Docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer: a meta-analysis.

OBJECTIVE: Although bevacizumab and trastuzumab have been widely added to the standard regimen for metastatic breast cancer, the clinical outcomes remain controversial. The purpose of this study was to conduct meta-analysis to verify the clinical efficacy and safety of docetaxel and bevacizumab with or without trastuzumab as first-line treatment for patients with metastatic breast cancer (MBC). MATERIALS AND METHODS: All available literature of clinical trials about docetaxel, bevacizumab, trastuzumab and metastatic breast cancer was pooled from PubMed, Embase and Cochrane library database. The meta-analysis combined the progression free survival (PFS), overall response rate (ORR) and incidence of all grades adverse events in MBC patients. RESULTS: Seven clinical trials were included by two reviewers. Docetaxel and bevacizumab with trastuzumab show the pooled PFS was 16.53 months (95% CI: 13.95-19.11 months), the pooled ORR was 0.75 (95% CI: 0.69-0.80) in HER2-positive MBC patients. Docetaxel and bevacizumab show that the pooled PFS was 8.49 months (95% CI: 7.80-9.18 months), the pooled ORR was 0.51(95% CI: 0.47-0.55) in HER2-negative MBC patients. CONCLUSIONS: Both for patients with HER2-positive and negative metastatic breast cancer, docetaxel and bevacizumab with or without trastuzumab as first-line treatment resulted in long survival, especially in terms of progression-free survival. Although the overall response rates are also significantly improved, it is still controversial based on the current evidence.

[Dose-effect relationship between serum polycyclic aromatic hydrocarbon adducts and serum complements among children in a city of East China].

Objective: To investigate the dose-response relationship between serum polycyclic aromatic hydrocarbon adducts and serum complement C3 and C4 levels among children from a city in East China. Methods: In September 2016, two boarding schools in the air pollution exposure area and the control area (beyond the upwind of 30 km in the air pollution exposure area) in a city in East China were selected as the research site, and the eligible school-age children were recruited as the research objects. A total of 273 children were included, including 163 in the exposure group and 110 in the control group. The annual air pollutant data (PM2.5, PM10 and NO2) of the two regions during the study period were collected. The exposure level of tobacco was evaluated by cotinine in urine. The levels of serum complement C3 and C4 were determined by automatic biochemical analyzer. The serum anti-7, 8, -dihydrodiol-9, 10-epoxide benzo[a]pyrene (BPDE)-albumin adduct levels were detected by ELISA. Linear regression model was used to explore the dose-response relationship between BPDE-albumin adducts and serum complement C3 and C4. Results: The age of 273 subjects was (13.67±0.37) years old, including 165 boys (60.4%). The average annual exposure levels of PM2.5, PM10 and NO2 and the level of serum BPDE-albumin adducts in the exposure group were higher than those in the control group (P<0.05). The results of linear regression model analysis showed that after adjusting age, sex, BMI z-score and urinary cotinine level, when the serum BPDE-albumin adduct level increased by 10%, the serum complement C4 level decreased by 1.2% (P=0.017). After adjusting age, BMI z-score and urinary cotinine level, for every 10% increase in serum BPDE-albumin adduct level in boys, the serum complement C4 level decreased by 1.68% (P=0.024). After adjusting age, sex and BMI z-score, the levels of serum complement C3 and C4 decreased by 1.31% and 3.57% respectively for every 10% increase in serum BPDE-albumin adducts among children in the urinary cotinine detection group (P<0.05). Conclusion: There is a significant dose-response relationship between serum BPDE-albumin adducts and the complement C4 among children.

Identification of PTK7 as a promising therapeutic target for thyroid cancer.

OBJECTIVE: To evaluate the possible involvement of PTK7 in the progression of human thyroid cancer and assess its potential effects on the proliferation and apoptosis of thyroid cancer. PATIENTS AND METHODS: Immunohistochemical (IHC) assays and clinical significance analysis were performed to explore the correlations between PTK7 expression and clinical characteristics of patients with thyroid cancer. Quantitative PCR assays and Immunoblot assays were performed to detect the expression of PTK7 in control or PTK7 shRNA plasmids transfected thyroid cancer cells. MTT assays were performed to detect the effects on the proliferation of thyroid cancer cells. Flow cytometry (FCM) assays were performed to assess the changes in cell apoptosis of thyroid cancer. Additionally, the effects of PTK7 on tumor growth were detected through in vivo tumor growth assays. RESULTS: PTK7 is highly expressed in human thyroid cancer tissues, and its expression levels are associated with the clinical characteristics, including TNM stage (p=0.015*), and intraglandular dissemination (p=0.024*) of patients with thyroid cancer. PTK7 ablation inhibits cell proliferation and stimulates cell apoptosis of thyroid cancer in vitro. Additionally, PTK7 contributes to tumor growth of thyroid cancer cells in mice. CONCLUSIONS: We demonstrated the involvement of PTK7in the progression of thyroid cancer, and therefore provided a novel and promising therapeutic target for thyroid cancer treatment.

[Influence of different timing of Saccharomyces boulardii combined with bismuth quadruple therapy for Helicobacter pylori eradication].

Objective: To assess the efficacy and safety of different opportunity of Saccharomyces boulardii (S. Boulardii) Sachets combined with bismuth quadruple therapy for Helicobacter pylori(H. pylori)eradication. Methods: This experiment was a prospective study. A total of 300 H. pylori-infected patients were enrolled and randomized assigned into three groups. Quadruple therapy group received pantoprazole 40 mg+bismuth potassium citrate capsule 220 mg+amoxicillin 1 000 mg+furazolidone 100 mg, bid, oral for 14 days. The simultaneous probiotic group received pantoprazole 40 mg+bismuth potassium citrate capsule 220 mg+amoxicillin 1 000 mg+furazolidone 100 mg+S. Boulardii Sachets 500 mg,bid,oral for 14 days.There after probiotic group:S.Boulardii Sachets was added on the first day after the end of 14 days in the quadruple group, for 500 mg, bid 14 days. The eradication rates and adverse reactions of the three groups were compared. Results: The eradication rates of H.pylori were 89.0%,90.4% and 91.3% in the quadruple therapy group, the simultaneous probiotic group and the there after probiotic group according to Per-protocol(PP) analysis,respectively,with no statistical difference (P=0.870). According to intention-to-treat(ITT)analysis, 81.0%, 85.0% and 84.0%, respectively, the difference was not statistically significant (P=0.732).The overall incidence of adverse reactions and the incidence of diarrhea and nausea in the simultaneous probiotic group, and the there after probiotic group were lower than those in the quadruple group(P<0.05),and the difference was statistically significant.The overall incidence of adverse reactions and diarrhea in the simultaneous probiotic were lower than those in the there after probiotic group (P=0.021, P=0.007), and the difference was statistically significant. Conclusions: S. Boulardii Sachets combined with quadruple therapy at the same time or after eradication treatment can not improve the H.pylori eradication rate,but can reduce the overall incidence of adverse reactions and the incidence of diarrhea and nausea. It is safer to add S. Boulardii Sachets at the same time than after eradication therapy.

Effluent trading planning and its application in water quality management: A factor-interaction perspective.

In this study, a Bayesian risk-induced interval stochastic modeling framework (BRISF) is proposed for planning effluent trading program among point and nonpoint sources as well as identifying interactions of important trading factors under system risk. BRISF incorporates nutrient fate modeling with soil and water assessment tool (SWAT), Bayesian inference with random walk Metropolis algorithm (RWM), and constraint-violation risk-based two-stage stochastic programming (CRTSP) within a general framework. Bayesian inference is employed for uncertainty analysis of SWAT model parameters and uncertain prediction of nutrient loadings; this process provides the random inputs for optimization process. CRTSP is capable of dealing with multiple uncertainties in modeling effluent trading program as well as system risk of environmental allowance violation. BRISF is applied to a real case of Xiangxihe watershed in China for water quality management. Solutions for optimal trading scheme corresponding to different risk levels are generated. Thousands of scenarios are examined to analyze the individual and interactive effects of trading ratios and treatment rates on trading system. Comparison between cross-industry and intra-industry effluent trading scheme is also conducted. It is proved that cross-industry trading would bring about higher benefit with reduced pollution loading; cross-industry effluent trading scheme would be recommended to achieve optimal water quality management and system benefit.

[Analysis on the exposure level and geographic distribution trend of toxicological indicators in rural drinking water, Shandong Province, in 2015].

Objective: To analyze the exposure level and the geographical distribution trend of toxicological indicators of rural drinking water in Shandong Province. Methods: The drawing method was used to randomly select no less than 60% villages and towns from 137 counties (cities, districts) of 17 cities in Shandong Province in 2015, and then 1-3 rural centralized water supply units were selected according to the circumstance of rural centralized water supply units in each village and town. In total, 735 villages and towns, 1 473 rural centralized water supply units were selected, and 1 473 water samples were collected. The water treatment process, water supply population and other circumstances of the rural centralized water supply units were investigated, the water quality was monitored, the content of toxicological indicators of drinking water in different areas was compared, and the trend surface isogram of excessive toxicological indicators was drawn. Results: The qualified rate of toxicological indicators in 1 473 water samples was 83.64% (n=1 232). The main toxicological indicators that affected the qualified rate of toxicological indicators of drinking water in rural areas in Shandong Province were nitrate and fluoride. The excessive rate of fluoride was 5.70% (n=84) and the exposed population was 1 736 709 (4.22%). The excessive rate of nitrate (as nitrogen) was 12.29% (n=181) and the exposed population was 1 393 612 (3.39%). The P(5)0 content of fluoride in the eastern, middle and western regions was 0.24, 0.29 and 0.59 mg/L, respective;which was higher in the western region than in the east and the middle regions (P<0.05). There was no significant difference between the eastern and the middle regions (P>0.05). The P(50) content of nitrate (as nitrogen) in the eastern, middle and western regions was 8.00, 7.48, and 2.00 mg/L, which was higher in the eastern and middle regions than in the west region (P<0.05), there was no significant difference between the eastern and the middle regions (P>0.05). The trend surface isogram of nitrate and fluoride content showed that the content of nitrate (as nitrogen) in rural drinking water in the eastern region was significantly higher than that in the western region, especially there was a high peak area in the northeastern region, and this high content distribution extended diagonally to the central region, while the other regions were in a relatively low range. The content of fluoride in rural drinking water in the western region was significantly higher than that in the eastern region, and there were high peaks in the southwest and northwest regions, and the other regions were in a relatively low range. Conclusion: The high exposed toxicological indicators in rural drinking water in Shandong Province were nitrate (as nitrogen) and fluoride, and their distribution showed obvious geographical distribution trend.

Novel Heating-Induced Reversion during Crystallization of Al-based Glassy Alloys.

Thermal stability and crystallization of three multicomponent glassy alloys, Al86Y7Ni5Co1Fe0.5Pd0.5, Al85Y8Ni5Co1Fe0.5Pd0.5 and Al84Y9Ni4Co1.5Fe0.5Pd1, were examined to assess the ability to form the mixture of amorphous (am) and fcc-aluminum (α-Al) phases. On heating, the glass transition into the supercooled liquid is shown by the 85Al and 84Al glasses. The crystallization sequences are [am] → [am + α-Al] → [α-Al + compounds] for the 86Al and 85Al alloys, and [am] → [am + α-Al + cubic AlxMy (M = Y, Ni, Co, Fe, Pd)] → [am + α-Al] → [α-Al + Al3Y + Al9(Co, Ni)2 + unknown phase] for the 84Al alloy. The glass transition appears even for the 85Al alloy where the primary phase is α-Al. The heating-induced reversion from [am + α-Al + multicomponent AlxMy] to [am + α-Al] for the 84Al alloy is abnormal, not previously observed in crystallization of glassy alloys, and seems to originate from instability of the metastable AlxMy compound, in which significant inhomogeneous strain is caused by the mixture of solute elements. This novel reversion phenomenon is encouraging for obtaining the [am + α-Al] mixture over a wide range of high temperature effective for the formation of Al-based high-strength nanostructured bulk alloys by warm working.

[Evaluation of health effect among occupational population exposed to nano-titanium dioxide: a cross-sectional study].

Objective: To characterize the health effects of nano-titanium dioxide exposure in an occupational cohort. Methods: Eighty-five male employees of a nano-titanium dioxide manufacturing enterprise in Shandong Province were evaluated in September 2014. Forty-four were exposed to nano-titanium dioxide (exposure group), and 41 were not exposed to nano-titanium dioxide (control group). We collected employees' basic information, smoking and drinking history, previous medical history, family history, and occupational history. Differences in blood pressure, hematological parameters, and blood biochemistry between the two groups were analyzed and compared. Multiple linear regression analysis was used to investigate the effect of nano-titanium dioxide exposure on blood pressure, hematological parameters, and blood biochemistry indices after controlling for age, smoking, drinking, and body mass index (BMI). Twenty-five employees from the exposure group and 25 employees from the control group were selected at random for measurement of genetic damage by cytokinesis-block micronucleus assay. Poisson regression analysis was used to investigate the effect of nano-titanium dioxide exposure on micronucleus frequency or micronucleus cell frequency after controlling for age, smoking, drinking, and BMI. Results: The median (P25-P75) surface area concentration of particles deposited in the tracheobronchial region, the surface area concentration of particles deposited in the alveolar region, and particle number concentration in the exposure group were 35.35(24.31-57.42) µ m2/cm3, 173.09(116.27-270.72) µ m2/cm3, and 40 244.00 (17 803.50-78 679.00) /cm3, respectively. These values were significantly higher than those in the control group 33.90 (27.44-43.29) µm2/cm3, 150.50(125.82-192.87)µm2/cm3, and 18 721.00 (12 721.00-51 898.50)/cm3, respectively. Z values were 15.47, 15.96, and 14.54, respectively (P<0.001 for all three values). Multiple linear regression analysis showed that exposure to nano-titanium dioxide contributed most to the alteration of mean corpuscular hemoglobin concentration, creatinine, and LDL-C, with standardized regression coefficients of 0.23, -0.51, and 0.30, respectively (P<0.05 for all three values), after adjusting for age, smoking, drinking, and BMI. There were no significant differences in micronucleus frequency and micronucleus cell frequency between the exposure group (3.00‰ (1.50‰-5.00‰) and 3.00‰ (2.00‰-4.00‰), respectively) and control group (2.00‰ (1.00‰-4.50‰) and 2.00‰ (1.00‰-4.00‰), respectively); P>0.05 for all comparisons. Poisson regression analysis showed that after adjusting for age, smoking, drinking, and BMI, there was still no statistically significant correlation between nano-titanium dioxide exposure and micronucleus frequency (OR=1.11, 95% CI: 0.81-1.54) or micronucleus cell frequency (OR=1.07, 95% CI: 0.75-1.51); P>0.05 for all comparisons. Conclusion: Nano-titanium dioxide particles exerted some health effects on the occupationally-exposed cohort, whose hematological parameters and blood biochemistry were influenced to some degree. However, a potential link between occupational exposure to nano-titanium dioxide and blood pressure or induction of genetic damage or was not found.

[Application of three control banding tools to occupational health risk assessment of titanium dioxide manufacturing factory].

Objective: To explore and validate suitable risk assessment methods for titanium dioxide though applying three risk assessment tools for nanomaterials based on the control banding (CB) approach. Methods: A factory manufacturing titanium dioxide in Jinan city, Shandong province, was assessed using a quantitative exposure method and qualitative risk assessment methods in September, 2014. A condensation particle counter equipment was used to monitor the number concentration of particles at packaging workshop and jet milling workshop. We employed three control banding tools, including CB nanotool, Stoffenmanager nano and the Guidance on working safely with nanomaterials and nanoproducts (GWSNN) to evaluate the two workshops, then compared the evaluation results. Results: The increases of particle concentrations were generated directly by packaging and jet milling processes, the number concentration from (3.52±1.46) ×10(4)/cm(3) to (14.70±8.86) ×10(4)/cm(3) at packaging workshop and from (0.97±0.25) ×10(4)/cm(3) to (1.26±0.35) ×10(4)/cm(3) at milling workshop (both P<0.05) . The number concentrations at packaging workshop were higher than those at jet milling workshop during both manufacturing and break times (both P<0.05) . The results of CB nanotool showed that the risk level of the packaging workshop was classified as high and the risk level of the jet milling workshop was classified asmedium. The results of Stoffenmanager nano showed that the risk level of the packaging workshop was classified as medium and the risk level of the jet milling workshop was classified as low. The results of GWSNN showed that the risk level of packaging workshop was classified as high and the risk level of jet milling workshop was classified as low. Conclusion: The results of evaluation based on the three control banding tools are related and aligned with the results of quantitative monitoring, so they are all suitable to perform occupational health risk assessment on industrial scale production of titanium dioxideto some extent.

A comparative cytogenetic study of the rice (Oryza sativa L.) autotetraploid restorers and hybrids.

We studied pollen fertility, seed set and cytogenetic characteristics of restorer lines and F1 hybrids of autotetraploid rice. T4002, T4063, T461A x T4002 and T461A x T4063 showed significantly higher pollen fertility and seed set than T4132 and T461A x T4132. Meiotic pairing configurations of T4002, T4063, T4132, T461A x T4002, T461A x T4063 and T461A x T4132 were 0.051 + 19.96II (9.89 rod + 10.07 ring) + 0.01III + + 2.00IV, 0.11I + 19.17II (8.90 rod + 10.37 ring) + 0.09III + 2.26IV + 0.01VI, 1.34I + 9.46II (4.50 rod + 4.96 ring) + 0.80III + 6.02IV + 0.09VI + 0.09VIII, 0.02I + 14.36II (6.44 rod + 7.91 ring) + 0.01III + 4.80IV + 0.01VIII, 0.06I + 17.67II (11.01 rod + 6.67 ring) + 0.06III + 3.10IV + 0.01VI and 1.11I + 11.31II (5.80 rod + 5.51 ring) + 0.41III + 5.63IV + 0.03VI + 0.03VIII, respectively. Configuration 16II + 4IV and 12II + 6IV occurred in the highest frequency among the autotetraploid restorers and hybrids. Meiotic chromosome behaviors were less abnormal in the tetraploids with high seed set than those with low seed set. The hybrids had fewer frequencies of bivalents, univalents, trivalents and multivalents than the restorers, but higher frequency of quatrivalents than the restorers at MI. The frequency of univalents at MI had the most impact on pollen fertility and seed set, i.e., pollen fertility decreased with the increase of univalents. The secondary impact factors were trivalents and multivalents, and bivalents and quatrivalents had no effect on pollen fertility and seed set. The correlative relationship between pollen fertility and cytogenetic behaviors could be utilized to improve seed set in autotetraploidy breeding.

[Study of genetic models of maize kernel traits].

Two sets of NCII mating design including 21 different maize inbreds were used to study the genetic models of five maize kernel traits--kernel length, width, ratio of kernel length and width, kernel thickness and weight per 100 kernels. Ten generations including P1, P2, F1, F2, B1, B2 and their reciprocal crosses RF1, RF2, RB1, RB2 were obtained. Three years' data were obtained and analyzed using mainly two methods: (1) precision identification for single cross and (2) mixed liner model MINQUE approach for diallel design. Method 1 showed that kernel traits were primarily controlled by maternal dominance, endosperm additive and dominance effect (maternal dominance > endosperm additive > endosperm dominance). Cytoplasmic effect was detected in one of the two crosses studied. Method 2 revealed that in the total variance of kernel traits, maternal genotypic effect contributed more than 60%, endosperm genotypic effect contributed less than 40%. Cytoplasmic effect only existed in kernel length and 100 kernel weight, with the range of 10% to 30%. The results indicated that kernel genetic performance was quite largely controlled by maternal genotypic effect.

[Genetic improvement of cotton varieties in Huang-Huai region in China since 1950's. III. Improvement on agronomy properties, disease resistance and stability].

Data from a set of 5-location and 2-year experiments on 10 representative historical cotton varieties and the data of Huang-Huai Regional Cotton Trials from 1973 to 1996 were analyzed to estimate the effects of genetic improvement in agronomy properties, disease resistance and stability of cotton in Huang-Huai Region in China. The results indicated that a great genetic progress of earliness and disease resistance had been achieved by breeding programs since 1950's. The maturity was shortened 3-5 days; The rate of preforst yield was increased about 7 percentages. The problem of resistance to Fususium wilt has been solved and the resistance to Verticillum wilt was improving. Some progress in stability of cotton varieties also has been achieved by breeding programs since 1950.