Serum levels of angiogenic and anti-angiogenic factors: their prognostic relevance in locally advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prototype tumor wherein angiogenesis plays a vital role in its progression. The role of VEGF, a major angiogenic factor in HCC is known; however, the role of anti-angiogenic factors simultaneously with the angiogenic factors has not been studied before. Hence, in this study, the serum levels of major angiogenic [Vascular Endothelial Growth Factor (VEGF), angiopoietin-2 (Ang-2)] and anti-angiogenic (endostatin, angiostatin) factors were analyzed and correlated with clinico-radiological features and with outcome. A total of 150 patients (50 HCC, 50 cirrhosis and 50 chronic hepatitis) and 50 healthy controls were enrolled in this study. Serum levels of VEGF, Ang-2, endostatin, and angiostatin were estimated by enzyme-linked immunosorbent assay. HCC shows significantly elevated serum levels of angiogenic factors VEGF and Ang-2 and of anti-angiogenic factors endostatin and angiostatin. ROC curve analysis for serum VEGF yielded an optimal cut-off value of 225.14 pg/ml, with a sensitivity of 78 % and specificity of 84.7 % for a diagnosis of HCC and its distinction from other group. Using this value, the univariate and multivariate analysis revealed significantly poor outcome in patients with higher levels of serum VEGF (p = 0.009). Combinatorial analysis revealed that patients with higher levels of both angiogenic and anti-angiogenic factors showed poor outcome. Serum VEGF correlates with poor survival of HCC patients and, therefore, serves as a non-invasive biomarker of poor prognosis. Moreover, elevated levels of anti-angiogenic factors occur endogenously in HCC patients.     

慢性肾病患者肠道菌群特征及与微炎症因子水平的相关性

目的 探究慢性肾病（CKD）患者肠道菌群特征及与微炎症因子水平的相关性。方法 选取2018年6月至2018年12月在莆田学院附属医院诊断及治疗的CKD患者25例（CKD组）和健康体检者25例（对照组）,对两组研究对象进行肠道微生物检测,同时比较两组研究对象炎症因子水平,应用Pearson模型探究患者肠道微生态特征与炎症因子水平的相关性。结果 CKD组与对照组研究对象的肠道菌群构成具有显著差异,其中对照组双歧杆菌、乳杆菌、产甲酸草酸杆菌、草酸杆菌属、草酸杆菌科和普拉梭菌相对丰度高于CKD组,CKD组克雷伯菌属、大肠埃希菌属、肠杆菌科、瘤胃菌科、毛螺菌科、梭杆菌属和拟杆菌目相对丰度高于对照组,CKD组患者的IL-6、TNF-α、CRP和LPa水平显著高于对照组（t=3.876、4.177、2.236、3.354,P=0.000、0.000、0.030、0.002）,Pearson相关性分析显示,双歧杆菌与IL-6、TNF-α水平呈明显负相关（r=‒0.272、‒0.482,P=0.009、0.002）,乳杆菌与IL-6、LPa水平呈明显负相关（r=‒0.438、‒0.384,P=0.005、0.014）,普拉梭菌与TNF-α水平呈明显负相关（r=-0.407,P=0.009）,瘤胃菌科与IL-6、CRP水平呈明显正相关（r=0.477、0.508,P=0.002、0.001）。结论 CKD患者肠道菌群与健康人群存在明显差异,其中益生菌水平与炎症因子呈负相关,瘤胃菌科与炎症因子呈明显的正相关     

Analysis of CCR5Delta32 geographic distribution and its correlation with some climatic and geographic factors

We studied the possible effects of climatic-geographic factors on the world distribution of the mutant allele for the chemokine receptor gene CCR5, which has a 32-bp deletion (CCR5Delta32) preventing cell invasion by the primary transmitting strain of HIV-1. New data on CCR5 polymorphisms in Russian, Ukrainian, and Moldavian populations are presented. All available data on CCR5Delta32 frequencies in the Old World (number of populations n = 77) were used for construction of a geographical gene map to analyze possible correlations between allele frequencies and eight climatic-geographic parameters. A strong positive correlation was found between the allele frequency and latitude (r = 0.72), a strong negative correlation with annual radiation balance (r = -0.66), and a weaker negative correlation with longitude (r = -0.34). Partial correlations were calculated excluding the influence of latitude. The negative correlation between the allele frequency and annual radiation balance decreased (r = -0.42), but remained large and significant. We propose that the existence of correlations between the cline of CCR5Delta32 frequencies and climatic-geographic parameters provides evidence for a possible effect of either natural environmental factors or large-scale population movements on the distribution of this allele.     

Serum cathepsin K levels of patients with longstanding rheumatoid arthritis: correlation with radiological destruction

Cathepsin K is a cysteine protease that plays an essential role in osteoclast function and in the degradation of protein components of the bone matrix by cleaving proteins such as collagen type I, collagen type II and osteonectin. Cathepsin K therefore plays a role in bone remodelling and resorption in diseases such as osteoporosis, osteolytic bone metastasis and rheumatoid arthritis. We examined cathepsin K in the serum of 100 patients with active longstanding rheumatoid arthritis. We found increased levels of cathepsin K compared with a healthy control group and found a significant correlation with radiological destruction, measured by the Larsen score. Inhibition of cathepsin K may therefore be a new target for preventing bone erosion and joint destruction in rheumatoid arthritis. However, further studies have to be performed to prove that cathepsin K is a valuable parameter for bone metabolism in patients with early rheumatoid arthritis.     

Serum cathepsin K levels of patients with longstanding rheumatoid arthritis: correlation with radiological destruction

Cathepsin K is a cysteine protease that plays an essential role in osteoclast function and in the degradation of protein components of the bone matrix by cleaving proteins such as collagen type I, collagen type II and osteonectin. Cathepsin K therefore plays a role in bone remodelling and resorption in diseases such as osteoporosis, osteolytic bone metastasis and rheumatoid arthritis. We examined cathepsin K in the serum of 100 patients with active longstanding rheumatoid arthritis. We found increased levels of cathepsin K compared with a healthy control group and found a significant correlation with radiological destruction, measured by the Larsen score. Inhibition of cathepsin K may therefore be a new target for preventing bone erosion and joint destruction in rheumatoid arthritis. However, further studies have to be performed to prove that cathepsin K is a valuable parameter for bone metabolism in patients with early rheumatoid arthritis.     

成年住院患者真菌感染的流行病学及预后因素分析

目的 了解成年住院患者真菌感染的流行病学特点及预后相关因素,为早期发现和治疗真菌感染提供依据。方法 分析2015年5月至2016年4月于浙江省人民医院进行住院治疗的真菌感染患者（共434例,年龄均大于16岁,均为院内感染,不含真菌性阴道炎）的流行病学特征,,并对影响患者预后的因素进行回顾性分析。结果 434例住院患者真菌感染病例中,病原菌主要为白假丝酵母,占78.81%,易感病区为主要呼吸内科、血液科、重症监护室,分别占21.89%、9.45%和8.76%。易感部位主要是下呼吸道,占74.66%。在真菌感染患者的预后因素分析中,性别（男）、年龄、肿瘤、呼吸衰竭、心脏疾病和免疫抑制剂方面差异均具有统计学意义（P呼吸衰竭>性别（男）>肿瘤>年龄>心脏疾病。结论 真菌感染主要由白假丝酵母引起,好发于下呼吸道;患者主要集中在呼吸内科、血液科和重症监护室等。年龄较大的男性真菌感染患者预后不及一般患者,当伴有肿瘤、呼吸衰竭、使用免疫抑制剂等预后因素时,预后会更差。因此,在治疗此类患者时,应密切监测患者情况,并及时给予抗真菌治疗,以提高患者的治愈率和存活率。     

Serum levels of interleukin-13 and interferon-gamma from adult patients with asthma in Mysore

Serum protein analysis for noninvasive quantification of airway inflammation in asthma is a promising research tool in the field of lung diseases. Cytokines are believed to have major role in inflammatory process of the airways of the lung. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4 and interleukin (IL)-13, and Th1 cells, which secrete interferon (IFN)-gamma in asthma. To test the hypothesis that serum IL-13 and IL-4 levels may be elevated whereas IFN-gamma would be decreased in this cohort of patients, a property that could make them possible candidate biomarkers in determining asthma occurrence and severity, we measured concentrations of IL-4, IL-13 and IFN-gamma in serum samples of 88 subjects (44 normal, 12 with mild asthma, 16 with moderate asthma, and 16 with severe asthma). Serum Levels of IL-4, IL-13, and IFN-gamma were determined by an enzyme-linked immune-sorbent assay (ELISA). Median serum level of IFN-gamma in asthmatic patients was 8.0pg/ml, while it was 11.4pg/ml in healthy controls. However, the difference was not significant. Among the different age groups in whom IFN-gamma was assessed, the highest median value in both cases and controls was observed in the age group of 31-40years. The median serum level of IL-13 was 40.0pg/ml in asthmatic patients and 58.25pg/ml in healthy controls. The difference was not significant. On subgroup analysis, no significant difference of IFN-gamma and IL-13 between asthma of different severities was observed. The study also revealed nonsignificant difference of serum cytokines with the duration of asthma, number of allergens, and severity of sensitization. Normal serum levels of IFN-gamma and IL-13 in asthmatic patients suggest their neutral role in the inflammatory process; however, more studies are required to establish the effect of these cytokines in adulthood asthma in different ethnic populations.     

Proteins expressed in osteosarcoma and serum levels as prognostic factors

Osteosarcoma is the most frequent highly malignant bone-tumor with a peak manifestation during the second and third decade of life. Although survival rate increased up to 60-70% within the last 20 years, the problem of non-response to chemotherapy remains. Initial tumor size and response to neoadjuvant chemotherapy are the most accepted prognostic factors used for postoperative stratification of chemotherapy. The identification of patients with a bad response to therapy at the time of diagnosis would facilitate already a preoperative stratification of chemotherapy or a more aggressive regime to increase survival. This review reflects on recently described molecular markers but not on clinical parameters in human osteosarcoma with respect to their prognostic potential. This includes p53, the p-glycoprotein, the multidrug resistance gene, the humen epidermal growth factor receptor and metallothionein expression. Heat shock proteins have recently become important in osteosarcoma because of their prognostic value and their role in drug resistance. A short overview of serological markers is also given. Further results on drug resistance and survival may be provided by ongoing studies, which investigate the role of proteins of the apoptotic and antiapoptotic families in human osteosarcoma.     

Serum ferritin in colorectal cancer patients and its prognostic evaluation

The aim of this study was to investigate the relationship between preoperative serum ferritin levels, clinico-pathological parameters and survival analysis of patients with colorectal cancer. Ninety-four patients (57 males) with a mean age of 65 years (39-87 years) underwent 63 curative and 31 palliative operations. Follow-up was at least 5 years. Patients were categorized with normal (30-215 ng/mL in men and 11-148 ng/mL in women), low, or high serum ferritin levels. Prognostic evaluation was undertaken with stratified survival analysis and Cox's regression model. Twenty-nine of the patients (30.9%) had raised ferritin levels and 14 (14.9%) had low values. Comparisons of the survival curves showed significant differences in stage C disease; specifically, patients with either low or high ferritin levels had a shorter survival than patients with normal levels. Patients who underwent palliative surgery and had high ferritin serum values also had a shorter survival. In multivariate analysis, the variables with a negative effect on survival were stage, serum ferritin levels and age. Our data suggest that patients with advanced colorectal cancer having normal preoperative serum ferritin levels may have a better prognosis, although the prognostic value related to this association requires further investigation.     

Serum levels of trace elements and iron-deficiency anemia in adult Vietnamese

This study was aimed at assessing the serum levels of vitamin A, copper, zinc, selenium, and iron among adult Vietnamese with and without iron-deficiency anemia. Blood was collected from adult Vietnamese living in the midland of northern Vietnam. One hundred twenty-three subjects in the age range 20–60 yr were included in the study. Anemia, where the concentration of hemoglobin in whole blood is less than 120 g/L in females and 130 g/L in males, was found in 30% (37/123) of the study population. The levels of vitamin A and selenium in the sera of anemic subjects (n=37) were significantly lower than that in nonanemic group (n=86). On the other hand, no significant differences were observed in the concentrations of copper and zinc between the two groups. This study was the first to show serum levels of trace elements in adult Vietnamese, providing useful baseline information for further studies.     

纳帕海高原湿地浮游病毒丰度及与环境因子相关性研究

目的 利用EFM技术对纳帕海湿地不同季节7个水样样品中的浮游病毒丰度开展了调查,并对影响浮游病毒丰度的环境因子进行了相关性分析。方法 元素检测,叶绿素a检测,荧光显微镜检测浮游细菌及浮游病毒的丰度。结果 从生态分布上来看旱季和雨季浮游病毒丰度的平均值分别为3.63×106/mL和3.71×107/mL,浮游病毒丰度季节性变化不显著。从对影响浮游病毒丰度的环境因子相关性分析来看,旱季浮游病毒与Chl-a具有弱负相关性（r=0.49,P<0.05）;而雨季浮游病毒丰度与Chl-a具有显著正相关性（r=0.37,P<0.05）,表明雨季纳帕海湿地浮游病毒丰度受Chl-a含量的影响较大。旱季浮游病毒丰度与温度显著负相关,虽然在雨季浮游病毒丰度与温度也呈负相关,但并不显著;在雨季,水体pH变化较明显,而浮游病毒丰度与水体pH呈显著负相关,表明湿地的来水主要在雨季,而离子组成变化大。虽然在雨季和旱季,从多点采样的平均值来看浮游病毒丰度并无明显差异,但从一些局部的采样点来看,雨季的浮游病毒丰度显著高于旱季,说明在纳帕海区域浮游病毒的分布并不平均,因采样点环境的不同会产生明显的区别。结论 对纳帕海高原湿地浮游病毒生态分布的调查,是对该地域生态学研究的补充,使得这一独特地理环境的微生物研究更加系统化。     

Bombyxin secretion in the adult silkmoth Bombyx mori: sex-specificity and its correlation with metabolism

Changes in the hemolymph bombyxin titer of the adult silkmoth Bombyx mori were investigated by time-resolved fluoroimmunoassay. Immediately after eclosion, hemolymph bombyxin titers were low in both males and females, and then increased steeply in males to a very high level and this high titer was maintained for at least 3 h, whereas the titer increment in females was small and transient. The difference in the change of bombyxin titer between males and females suggests that bombyxin is responsible for the regulation of physiological changes underlying sexually different activities of the adult moths. However, no evidence was obtained that bombyxin controls adult metabolism as far as the effects of bombyxin on the concentrations of carbohydrates and lipids in the hemolymph were investigated. The change in the hemolymph trehalose concentration was almost the same between sexes, and between intact and neck-ligated moths. Furthermore, bombyxin injection did not affect the hemolymph trehalose concentration nor trehalase activity in the muscle. Although the hemolymph lipid concentration rose after eclosion in males, it was not influenced by bombyxin. These results exhibit striking contrast to the results of our previous study, in which bombyxin showed hypotrehalosemic activity in the larval stage, thus indicating that the action of bombyxin changes during metamorphosis.     

Serum levels of angiogenic cytokines in systemic lupus erythematosus and their correlation with disease activity

We investigated the serum concentration of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) using an enzyme-linked immunosorbent assay (ELISA) in a group of 60 patients with systemic lupus erythematosus (SLE), and 20 healthy controls. We also examined the possible association between the serum concentrations of these factors and certain clinical, laboratory parameters and SLE activity. HGF, VEGF and TGF-beta1 were detectable in all patients with SLE, and in all normal individuals. bFGF was measurable in 70% of the patients with SLE and in 65% of the healthy controls. The HGF level was higher in active SLE (median 1,019.5pg/ml) than in inactive SLE (median 787.8 pg/ml) (p < 0.005) or in the control group (median 847.0 pg/ml) (p < 0.009). The level of VEGF in active SLE was also higher (203.5 pg/ml) than in inactive disease (116.1 pg/ml) (p < 0.05) or in healthy persons (133.5 pg/ml) (p < 0.04). The levels of bFGF and TGF-beta1 were similar for both the active and inactive SLE, and the control group (p > 0.05). We found a significant, positive correlation between the levels of HGF and bFGF (r = 0.268, p < 0.04), HGF and TGF-beta1 (r = 0.365, p < 0.005) and HGF and VEGF (r = 0.327, p < 0.02) as well as VEGF and TGF-beta1 (r = 0.543, p < 0.001). We found a positive correlation between VEGF serum levels and platelet counts (r = 0.272, p < 0.04), and the TGF-beta1 concentration and platelet count (r = 0.313; p < 0.02). There was also a positive correlation between HGF serum concentration and the SLE activity score (r = 0.435, p < 0.001), as well as between the level of VEGF and SLE activity (r = 0.252, p = 0.05). In conclusion, serum levels of the angiogenic factors HGF and VEGF may be relevant in SLE pathogenesis. Their concentrations seem to be markers of SLE activity.     

Identification of prognostic factors in canine mammary malignant tumours: a multivariable survival study

Background

Although several histopathological and clinical features of canine mammary gland tumours have been widely studied from a prognostic standpoint, considerable variations in tumour individual biologic behaviour difficult the definition of accurate prognostic factors. It has been suggested that the malignant behaviour of tumours is the end result of several alterations in cellular physiology that culminate in tumour growth and spread. Accordingly, the aim of this study was to determine, using a multivariable model, the independent prognostic value of several immunohistochemically detected tumour-associated molecules, such as MMP-9 and uPA in stromal cells and Ki-67, TIMP-2 and VEGF in cancer cells.

Results

Eighty-five female dogs affected by spontaneous malignant mammary neoplasias were followed up for a 2-year post-operative period. In univariate analysis, tumour characteristics such as size, mode of growth, regional lymph node metastases, tumour cell MIB-1 LI and MMP-9 and uPA expressions in tumour-adjacent fibroblasts, were associated with both survival and disease-free intervals. Histological type and grade were related with overall survival while VEGF and TIMP-2 were not significantly associated with none of the outcome parameters. In multivariable analysis, only a MIB-1 labelling index higher than 40% and a stromal expression of MMP-9 higher than 50% retained significant relationships with poor overall and disease-free survival.

Conclusions

The results of this study indicate that MMP-9 and Ki-67 are independent prognostic markers of canine malignant mammary tumours. Furthermore, the high stromal expressions of uPA and MMP-9 in aggressive tumours suggest that these molecules are potential therapeutic targets in the post-operative treatment of canine mammary cancer.     

不同哮喘控制水平患者流感嗜血杆菌的 感染水平及其与炎性水平的相关性

摘要：目的 探究不同哮喘控制水平患者流感嗜血杆菌感染程度及其与炎性因子水平的相关性。方法 选取我院2017年1月至2018年8月间诊断及治疗的285例哮喘患者,根据病情控制情况分为良好控制组（187例）、部分控制组（62例）及未控制组（36例）,比较三组流感嗜血杆菌感染情况,包括：检出率及细菌载量,同时比较患者哮喘控制测试量表（ACT）评分,诱导痰中炎症细胞及血清炎症因子水平,使用Pearson相关性分析模型探究流感嗜血杆菌载量与患者哮喘控制水平、炎症细胞及炎症因子水平的相关性。结果 三组患者ACT评分、中性粒细胞计数、嗜酸性粒细胞计数及血清IL-25、IL-33水平的差异具有统计学意义（F=7.556,4.557,7.023,16.436,11.772;均P＜0.05）,三组流感嗜血杆菌检出率（42.78% vs 58.06% vs 77.78%;χ2=16.593,P＝0.001）及细菌载量差异均具有统计学意义（t=25.150,P＜0.001）,且组内两两比较差异也具有统计学意义（均P＜0.05）。Pearson相关性分析显示流感嗜血杆菌载量与ACT评分及嗜酸性粒细胞数具有显著相关性（均P＜0.05）。结论 不同哮喘控制水平患者流感嗜血杆菌感染检出率及炎症因子水平差异明显,流感嗜血杆菌载量与ACT评分及嗜酸性粒细胞具有显著相关性。