Mechanism of synergistic DNA damage induced by the hydroquinone metabolite of brominated phenolic environmental pollutants and Cu(II): Formation of DNA-Cu complex and site-specific production of hydroxyl radicals.

2,6-Dibromohydroquinone (2,6-DBrHQ) has been identified as an reactive metabolite of many brominated phenolic environmental pollutants such as tetrabromobisphenol-A (TBBPA), bromoxynil and 2,4,6-tribromophenol, and was also found as one of disinfection byproducts in drinking water. In this study, we found that the combination of 2,6-DBrHQ and Cu(II) together could induce synergistic DNA damage as measured by double strand breakage in plasmid DNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, while either of them alone has no effect. 2,6-DBrHQ/Cu(II)-induced DNA damage could be inhibited by the Cu(I)-specific chelating agent bathocuproine disulfonate and catalase, but not by superoxide dismutase, nor by the typical hydroxyl radical (•OH) scavengers such as DMSO and mannitol. Interestingly, we found that Cu(II)/Cu(I) could be combined with DNA to form DNA-Cu(II)/Cu(I) complex by complementary application of low temperature direct ESR, circular dichroism, cyclic voltammetry and oxygen consumption methods; and the highly reactive •OH were produced synergistically by DNA-bound-Cu(I) with H2O2 produced by the redox reactions between 2,6-DBrHQ and Cu(II), which then immediately attack DNA in a site-specific manner as demonstrated by both fluorescent method and by ESR spin-trapping studies. Further DNA sequencing investigations provided more direct evidence that 2,6-DBrHQ/Cu(II) caused preferential cleavage at guanine, thymine and cytosine residues. Based on these data, we proposed that the synergistic DNA damage induced by 2,6-DBrHQ/Cu(II) might be due to the synergistic and site-specific production of •OH near the binding site of copper and DNA. Our findings may have broad biological and environmental implications for future research on the carcinogenic polyhalogenated phenolic compounds.

Association of leptin levels with pathogenetic risk of coronary heart disease and stroke: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to investigate the association of leptin levels with pathogenetic risk of CHD and stroke. MATERIALS AND METHODS: Studies were identified in the PubMed, Embase, and Springer link database without language restriction. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used as effect indexes. The association of leptin levels with pathogenetic risk of CHD and stroke, as well as the risk variation of CHD with each additional one unit of leptin level were examined via meta-analysis. The publication bias was assessed via Egger's linear regression test. RESULTS: Eight nested case-control studies consisting of 1,980 patients and 11,567 controls were included for current meta-analysis. ORs (95% CIs) of association of leptin levels with CHD and stroke was 1.90 (1.06, 3.43), and 2.14 (1.48, 3.08), respectively. In addition, significant result was obtained regarding the risk variation of CHD with each additional one unit of leptin level (OR =1.04, 95% CI =1.00-1.08, P=0.044). There was no significant publication bias as suggested by Egger test outcomes. CONCLUSION: There was a significant association of leptin with pathogenetic risk of CHD and stroke, and raised leptin levels could significantly increase the pathogenetic risk of CHD.

Association of leptin levels with pathogenetic risk of coronary heart disease and stroke: a meta-analysis / Associação entre as concentrações de leptina e o risco patogenético de doença arterial coronariana e acidente vascular cerebral: uma metanálise

Objective This meta-analysis aimed to investigate the association of leptin levels with pathogenetic risk of CHD and stroke. Materials and methods Studies were identified in the PubMed, Embase, and Springer link database without language restriction. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used as effect indexes. The association of leptin levels with pathogenetic risk of CHD and stroke, as well as the risk variation of CHD with each additional one unit of leptin level were examined via meta-analysis. The publication bias was assessed via Egger’s linear regression test. Results Eight nested case-control studies consisting of 1,980 patients and 11,567 controls were included for current meta-analysis. ORs (95% CIs) of association of leptin levels with CHD and stroke was 1.90 (1.06, 3.43), and 2.14 (1.48, 3.08), respectively. In addition, significant result was obtained regarding the risk variation of CHD with each additional one unit of leptin level (OR =1.04, 95% CI =1.00‐1.08, P=0.044). There was no significant publication bias as suggested by Egger test outcomes. Conclusion There was a significant association of leptin with pathogenetic risk of CHD and stroke, and raised leptin levels could significantly increase the pathogenetic risk of CHD. .

Objetivo O objetivo desta metanálise foi investigar a associação entre os níveis de leptina e o risco patogenético de doença arterial coronariana e acidente vascular cerebral. Materiais e métodos Foram identificados estudos nas bases de dados PubMed, Embase e Springer Link sem restrição quanto à língua. A razão de chances (OR) e os intervalos de confiança de 95% correspondentes (95% CI) foram usados como índices de efeitos. A associação entre os níveis de leptina e o risco patogenético de doença arterial coronariana e acidente vascular cerebral com cada unidade adicional na concentração de leptina foi analisada por meio de metanálise. O viés da publicação foi avaliado por meio do teste de regressão linear de Egger. Resultados Oito estudos com caso controle aninhado envolvendo 1.980 pacientes e 11.567 controles foram incluídos na metanálise. As ORs (95% CIs) da associação entre as concentrações de leptina e a doença arterial coronariana e o acidente vascular cerebral foram de 1,90 (1,06; 3,43) e 2,14 (1,48; 3,08), respectivamente. Além disso, foram obtidos resultados significativos com a variação de risco para a doença arterial coronariana a cada unidade adicional na concentração de leptina (OR =1,04; 95% CI =1,00‐1,08; P=0,044). Não houve viés de publicação significativo sugerido pelos desfechos no teste de Egger. Conclusão Há associação significativa entre a leptina e o risco patogenético de doença arterial coronariana e acidente vascular cerebral, e concentrações aumentadas de leptina podem elevar significativamente o risco patogenético de doença arterial coronariana. .

Detection of hepatitis B virus A1762T/G1764A mutant by amplification refractory mutation system

OBJECTIVE: To study the role of hepatitis B virus with A1762T/G1764A double mutation in liver cirrhosis and hepatocellular carcinoma, and create a sensitive, fast, accurate assay for detection of A1762T/G1764A double mutation. METHODS: We developed an accurate and fast real-time amplification refractory mutation system to detect A1762T/G1764A double mutation. Cloned hepatitis B virus genome was used as a control. Assay sensitivity was determined by serial dilution and mixed template experiments. Specificity was determined by cross experiments with wild and mutant hepatitis B virus. Fifty clinical samples were tested by the real-time amplification refractory mutation system and the results were compared with sequencing. RESULTS: The real-time amplification refractory mutation system had a sensitivity of 100 copies of virus with these mutations, and 0.1% weak population virus with double mutation could be found in mixtures. A total of 50 randomly collected clinical samples were detected by real-time amplification refractory mutation system, and the results were consistent with those by DNA sequencing. Hepatitis B virus genotype C was more prevalent in 39 of 50 samples than genotype B (11 samples), and about 75% of genotype C carried a double mutation compared to 45% of genotype B. However, the percentage of A1762T/G1764A double mutation in hepatitis B e antigen-negative (58.3%) samples was almost the same as in hepatitis B e antigen-positive (61%) samples. CONCLUSION: The real-time amplification refractory mutation system is sensitive and specific for detection of hepatitis B virus double mutation. .

Application of self-retaining bidirectional barbed absorbable suture in retroperito- neoscopic partial nephrectomy.

OBJECTIVE: To investigate the safety and feasibility of self-retaining bidirectional barbed absorbable suture application in retroperitoneoscopic partial nephrectomy. MATERIALS AND METHODS: From Sep 2011 and Aug 2012, 76 cases of retroperitoneoscopic partial nephrectomy were performed at our hospital. The patients were divided into two groups: self-retaining barbed suture (SRBS) group (n = 36) and non-SRBS group (n = 40). There was no significant difference in age, sex, tumor size and location between the two groups. Clinical data and outcomes were analyzed retrospectively. RESULTS: All 76 cases of retroperitoneoscopic partial nephrectomy were successfully performed, without conversion to open surgery or serious intraoperative complications. In the SRBS group, the suture time, warm ischemia time and operation blood loss were significantly shorter than that of non-SRBS group (p < 0.01), and operation time and hospital stay were shorter than that of non-SRBS group (p < 0.05). CONCLUSIONS: The application of self-retaining bidirectional barbed absorbable suture in retroperitoneoscopic partial nephrectomy could shorten suture time and warm ischemia time, with good safety and feasibility, worthy of being used in clinic.

Application of Self-retaining Bidirectional Barbed Absorbable Suture in Retroperito- neoscopic Partial Nephrectomy

ObjectiveTo investigate the safety and feasibility of self-retaining bidirectional barbed absorbable suture application in retroperitoneoscopic partial nephrectomy.Materials and MethodsFrom Sep 2011 and Aug 2012, 76 cases of retroperitoneoscopic partial nephrectomy were performed at our hospital. The patients were divided into two groups: self-retaining barbed suture (SRBS) group (n = 36) and non-SRBS group (n = 40). There was no significant difference in age, sex, tumor size and location between the two groups. Clinical data and outcomes were analyzed retrospectively.ResultsAll 76 cases of retroperitoneoscopic partial nephrectomy were successfully performed, without conversion to open surgery or serious intraoperative complications. In the SRBS group, the suture time, warm ischemia time and operation blood loss were significantly shorter than that of non-SRBS group (p < 0.01), and operation time and hospital stay were shorter than that of non-SRBS group (p < 0.05).ConclusionsThe application of self-retaining bidirectional barbed absorbable suture in retroperitoneoscopic partial nephrectomy could shorten suture time and warm ischemia time, with good safety and feasibility, worthy of being used in clinic.

Detection of hepatitis B virus A1762T/G1764A mutant by amplification refractory mutation system.

OBJECTIVE: To study the role of hepatitis B virus with A1762T/G1764A double mutation in liver cirrhosis and hepatocellular carcinoma, and create a sensitive, fast, accurate assay for detection of A1762T/G1764A double mutation. METHODS: We developed an accurate and fast real-time amplification refractory mutation system to detect A1762T/G1764A double mutation. Cloned hepatitis B virus genome was used as a control. Assay sensitivity was determined by serial dilution and mixed template experiments. Specificity was determined by cross experiments with wild and mutant hepatitis B virus. Fifty clinical samples were tested by the real-time amplification refractory mutation system and the results were compared with sequencing. RESULTS: The real-time amplification refractory mutation system had a sensitivity of 100 copies of virus with these mutations, and 0.1% weak population virus with double mutation could be found in mixtures. A total of 50 randomly collected clinical samples were detected by real-time amplification refractory mutation system, and the results were consistent with those by DNA sequencing. Hepatitis B virus genotype C was more prevalent in 39 of 50 samples than genotype B (11 samples), and about 75% of genotype C carried a double mutation compared to 45% of genotype B. However, the percentage of A1762T/G1764A double mutation in hepatitis B e antigen-negative (58.3%) samples was almost the same as in hepatitis B e antigen-positive (61%) samples. CONCLUSION: The real-time amplification refractory mutation system is sensitive and specific for detection of hepatitis B virus double mutation.