老年家庭照顾者的研究现状

从国内外对老年家庭照顾者概念的界定、服务内容及其照顾对家庭照顾者产生的影响方面,综述了老年家庭照顾者的研究状况。     

Detection of promoter methylation status of suppressor of cytokine signaling 3 (SOCS3) in tissue and plasma from Chinese patients with different hepatic diseases

SOCS3 as an important negative regulator of IL6/JAK/STAT3 signaling pathway may be early critical determinants of carcinogenesis. This study aimed to explore the aberrant promoter methylation of SOCS3 gene in circulating DNA as a noninvasive biomarker for screening hepatocellular carcinoma (HCC) high-risk individuals and for prognosis of HCC patients after partial hepatectomy. We detected its methylation status in 116 liver tissues and 326 plasma specimens of different hepatic diseases and healthy subjects, and its mRNA and protein expression in tissues. Higher methylation rate was remarkably detected in HCC (47.92%), compared with corresponding non-tumor (25.0%), liver cirrhosis (LC) (10.0%), benign liver diseases (0%) and normal liver tissues (0%) (all P < 0.05). SOCS3 mRNA level was significantly lower in methylated HCC tissues (P < 0.05). The expressions of SOCS3 and pSTAT3 were affected by methylation status. Correlation and consistency of SOCS3 methylation were found between cancer tissue and corresponding plasma (P < 0.001, κ = 0.747). The detection rate of plasma for HCC reached 73.91%, with no false positive error. SOCS3 methylation status both in tissue and plasma was significantly associated with AFP400, tumor size, tumor differentiation, LC, metastasis and recurrence (all P < 0.05). Patients with SOCS3 methylation were followed up a markedly poorer prognosis than those unmethylated for disease-free survival (P < 0.05). These data indicate that methylation status of SOCS3 in plasma cell-free DNA can correctly reflect that in tissue DNA and be used as a noninvasive potential biomarker for chronic liver disease monitoring, predicting the degree of malignancy and poor prognosis of HCC.     

Non-Invasive PET Imaging of EGFR Degradation Induced by a Heat Shock Protein 90 Inhibitor

Purpose The aim of this study is to non-invasively monitor the epidermal growth factor receptor (EGFR) response to a Hsp90 inhibitor–17-AAG treatment in a PC-3 prostate cancer model. Procedures Nude mice bearing PC-3 tumor were injected intraperitoneally with 17-AAG and then imaged with micro positron emission tomography (microPET) using ⁶⁴Cu-DOTA–cetuximab. Biodistribution studies, immunofluorescence staining, and Western blot were performed to validate the microPET results. Results PC-3 cells are sensitive to 17-AAG treatment in a dose-dependent manner. Quantitative microPET showed that ⁶⁴Cu-DOTA–cetuximab has prominent tumor activity accumulation in untreated tumors (14.6 ± 2.6%ID/g) but significantly lower uptake in 17-AAG-treated tumors (8.9 ± 1.6% ID/g) at 24 h post-injection. Both immunofluorescence staining and Western blot confirmed the significantly lower EGFR expression level in the tumor tissue upon 17-AAG treatment. Conclusions The early response to anti-Hsp90 therapy was successfully monitored by quantitative PET using ⁶⁴Cu-DOTA–cetuximab, which indicates that this approach may be valuable in monitoring the therapeutic response to Hsp90 inhibitor 17-AAG in EGFR-positive cancer patients.     

CA199、CA242、DKK1联合检测在胰腺癌中的诊断价值

目的探讨糖类抗原199(CA199)、糖类抗原CA242(CA242)、分泌型蛋白Dickkopf-1(DKK1)对胰腺癌的诊断价值。方法应用电化学发光免疫分析法和酶联免疫吸附测定法(ELISA)检测112例胰腺癌和58例胰腺良性疾病组及62例体检健康者血清CA199、CA242和DKK1水平,采用Kruskal-Wallis单因素方差分析与Mann-Whitney秩和检验进行统计学比较,Logistic回归模型绘制ROC曲线并计算曲线下面积(AUCROC)以评价各指标的诊断价值。结果胰腺癌患者血清CA199、CA242和DKK1水平明显高于胰腺良性疾病组及健康对照组,差异有统计学意义(H值分别为76.30、61.2、47.60,P0.05);CA199、CA242和DKK1对胰腺癌诊断的敏感度分别为76.7%、69.6%、85.7%,特异度分别为95.0%、96.7%、92.5%,准确度分别为86.2%、83.6%、89.2%,3项指标运用回归方程P=1/[1+e-(-4.163+0.21 X1+0.156 X2+0.342 X3)]综合分析诊断胰腺癌,敏感度、特异度和准确度分别为94.4%、90.8%、92.2%;CA199、CA242、DKK1及pre-1的ROC曲线下面积分别为0.736、0.862、0.886、0.949。结论检测血清CA199、CA242和DKK1水平对胰腺癌的诊断具有重要的价值,3种标志物联合检测能明显提高胰腺癌诊断的敏感度和准确度。     

Biorheological changes of dendritic cells at the different differentiation stages

The differentiation, maturation and functioning of Dendritic cells (DCs) are dynamic processes. This study investigated the changes of DCs' migration ability and biorheological properties during their differentiation. Transmigration assay showed that, DCs' migration rate was improved significantly as they differentiate (p < 0.05); NSC (Rac1 blocker) treatment could significantly decrease their migration rates (p < 0.05). Confocal images showed that, F-actin uniformly distributed in monocytes; with DC's differentiation, F-actin began to remodel and gather at the site of dendrites; the images presented surface ruffles and uneven sawtooth-like cytoskeletal structures. Fluorescence polarization analysis showed that, membrane fluidity was increased significantly with DC's differentiation (p < 0.05). CD62L was upregulated significantly (p < 0.05) on the third and ninth days. CD2 was upregulated significantly (p < 0.05) until the seventh day. DC's electrophoretic mobility was increased continuously, especially increased significantly from the third day to the fifth day and the final stage (p < 0.05). These results indicate that there are significant changes in the biorheological properties of DCs during their differentiation.     

妊娠期维生素A、E营养状态对母体和胎儿结局的影响

目的 了解妊娠期维生素A、E营养状况对母体和胎儿结局的影响.方法 收集2015-03至2017-07在北京市顺义区妇幼保健院产科门诊建档并规律产检的孕妇4788名,采集妊娠早期(≤12周)、中期(24～28周)、晚期(≥32周)血清标本10289份,采用高效液相色谱法定量测定血清维生素A、E的浓度.分析孕妇孕期维生素A...     

A Recurrent Mutation c.617G>A in the ACVR1 Gene Causes Fibrodysplasia Ossificans Progressiva in Two Chinese Patients

Fibrodysplasia ossificans progressiva (FOP; OMIM 135100) is a rare heritable disorder of connective tissue characterized by congenital malformations of the great toes and recurrent episodes of painful soft tissue swelling that lead to heterotopic ossifications. Recent studies have shown that the ACVR1 (activin A receptor, type I; OMIM 102576) gene, which encodes the BMP type I receptor protein, is responsible for this disease. We observed two Chinese patients who suffered from progressive pain and ankylosis of major joints with congenital bilateral hallus valgus malformation, neck stiffness, and several posttraumatic ossified lesions on the head and dorsum. Both patients were diagnosed as having FOP. This study aimed to investigate the ACVR1 gene mutation in Chinese FOP patients. Direct sequence analysis of genomic DNA and restriction enzyme digestion demonstrated the presence of a single heterozygous c.617G>A (p.R206H) mutation in the ACVR1 gene in both patients. This mutation is first reported in Chinese patients with FOP and it was de novo in both affected families.     

Exogenous wild-type p53 gene improved survival of nude mice injected with murine erythroleukemia cell line through amelioration of hemorheological changes

OBJECTIVES: Previous investigations have shown that human wild-type p53 gene (WTp53) inhibits the growth of leukemia and tumor cells in vitro. In the present study, the authors used nude mice and examined the therapeutic role of p53 gene for erythroleukemia in vivo in the absence of MHC effects. METHODS: The nude mice were injected with murine erythroleukemia cells (MEL), MEL cells transfected with wild-type p53 gene (MEL-W), and MEL cells transfected with mutated p53 gene (MEL-M). Abnormalities were found in the hemorheological and biophysical properties of red blood cells in all 3 groups of animals, but the abnormalities were lesser in degree and later in appearance in MEL-W group than in MEL and MEL-M groups. Furthermore, the nude mice in MEL-W group lived longer than those in MEL and MEL-M groups. RESULTS: The results showed that WTp53 restrained the growth of erythroleukemia cells in vivo and reduced the erythroleukemia tumorigenesis in the microcirculation by improving the hemorheological and biophysical properties of MEL cells, which helped to prolong the life span of nude mice suffering from erythroleukemia. CONCLUSION: These results contribute to our knowledge on the use of wild-type p53 gene for the treatment of erythroleukemia disease.     

Activation of protease-activated receptors in astrocytes evokes a novel neuroprotective pathway through release of chemokines of the growth-regulated oncogene/cytokine-induced neutrophil chemoattractant family

Activation of protease-activated receptors (PARs) is known to exert neuroprotection when low concentrations of the agonist protease thrombin are applied. However, the mechanism of protection is still unclear. Here, we showed that activation of multiple PARs, including PAR-1, PAR-2 and PAR-4, was able to elevate the release of the chemokine cytokine-induced neutrophil chemoattractant (CINC)-3 from rat astrocytes, in addition to evoking CINC-1 secretion. Different molecular mechanisms were identified as being involved in the secretion of CINC-1 and CINC-3, upon activation of different PARs. Importantly, we found that both CINC-1 and CINC-3 could signal to rat cortical neurons. Both chemokines acted via CXCR2 to prevent C2-ceramide-induced cytochrome c release from mitochondria. Consequently CINC-1 and CINC-3 protected neurons from apoptosis. We further revealed that conditioned media obtained from PAR-activated astrocytes similarly protected cortical neurons against C2-ceramide-induced cell death. The neuroprotection was considerably suppressed by a CXCR2 antagonist. CXCR2 is the cognate receptor for CINC. Therefore, our findings demonstrate that PAR-activated astrocytes are able to protect neurons against neurodegeneration and cell death via regulation of the secretion of chemokines CINC-1 and CINC-3. These data indicate a previously unknown mechanism for astrocyte-mediated neuroprotection achieved by PAR activation.     

PET imaging of acute and chronic inflammation in living mice

Purpose In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF-α and integrin α_vβ₃ expression. Methods TPA was topically applied to the right ear of BALB/c mice every other day to create the inflammation model. ⁶⁴Cu-DOTA-etanercept and ⁶⁴Cu-DOTA-E{E[c(RGDyK)]₂}₂ were used for PET imaging of TNF-α and integrin α_vβ₃ expression in both acute and chronic inflammation. Hematoxylin and eosin staining, ex vivo autoradiography, direct tissue sampling, and immunofluorescence staining were also performed to confirm the non-invasive PET imaging results. Results The ear thickness increased significantly and the TNF-α level more than tripled after a single TPA challenge. MicroPET imaging using ⁶⁴Cu-DOTA-etanercept revealed high activity accumulation in the inflamed ear, reaching 11.1 ± 1.3, 13.0 ± 2.0, 10.9 ± 1.4, 10.2 ± 2.2%ID/g at 1, 4, 16, and 24 h post injection, respectively (n = 3). Repeated TPA challenges caused TPA-specific chronic inflammation and reduced ⁶⁴Cu-DOTA-etanercept uptake due to lowered TNF-α expression. ⁶⁴Cu-DOTA-E{E[c(RGDyK)]₂}₂ uptake in the chronically inflamed ears (after four and eight TPA challenges) was significantly higher than in the control ears and those after one TPA challenge. Immunofluorescence staining revealed increased integrin β₃ expression, consistent with the non-invasive PET imaging results using ⁶⁴Cu-DOTA-E{E[c(RGDyK)]₂}₂ as an integrin α_vβ₃-specific radiotracer. Biodistribution and autoradiography studies further confirmed the quantification capability of microPET imaging. Conclusion Successful PET imaging of TNF-α expression in acute inflammation and integrin α_vβ₃ expression in chronic inflammation provides the rationale for multiple target evaluation over time to fully understand the inflammation processes. Qizhen Cao and Weibo Cai contributed equally to this work.