OBJECTIVETo investigate the relationship between the -629C/A polymorphism in the promoter region of the CETP gene, serum Levels, lipid metabolism, and coronary heart disease (CHD) among Tianjin Han Chinese population.

METHODSA hospital-based case-control study was conducted in Tianjin Chest Hospital from 2010 October to 2011 October. The subjects underwent angiography were divided into a case group (n = 429) and a control group (n = 275). The CETP gene promoter polymorphism at position -629 was determined by restricted fragment length polymorphism using the polymerase chain reaction (PCR-RFLP) method.The serum CETP levels was determined by enzyme-linked immunosorbent assay (ELISA) method.

RESULTS(1)The lower frequency of -629A allele in Tianjin Han Chinese population was 0.408, significantly lower than that in other domestic and foreign populations (0.479-0.701, P < 0.05). (2) Variant AA genotype showed reduced CETP levels(P > 0.05) and higher HDL-C levels (P < 0.05), compared to wild CC genotype. (3) Although there was a negative trend correlation between serum CETP and HDL-C levels, it did not reach statistical significance(P > 0.05). (4)There were significant differences in the frequencies of CETP gene -629 genotype and allele between the two groups (P < 0.001),carries with CA/AA genotype and A allele showed higher risk of CHD, OR (95%CI) values were 4.627 (3.163-6.769), 8.779 (4.799-16.059) and 3.173 (2.453-4.104) respectively. There was no relationship between CETP-629C/A polymorphism and coronary artery stenosis degree(χ(2) = 3.588, P = 0.166).

CONCLUSIONThe frequencies of CETP gene -629 genotype and allele in the Tianjin Han Chinese population was significantly different from that in Other domestic and foreign populations. Variant AA genotype, which showed reduced CETP levels and higher HDL-C levels, is paradoxically associated with increased risk of CHD. Thus, CETP gene variation may affect coronary risk apart from the level of HDL-C.

Aged ; Case-Control Studies ; Cholesterol Ester Transfer Proteins ; blood ; genetics ; Cholesterol, HDL ; blood ; Coronary Disease ; blood ; genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic

Integrins are allosteric cell adhesion receptors that cycle from a low to a high affinity ligand binding state, a complex process of receptor activation that is of particular importance in blood cells such as platelets or leukocytes. Here we highlight recent progress in the understanding of the molecular pathways that regulate integrin activation in platelets and leukocytes, with a special focus on the structural changes in platelet integrin αIIbβ3 brought about by key intracellular proteins, namely talin and kindlins, that are of crucial importance in the regulation of integrin function. Evidence that the small GTPase Rap1 and its guanine exchange factor CalDAG-GEF1, together with RIAM, a Rap1GTP adaptor protein, promote the interaction of talin with the integrin β subunit, has greatly contributed to fill the gap in our understanding of the signaling pathway from G-coupled agonist receptors and their phospholipase C-dependant second messengers, to integrin activation. Studies of patients with the rare blood cell disorder LAD-III have contributed to the identification of kindlins as new co-regulators of the talin-dependent integrin activation process in platelets and leukocytes, underlining the relevance for the in-depth investigation of patients with rare genetic blood cell disorders.
Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cell Adhesion ; Cytoskeleton ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; metabolism ; Models, Molecular ; Molecular Sequence Data ; Platelet Glycoprotein GPIIb-IIIa Complex ; metabolism ; Protein Interaction Domains and Motifs ; Recombinant Proteins ; metabolism ; Sequence Alignment ; Talin ; metabolism

Objective To explore the risk factors on the symptoms of lumbar intervertebral disc herniation so as to develop a predictive model for the disease. Methods With a populationbased case-control study, 303 of 50 123 residents were diagnosed as having lumbar intervertebral disc herniation symptoms. 152 cases and 167 healthy controls, matched by gender and age, were randomly chosen as case and control groups. Questionnaires were used to collect information on the exposure to risk factors and logistic predictive model was then established. Results Through non-conditional logistic regression analysis, data showed that the positive family history of lumbar vertebra disorder, lumbar treatment or surgery, mental stress, acute low back injury, permanent work pose, and body mass index ≥23.0 kg/m2 were the risk factors among residents from the countryside. The area under the receiver operator characteristic curve of logistic predictive model was 0.809. When 0.4 was set as the classification cutoff, the total predictive correct rate, sensitivity, and specificity were 74.0%, 73.7%, and 74.3% respectively. Conclusion The occurrence of lumbar disk herniationcan in countryside population was affected by multi-variables including genetic and environmental, and could be predicted with the logistic regression model established by our group.The positive predictive results could be used to alarm the patients and doctors for prevention and treatment of the disease.

OBJECTIVETo observe the effect of Modified Zuoguiwan (MZ) on the balance between helper T cell subsets 17 (Th17) and regulatory T cell subsets (Treg) in estrogen deficiency induced bone loss mice and to explore its mechanism.

METHODSTotally 50 BALB/c mice were divided into the sham-operation group, the ovariectomy model group, the low dose MZ group, the middle dose MZ group, and the high dose MZ group by random digit table, 10 in each group. Mice in the low, middle, and high dose MZ groups were respectively administered with MZ at the daily dose of 7.25, 14.50, and 29.00 g/kg by gastrogavage, 0.5 mL each time for 12 successive weeks. Meanwhile, mice in the sham-operation group and the ovariectomy model group were administered with equal volume by gastrogavage, 0.50 mL each time. The serum estradiol (E2) level was assessed by enzyme linked immunosorbent assay (ELISA). Bone mineral density (BMD) of thigh bone was measured with dual energy X ray absorptiometry. In addition, the population of Th17/Treg subsets in spleen mononuclear cells was analyzed by extracellular and intracellular staining method using flow cytometry. Moreover, the mRNA expression of IL-17A and TGF-β in the spleen mononuclear cells was detected by reverse transcription polymerase chain reaction (RT-PCR).

RESULTSCompared with the sham-operation group, both E2 and BMD significantly decreased, the percentage of Th17 subset and Th17/Treg ratio both increased, the percentage of Treg subset obviously decreased, the expression of IL-17A mRNA significantly increased, and the expression of TGF-β mRNA significantly decreased in the ovariectomy model group (all P < 0.05). Compared with the model group, BMD obviously increased, the percentage of Th17 subset and Th17/Treg ratio both decreased, the percentage of Treg subset obviously increased, the expression of IL-17A mRNA significantly decreased, and the expression of TGF-β mRNA significantly increased in the middle dose MZ group and the high dose MZ group (all P < 0. 05). Correlation analyses showed that BMD was positively related to both the serum E2 level and the percentage of Treg subset (P < 0.05), but negatively related to the percentage of Th17 subset (P < 0.05). In addition, the serum E2 level was positively related to the percentage of Treg subset, but obviously negatively related to that of Th17 subset (P < 0.05).

CONCLUSIONSThere was correlation between Th17/Treg imbalance and E2 deficient bone loss. MZ could decrease the proportion of Th17 subset, but elevate the proportion of Treg subset in E2 deficient bone loss mice. It could achieve therapeutic effect through adjusting the balance of Th17/Treg in E2 deficient bone loss mice.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Estrogens ; deficiency ; metabolism ; Female ; Flow Cytometry ; Humans ; Interleukin-17 ; Mice ; Mice, Inbred BALB C ; Osteoporosis, Postmenopausal ; drug therapy ; RNA, Messenger ; Spleen ; T-Lymphocyte Subsets ; T-Lymphocytes, Helper-Inducer ; T-Lymphocytes, Regulatory ; Th17 Cells ; Transforming Growth Factor beta ; metabolism

OBJECTIVETo investigate the expression and clinical significances of HGFA, Matriptase, HAI-1 and HAI-2 in patients with acute myeloid leukemia (AML).

METHODSThe bone marrow samples from 91 AML patients, 41 AML patients in complete remission, and 32 normal controls were collected. Real time fluorescence quantitative RT-PCR (qRT-PCR) was used to detect the mRNA expressions levels of HGFA, Matriptase, HAI-1, HAI-2 . The expressions of these genes were compared among AML untreated group, the complete remission group and the healthy control group. The correlation of their expression with clinical characteristics was analyzed.

RESULTSThe level of HGFA in the AML untreated group was higher than that in the healthy control group（P<0.05）, while the HAI-2 mRNA level was lower than that in the healthy control group（P<0.05）. The mRNA levels of HAI-1 and Matriptase were not changed significantly in all groups. The HAI-2 mRNA expression level was significantly lower in the high white blood cell group (P<0.05).

CONCLUSIONThe abnormal activation of HGF/c-Met signaling system in AML may result from the increase of HGFA expression and the decrease of HAI-2 expression of the upstream regulatory factors.

Hepatocyte Growth Factor ; Humans ; Leukemia, Myeloid, Acute ; Membrane Glycoproteins ; Proteinase Inhibitory Proteins, Secretory ; Serine Endopeptidases

[摘 要] 目的：探讨1, 25-二羟维生素D3（VD3）对人乳腺癌MCF-7细胞凋亡的影响及其作用机制。方法：取体外培养的人乳腺癌MCF-7细胞，随机分为6组：对照组、2-脱氧葡萄糖（2-DG，葡萄糖抑制剂）组、1 µmol/L VD3组、10 µmol/L VD3组、2-DG+1 µmol/L VD3组和2-DG+10 µmol/L VD3组。药物干预6组细胞48 h后，以葡萄糖摄取测定试剂盒检测细胞的葡萄糖摄取量、ATP试剂盒检测细胞中ATP含量和乳酸试剂盒检测细胞的乳酸水平，WB法检测MCF-7细胞中细胞色素C（Cyt c）和凋亡相关蛋白（Bcl-2、BAX、PARP1、caspase9和caspase3）的表达水平。结果：与对照组比较，VD3干预后，MCF-7细胞的凋亡率明显增加（P<0.05或P<0.01），同时细胞的葡萄糖摄取量、ATP含量及乳酸水平均明显降低（P<0.05或P<0.01），Cyt c、BAX、PARP1、caspase9及caspase3蛋白表达量明显升高（均P<0.05），Bcl-2蛋白表达量降低（P<0.05或P<0.01）；VD3联合2-DG干预后，各组细胞检测指标的变化更为明显（P<0.05或P<0.01）。结论：VD3可通过抑制人乳腺癌MCF-7细胞的糖酵解过程并以线粒体的Cyt c途径促进细胞凋亡。

[摘 要] 目的：探讨碱性核蛋白1（BNC1）对食管鳞状细胞癌（ESCC）细胞增殖、迁移、侵袭、细胞周期和凋亡的影响及其作用机制。方法：通过qPCR法检测ESCC细胞和正常食管上皮细胞中BNC1 mRNA的表达水平，免疫组织化学染色法检测10例ESCC患者癌及癌旁组织中BNC1的蛋白表达水平。利用siRNA敲低BNC1在KYSE-150和KYSE-30细胞中的表达，CCK-8法、划痕愈合实验、Transwell实验和流式细胞术检测BNC1对细胞增殖、迁移、侵袭、细胞周期和凋亡等的影响。通过CHIP-seq实验和GEPIA在线网站数据分析并结合敲低BNC1后的转录组测序数据分析筛选BNC1调控的下游靶基因，qPCR法验证BNC1敲低后靶基因的表达变化，并用双荧光素酶报告基因实验验证BNC1对靶基因的调控作用。结果：BNC1 mRNA和蛋白水平在ESCC组织中较癌旁组织高表达（均P<0.01）。敲低BNC1可明显抑制KYSE-150、KYSE-30细胞的增殖、迁移和侵袭能力（P<0.05或P<0.01），将细胞阻滞于G1期并促进细胞的凋亡（均P<0.01）。CHIP-seq实验结果和在线网站GEPIA数据分析结合敲低BNC1后的转录组测序数据显示，G蛋白通路抑制因子1（GPS1）可能为BNC1正向调控的致癌靶基因。qPCR法和双荧光素酶报告基因实验结果显示，BNC1对GPS1有调控作用（P<0.01）。结论：BNC1在ESCC组织和细胞中高表达，干扰BNC1可显著抑制ESCC细胞的增殖、迁移和侵袭能力，阻滞细胞于G1期并促进细胞凋亡，其机制可能是BNC1通过靶向GPS1调控ESCC细胞的恶性生物学行为。