Soluble CD4 effectively prevents excessive TLR activation of resident macrophages in the onset of sepsis.

T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

Expression of AQP2, AQP4 and AQP 8 in mouse intestine induced by unprocessed and processed Euphorbia lathyris.

The present research was designed to study expression of AQP2, AQP4 and AQP8 in mouse intestines induced by unprocessed and processed Euphorbia lathyris. KM mice were given by different dose lavage of unprocessed and processed Euphorbia lathyris, Euphorbia factor L1, Euphorbia factor L2, Euphorbia factor L3. Samples of mouse intestine were collected for protein levels of AQP2, AQP 4 and AQP 8 which were assessed by immunohistochemical staining and mRNA expression of AQP2, AQP 4 and AQP 8 which were quantified by Real Time-PCR. Comparing to the normal control group, the protein levels of AQP2, AQP 4 and AQP 8 were significantly decreased (P<0.05)by Semen Euphorbiae group and Semen Euphorbiae Pulveratum group (unprocessed and processed Euphorbia lathyris) induced. Protein expression of AQP2, AQP 4 and AQP 8 in the Euphorbia factor L1, Euphorbia factor L2 and Euphorbia factor L3 group were not significantly lower than normal control group. There had no differences on the levels of AQP2 and AQP 8 mRNA expressions between the high-dose group of semen Euphorbiae group, semen Euphorbiae Pulveratum group and positive control group, while significantly lower than normal control group (P<0.05). Expression of AQP4 mRNA in the Semen Euphorbiae group and Semen Euphorbiae Pulveratum group has not significantly decreased. But levels of AQP2, AQP 4 and AQP 8 mRNA in the Euphorbia factor L1 group had no significant differences in normal control group and positive control group. These findings suggest that semen Euphorbiae could regulate expression of AQP2, AQP 4 and AQP 8 protein and mRNA, which may be the possible one reason of semen Euphorbiae induces diarrhea. The semen Euphorbiae group has more significant effects on the levels of AQP2, AQP 4 and AQP 8 protein and mRNA than semen Euphorbiae Pulveratum group, which may be one of the mechanisms of processing attenuation.

Use of portable X-ray fluorescence spectroscopy and geostatistics for health risk assessment.

Laboratory analysis of trace metals using inductively coupled plasma (ICP) spectroscopy is not cost effective, and the complex spatial distribution of soil trace metals makes their spatial analysis and prediction problematic. Thus, for the health risk assessment of exposure to trace metals in soils, portable X-ray fluorescence (PXRF) spectroscopy was used to replace ICP spectroscopy for metal analysis, and robust geostatistical methods were used to identify spatial outliers in trace metal concentrations and to map trace metal distributions. A case study was carried out around an industrial area in Nanjing, China. The results showed that PXRF spectroscopy provided results for trace metal (Cu, Ni, Pb and Zn) levels comparable to ICP spectroscopy. The results of the health risk assessment showed that Ni posed a higher non-carcinogenic risk than Cu, Pb and Zn, indicating a higher priority of concern than the other elements. Sampling locations associated with adverse health effects were identified as 'hotspots', and high-risk areas were delineated from risk maps. These 'hotspots' and high-risk areas were in close proximity to and downwind from petrochemical plants, indicating the dominant role of industrial activities as the major sources of trace metals in soils. The approach used in this study could be adopted as a cost-effective methodology for screening 'hotspots' and priority areas of concern for cost-efficient health risk management.

Time Series Models for Short Term Prediction of the Incidence of Japanese Encephalitis in Xianyang City, P R China△.

Objective To construct a model of Seasonal Autoregressive Integrated Moving Average (SARIMA) for forecasting the epidemic of Japanese encephalitis (JE) in Xianyang, Shaanxi, China, and provide valuable reference information for JE control and prevention. Methods Theoretically epidemiologic study was employed in the research process. Monthly incidence data on JE for the period from Jan 2005 to Sep 2014 were obtained from a passive surveillance system at the Center for Diseases Prevention and Control in Xianyang, Shaanxi province. An optimal SARIMA model was developed for JE incidence from 2005 to 2013 with the Box and Jenkins approach. This SARIMA model could predict JE incidence for the year 2014 and 2015. Results SARIMA (1, 1, 1) (2, 1, 1)12 was considered to be the best model with the lowest Bayesian information criterion, Akaike information criterion, Mean Absolute Error values, the highest R2, and a lower Mean Absolute Percent Error. SARIMA (1, 1, 1) (2, 1, 1)12 was stationary and accurate for predicting JE incidence in Xianyang. The predicted incidence, around 0.3/100 000 from June to August in 2014 with low errors, was higher compared with the actual incidence. Therefore, SARIMA (1, 1, 1) (2, 1, 1)12 appeared to be reliable and accurate and could be applied to incidence prediction. Conclusions The proposed prediction model could provide clues to early identification of the JE incidence that is increased abnormally (≥0.4/100 000). According to the predicted Results in 2014, the JE incidence in Xianyang will decline slightly and reach its peak from June to August.

Acupuncture for the treatment of obesity in adults: a systematic review and meta-analysis.

OBJECTIVE: Meta-analysis was used to assess the clinical efficacy of acupuncture treatment for simple obesity and to provide evidence-based medical data for treating obesity with acupuncture. METHODS: A comprehensive search of studies on MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Chinese databases (Wan Fang,CNKI and VIP) from 1 January 1915 through 30 November 2015 (MEDLINE search updated through 31 December 2015) was performed. We included only randomised controlled trials (RCTs) that used acupuncture and sham acupuncture to treat simple obesity. The effect of acupuncture on simple obesity was measured using body mass index (BMI), body fat mass (BFM), waist circumference (WC), hip circumference (HC), and body weight (BW). The Jadad scale was used to assess methodological quality. The random effects model was used in the pooled analysis to adjust for the heterogeneity of the included studies, and funnel plots were used to examine publication bias. The differences between treatment groups were reported as mean differences (MD). RESULTS: Eleven RCTs were selected after all relevant literature from the electronic databases had been screened. There were 338 and 305 participants in the acupuncture and sham acupuncture groups, respectively. Auricular and electro acupuncture were both able to reduce BMI in obese patients (MD 0.47 kg/m2, 95% CI 0.35 to 0.58, p<0.001; MD 0.50 kg/m2, 95% CI 0.38 to 0.62, p<0.001). BFM change after acupuncture treatment compared with sham treatment was statistically significant (MD 0.66 kg, 95% CI 0.51 to 0.80, p<0.001). There were also significant differences in WC and HC between the acupuncture and sham acupuncture groups (MDwc2.02 cm, 95% CI 0.21 to 3.83, p=0.03; MDHC2.74 cm, 95% CI 1.21 to 4.27, p=0.0004). BW was not statistically significantly different between the acupuncture and sham acupuncture groups (MD 0.60 kg, 95% CI -0.20 to 1.39, p=0.14). Begg's test and funnel plots showed that the potential publication bias of the included studies was very slight (p>0.05). CONCLUSION: Acupuncture for simple obesity appeared to be an effective treatment, but more studies on the safety of acupuncture used to treat simple obesity are required.

Epidemiological characteristics of measles from 2000 to 2014: Results of a measles catch-up vaccination campaign in Xianyang, China.

This study was a cross-sectional case-control study aimed at (1) identifying risk factors contributing to the measles epidemic and (2) evaluating the impacts of measles-containing vaccines (MCVs), with the goal of providing evidence-based recommendations for measles elimination strategies in China. Data on measles cases from 2000 to 2014 were obtained from a passive surveillance system at the Center for Diseases Prevention and Control in Xianyang. The effectiveness of MCVs was evaluated in 357 patients with a vaccination history and 503 healthy randomly selected controls. Patient data were subjected to multivariable logistic regression modeling. From 2005 to 2014, the average incidence of measles in Xianyang was 5.42 cases per 100,000 people. The second MCV dose was highly protective in 8-month-old infants. MCVs in general have been highly protective in 8-month-old infants. Multivariable logistic regression modeling indicated that age (≥2 years vs. <2years), MCV dose 2 vaccination, and MV vaccination were each independently associated with measles case status. In conclusions: A MCV should be administered on time to all age-eligible children, reproductive-age women, and migrant populations, to maximize herd immunity to measles.

[Magnetic Response of Heavy Metal Pollution in Playground Dust of an Industrial Area].

The use of mineral magnetic measurements as a potential pollution proxy is explored as an alternative means of monitoring heavy metal pollution in playground dust in industrial areas. Dust samples were collected from playgrounds in an industrial area in Nanjing. The magnetic properties of the samples were analyzed, and the total and acid-extractable concentrations of heavy metals were measured.Mineral magnetic concentration parameters[mean magnetic susceptibility (χlf) 939.31×10-8 m3·kg-1 and saturation isothermal remanent magnetization (SIRM) 16618.74×10-5 A·m2·kg-1] indicate that the dust samples contain high concentrations of magnetic minerals when compared to the non-industrial zone of the city. High and stable S-ratio values (mean 0.97, standard deviation 0.01) indicate the prominence of ferromagnetic minerals. Low values of anhysteretic remanent magnetization (χARM)/χlf(2.35) and χARM/SIRM (0.12×10-3 m·A-1) indicate predominantly coarse pseudo single domain (PSD) and multi-domain (MD) magnetic grain size assemblages. The playground dust is considered moderately to highly polluted, and the enrichment factor values for Cd, Zn, Cu, and Pb indicate extremely high contamination levels in the playground dust. Mineral magnetic parameters[χlf, SIRM, hard isothermal remanent magnetization (HIRM), χARM, and χARM/SIRM] reveal significant correlations with total and acid-extractable concentrations of the trace metals, and the correlations with total concentrations are stronger. The most significant correlations were found with mineral magnetic concentrations (χARM and SIRM) and total concentrations of the elements Mn, Ni, and Cr and the Tomlinson pollution load index (PLI) (0.69 ≤ r ≤ 0.86, P<0.01). Consistent spatial characteristics between them were also found, showing that the total concentrations of heavy metals and magnetic parameter values are higher in the playgrounds near and downwind of the power plant. Results of a principal component analysis indicate that anthropogenic activities (mainly from coal consumption by power plants) are the main sources for both heavy metals and magnetic minerals. In summary, significant correlations and consistent spatial characteristics between heavy metal contents and magnetic parameters and the same anthropogenic source for heavy metals and magnetic minerals confirm that magnetic parameters could be considered as efficient indicators for heavy metal contamination in the playground dust in industrial areas.

[Pollution Characteristics and Light Extinction Contribution of Water-soluble Ions of PM2.5 in Hangzhou].

The pollution characteristics and light extinction contribution of water-soluble ions of PM2.5 in Hangzhou were investigated by sampling and laboratory analysis of aerosol samplers in 2013. The water-soluble ions were dominant in PM2.5 and the total mass concentration was 37.5 µg·m-3, accounting for 44.4% of the PM2.5 mass concentration. Water-soluble ions were mainly composed of secondary ions(SO42-,NO3- and NH4+), which accounted for 83.4% of total ions. The highest mass concentrations of PM2.5 and major ions were observed in winter and the lowest in summer. The proportions of water-soluble ions in PM2.5 in summer and autumn were obviously higher than those in winter and spring and proportions of secondary ions in water-soluble ions were very close in each season. The contribution was the greatest to PM2.5 from secondary ions generation caused by fuel combustion and automobile exhaust. The annual average values of SOR and NOR were 0.27 and 0.15 respectively, the conversion rate of SO2 in atmosphere was greater than that of NOx. There was obvious positive correlation between SOR or NOR and humidity which indicated the important contribution of heterogeneous oxidation process to the generation of SO42- and NO3-. The annual average of[NO3-]/[SO42-] was 0.63, and the aerosol pollution was primarily affected by emissions from coal burning. In haze days, with the increase of haze pollution level, the mass concentrations of PM2.5, water-soluble ions, secondary ions as well as SOR and NOR all increased gradually, and the stable weather condition in haze days could efficiently promote the accumulation and secondary conversion of pollutants. There were obvious positive correlations between mass concentrations of PM2.5 and SNA and the atmospheric light extinction coefficient. The IMPROVE formula which was used to calculate the light extinction coefficients of different chemical components could efficiently indicate the tendency of aerosol scattering. The extinction contribution of SNA could reach 60.8%. The extinction coefficient of SNA was the highest in winter and lowest in summer, and its value and contribution proportion both increased gradually as the haze pollution level rose.

[Pollution Characteristics of Aerosol Number Concentration in Winter and Spring in a Northern Suburb of Nanjing].

Using APS-3321, the atmospheric aerosol number concentrations (0.5-20 µm) were continuously monitored to analyze the characteristics of winter and spring pollution in 2014 in a northern suburb of Nanjing. The average number concentrations were (364.8±297.8) cm-3 and (79.6±62.4) cm-3 in winter and spring, respectively; fine particles (0.5-1.0 µm) accounted for 87.8% and 86.6% of the total, respectively. There were significant variations in number concentration at different periods. The diurnal variations in number concentrations were evident with high concentrations at night and low concentrations during the day. The early peaks were at 07:00 and 09:00, and number concentrations began to increase rapidly starting at 17:00 and 18:00 in winter and spring, respectively. The distribution of the number concentrations was unimodal, with peak sizes between 0.583 and 0.626 µm in winter and less than 0.542 µm in spring. With the increase in relative humidity, aerosol number concentrations increased gradually; at the same time, the peak size moved to a larger diameter which reflected the influence of hygroscopic growth of aerosols. During the total observation period, it reached 83.3% of the proportion of hazy days. The number concentration of particles less than 2.0 µm increased significantly with the increase in the haze pollution level, which was more obvious in winter. In spring, the proportion of fine particles increased with the increase in the haze level but in winter, it decreased during hazy days due to a significant increase in particle size caused by aging. The analysis of the typical pollution process in January indicated that there was a strong correlation between the source of air mass and the surface wind direction. Pollutants transmitted from the northern Jiangsu Province and the accumulation of pollutants due to slow winds were important causations of the pollution process.

Protease activated receptor 1 (PAR1) enhances Src-mediated tyrosine phosphorylation of NMDA receptor in intracerebral hemorrhage (ICH).

It has been demonstrated that Src could modulate NMDA receptor, and PAR1 could also affect NMDAR signaling. However, whether PAR1 could regulate NMDAR through Src under ICH has not yet been investigated. In this study, we demonstrated the role of Src-PSD95-GluN2A signaling cascades in rat ICH model and in vitro thrombin challenged model. Using the PAR1 agonist SFLLR, antagonist RLLFS and Src inhibitor PP2, electrophysiological analysis showed that PAR1 regulated NMDA-induced whole-cell currents (INMDA) though Src in primary cultured neurons. Both in vivo and in vitro results showed the elevated phosphorylation of tyrosine in Src and GluN2A and enhanced interaction of the Src-PSD95-GluN2A under model conditions. Treatment with the PAR1 antagonist RLLFS, AS-PSD95 (Antisense oligonucleotide against PSD95) and Src inhibitor PP2 inhibited the interaction among Src-PSD95-GluN2A, and p-Src, p-GluN2A. Co-application of SFLLR and AS-PSD95, PP2, or MK801 (NMDAR inhibitor) abolished the effect of SF. In conclusion, our results demonstrated that activated thrombin receptor PAR1 induced Src activation, enhanced the interaction among Src-PSD95-GluN2A signaling modules, and up-regulated GluN2A phosphorylation after ICH injury. Elucidation of such signaling cascades would possibly provide novel targets for ICH treatment.

Overexpression of CXCL3 can enhance the oncogenic potential of prostate cancer.

PURPOSE: CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. METHODS: Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. RESULTS: Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. CONCLUSION: Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.

[Variation of Size Distribution and the Influencing Factors of Aerosol in Northern Suburbs of Nanjing].

The size distribution of particulate was analyzed by the FA-3 9 stage sampler in Northern-suburb of Nanjing from January to November in 2014. First, the monitoring result from FA-3 was compared with the results of the same period obtained from a medium flow size grading sampler (KC-120H) and online monitoring instrument of the Environmental Protection Agency. The data correlation coefficients were all greater than 0.95. The fine particle concentration from FA-3 was lower by 13.9% and 16.6%, while PM10 concentration was higher by 15.2% and 13.3% respectively. However, the deviations were in the acceptable range of atmospheric sampling which could indicate the accurate classification and sampling of particulate for FA-3. Particulate pollution in Northern-suburb Nanjing was serous in which the annual average concentrations of PM1.1, PM2.1 and PM10 were(65.6±37.6), (91.0±54.7) and (168.0±87.0) µg·m-3 respectively; fine particles dominated and most of them had a diameter of less than 1.1 µm. Particle size distribution was bimodal with peaks at 0.43-0.65 and 9-10 µm; the median diameter was 1.83 µm which was in the accumulation mode. In winter, the concentration of fine particle size was higher and in spring the coarse particle size was higher; in summer, the fine particle size concentration was not significantly reduced but coarse particle size was obviously lower than those in other seasons. The differences of particle size distribution in day and at night were very small in coarse segment and in fine segment, the nocturnal concentrations were mostly higher than diurnal concentrations. The precipitation had cleaning effect for each size range of particulate except in summer and the effect was more distinct in fine particle size. In haze days, with the aggravation of haze level, the particle concentration in the diameter range of 0.43-2.1 µm increased gradually while in this segment the particle concentration was significantly negatively correlated with visibility. Using relative humidity of 70% as the demarcation, the particle size distribution changed significantly:when humidity was greater than 70%, mass concentration of particle with a diameter of less than 0.43 µm reduced significantly but that with diameter range of 0.43-2.1 µm increased obviously which should be related to the particle hygroscopic growth. The air mass sources could be divided into four categories in northern-suburb of Nanjing. Air mass from the northwest with rapid transport velocity was the cleanest in which the fine particle size concentration was significantly lower than those in other directions; the air mass from local and surrounding was the most severely polluted with high concentrations in both fine and coarse segment, its transmission distance was short and wind speed was small which contributed greatly to air pollution of Nanjing with probability of occurrence of pollution reaching 73.9%.

Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway.

It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.

[A review of multi-scale studies on spatial variation of the lead (Pb) concentration in urban soils].

The accumulation of Pb in urban soils is still apparent in China, and scientific assessment and management of risks from Pb-contaminated soils is necessarily based on contamination levels and extent evaluated accurately. Lead concentration in urban soils has a strong spatial variation and complex spatial structures. Carried out in a single spatial scale, most current investigations cannot comprehensively reveal characteristics of spatial structures, and did not promote more scientific assessment and management of risk. Exploring a new method which can help identify the overall spatial structures is needed. To achieve this aim, this paper firstly investigated the factors linked to the spatial variability of Pb concentration in urban soils, and three major factors were identified: various pollution sources, hierarchical pollution processes and heterogeneous urban landscape. These factors were form a nested hierarchical spatial structure with three spatial levels. Based on the conceptual spatial structure, we proposed a method framework guided by geostatistical theory and focused on linear mixed model (LMM). This proposed framework can divide the nested hierarchical spatial structures of Pb concentration in urban soils into three levels: global trend, random variation with spatial autocorrelation, and outliers. Two recommendations were given to promote the multiple-scale investigation in spatial variation of soil Pb contamination in urban area including: finding more efficient sampling strategy and determining the characteristic scale.

The levels of carbohydrate antigen 19-9 are associated with gender and age in Chinese population.

BACKGROUND: CA 19-9 is one of the most frequently used biomarkers for tumors. METHODS: We analyzed the influential factors of the Carbohydrate Antigen 19-9 (CA 19-9) levels in Chinese general population to better interpret the results of the CA 19-9 screening tests. 36,924 apparently healthy individuals and 1,335 patients with gastrointestinal (GI) tumors were involved in this study. Serum CA 19-9 levels were measured using a Roche Cobas E601. RESULTS: The serum CA 19-9 levels in apparently healthy individuals were correlated with age and gender. Its level was positively correlated with the age of males, while it showed a V-shape curve in female populations. This effect could be due to sex hormones, such as prolactin, which were found to have a negative effect on the level of CA 19-9 in the present study. CONCLUSIONS: Our data indicates that gender and age could affect the CA19-9 serum level. We can set up different cut-off values according to the patient's gender and age, which can help us to get a more individualized representation in different populations.

Meta-analysis of excision repair cross-complementation group 1 (ERCC1) association with response to platinum- based chemotherapy in ovarian cancer.

Recent studies suggested that the ovarian cancers with negative excision repair cross-complementation group 1 enzyme (ERCC1) expression have a better response to platinum-based chemotherapy than those with positive ERCC1 expression. The objective of this study was to evaluate whether ERCC1 expression is associated with response to platinum-based chemotherapy in ovarian cancers. MEDLINE, PubMed, Web of Science and CNKI databases were used for searching studies relating to ERCC1 protein expression and response to platinum-based chemotherapy in ovarian cancers. Statistical analysis was based on the method for a fixed effects meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals for ERCC1 protein expression and response to platinum- based chemotherapy were generated. Publication bias was investigated with Begg's test. Five studies involving 306 patients with ovarian cancer were included. Compared to patients with positive ERCC1 expression, those with negative ERCC1 expression had a better response to platinum-based chemotherapy. The pooled OR was 5.264 (95% CI: 2.928 - 9.464, P < 0.001) and publication bias was not found (P = 0.904). The result was similar in both in Asians and Caucasians (P < 0.001 and P = 0.028, respectively). ERCC1 protein expression status is significantly associated with response to platinum-based chemotherapy in ovarian cancers.

Relationships between serum levels of thyroid hormones and serum concentrations of asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) in patients with Graves' disease.

Endothelial dysfunction as well as abnormal thyroid hormone levels may be responsible for increased cardiovascular risk in Graves' disease (GD). Asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) are new markers of endothelial and myocardial dysfunction, respectively. The purpose of this study was to investigate the relationship among the serum levels of ADMA, NT-proBNP, and thyroid hormones in GD patients. This was a cross-sectional investigation conducted in a university teaching hospital. Two hundred and thirty-nine GD (Female: 182, Male: 57) patients and 81 normal controls were enrolled in this study. Serum levels of ADMA were positively related with FT3 (r = 0.584, P < 0.001), FT4 (r = 0.551, P < 0.001), and TRAb levels (r = 0.502, P < 0.001). Serum NT-proBNP levels were positively associated with FT3 (r = 0.243, P < 0.001) and FT4 levels (r = 0.274, P < 0.001), as well as heart rate (r = 0.271, P < 0.03). The elevation of serum ADMA and NT-proBNP levels were also observed in patients with controlled hyperthyroidism. It is thus concluded that serum ADMA and NT-proBNP levels were increased in GD patients. Future studies may determine the usefulness of these two biomarkers to detect early signs of endothelial dysfunction, vascular stiffness, and fluid volume in GD patients.

Association of XIAP and P2X7 receptor expression with lymph node metastasis in papillary thyroid carcinoma.

The expression of X-linked inhibitor of apoptosis (XIAP) and the P2X7 receptor were demonstrated in a variety of tumors. The purpose of the present study was to investigate the associations of XIAP and P2X7 receptor expression with the clinicopathological features of patients with papillary thyroid carcinoma (PTC). In this cross-sectional study, a total of 62 cases were examined, including 43 patients with PTCs and 19 with benign nodular goiters. XIAP and P2X7 receptor expression were examined by immunohistochemical methods on formalin-fixed, paraffin-embedded thyroid tissues. The staining intensity and extent were evaluated and scored using a semi-quantitative method. The immunohistochemical staining score integrating the intensity and extent of XIAP and P2X7 receptors in PTCs was higher than in nodular goiters. XIAP (OR: 5.6, 95% CI: 1.5-21.1, P=0.009) and P2X7 receptor (OR: 6.1, 95% CI: 1.5-24.4, P=0.007) expression were associated with lymph node metastasis in PTCs. In logistic regression analysis, P2X7 receptor expression, tumor size, and capsular infiltration were predictors for lymph node metastasis (P=0.001). Our results suggested that XIAP and P2X7 receptor expression may predict the aggressiveness of PTC.

RegIV expression showing specificity to gastrointestinal tract and its potential role in diagnosing digestive tract neuroendocrine tumor.

Regenerating gene IV (RegIV), a member of the regenerating gene family discovered in 2001, has been found to be involved in malignancy in several different organs including the stomach, colorectum, pancreas and prostate, but the overall expression profile of RegIV has not been reported. To learn more about RegIV, we evaluated its distribution by immunohistochemistry (IHC) in a total of 360 samples including 24 types of normal tissue, 40 benign and malignant lesions, and 18 neuroendocrine tumors. We found that in normal tissues, in addition to its relative specificity for the gastrointestinal tract, RegIV was detected in the adrenal gland and mammary gland. Among all the malignancies of various histological types under evaluation, RegIV was found mostly in adenocarcinomas. Studies on additional sets of colorectal tumor samples showed that RegIV expression was predominant in colorectal adenoma (87.5%) and peritumoral tissue (100%) but not in cancer tissue (30.8%). Among neuroendocrine tumors, RegIV had a relatively restricted expression to those of digestive system.

BRAFV600E mutation and X-linked inhibitor of apoptosis expression in papillary thyroid carcinoma.

BACKGROUND: The BRAF mutation V600E (BRAF(V600E)) is the most common genetic alteration in papillary thyroid carcinoma (PTC), while overexpression of X-linked inhibitor of apoptosis (XIAP) has been found in various tumors. Both of these events are implicated in carcinogenesis, tumor progression, recurrence, etc. There are few reports, however, of the BRAF(V600E) mutation and XIAP overexpression in PTC patients. The aim of this study was to investigate the frequency of the BRAF(V600E) mutation in PTC and its relationship to clinicopathological parameters and the expression of XIAP. METHODS: Genomic DNA was extracted from 123 paraffin-embedded PTC tumor tissue samples and amplified for analysis of the V600E mutation in exon 15 of the BRAF gene by polymerase chain reaction. XIAP expression was examined by immunohistochemical methods in 46 PTCs, 18 benign nodular goiters, and 10 Hashimoto's thyroiditis samples. RESULTS: The BRAF(V600E) mutation was found in 34.1% of PTC, and was especially prevalent in the classic type. BRAF(V600E) was significantly correlated with younger age at diagnosis (p = 0.026), tumor size (p = 0.009), and histological variants (p = 0.024). There was a trend towards association with extrathyroidal invasion (p = 0.067). By logistic regression analysis, a significant relationship was found between tumor size and the BRAF(V600E) mutation (p = 0.03). XIAP was expressed in 82.6% of PTCs, which was a higher percentage than observed in the group of benign thyroid disorders (35.7%, p < 0.001). Neither the intensity (p = 0.611) nor the extent (p = 0.723) of XIAP staining was correlated with the presence of BRAF(V600E) in PTC patients. CONCLUSIONS: These data indicate that BRAF(V600E) is associated some of the aggressive clinicopathological features of PTC including younger age at diagnosis, larger tumor size, and classic histological type, as well as also extrathyroidal invasion. XIAP-positive staining was more prevalent in PTCs than in the benign thyroid disorders. Although BRAF(V600E) and XIAP expression are commonly seen in PTC, their presence together seems unrelated.