丹参多酚酸与三七总皂苷合用保护OGD/R损伤胶质细胞线粒体、促进神经因子表达作用研究*

目的 探讨丹参多酚酸（Salvianolate Acid，SAL）和三七总皂苷（Panax Notoginseng Saponins，PNS）合用保护氧糖剥夺/复氧复糖（Oxygen-Glucose Deprivation/Reoxygenation，OGD/R）损伤后星形胶质细胞线粒体、促进神经营养因子表达的作用及机制。方法 大鼠星形胶质细胞原代培养，建立OGD/R损伤模型。Cell counting kit-8（CCK-8）法检测星形胶质细胞活力，流式细胞仪检测活性氧（reactive oxygen species，ROS）释放量、胞内Ca2+ 浓度、线粒体膜电位（mitochondrial membrane potential，MMP）变化，实时定量PCR（real time polymerase chain reaction，RT-PCR）和蛋白质免疫印迹（western blot，WB）法检测HIF-1α、PI3K/Akt/mTOR信号通路蛋白及脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）、神经生长因子（nerve growth factor，NGF）、胰岛素样生长因子（insulin-like growth factors，IGF-1α）的表达情况。结果 胶质细胞OGD/R条件确定为OGD4h/R24h，给药浓度确定为SAL 25 μg·mL-1、PNS 6.25 μg·mL-1。与OGD/R组相比，SAL 25 μg·mL-1、PNS 6.25 μg·mL-1、SAL 25 μg·mL-1与PNS 6.25 μg·mL-1合用均能增强损伤后星形胶质细胞活力（P＜0.05），升高MMP，降低ROS释放量（P＜0.05），降低损伤后星形胶质细胞HIF-1α蛋白和mRNA的表达，升高磷脂酰肌醇激酶（PI3K）磷酸化水平（P＜0.05）；SAL还可升高mTOR蛋白磷酸化水平（P＜0.05），PNS可提高Akt磷酸化水平（P＜0.05），增加损伤星形胶质细胞BDNF mRNA 表达（P＜0.05）；SAL、SAL与PNS合用能增加损伤后星形胶质细胞 BDNF、NGF、IGF-1α mRNA 表达（P＜0.05）。结论 丹参多酚酸和三七总皂苷组分合用可保护OGD/R损伤后星形胶质细胞线粒体、促进胶质细胞表达神经营养因子BDNF、NGF、IGF-1α。     

Synergistic actions of pemphigus vulgaris IgG,Fas-ligand and tumor necrosis factor-α during induction of basal cell shrinkage and acantholysis

This study tested a recently proposed “Basal Cell Shrinkage” hypothesis of pemphigus acantholysis through a quantitative analysis of individual and cooperative effects of pemphigus vulgaris (PV) IgG, Fas-ligand (Fas-L) and tumor necrosis factor-α (TNFα) on keratinocyte (KC) volume (i.e. cell size) and adhesive properties. Exposure of KC monolayers and MatTek EpiDermFT? tissues cultures to the physiologic concentrations of Fas-L, TNFα or IgGs from two PV patients resulted in various degrees of reversible changes, which were not observed in control cultures either exposed to normal IgG or left intact. Within 12–24 h of exposure, basal cells in experimental cultures lost their ability to form stress fibers, retracted cytoplasmic aprons and formed keratin aggregates, indicating that their cytoskeleton collapsed. The cell volume decreased significantly (p < 0.05) as the polygonal cell shape changed to a round one. The shrunk cells detached from their neighbors and the substrate, resulting in a reciprocal increase of both the areas of acantholysis and the number of detached KCs, respectively. Since in the skin of PV patients, KCs are targeted by autoantibodies concomitantly with being exposed to autocrine and paracrine pro-apoptotic and pro-inflammatory cytokines, we combined PV IgG with Fas-L and/or TNFα in the cell culture experiments. This amplified several fold an ability of PV IgG to cause basal cell shrinkage and detachment. The obtained results demonstrated for the first time that PV IgG works together with Fas-L and TNFα to induce acantholysis via basal cell shrinkage, which provides a novel mechanism explaining successful treatment of PV patients with TNFα inhibitors.     

Rinderpest Virus Sequestration and Use in Posteradication Era

After the 2011 declaration of rinderpest disease eradication, we surveyed 150 countries about rinderpest virus stocks. Forty-four laboratories in 35 countries held laboratory-attenuated strains, field strains, or diagnostic samples. Vaccine and reagent production and laboratory experiments continued. Rigorous standards are necessary to ensure that stocks are kept under safe conditions.     

Factors Contributing to Vitamin D Status at Hospital Admission for Pulmonary Exacerbation in Adults With Cystic Fibrosis

BackgroundIndividuals with cystic fibrosis (CF) have difficulty maintaining optimal vitamin D status due to pancreatic insufficiency-induced malabsorption, inadequate sunlight exposure, and poor intake of vitamin D containing foods. Vitamin D deficiency may increase the risk of pulmonary exacerbations of CF. The objective of this study was to assess factors impacting vitamin D status in patients with CF recently hospitalized for a pulmonary exacerbation of CF.MethodsThis was a pre-planned analysis of vitamin D intake in patients enrolled in a multi-center, double-blind, randomized controlled study examining vitamin D therapy for pulmonary exacerbation of CF. Demographic information, responses from a habitual sun exposure questionnaire and food frequency questionnaire, and vitamin D supplement usage were queried and compared to serum 25-hydroxyvitamin D (25(OH)D) concentrations.ResultsA total of 48 subjects were included in this analysis. Subjects were taking approximately 1,200 IU of vitamin D daily. Reported vitamin D intake, age, race, employment, and education were not significantly associated with vitamin D status in this population. However, smoking status, sunlight exposure in the last 3 years, and skin type (in the bivariate model) were all significantly associated with vitamin D status (all p<0.05).ConclusionsSunlight exposure was the most predictive determinant of vitamin D status in patients with CF prior to pulmonary exacerbation. Subjects reported vitamin D intake below the recommended amounts. The role and mode of optimizing vitamin D status prior to a pulmonary exacerbation needs further investigation.     

Expression and clinical significance of B cell translocation gene 2 in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is widely known as a highly fatal cancer, and thus it is important to identify tumor-specific and radiosensitivity-specific markers in ESCC. B cell translocation gene 2 (BTG2) has been considered a novel tumor suppressor gene or radiotherapy sensitivity-associated gene. However, the relationship between BTG2 and ESCC development and radiotherapy sensitivity is uncertain. The present study aims to explore the expression and clinical significance of B cell translocation gene 2 (BTG2) in ESCC by analyzing the RNAseq data from the TCGA and immunohistochemical staining of ESCC samples. We found that the level of BTG2 mRNA was significantly decreased in ESCC patients, and further decreased significantly in radiotherapy resistant patients compared to sensitive patients. The positive expression rate of BTG2 protein was 56.0% (103/184) in 184 ESCC tissue samples and 84.0% (42/50) in normal esophageal mucosal samples, respectively. The positive ratios of BTG2 expression in radiotherapy-sensitive group and radiotherapy resistant group were 57.9% (22/38) and 23.5% (4/17), respectively. Furthermore, the analysis indicates that the expression level of BTG2 significantly correlated with lymph node metastasis and clinical staging in ESCC patients. A multivariate analysis with Cox regression model showed that BTG2 level was an independent risk factor affecting the prognosis of ESCC patients. Above all, the downregulation of BTG2 may be used as a molecular marker to identify and predict ESCC progression and radiosensitivity.     

Concurrent Validity and Reliability of a Low-Cost Dynamometer to Assess Maximal Isometric Strength in Neck Movements

ObjectiveThis study aimed to evaluate the concurrent validity and reliability of a low-cost digital dynamometer to assess maximal isometric strength in neck movements.MethodsTwelve recreationally active participants (6 women, 6 men; age: 24.1 ± 3.4 years; height: 1.71 ± 0.06 m; weight: 64.6 ± 11.7 kg) performed neck flexion, extension, and lateral flexion, and maximal isometric strength was simultaneously measured using an isokinetic dynamometer (gold standard) and a digital dynamometer to evaluate the concurrent validity of the latter. One week later, all the participants repeated 3 trials of each neck movement (3 minutes apart) registered only with the digital dynamometer. The first and second trial were guided by tester 1 and the third trial was guided by tester 2.ResultsThe concurrent validity of the digital dynamometer showed a nearly perfect correlation between both devices (r > 0.986, P < .001), with Bland-Altman plots showing absolute agreement. Intertester and intratester reliability were nearly perfect for all neck movements (intraclass correlation coefficient > 0.86).ConclusionThe low-cost digital dynamometer showed valid and reliable measurements of maximal isometric strength in neck movements.     

The effect of folic acid on genetic damage induced by ethanol in human lymphoblast cell line

目的:探讨叶酸(folic acid,FA)对乙醇(ethanol,EtOH)诱发的人成淋巴细胞遗传损伤的影响.方法:人成淋巴细胞株GM12593培养在含有不同FA浓度(20、200、2 000 nmol/L)的RPMI-1640培养基中,并同时在每种FA浓度的培养体系中分别加入0.09％、0.36％和1.34％ (V/V)的EtOH,8 d后用细胞松弛素B(cytochalasin B,CB)处理28 h,胞质阻断微核细胞组分析(cytokinesis-block micronucleus cytome assay,CBMN Cyt)比较不同培养条件下的细胞遗传损伤,包括微核化双核细胞(micronucleated binueleated cell,MNed BNC)、核芽(nuclear bud,BUD)、核质桥(nucleoplasmic bridges,NPB)的频率差异.结果:乙醇在受试细胞中诱发MNed BNC、BUD和NBP频率显著升高(P＜0.01)；2 000 nmol/L的叶酸能显著降低由乙醇诱发的MNed BNC、BUD和NBP频率(P＜0.01).结论:乙醇对细胞遗传物质具有损伤效应,叶酸对乙醇的遗传毒性具有防护效应.     

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10–50?ng ml?1

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the ‘grey zone'' (2.0–10.0 ng ml⁻¹). However, the PSA ‘grey zone'' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10–50 ng ml⁻¹. Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10–19.9 ng ml⁻¹ PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20–50 ng ml⁻¹ were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10–50 ng ml⁻¹. In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10–50 ng ml⁻¹ regarding their PCa risks.