Hypoxia-induced factor-1 alpha upregulates vascular endothelial growth factor C to promote lymphangiogenesis and angiogenesis in breast cancer patients

Hypoxia-induced factor-1 alpha （HIF-1α） affects many effector molecules and regulates tumor lymphangio- genesis and angiogenesis during hypoxia. The aim of this study was to investigate the role of HIF-1α in the regu- lation of vascular endothelial growth factor C （VEGF-C） expression and its effect on lymphangiogenesis and an- giogenesis in breast cancer. Lymphatic vessel density （LVD）, microvessel density （MVD） and the expressions of HIF-1α and VEGF-C proteins were evaluated by immunohistochemistry in 75 breast cancer samples. There was a significant correlation between HIF-1α and VEGF-C （P = 0.014, r = 0.273, Spearman＇s coefficient of correlation）. HIF-1α and VEGF-C overexpression was significantly correlated with higher LVD （P = 0.003 and P = 0.017, re- spectively）, regional lymph nodal involvement （P = 0.002 and P = 0.004, respectively） and advanced tumor, node, metastasis （TNM） classification （P = 0.001 and P = 0.01, respectively）. Higher MVD was observed in the group expressing higher levels of HIF-1α and VEGF-C （P = 0.033 and P = 0.037, respectively）. Univariate analysis showed shorter survival time in patients expressing higher levels of HIF-1α and VEGF-C. HIF-1α was also found to be an independent prognostic factor of overall survival in multivariate analysis. The results suggest that HIF-1α may affect VEGF-C expression, thus acting as a crucial regulator of lymphangiogenesis and angiogenesis in breast cancer. This study highlights promising potential of HIF- 1α as a therapeutic target against tumor lymph node me- tastasis.     

Expression feature of CD3, FcεRIγ, and Zap-70 in patients with chronic lymphocytic leukemia

In leukemia patients, T-cell function has been suppressed with the disease progress. Patients with chronic lymphocytic leukemia (CLL) are all to a degree immunodeficient. In order to elucidate the feature of T-cell receptor signal transduction in CLL, the expression levels of CD3γ, δ, ε, and ζ chain, FcεRIγ, and Zap-70 genes in peripheral blood mononuclear cells (PBMCs) were analyzed. Real-time polymerase chain reaction with SYBR Green technique was used for detecting the gene expression level in PBMCs from 13 patients with CLL, 13 healthy individuals, and 10 B-cell acute lymphocytic leukemia (B-ALL) served as control. The β2-microglobulin gene was used as an endogenous reference. Relative mRNA expression level of genes was analyzed by using the 2(-ΔCt) × 100% method. Significant lower expression levels of CD3γ, ε, and ζ chain genes, as well as FcεRIγ gene were found in CLL samples. Moreover, there was lost the negative correlation of the expression levels between CD3ζ and FcεRIγ genes. The expression level of Zap-70 in CLL was lower than those from healthy controls, while higher than those from B-ALL group. There was no significant correlation between the expression levels of CD3ζ and Zap-70 genes neither in the healthy group nor in the CLL group. In conclusion, the results provide a global gene expression profile of CD3γ, δ, ε, and ζ chains, and the CD3ζ-related genes FcεRIγ and Zap-70 in CLL. Deficiency of these gene expression levels might represent the feature related to T-cell immunodeficiency. The study might contribute to better understand the cellular immune features in CLL patients.     

HIV感染者健康教育满意状况及影响因素调查

目的 了解上海市某艾滋病定点收治医院HIV感染者对护理健康教育的满意度,为开展针对性健康教育提供参考.方法 采用自行设计的问卷对209例HIV感染者进行健康教育满意度的调查.结果 209例HIV感染者中,健康教育满意率不足50%;不同诊疗方式、文化程度及身体状况患者健康教育满意度比较,差异有统计学意义（P＜0.05,P＜0.01）.结论 HIV感染者对医院提供的健康教育满意度不高.艾滋病专科护士应根据患者不同特质有针对性地开展内容丰富、形式多样的健康教育.     

Guided bone regeneration using collagen membranes for sinus augmentation

We investigated the effect of guided bony regeneration using collagen membranes for sinus augmentation in the first maxillary molars of 18 adult female beagle dogs. The teeth were extracted bilaterally and the sinus floors were lifted with simultaneous implantation. The grafted material composed of a combination of autografts and Bio-oss in a 2:1 ratio. On the experimental side in each dog, collagen membrane was folded at the lateral osteotomy window, at the apex of the implants, and at a certain part of the palatal bone. On the opposite (control) side, the collagen membrane covered the osteotomy window. Six animals were killed at each of 4, 12, and 24 weeks postoperatively. Gross observation, biomechanical testing, and histological examinations were made. On the experimental side, grafted materials showed no obvious resorption or subsidence, and a new bone had formed at the apex of the implants. On the control side, the grafted materials had been shifted and absorbed. Histological examination showed increased formation of a new bone in the experimental group, which matured over time. At 4 weeks, inflammatory cells were present in the control group, which showed less maturation of the new bone. The pull-out force increased with time and, at week 24, there was a significant difference in pull-out force between the two groups (p<0.01). Guided bony regeneration with the enfolded coverage of membrane can effectively reduce resorption of grafted bone on the apical surface of implants and stimulate formation of the new bone in sinus augmentation.     

Genetic polymorphisms of new 22 autosomal STR loci in the Mongolian ethnic group

The Microreader™ 23SP ID System is a novel STR kit, but there are no Mongolian data related to this kit. In this study, allelic frequencies and forensic parameters were obtained from 505 unrelated healthy Mongolians. These samples were amplified using the kit. The dataset successfully passed quality control after being submitted to STRidER (STRidER dataset reference STR000198). A total of 264 alleles were observed, with corresponding allelic frequencies ranged from 0.001 to 0.378. The combined power of discrimination (CPD) and combined probability of exclusion (CPE) of the 22 autosomal STR loci were 0.999999999999999999999999999217318 and 0.999999999776042, respectively. Furthermore, population differentiation comparisons involving previously reported groups were conducted.

     

Administration of Pigment Epithelium-Derived Factor Inhibits Airway Inflammation and Remodeling in Chronic OVA-Induced Mice via VEGF Suppression

Purpose

Pigment epithelium-derived factor (PEDF) is a recently discovered antiangiogenesis protein. PEDF possesses powerful anti-inflammatory, antioxidative, antiangiogenic, and antifibrosis properties. It has been reported that PEDF can regulate vascular endothelial growth factor (VEGF) expression. This study aimed to evaluate whether recombinant PEDF protein could attenuate allergic airway inflammation and airway remodeling via the negative regulation of VEGF using a murine model of chronic ovalbumin (OVA)-induced asthma and BEAS-2B human bronchial epithelial cells.

Methods

In an in vivo experiment, mice sensitized with OVA were chronically airway challenged with aerosolized 1% OVA solution for 8 weeks. Treated mice were given injections of recombinant PEDF protein (50 or 100 µg/kg body weight) via the tail vein. In an in vitro experiment, we investigated the effects of recombinant PEDF protein on VEGF release levels in BEAS-2B cells stimulated with IL-1β.

Results

Recombinant PEDF protein significantly inhibited eosinophilic airway inflammation, airway hyperresponsiveness, and airway remodeling, including goblet cell hyperplasia, subepithelial collagen deposition, and airway smooth muscle hypertrophy. In addition, recombinant PEDF protein suppressed the enhanced expression of VEGF protein in lung tissue and bronchoalveolar lavage fluid (BALF) in OVA-challenged chronically allergic mice. In the in vitro experiment, VEGF expression was increased after IL-1β stimulation. Pretreatment with 50 and 100 ng/mL of recombinant PEDF protein significantly attenuated the increase in VEGF release levels in a concentration-dependent manner in BEAS-2B cells stimulated by IL-1β.

Conclusions

These results suggest that recombinant PEDF protein may abolish the development of characteristic features of chronic allergic asthma via VEGF suppression, providing a potential treatment option for chronic airway inflammation diseases such as asthma.     

主要抗结核药物肝脏毒性的动物实验研究

目的探讨肝脏脂质过氧化反应和肝药酶活性改变与抗结核药物肝毒性的关系.方法健康成年SD大鼠56只,随机分为7组：INH（isoniazid,H）组、RFP（rifampicin,R）组、PZA（pyrazinamide,Z）组、HR组、RZ组、HRZ组和生理盐水对照组.分别灌药10 d后处死大鼠,取肝脏切片,电子显微镜下观察肝脏病理变化,制备肝匀浆测定MDA（Maleic Dialdehyde）、SOD（Superoxide Dismutase）、GSH（reduced glutathione）和P450含量.结果各实验组MDA和P450均有不同程度升高,SOD和GSH有不同程度降低,肝脏病理变化与脂质过氧化反应、肝药酶有相关性.结论异烟肼、利福平、吡嗪酰胺均可引起大鼠的脂质过氧化指标的改变及肝脏细胞的病理损害,多种药物联用比单用改变明显;抗结核药物肝脏毒性与脂质过氧化反应程度关系密切,吡嗪酰胺组比其他单用药组肝脏毒性大.利福平有明显肝药酶诱导活性.     

比例辅助通气对胎粪吸入综合征新生儿血浆中肿瘤坏死因子-α、白细胞介素-8和血管内皮生长因子水平的影响

目的：探讨比例辅助通气（PAV）对新生儿胎粪吸入综合征（MAS）患儿血浆中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-8和血管内皮生长因子（VEGF）水平的影响。方法选择2011年1月至2013年10月在扬州大学医学院附属淮安市妇幼保健院住院治疗的30例新生儿 MAS患儿为研究对象,按照随机数字表法,将其分为PAV组（n=15,给予PAV模式支持）和同步间隙指令通气（SIMV）组（n=15,给予SIMV模式支持）。随机选取同期在本院产科出生的10例健康足月新生儿纳入对照组。3组患儿的性别、胎龄、出生体质量等一般临床资料比较,差异无统计学意义（P〉0.05）。采用酶联免疫吸附测定法测定各组新生儿生后1 d和3 d时血浆 TNF-α、IL-8和 VEGF的水平（本研究遵循的程序符合扬州大学医学院附属淮安市妇幼保健院伦理委员会制定的伦理学标准,得到该委员会批准,分组征得受试对象监护人的知情同意,并与之签署临床研究知情同意书）。结果3组血浆 TNF-α水平在生后1 d、3 d 比较[（1395.80±426.46）ng/L vs.（1428.27±414.24）ng/L vs.（374.30±229.91）ng/L;（1356.87±315.54）ng/L vs.（1602.13±371.10）ng/L vs.（383.30±187.00））ng/L],差异均有统计学意义（F=27.573,48.142,P=0.000）;IL-8水平在生后1 d、3 d 比较[（2.231±1.063）μg/L vs.（2.409±1.058）μg/L vs.（0.398±0.214）μg/L;（1.813±0.701）μg/L vs.（2.484±1.049）μg/L vs.（0.409±0.231）μg/L],差异均有统计学意义（F=216.198,21.173,P=0.000）,VEGF 水平于生后1 d、3 d 比较[（167.07±77.23）ng/L vs.（179.93±78.83）ng/L vs.（41.90±13.51）ng/L;（141.73±52.69）ng/L vs.（186.27±68.25）ng/L vs.（39.10±10.14）ng/L],差异亦有统计学意义（F=14.092,22.987,P=0.000）。结论在维持正常血氧饱和度和血气值的情况下,PAV模式所致肺损伤程度较 SIMV模式小。