of olfactory three needle therapy on Parkinson's disease dementia(PDD)by observing its effects on expression of apolipoprotein E(ApoE)、glial fibrillary acidic protein(GFAP)and related core pathology substrates in the hippocampus of PDD model mice. Method:Male C57BL/6 mice were randomly divided into four groups:control group(Control),sham opera-tion group(Sham),model group(Model)and acupuncture electrotherapy group(AE),with 10 mice in each group.The PD model was established by injecting 6-OHDA into the medial forebrain tract(MFB)and PDD mice were selected.After successful modeling and selection,the AE group received"olfactory three needle"electro acupuncture treatment.After 14 days of intervention,Morris water maze test and shuttle box test were used to evaluate the learning and memory ability of mice in each group.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of hippocampal CA1 region.Western blotting was used to detect the expression of α-syn,Aβ and ApoE proteins in hippocampal CA1 region.The co-location rate of ApoE and GFAP in hippocampal CA1 region was observed by double immunofluorescence markers. Result:Compared with Model group,the AE group exhibited a shortened escape latency in water maze(P＜0.01),increased platform crossing(P＜0.05),increased active escape times of shuttle box(P＜0.05),and reduced the average total time of electric stimulation(P＜0.01).In the Model group,the neurons in the hippocampal CA1 area were sparsely arranged and showed signs of degeneration and necrosis;and cell nuclei were small,hyperchromatic and had unclear structures,indicating the appearance of nuclear pyrosis.In contrast,the AE group showed significant improvements in neuronal pathology,with most cells regularly arranged,round and large nuclei,lightly stained and clearly shaped.Compared with the Model group,the expression levels of α-syn,Aβ,ApoE protein and the co-localization rate of ApoE and GFAP in hippocampal CA1 region in AE group were decreased(P＜0.01,P＜0.01,P＜0.01,P＜0.05). Conclusion:The"Olfactory three needle"acupuncture can improve the cognitive ability and restore the morpho-logical structure and function of neurons in PDD mice.The mechanism may be related to the inhibition of ApoE expression in astrocytes and the reduction of α-syn and Aβ deposition in hippocampal CA1 region.

Apolipoprotein ApoE Combined with Clinical Related Indices to Predict and Verify a Model for Alzheimer's Disease / 中国卫生统计

Objective To construct a clinical prediction model for the risk of Alzheimer's disease based on ApoE,combined with risk factors and common clinical indicators.Methods There were 61 cases of Alzheimer's disease patients and 111 cases of fuzzy matching healthy physical examination from Nanjing Hospital of Chinese Medicine data platform from January 2019 to January 2021.Using LASSO regression screening of risk factors,constructing logistic regression forecasting model,10 fold cross verifies the degree of differentiation,validation the calibration of the bootstrap method.The clinical guidance of the prediction model was evaluated by the clinical decision curve,and finally,the clinical prediction model was visualized by nomogram.Results 12 variables were screened out and four risk factors were included,which are age,free triiodothyroxine(FT3),gender and ApoE.The AUC of ROC of the whole sample was 0.879,and the average AUC of ROC after 10 folded and 9 crossed training sets verification was 0.864.Bootstrap method and Hosmer-Lemeshow were used to test the calibration degree.Results χ2 =6.496,P=0.592>0.05.The threshold probability of clinical decision curve ranged from 1%to 88.6%.Conclusion Individualized evaluation of patients using clinical prediction models constructed by age,FT3,gender and ApoE can provide early warning of Alzheimer's disease,carry out early prevention intervention and slow down the development of the disease.

The impact of apoB/apoA1 on lupus nephritis and renal insufficiency and its diagnostic value / 中国医师杂志

Objective:To analyze the impact and diagnostic value of apoB/apoA1 on lupus nephritis (LN) and its renal dysfunction.Methods:A total of 134 patients diagnosed with systemic lupus erythematosus (SLE) at the Taihe Hospital of Anhui University of Traditional Chinese Medicine from July 2019 to January 2023 were selected and divided into LN group ( n=82) and simple SLE group ( n=52). According to the glomerular filtration rate (e-GFR), LN was divided into a group with normal renal function ( n=42) and a group with renal insufficiency ( n=40). We compared the differences in clinical data between different groups and analyzed the diagnostic value of apoB, apoA1, and apoB/apoA1 for LN and its renal insufficiency. Results:The results of binary logistic regression analysis showed that apoB/apoA1, SLE disease activity index (SLEDAI), anti double stranded DNA (dsDNA), complement 3 (C3), and albumin (ALB) were independent influencing factors for LN ( OR=4.033, 1.179, 3.148, 0.374, 0.879, all P<0.05). The area under the curve (AUC) of apoB, apoA1, and apoB/apoA1 for diagnosing LN were 0.623, 0.662, and 0.742, respectively. The diagnostic efficacy of apoB/apoA1 was higher than that of apoB and apoA1, and the differences are statistically significant (all P<0.05). Regardless of whether confounding factors were adjusted or not, apoB/apoA1 were all risk factors for LN with e-GFR>60 ml/(min·1.73 m 2), e-GFR 30-60 ml/(min·1.73 m 2), and e-GFR<30 ml/(min·1.73 m 2) (all P<0.05). ApoB/apoA1, anti dsDNA, C3, and ALB were all independent influencing factors for renal insufficiency LN ( OR=3.778, 2.669, 0.415, 0.884, all P<0.05). The AUC for diagnosing renal insufficiency LN in apoB, apoA1, and apoB/apoA1 were 0.623, 0.640, and 0.730, respectively. The diagnostic efficacy of apoB/apoA1 was higher than that of apoB and apoA1, and the differences were statistically significant (all P<0.05). Conclusions:ApoB/apoA1 is an independent influencing factor for the occurrence of LN and renal insufficiency LN, and has good diagnostic value for LN and renal insufficiency LN.

Mechanisms of Apolipoprotein E in Malignancies / 生物化学与生物物理进展

Apolipoprotein E (apoE) is a critical molecule in lipid metabolism, which also plays important roles in the occurrence and development of several kinds of cancers by regulating processes including cell proliferation, energy metabolism, oxidative stress and innate immune, etc., and shows influence in patients’ response to treatment. Therefore, apoE has become a potential biomarker and treatment target for cancer. Further research of apoE will help us build deep and systematic understanding of etiology of cancer to promote the prevention and to develop new therapeutic strategies for cancer. In this review, we introduced the properties of apoE from the views of biophysics, biochemistry, molecular biology, evolution and epidemiology, in which we demonstrated the similarities and differences among the structures of 3 subtypes of apoE; we also recapitulated the role of apoE in the genesis and development of cancers in main types of malignancies including gastric cancer, colorectal cancer, hepatobiliary cancer, melanoma, pancreatic cancer, etc.; we summarized the relationship between apoE and the hallmarks of cancer, highlighting the position of apoE in immune system and its critical role for understanding the different nature of immunological background of cancers originated from different organs, and discussed its potential value for application as tumor biomarkers and therapeutic targets by demonstrating the structures of its subtypes. We further discussed the possibility of transferring the drug designing strategy of “structure corrector” from neurology to oncology.

CETP gene polymorphisms and haplotypes are explanatory variables for HDL cholesterol level in sickle cell disease

Variations in lipid profile have been observed in sickle cell disease (SCD) and understanding their relationship with disease severity is crucial. This study aimed to investigate the association of polymorphisms of the CETP gene and laboratory markers of disease severity with lipid profile in a pediatric population with SCD. Biochemical and anthropometric analyses and CETP and alpha-thalassemia genotyping were performed. The study included 133 children and adolescents with sickle cell anemia (SCA) or hemoglobin SC disease (SCC), in steady-state. The SCA and no hydroxyurea (no HU) groups had higher values of ApoB, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) compared to the SCC and HU groups. However, there were no significant differences in ApoA1 and HDL-C levels between the groups based on genotype. Furthermore, the groups with altered levels of ApoA1, HDL-C, and the triglyceride/HDL ratio exhibited lower hemoglobin (Hb) levels and higher white blood cell counts. Hb level was associated to HDL-C levels. Analysis of CETP gene variants showed that the minor alleles of rs3764261 (C>A), rs247616 (C>T), and rs183130 (C>T), as well as the TTA haplotype, are explanatory variables for HDL-C levels. These findings suggested that dyslipidemia in SCD, specifically related to HDL-C levels, may be influenced by individual genetic background. Additionally, further investigation is needed to determine if clinical manifestations are impacted by CETP gene variants.

Investigation of associations between apolipoprotein A5 and C3 gene polymorphisms with plasma triglyceride and lipid levels

SUMMARY OBJECTIVE: The aim of this study was to determine frequency and associations between APOA5 c.56C>G, −1131T>C, c.553G>T, and APOC3 −482C>T and SstI gene polymorphisms with hypertriglyceridemia. METHODS: Under a case-control study model, 135 hypertriglyceridemic and 178 normotriglyceridemic control participants were recruited. Polymerase chain reaction and restriction fragment length polymorphism methods were utilized for genotyping. Statistical calculations were performed by comparing allele and genotype frequencies between groups. Clinical characteristics were compared between groups and intra-group genotypes. RESULTS: APOC3 gene −482C>T and SstI polymorphic genotypes and allele frequencies were significantly higher in hypertriglyceridemic group (genotype frequencies, p=0.035, p=0.028, respectively). Regression analysis under unadjusted model confirmed that APOC3 −482C>T and SstI polymorphisms were significantly contributing to have hypertriglyceridemia (p=0.02, odds ratio [OR]=1.831 (95% confidence interval [CI] 1.095-3.060); p=0.04, OR=1.812 (1.031-3.183), respectively). APOA5 c.56C>G was in complete linkage disequilibrium with APOA5 c.553G>T polymorphism (D'=1). CONCLUSION: For the first time in a population sample from Turkey, among the five polymorphisms of APOA5 and APOC3 genes investigated, APOC3 −482C>T and SstI polymorphisms were associated with elevated serum TG levels, while APOA5 c.56C>G, −1131T>C, and c.553G>T polymorphisms were not.

Berberine Inhibits Atherosclerosis by Regulating Lipophagy Via Targeting Wnt5a/NPC1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the regulatory effect and molecular mechanism of berberine （BBR） on lipophagy in the prevention and treatment of atherosclerotic （AS） lesions in mice. MethodFifty apolipoprotein E-knockout （ApoE-/-） mice were randomly divided into an AS model group， an atorvastatin group （5 mg·kg-1）， and low-， medium-， and high-dose BBR groups （2.5， 5， 10 mg·kg-1）. Ten C57BL/6J mice were assigned to the control group. After 12 weeks， hematoxylin-eosin （HE） and oil red O staining were performed to assess the histopathological changes of AS plaques in the aorta. Biochemical analysis was used to measure serum lipid levels， and enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory cytokines interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， oxidative stress marker reactive oxygen species （ROS）， and serum lipophagy marker Beclin1 and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）. The xanthine oxidase method was used to measure serum superoxide dismutase （SOD） activity. Immunohistochemistry （IHC） was used to detect the distribution of wingless-type MMTV integration site family member 5a （Wnt5a） and Nieman Pick type C1 （NPC1） in the aorta， and Western blot was used to determine the protein expression of Wnt5a and NPC1 in the aorta. ResultCompared with the control group， the AS model group showed significant AS plaque formation， significantly elevated levels of serum total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， IL-6， TNF-α， and ROS， aortic Wnt5a distribution and protein expression （P<0.01）， and significantly reduced levels of serum high-density lipoprotein cholesterol （HDL-C）， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.01）. Compared with the AS model group， the atorvastatin group， and high- and medium-dose BBR groups showed a significant reduction in AS plaque area （P<0.05， P<0.01）， significantly decreased levels of serum TC， TG， LDL-C， IL-6， TNF-α， ROS， and aortic Wnt5a distribution and protein expression （P<0.05， P<0.01）， and significantly increased levels of serum HDL-C， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.05， P<0.01）. There was no statistically significant difference in the above indicators between the atorvastatin group and the medium-dose BBR group. ConclusionBBR can competitively bind to Wnt5a to activate NPC1 expression， upregulate lipophagy levels， reduce blood lipids， and inhibit the release of inflammatory mediators and oxidative stress damage， thereby exerting a preventive and therapeutic effect on AS.

Research progress on the molecular mechanism of periodontal pathogens promoting the development of cardiovascular diseases / 口腔疾病防治

@#Periodontitis is a multifactorial infectious and inflammatory disease occurring in tooth-supporting tissues. In recent decades, many studies have reported a potential relationship between periodontitis and cardiovascular disease, and periodontal pathogens are an important factor linking periodontitis and cardiovascular disease. In this review, we summarize updated preclinical studies and epidemiological evidence on the association of these two diseases. Moreover, possible mechanisms accounting for such links are introduced, including bacteremia and direct invasion of pathogens, endotoxemia caused by virulence factors of periodontal pathogens leading to systemic inflammation, abnormal lipid metabolism and oxidative stress, which further affect the inflammatory states of the cardiovascular system. The molecular mimicry theory and the intrinsic correlation of apolipoprotein E between periodontitis and cardiovascular disease require further study. Combined with existing studies, it is reasonable to assume that periodontal treatment and oral hygiene can reduce the risk of cardiovascular disease in patients with periodontitis. More studies are needed to focus on the molecular mechanism linking periodontal pathogens and cardiovascular diseases. These studies will provide evidence that periodontal pathogens directly invade the cardiovascular system or indirectly invade host cells as well as isolate and culture bacteria from the tissues of lesions. Studies should also explore how the local inflammatory state, periodontal pathogens and their products directly influence cardiovascular disease-related biomarkers (C-reactive protein, vascular endothelial growth factor, heat shock protein, etc.) and the mechanism. This information may provide a reference for the effective prevention and treatment of periodontitis and cardiovascular disease in the future.

Correlation between serum cystatin C and lipid level in patients with chronic heart failure / 中南大学学报(医学版)

OBJECTIVES@#Serum cystatin C (Cys C) and blood lipid levels are related to the occurrence and development of chronic heart failure (CHF). However, there are few reports on the correlation between blood lipid level and serum Cys C level in patients with CHF. The aim of this study is to explore the correlation between serum Cys C level and blood lipid level in patients with CHF, and to provide valuable reference for clinical diagnosis and treatment of CHF.@*METHODS@#A total of 336 CHF patients who were hospitalized in the Department of Cardiovascular Medicine of Shaanxi Provincial People's Hospital from October 2017 to July 2018 were included and they were divided into a Cys C normal group (n=180) and a Cys C abnormal group (n=156) according to serum Cys C level of the patients. The general data, laboratory indicators, and cardiac ultrasound results were compared between the 2 groups. Pearson correlation analysis was used to detect the correlation between serum Cys C level and blood lipid level and other factors, and the data related to Cys C were further analyzed by multivariate logistic regression.@*RESULTS@#Compared with the Cys C normal group, patients in the Cys C abnormal group had lower left ventricular ejection fraction (LVEF) (P<0.001), older age (P=0.030), higher incidence rate of diabetes and smoking index (P=0.002 and P=0.003, respectively). The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and total bilirubin (TBIL) were higher (all P<0.001), while the levels of high density lipoprotein (HDL), apolipoprotein (Apo) A, and albumin (ALB) were lower (P<0.001, P=0.001, and P=0.003, respectively) in the Cys C abnormal group. Pearson correlation analysis showed that serum Cys C level was negatively correlated with platelet count, HDL, Apo A, ALB, and LVEF. It was positively correlated with smoking index, mean platelet volume, neutrophil ratio, BUN, and TBIL (all P<0.05). The results of multivariate logistic regression analysis showed that the decreased HDL level was a risk factor for the abnormality of serum Cys C in patients with CHF (OR=0.119, P=0.003), while Apo A was not a risk factor for its abnormality (P=0.337).@*CONCLUSIONS@#HDL might be the only blood lipid index associated with abnormal serum Cys C in patients with CHF.

Apolipoprotein E enhances migration of endometrial cancer cells byactivating the ERK/MMP9 signaling pathway / 南方医科大学学报

OBJECTIVE@#To study the role of apolipoprotein E (APOE) in regulating endometrial cancer metastasis and explore the signaling pathway in the regulatory mechanism.@*METHODS@#Human endometrial cancer cell line HEC-1B was transfected with a control siRNA (siCtrl) or a specific siRNA targeting APOE (siAPOE) or with either pEGFP-N1 plasmid or an APOEoverexpressing plasmid. The changes in migration, proliferation, apoptosis and cell cycle of the transfected cells were examined using wound healing assay, Transwell migration assay, MTT assay, flow cytometry, and Hoechst staining. The activity of the ERK/MMP9 signaling pathway in the transfected cells was assessed using RT-qPCR and Western blotting. The expression level of APOE in clinical specimens of endometrial cancer tissues were detected using immunohistochemistry and its correlation with differentiation of endometrial cancer tissues was analyzed.@*RESULTS@#Wound healing assay and Transwell migration assay showed that compared with those in siCtrl group, HEC-1B cells transfected with siAPOE showed significantly reduced migration ability (P < 0.05), whereas APOE overexpression significantly promoted the migration of the cells (P < 0.05). Neither APOE knockdown nor overexpression produced significant effects on HEC-1B cell proliferation as shown by MTT assay and flow cytometry. Hoechst staining revealed that transfection with siAPOE did not significantly affect apoptosis of HEC-1B cells. APOE knockdown obviously reduced and APOE overexpression enhanced ERK phosphorylation and MMP9 expression in HEC-1B cells (P < 0.05). Treatment with U0126 partially reversed the effects of APOE overexpression on ERK phosphorylation, migration and MMP9 expression in HEC-1B cells (P < 0.05). APOE is highly expressed in clinical samples of endometrial cancer tissues as compared with the adjacent tissues.@*CONCLUSION@#APOE is highly expressed in endometrial cancer tissues to promote cancer cell migration by enhancing ERK phosphorylation and MMP9 expression.

Correlation of related indexes of blood lipid and insulin resistance with cognition scores in middle-aged and elderly people with mild cognitive impairment / 中华健康管理学杂志

Objective:To analyze the correlation between related indexes of serum lipid and insulin resistance and cognitive impairment in middle-aged and elderly people with mild cognitive impairment (MCI).Methods:In this cross-sectional study, 262 middle-aged and elderly patients with a Montreal Cognitive Function Scale (MoCA) cognitive score greater than or equal to 18 points who underwent physical examination in the Health Management Center of Beijing Tiantan Hospital Affiliated to Capital Medical University from January 1 to July 31, 2021 were selected as subjects. According to the cognitive function and MoCA score, the patients were divided into MCI group (143 cases) and normal cognition group (119 cases). Basic data, fasting blood glucose, triglyceride (TG), total cholesterol, apolipoprotein E(ApoE) genotype and other clinical indicators were collected. Hypothesis test was used to compare the differences in basic data, related indicators of blood lipid and insulin resistance between the two groups. Spearman correlation analysis was used to analyze the correlation between related indicators of blood lipid and insulin resistance and MoCA score in the two groups.Results:The age and the proportion of patients with hypertension, coronary heart disease and diabetes in the MCI group were all significantly higher than those in normal cognition group [(54.83±8.29) vs (50.76±6.34) years, 37.76% vs 31.93%, 4.20% vs 0.84%, 16.08% vs 8.40%] (all P<0.05). The elevation of serum TG ( r=-0.50, 95% CI:-0.88--0.12), TG glucose product index (TyG) ( r=-0.75, 95% CI:-1.29--0.20) and TG to high-density lipoprotein cholesterol ratio (TG/HDL-C) ( r=-0.52, 95% CI:-0.91--0.13) were all negatively correlated with MoCA score (all P<0.05). After adjusting for age and gender, the elevation of TG ( r=-0.39, 95% CI:-0.75--0.31) and TG/HDL-C ( r=-0.43, 95% CI:-0.80--0.05) were both still negatively correlated with MoCA score (both P<0.05). There was no significant correlation between all indexes and MoCA scores in the normal cognition group (all P>0.05). The elevated TG was negatively correlated with MoCA score in the MCI group ( r=-0.70, 95% CI:-1.23-0.16, P=0.017). There was no significant correlation between elevated TG and MoCA score in patients carrying ApoE ε2 and ApoE ε3 genotypes in MCI group (all P>0.05). Conclusion:Elevated related indexes of blood lipids and insulin resistance are negatively correlated with cognitive scores in middle-aged and elderly people with MCI, and it′s more obvious in patients with ApoE ε4 genotype.

Clinical value of combined detection of ApoA1 and AFP in young and middle-aged patients with pulmonary tuberculosis / 国际检验医学杂志

Objective To explore the clinical application value of combined detection of apolipoprotein A1(ApoA1)and alpha-fetoprotein(AFP)in young and middle-aged patients with pulmonary tuberculosis.Meth-ods A total of 82 young and middle-aged patients with pulmonary tuberculosis admitted to the hospital from December 2020 to December 2021 were selected as the observation group,and 85 healthy people who under-went physical examination in the hospital during the same period were selected as the control group.The clini-cal,lipid,inflammation and iron metabolism related indexes were compared between the two groups.Multiva-riate Logistic regression was used to analyze the influencing factors of pulmonary tuberculosis in young and middle-aged patients.The area under the receiver operating characteristic(ROC)curve(AUC)was used to e-valuate the application value of ApoA1,AFP and their combination in the diagnosis of pulmonary tuberculosis in young and middle-aged patients.Results Compared with the control group,the observation group had sig-nificantly higher levels of direct bilirubin,creatinine,AFP and high-sensitivity C-reactive protein(P<0.05),and significantly lower levels of triglyceride,total cholesterol,high-density lipoprotein cholesterol and ApoA1(P<0.05).Multivariate Logistic regression analysis showed that ApoA1 was an independent protective factor(OR=0.119,95%CI 0.019-0.754,P=0.024)and AFP was an independent risk factor(OR=1.554,95%CI 1.138-2.122,P=0.006)for pulmonary tuberculosis in young and middle-aged patients.ApoA1,AFP and the combined prediction of young and middle-aged tuberculosis AUC were 0.644(P=0.006),0.262(P<0.001),0.678(P=0.001),respectively.Conclusion The low level of ApoA1 is an independent protec-tive factor for pulmonary tuberculosis in young and middle-aged patients,and the high level of AFP is an inde-pendent risk factor for pulmonary tuberculosis in young and middle-aged patients.The combined detection of ApoA1 and AFP has good value in predicting pulmonary tuberculosis in young and middle-aged patients.

Prediction model construction of depression in patients with lacunar cerebral infarction / 中华急诊医学杂志

Objective:To investigate the risk factors of depression in patients with lacunar cerebral infarction 3 months after discharge, and build a risk prediction model.Methods:The clinical data of 237 patients with lacunar cerebral infarction diagnosed and treated in the Second Affiliated Hospital of Wannan Medical College from January 1, 2021 to January 1, 2022 were retrospectively analyzed. Demographic data, laboratory indicators and risk factors of cardiovascular disease were collected when the patients were admitted to hospital. The patient health questionnaire-9 (PHQ-9) score was used to assess the risk of post-stroke depression (PSD) 3 months after discharge. Univariate and multivariate logistic regression analyses were used to identify independent risk factors of depression. A predictive model was constructed based on the above risk factors. The predictive efficacy was evaluated by receiver operating characteristic (ROC) curve, and the clinical applicability of the predictive model was measured by calibration curve and decision curve.Results:Fifty-four patients with lacunar infarction (22.80%) showed symptoms of depression at 3 months after discharge. Multivariate logistic regression showed that women ( OR=2.952, 95% CI: 1.403-6.213, P=0.004), cystatin C ( OR=2.964, 95% CI: 1.222-7.191, P=0.016), apolipoprotein B ( OR=4.836, 95% CI: 1.533-15.258, P=0.007) were the independent risk factors for PSD in patients with lacunar infarction. Activity of daily living (ADL) score ( OR=0.939, 95% CI: 0.915-0.964, P<0.001) was a protective factor for PSD in patients with lacunar infarction. The area under the curve (AUC) of the prediction model was 0.779 (95% CI: 0.703-0.855, P<0.001), which was better than other predictors. Hosmer-Lemeshow H test showed that the model was well calibrated ( P=0.588). In addition, the prediction model of decision curve analysis had a good clinical applicability. Conclusions:The predictive model based on gender, laboratory indicators and daily life ability score can evaluate the risk of PSD in patients with lacunar infarction 3 months after discharge. It is good predictive efficacy and clinical applicability which worth clinical promotion and application.

Relationship Between Preoperative Inflammatory Markers,Fibrinogen,Apolipoprotein B and Lymph Node Metastasis in Early Colorectal Cancer / 胃肠病学

Background:With the improvement of national health awareness and the popularization of a series of screening methods,the number of early colorectal cancer is gradually increasing,accurate prediction of lymph node metastasis of T1 colorectal cancer is the key to determine the optimal therapeutic solutions.Aims:To investigate the relationship between preoperative inflammatory markers,fibrinogen,apolipoprotein B and lymph node metastasis in patients with early colorectal cancer.Methods:The clinical data of 102 patients with early colorectal cancer who received surgical treatment in the Department of General Surgery,Affiliated Hospital of Jiangsu University from January 2014 to December 2022 were retrospectively analyzed.The patients were divided into positive lymph node group and negative lymph node group according to postoperative pathological results.Univariate and multivariate Logistic regression analysis were employed to explore the correlation between lymph node metastasis and clinical test parameters in early colorectal cancer.Results:A total of 102 patients in T1 colorectal cancer were enrolled in this study,including 53 males and 49 females,and the mean age was(64±10)years.Postoperative pathological diagnosis of lymph node metastasis was 13 cases and no lymph node metastasis was 89 cases.The univariate analysis showed that age,fibrinogen and apolipoprotein B-monocyte ratio(AMR)were related to lymph node metastasis in early colorectal cancer(P<0.05).The multivariate Logistic regression analysis showed that age,fibrinogen and AMR were independent predictors of lymph node metastasis.Conclusions:The age,fibrinogen and AMR may play an important role in predicting lymph node metastasis in early colorectal cancer.They can be combined with pathological factors to further create a new prediction model,so as to provide some reference for patients in colorectal cancer to choose the therapeutic regimen.

Protective effect of COG1410 on the survival of retinal ganglion cells in mice with retinal ischemia-reperfusion injury and its mechanism / 中华实验眼科杂志

Objective:To explore the effects of apolipoprotein E-mimetic peptide COG1410 on M1/M2 microglia polarization and retinal ganglion cells (RGCs) survival after ischemia-reperfusion (IR) injury in the mouse retina and its possible mechanisms.Methods:Eighteen 8-week-old C57BL/6J male mice were divided into control group (6 mice), IR 3 days group (6 mice), IR 7 days group (3 mice), and IR 14 days group (3 mice) according to the randomized number table method.Mice in IR group were perfused in the anterior chamber using saline, and the intraocular pressure (IOP) was raised to 100 mmHg (1 mmHg=0.133 kPa) and maintained for 1 hour in order to establish a model of IR injury in the retina.Three mice from control group and 3 mice from IR 3 days group were taken to observe the distribution of retinal microglia by immunofluorescence staining of retinal frozen sections.Three mice were taken from normal control, IR 3 days, IR 7 days, and IR 14 days groups respectively to observe the changes of retinal M1-type and M2-type microglial cells with time after IR injury by immunofluorescence staining of retina.Another 91 C57BL/6J mice were randomly divided into normal control group (19 mice), IR group (24 mice), saline group (24 mice), and COG1410 group (24 mice) according to the random number table method.Mice in normal control group maintained a normal IOP, and the IR injury model was established in the other three groups.In addition, COG1410 group and saline group were injected with 1 mg/kg COG1410 and an equal volume of saline by tail vein injection, respectively.The microglia phenotype and survival rate of RGCs were observed by immunofluorescence staining of retinal wholemount.The relative expressions of retinal tumor necrosis factor-ɑ (TNF-ɑ) and interleukin-1β (IL-1β) mRNA were detected by real-time fluorescence quantitative PCR.The apoptosis of retinal neuronal cells was observed by the TUNEL assay.The expression levels of retinal nuclear factor-κB (NF-κB), B lymphocyte-2 (Bcl-2), and Bcl-2-associated X protein (Bax) proteins were detected by Western blot.Use and care of animals strictly complied with the Hubei Provincial Regulations on the Management of Laboratory Animals and the experiment was approved by the Animal Ethics Committee of the Renmin Hospital of Wuhan University (No.WDRM20190113).Results:Retinal microglia in normal control group and IR 3 days group were mainly distributed in the ganglion cell layer, inner plexiform layer, and outer plexiform layer.There were statistically significant differences in the comparison of the proportions of M1-type and M2-type microglia among normal control, IR 3 days, IR 7 days, and IR 14 days groups ( F=29.83, 57.62; both at P<0.001). Compared with normal control group, the number of M1-type microglia was higher in IR 3 days group, and the number of M2-type microglia was higher in IR 7 days group, and the differences were statistically significant (all at P<0.05). The proportions of M1-type microglia in normal control group, IR group, saline group, and COG1410 group were (4.25±0.57)%, (65.26±10.43)%, (63.01±4.93)%, and (33.13±4.46%), respectively, and the proportions of M2-type microglia in the four groups were (4.50±0.20)%, (11.47±0.24 )%, (11.75±0.17)%, and (38.93±4.26)%, showing statistically significant differences among them ( F=23.33, 50.82; both at P<0.001). The proportions of M1-type microglia decreased while the proportions of M2-type microglia increased in COG1410 group when compared with IR group, and the differences were statistically significant (both at P<0.05). There were statistically significant differences in RGCs survival rate, relative expression of retinal TNF-ɑ and IL-1β mRNA, retinal apoptotic cell count, retinal NF-κB and Bax protein expression levels, and Bax/Bcl-2 ratio among the four groups ( F=30.77, 12.52, 6.74, 28.72, 13.02, 7.94, 7.58; all at P<0.05). Compared with normal control group, there were significant decreases in the survival rate of RGCs and increases in retinal apoptotic cell number, TNF-ɑ and IL-1β mRNA expression, retinal NF-κB and Bax protein expression levels, and Bax/Bcl-2 ratio in IR group (all at P<0.05). Compared with IR group, the COG1410 group had increased retinal RGCs survival rate, decreased TNF-ɑ and IL-1β mRNA expression levels, decreased TUNEL-positive cells, decreased NF-κB and Bax proteins expression levels, and decreased Bax/Bcl2 ratio, and the differences were statistically significant (all at P<0.05). Conclusions:Three days after retinal IR modeling, COG1410 promotes the polarization of M1-type microglia to M2-type, inhibits the expression of retinal NF-κB and downstream inflammatory factors, and attenuates the retinal inflammatory response, as well as inhibits the expression of apoptosis-related proteins, which promotes the survival of RGCs.

Progress in regulation of vascular function by sphingosine-1-phosphate in atherosclerosis / 中国病理生理杂志

Sphingosine-1-phosphate(S1P)is a bioactive lipid that regulates a variety of physiological processes,including immune surveillance,immune cell transport,vascular development,and cell differentiation.S1P also plays an important role in regulating vascular function and balancing endothelial barrier homeostasis.The majority of S1P mole-cules are located in their chaperone proteins,such as apolipoprotein M or albumin.The chaperone protein is also a carrier and modulator of S1P molecules,and the combination of the two can protect the S1P structure.S1P-binding chaperone pro-tein selectively activates S1P receptor in the form of a complex that opens downstream pathways by coupling with different S1P receptor targets to exert its effects in vivo.The present review elucidates the metabolism and function of S1P,as well as the effect of chaperones on its function,and clarifies the regulation of S1P in vascular activity and pathogenesis of atherosclerosis.

Correlations of urinary Alzheimer-associated neuronal thread protein with apolipoprotein E allele and cognitive function in patients with subjective cognitive decline, mild cognitive impairment or Alzheimer's disease / 中华神经医学杂志

Objective:To investigate the correlations of urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) with apolipoprotein E (ApoE) allele and cognitive function in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and Alzheimer's disease (AD).Methods:Two hundred and fifty-nine AD patients or patients at prodromal AD stage, including SCD ( n=148), MCI ( n=65), and AD ( n=46), admitted to Department of Neurology, Xuanwu Hospital, Capital Medical University from January 2019 to January 2021, were chosen. Results of neuropsychological assessment, ApoE alleles and urinary AD7c-NTP level were collected in all subjects. Correlations of AD7c-NTP with grading of ApoE alleles and neuropsychological assessment results were analyzed by Spearman's rank correlation. Results:Urinary AD7c-NTP level in AD group was significantly higher than that in MCI group and SCD group ( P<0.05). ApoE genotype test showed that, in these 259 subjects, 24 had ApoE genotype grading 1, 150 had APOE genotype grading 2, 10 had APOE genotype grading 3, and 75 had APOE genotype grading 4; compared with patients with ApoE genotype grading 1 and 2, patients with ApoE genotype grading 4 had significantly increased urinary AD7c-NTP level ( P<0.05). Correlation analysis showed that urine AD7c-NTP level was positively correlated with ApoE genotype grading ( r s=0.264, P<0.001). Urinary AD7c-NTP level was negatively correlated with scores of Montreal cognitive assessment, auditory verbal learning test-N5, animal verbal fluency test and Boston naming test ( P<0.05), and positively correlated with shape trails tests-A and shape trails tests-B scores ( P<0.05). Conclusion:In AD patients or patients at prodromal AD stage, the higher the urinary AD7c-NTP level, the higher the ApoE genotype grading and the greater the decline in cognitive function.