[Whole genomic copy number variation score: an indicator of potential diagnostic and prognostic value for lung adenocarcinoma].

Objective: To verify the value of whole genomic copy number variation (WGCNV) detection and scoring system in the diagnosis and prognosis of lung adenocarcinoma. Methods: Seventy-six lung adenocarcinoma specimens including ninety-one tumor samples and twenty adjacent non-tumor lung tissue samples were collected using Laser capture microdissection (LCM). Whole genomic amplification (WGA) was used to enrich DNA and construct a sequencing library for next generation sequencing (NGS). Changes of larger than 5Mb CNV in this study were analyzed and scored. The nuclear grading and score of tumor cells in the surgery and pleural effusion cytology of lung adenocarcinoma specimens were evaluated separately. For each case, we evaluated (1) nuclear size, (2) mitotic counts, (3) nuclear atypia, (4) atypical mitoses. The data of disease-free survive (DFS) and overall survive (OS) were collected for assessing the prognostic value of WGCNV score. Meanwhile, receiver operating characteristic (ROC) and area under curve (AUC) were used to define a cut-off value and evaluate the diagnostic significance in lung adenocarcinoma. Results: The WGCNV scores of twenty adjacent non-tumor lung tissue samples were treated as normal control and all of WGCNV scores of tumor samples range from 0 to 9.95, the median score was 2.7. The WGCNV scores were divided into three groups: low score group <1.74, medium score grade 1.74~4.23, high score grade >4.23. The WGCNV score was positively associated with the nuclear grade scoring (r=0.780 90, P<0.001). The result for evaluation of prognostic value of the WGCNV scores showed that comparing with low WGCNV score group, Hazard Ratio (HR) of medium score group was 4.11 (95%CI=0.72~23.57) and high score group was 2.07 (95%CI=0.30~14.12). These results suggested that the risks of the medium and high WGCNV score group elevated. According to the analysis results of ROC curve, when the cut off value was 0.01, the sensitivity and specificity for lung adenocarcinoma diagnosis were 97.8% and 95.0% respectively, the positive predictive value (PPV) and negative predictive value (NPV) were 99.0% and 90.1%, respectively, the AUC was 0.981. In the differentiation of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) group and invasive adenocarcinoma group, when the cut off value was 1.8, the sensitivity and specificity between the two groups were 78.1% and 94.4%, and the PPV and NPV were 98.0% and 52.0%, respectively, the AUC was 0.896. Conclusion: This study verifies that WGCNV scoring system has a potential diagnostic and prognostic value in lung adenocarcinoma.

Evaluation of safety and efficacy of different continuous blood Purification methods in treating infantile sepsis.

The aim of this study was to compare the safety and the efficacy of two methods of continuous blood purification (CBP), continuous veno-venous hemofiltration (CVVH) and high volume hemofiltration (HVHF), for treatment of infantile sepsis. Eighty-six children with sepsis were enrolled in this study and randomly divided into two groups with 47 cases in the CVVH group and 39 cases in the HVHF group. Survival rate, duration of blood filtration, mean arterial pressure (MAP), mean heart rate and SaO2, APACHE II score, procalcitonin, hs-CRP and TXB2 were compared between the two groups. Results showed that survival rate, MAP, mean heart rate and SaO2 in the two groups did not have any significant differences. Duration of blood filtration and APACHE II score in the HVHF group was significantly shorter than that in the CVVH group. After therapy, levels of procalcitonin, hs-CRP and TXB2 declined dramatically in both groups, however this reduction was more significant in the HVHF group. We conclude that HVHF is a safer and more effective method as it produced stable hemodynamics, shorter filtration time, better APACHE II scores and better results in alleviating inflammatory reactions.

Effects of stocking density on growth performance, feather growth, intestinal development, and serum parameters of geese.

This experiment was conducted to evaluate the effects of stocking density on the growth performance, feather growth, intestinal development, and serum parameters of geese. In total, 336 healthy, 28-day-old, male Yangzhou goslings were randomly allotted to 30 plastic wire-floor pens according to 5 stocking densities (2, 3, 4, 5 and 6 birds/m2). The results showed that with the stocking density increased from 2 birds/m2 to 6 birds/m2, the body weights of geese at 42 d (P < 0.001) and 70 d (P < 0.001) were reduced by 10.53% and 10.43% respectively, the primary feather lengths of geese at 42 d (P < 0.001) and 70 d (P = 0.021) were reduced by 20.38% and 6.62% respectively, whereas the feed/gain ratios for 28- to 42-d period and 28- to 70-d period increased from 2.50 to 2.90 (P = 0.001), and 3.80 to 4.24 (P < 0.001), respectively. The relative weights of the jejunum, ileum, and small intestine and the lengths of the jejunum, ileum, and small intestine were all adversely affected (P < 0.05) when stocking density was increased to 6 birds/m2. Serum concentrations of alkaline phosphatase (P = 0.013) and triiodothyronine (P < 0.001) decreased as the stocking density increased. The serum thyroxine concentration of geese from the 6 birds/m2 group was lower than that of geese from the other groups (P < 0.05). The reduction in thyroid hormone concentrations was similar to what was observed in growth rate. All the results suggested that high stocking density will adversely influence thyroid function and the developments of the body weight, body size, feathers, and small intestine. Under our experimental conditions, we recommend that the stocking density of geese should be kept to 5 or fewer birds/m2 to avoid the negative effects of high stocking density on geese.

The upper-limb volumetric changes in breast cancer survivors with axillary web syndrome.

Whether upper-limb swelling is associated with axillary web syndrome (AWS) is unknown. We recruited unilateral breast cancer (BC) patients who were scheduled for surgical intervention and lymph node dissection. The pre-operative assessment and post-operative assessment 3-4 weeks after surgery evaluated the upper-limb circumferential measurements, segmental limb volume, pain scores, grasp, shoulder range of motion (ROM), shoulder muscle power and quality-of-life scores. In the control group, the peri-elbow volume and upper-arm volume were significantly higher post-operatively than pre-operatively. In the AWS group, no significant difference was found. In comparison with the control group, the AWS group had significantly more pain, less active ROM in shoulder abduction and a lower upper-limb volume at 0-10 cm proximal to the lateral epicondyle. The incidence of lymphedema was 9.9% and was not associated with AWS. AWS is a common morbidity of lymph node dissection and causes significant pain and restricted shoulder abduction in the affected limb in BC survivors. This study is the first to investigate post-operative upper-limb volumetric changes in BC survivors with and without AWS. Our findings are of great value for the clinical effect of AWS in BC survivors, for patient education, and for developing diagnostic tools for detecting AWS.

[Current advance in saliva-derived exosome study].

There is growing interest in the whole saliva as a diagnostic fluid because of the relatively simple and non-invasive collection. Research on salivary proteomic and genomic has greatly facilitated the diagnosis and therapy of oral diseases, also revealed the molecular mechanism of the diseases. Saliva-derived exosome as a new source, with various molecular constituents of their cells of origin, including proteins, mRNA and miRNA might serve as potential biomarker. This article reviews the biological properties of saliva exosome, its separation and other aspects associated with disease.

Association between serum 25(OH) vitamin D, incident liver cancer and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case-control study.

BACKGROUND: Although vitamin D deficiency has been noted in cross-sectional studies of chronic liver disease and laboratory studies suggest possible benefits of vitamin D in preventing liver cancer, little epidemiologic data are available. METHODS: We performed a nested case-control study in the Linxian Nutrition Intervention Trials on participants developing incident liver cancer or dying from chronic liver disease over 22 years of follow-up. Baseline serum 25(OH) vitamin D was measured for 226 incident liver cancer cases, 282 chronic liver disease deaths and 1063 age-, sex- and trial-matched controls. Unconditional logistical regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The median serum vitamin D level in controls was low (20 nmol l(-1)). Compared with the lowest quartile, subjects in the fourth quartile had lower risk of chronic liver disease death (OR=0.34, 95% CI=0.21-0.55). For liver cancer incidence, risk estimates were below one, but were not statistically significant. Associations, however, were significant among participants with higher serum calcium levels (Q4 vs Q1, OR=0.43, 95% CI=0.21-0.89). Results for chronic liver disease did not vary by serum calcium level. CONCLUSION: In a low vitamin D population, higher serum 25(OH) vitamin D concentrations were associated with significantly lower risk of chronic liver disease deaths, and among those with higher serum calcium, incident liver cancer. Our results suggest a possible protective role for vitamin D in these diseases.

Identification of CHIP, a novel tetratricopeptide repeat-containing protein that interacts with heat shock proteins and negatively regulates chaperone functions.

The chaperone function of the mammalian 70-kDa heat shock proteins Hsc70 and Hsp70 is modulated by physical interactions with four previously identified chaperone cofactors: Hsp40, BAG-1, the Hsc70-interacting protein Hip, and the Hsc70-Hsp90-organizing protein Hop. Hip and Hop interact with Hsc70 via a tetratricopeptide repeat domain. In a search for additional tetratricopeptide repeat-containing proteins, we have identified a novel 35-kDa cytoplasmic protein, carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP is highly expressed in adult striated muscle in vivo and is expressed broadly in vitro in tissue culture. Hsc70 and Hsp70 were identified as potential interaction partners for this protein in a yeast two-hybrid screen. In vitro binding assays demonstrated direct interactions between CHIP and both Hsc70 and Hsp70, and complexes containing CHIP and Hsc70 were identified in immunoprecipitates of human skeletal muscle cells in vivo. Using glutathione S-transferase fusions, we found that CHIP interacted with the carboxy-terminal residues 540 to 650 of Hsc70, whereas Hsc70 interacted with the amino-terminal residues 1 to 197 (containing the tetratricopeptide domain and an adjacent charged domain) of CHIP. Recombinant CHIP inhibited Hsp40-stimulated ATPase activity of Hsc70 and Hsp70, suggesting that CHIP blocks the forward reaction of the Hsc70-Hsp70 substrate-binding cycle. Consistent with this observation, both luciferase refolding and substrate binding in the presence of Hsp40 and Hsp70 were inhibited by CHIP. Taken together, these results indicate that CHIP decreases net ATPase activity and reduces chaperone efficiency, and they implicate CHIP in the negative regulation of the forward reaction of the Hsc70-Hsp70 substrate-binding cycle.

Induction of vascular endothelial growth factor in balloon-injured baboon arteries. A novel role for reactive oxygen species in atherosclerosis.

Neovascularization is a hallmark of neointimal formation in atherosclerotic plaques and restenotic lesions. Vascular endothelial growth factor (VEGF) promotes neovascular growth, whereas oxidative stress is a potent factor in vascular cell proliferation. To investigate the mechanisms of neovascular formation, we treated human and rat vascular smooth muscle cells (VSMCs) with H2O2. Northern blot analysis demonstrated a dose- and time-dependent increase in VEGF mRNA, with a maximum of 4-fold at 3 hours (200 mumol/L). As determined by immunoblotting and enzyme-linked immunosorbent assay, VEGF protein expression and secretion were similarly increased. Human umbilical vein endothelial cells were treated with conditioned medium from VSMCs incubated with 200 mumol/L H2O2. DNA synthesis, measured by thymidine incorporation, was increased 4-fold compared with control, an effect that was blocked by a neutralizing anti-VEGF antibody. The lipid peroxidation product 4-hydroxynonenal (1 mumol/L), an endogenous reactive oxygen species present in human atherosclerotic lesions, also increased VEGF secretion in VSMCs in a similar time-dependent fashion. Immunohistochemical staining and in situ hybridization of aortic sections from balloon-injured baboons demonstrated increased VEGF expression in discrete areas of the neointima and media compared with control sections, and expression correlated with the generation of 4-hydroxynonenal. Regulators of VEGF expression, such as reactive oxygen species, may enhance neovascularization of atherosclerotic and restenotic arteries.

[Dynorphin and atriopeptin may be involved in the depressor mechanism of clonidine].

Intravenous injection (iv) of clonidine significantly induced depressor and bradycardiac responses in rats. These responses were found to be blocked by iv alpha-adrenoreceptor blocker phentolamine, intraperitoneous injection (ip) of naloxone (10mg/kg) or iv antidynorphin-IgG(80 microliters). Furthermore, clonidine (iv) induced a significant increase of urine volume, which was also partly blocked by naloxone (10mg/kg). A dramatic increase of rat plasma immunoreactive atriopeptin induced by clonidine (iv) was partly antagonised by pretreatment with naloxone (4mg/kg) or phentolamine (10mg/kg). These results show that dynorphin and atriopeptin may be involved in the depressor mechanism of clonidine.

A dynorphin peptide induces hypotension by stimulating the release of atrial natriuretic peptide from rat atrium.

Intravenous injection of dynorphin A-(1-10) amide (Dyn, 81-324 nmol/kg) induced a dose-dependent hypotensive effect in the rat. This effect was antagonized by pretreatment with immunoglobulin G, purified from a specific antiserum raised against alpha-human atrial natriuretic peptide (anti-hANP-IgG), as well as by high doses of naloxone (2 or 10 mg/kg). In addition, a 12-fold increase in plasma level of atrial natriuretic peptide-like immunoreactivity (ANP-IR) was found following Dyn administration, which was accompanied by a significant decrease of atrial ANP-IR. These results suggest that the stimulated release of ANP-IR from the atrium may constitute one of the mechanisms for the depressor effect of dynorphin peptides.