Uso de estatinas melhora a proteção cardiometabólica promovida pelo treinamento físico em ambiente aquático: Um ensaio clínico randomizado / Statin use improves cardiometabolic protection promoted by physical training in an aquatic environment: A Randomized Clinical Trial

Resumo Fundamento: O uso de estatinas destaca-se como a terapia mais frequentemente utilizada para o tratamento de dislipidemias e pode ser considerado a intervenção farmacológica mais eficiente para a redução da lipoproteína de baixa densidade (LDL). Por outro lado, o treinamento físico pode ser considerado uma estratégia não farmacológica eficiente e segura para promover melhorias no perfil lipídico. No entanto, não se sabe qual seria a influência das estatinas nas adaptações lipídicas decorrentes do treinamento aquático em populações com dislipidemia. Objetivos: Analisar a influência do uso de sinvastatina nas adaptações lipídicas decorrentes do treinamento aeróbico em meio aquático e de resistência em mulheres idosas com dislipidemia. Métodos: Sessenta e nove mulheres idosas (66,13 ± 5,13 anos), sedentárias e dislipidêmicas, tanto não usuárias quanto usuárias de sinvastatina (20 mg e 40 mg), foram randomizadas nos 3 grupos seguintes: treinamento aeróbico em meio aquático (WA), treinamento de força em meio aquático (WR) e grupo controle (GC). A duração total das intervenções, para todos os grupos experimentais, foi de 10 semanas, com 2 sessões semanais. As análises bioquímicas foram realizadas antes do início das intervenções e repetidas após o final do ensaio. Foram utilizadas equações de estimativa generalizada para comparar esses dados, estabelecendo α = 0,05. Resultados: Na análise por intenção de tratar, as participantes medicadas demonstraram uma redução de magnitude maior do colesterol total (CT) (−3,41 a −25,89 mg.dl−1; p = 0,038), LDL (−5,58 a −25,18 mg.dl−1; p = 0,007) e da relação CT/HDL (−0,37 a −0,61; p = 0,022) quando comparadas às participantes não medicadas, essa redução sendo estatisticamente significativa apenas no grupo WR. Conclusões: O uso de estatina incrementa as adaptações promovidas pelo treinamento físico aquático no CT, nos níveis de LDL e na relação CT/HDL, sendo mais pronunciado após WR.

Abstract Background: Statin use is highlighted as the most commonly utilized therapy for the treatment of dyslipidemias and can be considered as the most efficient pharmacological intervention for low-density lipoprotein (LDL) reduction. On the other hand, physical training can be considered an efficient and safe non-pharmacological strategy to promote improvements in lipid profile. However, the influence of statins on lipid adaptations arising from water-based training in populations with dyslipidemia is not known. Objectives: To analyze the influence of simvastatin use on lipid adaptations arising from water-based aerobics and resistance training in elderly women with dyslipidemia. Methods: Sixty-nine elderly (66.13 ± 5.13 years), sedentary, and dyslipidemic women, both non-users and users of simvastatin (20 mg and 40 mg), were randomized into the following 3 groups: water-based aerobic training (WA), water-based resistance training (WR), and control group (CG). Total duration of interventions, for all experimental groups consisted of 10 weeks, with 2 weekly sessions. Biochemical analyses were performed before the beginning of the interventions and repeated after the end of the trial. Generalized estimating equations were used to compare these data, setting α = 0.05. Results: In intention-to-treat analysis, the medicated participants obtained a greater magnitude of decrease in total cholesterol (TC) (−3.41 to −25.89 mg.dl−1; p = 0.038), LDL (−5.58 to −25.18 mg.dl−1; p = 0.007) and TC/HDL ratio (−0.37 to −0.61; p = 0.022) when compared to the non-medicated participants, and this decrease was statistically significant only in the WR group. Conclusions: Statin use enhances the adaptations promoted by water-based physical training in CT, LDL levels, and CT/HDL ratio, and it is more pronounced after WR.

Overexpression of ribonucleotide reductase small subunit, RNRM, increases cordycepin biosynthesis in transformed Cordyceps militaris / 中国天然药物

Cordycepin was the first adenosine analogue used as an anticancer and antiviral agent, which is extracted from Cordyceps militaris and hasn't been biosynthesized until now. This study was first conducted to verify the role of ribonucleotide reductases (RNRs, the two RNR subunits, RNRL and RNRM) in the biosynthesis of cordycepin by over expressing RNRs genes in transformed C. militaris. Quantitative real-time PCR (qRT-PCR) and western blotting results showed that the mRNA and protein levels of RNR subunit genes were significantly upregulated in transformant C. militaris strains compared to the control strain. The results of the HPLC assay indicated that the cordycepin was significantly higher in the C. militaris transformants carrying RNRM than in the wild-type strain, whereas the RNRML was preferentially downregulated. For the C. militaris transformant carrying RNRL, the content of cordycepin wasn't remarkably changed. Furthermore, we revealed that inhibiting RNRs with Triapine (3-AP) almost abrogated the upregulation of cordycepin. Therefore, our results suggested that RNRM can probably directly participate in cordycepin biosynthesis by hydrolyzing adenosine, which is useful for improving cordycepin synthesis and helps to satisfy the commercial demand of cordycepin in the field of medicine.

Effects of CYP2C9 and VKORC1 genetic polymorphisms in Chinese Han population on maintenance dosage of warfarin / 中华检验医学杂志

Objective@#To analyze CYP2C9 and VKORC1 gene polymorphisms in Chinese Han population and their correlation with the maintenance dosage of warfarin.@*Methods@#From October 2017 to April 2018, 458 Chinese Han patients (213 males and 245 females, aged from 26 to 94 years old) who underwent coagulation analysis in Peking University People′s Hospital were included in this retrospective study. PCR-Fluorescent probe method was applied to detect CYP2C9*3 and VKORC1-1639A>G gene polymorphisms in 458 patients, and among them, 130 patients who took warfarin for anticoagulant therapy and reached the international standard ratio of prothrombin time (INR) within the range of 2.0-3.0 were recorded. The basic information, dosage of warfarin and INR were also recorded. The statistical analysis data were compared with the reference table of recommended dosage of warfarin for different genotypes of patients recommended by FDA and the formula of predicted dosage of warfarin was simply verified by SPSS.@*Results@#Among the 458 patients who took anticoagulant therapy, the genotype frequencies of CYP2C9*1/*1(AA), CYP2C9*1/*3(AC) and CYP2C9*3/*3(CC) were 90.8%, 8.5%, and 0.7%; the genotype frequencies of VKORC1-1639GG and VKORC1-1639AG were 0.9% and 14.2%; the genotype frequencies of VKORC1-1639AA was 84.9%. After INR was reached, the results showed that the variant CYP2C9*1/*3 and CYP2C9*3/*3 required lower daily maintain dosage [(2.92±1.29) mg] than wild-type CYP2C9*1/*1 patients did [(3.91±1.63) mg], with statistically significant difference (P=0.018). And variant VKORC1-AA required lower daily maintain dosage [(3.68±1.64) mg] than variant VKORC1-AG patients did [(4.54±1.29) mg], with statistically significant difference (P=0.001). The application dosage of warfarin in patients with different VKORC1+CYP2C9 genotypes was consistent with the recommended dosage of the FDA reference table. The prediction accuracy of miao 2007 formula was lower than that of IWPC formula, and 94.1% of patients′ dosages of warfarin were underestimated.@*Conclusion@#Patients with CYP2C9*3 or VKORC1-AA genotype required lower warfarin dosage. The CYP2C9 and VKORC1 gene polymorphisms had a certain correlation with maintenance dosage of warfarin.

Effect of peroxiredoxin 6 on proliferation and differentiation of bone marrow mesenchymal stem cells into neural lineage in vitro / 中国组织工程研究

BACKGROUND: It has been found that many substances can promote the differentiation of bone marrow mesenchymal stem cells into neural lineage in vitro, but the effect of peroxiredoxin 6 on bone marrow mesenchymal stem cells has not been studied. OBJECTIVE: To explore the effects of peroxiredoxin 6 on the proliferation of rat bone marrow mesenchymal stem cells and the ability to differentiate into neural lineages in vitro. METHODS: Bone marrow mesenchymal stem cells of Sprague-Dawley rats were cultured and passaged by whole bone marrow adherent culture in vitro into passage 3. The cells were assigned to five groups: PBS group, 1, 10, 100 μg/L and 1 mg/L peroxiredoxin 6 groups. CCK-8 assay was used to measure the absorbance at 450 nm of each group of cells for 9 consecutive days. Cell growth curves were drawn. Enzyme linked immunosorbent assay was utilized to measure absorbance at 450 nm in platform period. A relatively optimal concentration of peroxiredoxin 6 was selected to induce bone marrow mesenchymal stem cells to differentiate into neural lineages. PBS served as the control group. After 7 days of differentiation, immunofluorescence staining and western blot assay were used to detect the expression of neuronal marker protein NSE and glial cell marker protein GFAP. RESULTS AND CONCLUSION: (1) 1, 10 and 100 μg/L peroxiredoxin 6 groups complied with the general growth rule of bone marrow mesenchymal stem cells, and 10 μg/L was the optimal mass concentration. (2) NSE and GFAP immunofluorescence staining showed positive reaction after peroxiredoxin 6 induction; NSE and GFAP expression levels were higher than those in the control group. (3) The results of in vitro experiments show that the proper concentration of peroxiredoxin 6 can promote the proliferation of bone marrow mesenchymal stem cells and induce differentiation into neural lineage.

Effects of different transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, HSL and HMG-CoA reductase in hyperlipidemia rabbits / 针灸推拿医学（英文版）

Objective: To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, hormone-sensitive lipase (HSL) and hydroxymethylglutaryl CoA (HMG-CoA) reductase in hyperlipidemia rabbits.Methods: Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with a normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not given any intervention. After the model was prepared successfully, rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, the serum was isolated and enzyme-linked immunosorbent assay (ELISA) was applied for the detection of HSL and HMG-CoA reductase. The liver tissues were isolated, and total cholesterol (TC) and triglycerides (TG) were measured by enzymatic methods. One-step method was applied for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) detection, and transmission turbidimetry was for apolipoprotein A1 (Apo-A1) and apolipoprotein B (Apo-B) detection. Results: The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group (both P<0.05); all drug penetrations in the borneol group were significantly higher than those in the laurocapram group (both P<0.05), except for tanshinone ⅡA. Compared with the non-transdermal penetration enhancer group, the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups (both P<0.05); between groups, the HSL in the borneol group was significantly higher than that in the laurocapram group (P<0.05). Compared with the blank group, the levels of LDL-C, TG, TC and Apo-B in rabbit liver were significantly increased in the model group (P<0.05); compared with the model group, the levels of LDL-C, TG, TC and Apo-B in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups were significantly decreased (all P<0.05); between groups, the TG and TC in the laurocapram group and the LDL-C, TG, TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group (all P<0.05), and the TG, LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group (all P<0.05). Compared with the blank group, the HDL-C and Apo-A1 were significantly decreased in the model group (both P<0.05), while compared with the model group, the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups (all P<0.05). Between groups, the Apo-A1 in the laurocapram group, the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group (all P<0.05).Conclusion: The application of laurocapram and borneol, as transdermal penetration enhancers, in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake, increase the levels of HDL-C and Apo-A1, improve the metabolism of HSL and HMG-CoA reductase, and also simultaneously reduce the levels of TC, TG, LDL-C and Apo-B in the liver. The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.

Research advances in pleiotropic effects of statins in elderly patients / 中华老年医学杂志

Statins are collectively referred to as hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors.They exert powerful cholesterol-lowering effects by inhibiting key steps in the sterol biosynthetic pathway.At present,nearly 200 million people worldwide use statins.As clinical research progresses,the pleiotropic effects of statins are gradually discovered,especially those in the prevention and treatment of diseases of the circulatory system,nervous system and digestive system with high incidences in the elderly.We should to be alert to the adverse effects of statins and pay attention to the pleiotropic effects of statins in the elderly at the same time.

Cloning and Characterization of the Gene Encoding 3-hydroxy-3- Methylglutaryl-coenzyme A (HMG-CoA) Reductase from Fritillaria Cirrhosa D. Don

ABSTRACT The enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR; EC1.1.1.34) catalyzes the first committed step of isoprenoids biosynthesis in Mevalonate (MVA) pathway. Here we report for the first time the cloning and characterization of a full-length cDNA encoding HMGR from Fritillaria cirrhosa (FcHMGR), a bulbous medicinal plant. The full-length cDNA of FcHMGR was 2072 base pair (bp), containing a 1680-bp open reading frame. Bioinformatical analyses revealed that FcHMGR had HMG CoA-binding domains and two NADPH binding domains, which are required for HMGR activity. Quantitative real-time PCR (qRT-PCR) analysis revealed that FcHMGR expressed high in mature bulbs. A truncated version of FcHMGR protein lacking the N-terminal 249-bp GC rich area was expressed in Escherichia coli. The crude cell lysate containing the recombinant protein showed a better HMGR activity than the control and the relative enzyme activity was calculated to be 1.62 U/mg. The cloning, characterization and functional analysis of FcHMGR gene allowed us to further understand the role of FcHMGR involved in steroidal alkaloid biosynthetic pathway in F. cirrhosa at the molecular level.

Cardiovascular Risk Stratification and Statin Eligibility Based on the Brazilian vs. North American Guidelines on Blood Cholesterol Management / Estratificação de Risco Cardiovascular e Elegibilidade para Estatina com Base na Diretriz Brasileira vs. Norte-Americana para Manejo do Colesterol

Abstract Background: The best way to select individuals for lipid-lowering treatment in the population is controversial. Objective: In healthy individuals in primary prevention: to assess the relationship between cardiovascular risk categorized according to the V Brazilian Guideline on Dyslipidemia and the risk calculated by the pooled cohort equations (PCE); to compare the proportion of individuals eligible for statins, according to different criteria. Methods: In individuals aged 40-75 years consecutively submitted to routine health assessment at one single center, four criteria of eligibility for statin were defined: BR-1, BR-2 (LDL-c above or at least 30 mg/dL above the goal recommended by the Brazilian Guideline, respectively), USA-1 and USA-2 (10-year risk estimated by the PCE ≥ 5.0% or ≥ 7.5%, respectively). Results: The final sample consisted of 13,947 individuals (48 ± 6 years, 71% men). Most individuals at intermediate or high risk based on the V Brazilian Guideline had a low risk calculated by the PCE, and more than 70% of those who were considered at high risk had this categorization because of the presence of aggravating factors. Among women, 24%, 17%, 4% and 2% were eligible for statin use according to the BR-1, BR-2, USA-1 and USA-2 criteria, respectively (p < 0.01). The respective figures for men were 75%, 58%, 31% and 17% (p < 0.01). Eighty-five percent of women and 60% of men who were eligible for statin based on the BR-1 criterion would not be candidates for statin based on the USA-1 criterion. Conclusions: As compared to the North American Guideline, the V Brazilian Guideline considers a substantially higher proportion of the population as eligible for statin use in primary prevention. This results from discrepancies between the risk stratified by the Brazilian Guideline and that calculated by the PCE, particularly because of the risk reclassification based on aggravating factors.

Resumo Fundamento: Existe controvérsia sobre a melhor forma de selecionar indivíduos para tratamento hipolipemiante na população. Objetivos: Em indivíduos saudáveis em prevenção primária: avaliar a relação entre o risco cardiovascular segundo a V Diretriz Brasileira de Dislipidemias e o risco calculado pelas pooled cohort equations (PCE); comparar a proporção de indivíduos elegíveis para estatinas, de acordo com diferentes critérios. Métodos: Em indivíduos de 40 a 75 anos submetidos consecutivamente a avaliação rotineira de saúde em um único centro, quatro critérios de elegibilidade para estatina foram definidos: BR-1, BR-2 (LDL-c acima ou pelo menos 30 mg/dL acima da meta preconizada pela diretriz brasileira, respectivamente), EUA-1 e EUA-2 (risco estimado pelas PCE em 10 anos ≥ 5,0% ou ≥ 7,5%, respectivamente). Resultados: Foram estudados 13.947 indivíduos (48 ± 6 anos, 71% homens). A maioria dos indivíduos de risco intermediário ou alto pela V Diretriz apresentou risco calculado pelas PCE baixo e mais de 70% daqueles considerados de alto risco o foram devido à presença de fator agravante. Foram elegíveis para estatina 24%, 17%, 4% e 2% das mulheres pelos critérios BR-1, BR-2, EUA-1 e EUA-2, respectivamente (p < 0,01). Os respectivos valores para os homens foram 75%, 58%, 31% e 17% (p < 0,01). Oitenta e cinco por cento das mulheres e 60% dos homens elegíveis para estatina pelo critério BR-1 não seriam candidatos pelo critério EUA-1. Conclusões: Comparada à diretriz norte-americana, a V Diretriz Brasileira considera uma proporção substancialmente maior da população como elegível para estatina em prevenção primária. Isso se relaciona com discrepâncias entre o risco estratificado pela diretriz brasileira e o calculado pelas PCE, particularmente devido à reclassificação de risco baseada em fatores agravantes.

Advances in nucleotide reductase inhibitors for antiviral therapy / 中华临床感染病杂志

Ribonucleotide reductase ( RR ) is a rate-limiting enzyme, and it is responsible for reducing ribonucleotides to their corresponding deoxyribonucleotides , which are the building blocks required for DNA replication and repair .Recent studies have revealed that RR activity is associated with DNA replication in virus , and RR inhibitors have been used for clinical antiviral treatment .This paper reviews research progress on RR and its inhibitors , including the classification , structure and function of RR; the classification, mechanism and clinical application of RR inhibitors in antiviral therapy and the future prospects of RR inhibitors .

The effects of low dose radiation on the levels of oxidative damage and antioxidant in population of high background radiation area of Guangdong / 中华放射医学与防护杂志

Objective To investigate the effects of low dose radiation on the level of oxidative damage and antioxidant in population of high background radiation area of Guangdong.Methods A total of 48 male residents who lived in high background radiation area(HBRA) of Guangdong province and 48 male residents who lived in neighboring Enping control area were chosen as the objectives and control respectively.The peripheral venous blood of two groups was collected,and then the levels of 8-OHdG and TrxR were determined by enzyme linked immunosorbent assay (ELISA).Results Compared with the CA group [(315.39 ± 100.59) ng/ml],the level of 8-OHdG [(272.64 ± 96.85) ng/ml] decreased significantly in HBRA (t =2.121,P ＜0.05).Compared with the CA group [(0.467 ±0.056) ng/ml],the level of TrxR [(0.496 ± 0.044) ng/ml] increased significantly in HBRA (t =-2.823,P ＜ 0.05).The results of multiple linear regression analysis demonstrated that the chronic exposure to low dose of radiation had significant effects on the expression level of 8-OHdG and TrxR (t =-2.327,2.367,P ＜ 0.05) after adjustment for confounding factors such as age,drinking,tea drinking,smoking,medical exposure and stressful events.Conclusions Chronic exposure to low dose radiation may decrease the level of oxidative and enhance the level of antioxidant.

Efeitos pleiotrópicos das estatinas na sepse / Pleiotropic effects of statins in sepsis

O objetivo do presente estudo foi revisar os efeitos da terapia com estatinas em pacientes com quadro de sepse. Foi realizada uma busca bibliográfica de artigos na base de dados MEDLINE/PubMed, SciELO e LILACS, no período de publicação delimitado entre 2009 e 2013. Foram incluídos artigos referentes a ensaios clínicos randomizados controlados e estudos de coorte observacionais clínicos. Foram encontrados diversos estudos clínicos e observacionais que investigaram o efeito do uso de estatinas em infecções e em sepse, tanto de uso contínuo pré-hospitalar (com ou sem interrupção durante internação) ou com início imediato pós-internação. Alguns estudos descrevem prováveis efeitos positivos e benéficos da terapia com estatinas no quadro de sepse, dentre eles a melhora dos parâmetros inflamatórios e da taxa de mortalidade, porém, esses resultados não se sustentam quando são aplicados métodos estatísticos que levamem conta diferentes variáveis, tais como idade, sexo, comorbidades e gravidade da doença. Até o momento nenhum estudo demonstrou evidências sólidas e significativas quanto à redução de mortalidadee morbidade no quadro séptico associado ao uso de estatinas, indicando que seu efeito benéfico e protetor ainda não foi plenamente delimitado, sendo necessários mais estudos que confirmem os resultados até agora encontrados.

The objective of this study was to review the effects of statin therapy in patients with signs of sepsis. A bibliographic search of articles published between 2009-2013 was performed in the MEDLINE/PubMed, SciELO and LILACS databases. Randomized controlled trials and observational clinical cohort studies were included. The results show that several clinical and observational studies have investigated the effect of statin in infection and sepsis, both pre-hospital continuous use (with or without interruption during hospitalization) or starting immediately post-hospitalization. Some studies describe positive and beneficial effects of statin therapy in the contextof sepsis, including improvement on inflammatory parameters and mortality rates. However, these results do not hold on when statistic methods, which take into account different variables such as age, sex, comorbidities and severity disease, are applied. To date, no study has demonstrated strong and significant evidence regarding the reduction of morbidity and mortality in sepsis associated with the use of statin. This indicates that beneficial and protective effects have not been fully defined yet. More researches are required to confirm the results found so far.

Determinação de nitrato redutase em isolados de Fusarium graminearum / Determination of nitrate reductase in strains of Fusarium graminearum

Os fungos filamentosos como o Fusarium graminearum são fungos que produzem expressiva quantidade de metabólitos secundários. A pesquisa da atividade da enzima nitrato redutase, enzima diretamente associada ao processo de desnitrificação, em fungos do gênero Fusarium tem sido tema controverso. O objetivo deste estudo foi avaliar a atividade da enzima nitrato redutase em cepas de Fusarium graminearum. As cepas de F. graminearum foram cultivadas na presença de nitrato e nitrito, apresentando níveis de nitrato redutase diferentes. Os resultados obtidos apontam para a utilização da via assimilatória de nitrato pelos organismos de F. graminearum avaliados neste estudo.

Fusarium graminearum are filamentous fungi that produce significant amounts of pigments. Studying the activity of the enzyme nitrate reductase, which is closely associated with the process of denitrification in Fusarium, has been controversial. The aim of the present study was to evaluate two strains of F. graminearum that have grown in the presence of nitrate and nitrite, showing different levels of nitrate reductase. The results point the use of nitrate assimilation pathway for the fungus F. graminearum evaluated in this study.

The relationship between polymorphisms of NQO1 genes and hepatocellular carcinoma in Zhengzhou and Guilin areas / 中华肝胆外科杂志

Objective To study the relationship between polymorphisms of NQO1 and hepatocellular carcinoma (HCC) in Zhengzhou and Guilin area.Methods The Zhengzhou group was a hospital-based case-control study which included 146 cases of HCC and 151 cases of controls with nontumor seen in the People's Hospital of Zhengzhou.The Guilin group was a hospital-based case-control study which included 136 cases of HCC and 123 cases of controls with non-tumor seen in the Guilin Medical University Hospital.NQO1 polymorphisms were determined by polymerase chain restriction with TaqMan MGB probe.All data were analyzed by conditional logistic multiple factor regression analysis with SPSS 18.0 statistical package.Results The frequency with mutation allele (T) in the case group was significantly different between the Zhengzhou and Guilin groups (x2=23.307,P＜ 0.05).The odds risk of NQO1 mutation homozygote and mutation heterozygote to wild homozygote were significantly increased (OR=2.476,CI:1.518～4.038).Conclusions NQO1 mutation genotype is the predisposing gene with relatively different susceptibility to the development of HCC in the Zhengzhou and Guilin regions.There are synergistic effects between the NQO1 predisposing genotype,drinking and smoking.

Influence of human cytomegalovirus infection on cholesterol metabolism in smooth muscle cells of umbilical arteries and the related mechanisms / 第二军医大学学报

Objective: To investigate the effect of human cytomegalovirus(HCMV) infection on cholesterol metabolism in smooth muscle cells of the umbilical arteries and the related mechanisms. Methods: Vascular smooth muscle cells were isolated from umbilical arteries and were challenged with 1 MOI HCMV, and the intercellular content of cholesterol was determined. Cells treated with DMEM/F12 solution containing 3% fetal bovine serum were taken as mock infection controls. The differentially expressed genes were screened by cDNA microarray in each group, and the abnormally expressed genes associated with cholesterol metabolism were identified by fluorescence quantitative RT-PCR. Results: The intracellular content of cholesterol ([0.71±0.06] μmol/106 cells) was significantly higher in HCMV infection group at 72 h after infection compared with that in the control group (t = 7.950, P = 0.0002). cDNA microarray and fluorescence quantitative RT-PCR showed that the expressions of HMG-CoA synthetase and HMG-CoA reductase were greatly up-regulated compared with those in the mock infection group 48 and 72 h after infection (P<0.01). Conclusion: Human cytomegalovirus infection can increase the synthesis of cholesterol through up-regulating cholesterol metabolism-associated genes in vascular smooth muscle cells, leading to unbalancd cholesterol metabolism.

Uso crônico e regular de estatina previne fibrilação atrial no pós-operatório de cirurgia cardíaca / Chronic and regular use of statin prevents atrial fibrillation in period after cardiac surgery

FUNDAMENTO: Fibrilação atrial é uma complicação frequente no pós-operatório de cirurgia cardíaca. O uso prévio de estatinas pode reduzir a incidência dessa arritmia. OBJETIVO: Avaliar se o uso crônico e regular de estatina, por um período de seis meses, previne fibrilação atrial no pós-operatório de cirurgia cardíaca eletiva. MÉTODOS: Estudo realizado em 107 pacientes submetidos à cirurgia cardíaca, 66 por cento do sexo masculino e com idade média de 60,4 anos (25 a 84). Avaliou-se a presença de fibrilação atrial entre os pacientes que usavam ou não estatina de forma regular no pré-operatório. Foram excluídos pacientes com cirurgia cardíaca de urgência, insuficiência renal, doenças inflamatórias, fibrilação atrial prévia, portadores de tireoidopatia e aqueles em uso de marca-passo definitivo. RESULTADOS: No período pós-operatório, fibrilação atrial esteve presente em 42 pacientes (39 por cento) da amostra, sendo 11 (26 por cento) em uso regular de estatina no período pré-operatório e 31 (74 por cento) não. Observou-se que, em 22 por cento do total de pacientes em uso de estatina, não houve desenvolvimento de fibrilação atrial, enquanto 45 por cento dos que não usavam estatina apresentaram arritmia (ρ=0,02). Na revascularização miocárdica isolada, 47 por cento dos pacientes que não usavam estatina e 23 por cento dos que usavam desenvolveram fibrilação atrial (ρ =0,02). Não houve diferença estatística significativa na análise dos grupos com ou sem estatina quanto à presença dos fatores de risco para desenvolvimento de fibrilação atrial ( ρ=0,34). CONCLUSÃO: O uso regular de estatina, por seis meses ou mais no período pré-operatório, reduziu a incidência de fibrilação atrial no pós-operatório de cirurgia cardíaca eletiva.

BACKGROND: Atrial fibrillation is a common complication after cardiac surgery. The previous use of statins may reduce the incidence of this arrhythmia. OBJECTIVE: To evaluate whether the chronic and regular use of statins, for a period of six months, prevents atrial fibrillation after elective cardiac surgery. METHODS: A study carried out with 107 patients that underwent cardiac surgery, including 66 percent of males and their mean age was 60.4 years (25 to 84). We evaluated the presence of atrial fibrillation among patients that used statins or not on a regular basis in the preoperative period. We excluded patients with urgent heart surgery, kidney failure, inflammatory diseases, previous atrial fibrillation, patients with thyroid disease and those using a permanent pacemaker. RESULTS: In the postoperative period, atrial fibrillation was present in 42 patients (39 percent) of the sample, including 11 (26 percent) people that had used statins on a regular basis in the preoperative period and 31 (74 percent) who had not. It was possible to observe that, in 22 percent of the patients that were using statin, there was no development of atrial fibrillation, while 45 percent of those who did not take statin had arrhythmia (ρ = 0.02). In the isolated myocardial revascularization, 47 percent of the patients that did not take statin and 23 percent of those that took statin developed atrial fibrillation ( ρ = 0.02). There was no statistically significant difference in the analysis of groups with or without statin for the presence of risk factors for the development of atrial fibrillation (ρ = 0.34). CONCLUSION: The regular use of statin, for six months or more in the preoperative period, reduced the incidence of atrial fibrillation after elective cardiac surgery.

The Progress on Electron Transport Pathway and Catalytic Mechanism of Copper-containing Nitrite Reductase / 微生物学通报

Nitrite reductases (NiRs) are the key enzymes in the denitrification pathway of the nitrogen cycle. By the catalysis of NiRs, the nitrites are turned into nitric oxides and the nitrogen pollution is decreased in water body. NiRs are divided into two different types based on their prosthetic groups, namely heme-containing nitrite reductases (cd1-NiRs) and Copper-containing nitrite reductases (Cu-NiRs). As all know, Cu-NiRs have trimeric structures, in their each monomer, there exist two types of Cu centers that play pivotal roles as the components of electron transfer pathway in the process of catalysis. Furthermore, some residues alteration of Cu-NiRs would contribute to the catalytic reaction. In this review, the latest progresses about the construction features, the process of electron transfer and catalytic mechanism of Cu-NiRs were discussed.

Detection of expression of RRM1 mRNA by real-time fluorescent quantitative PCR in non-small cell lung cancer tissues and peripheral blood / 肿瘤

Objective: We tired to develop a method of detecting the expression level of RRM1 mRNA in tumor tissues and peripheral blood by real-time fluorescent quantitative PCR and compare the detection methods and results between the two different samples. We aimed to provide the basis for predicting clinical outcome from the expression of RRMI gene. Methods: The plasmid standard of RRM1 gene was constructed. Real-time quantitative analysis was performed using ABI7000 PCR kit. The PCR condition was optimized and the standard curve was established to detect the clinical samples. Results: The RRMI gene expression was detected in lung cancer tissues and normal lung tissues from 18 patients and in peripheral blood samples from 17 patients. The relative expression of RRM1 normalized by β-actin was 4.46 × 10-3 in lung cancer tissues, 3.43 × 10-3 in normal tissues, 2.54 × 10-3 in peripheral blood. The linear correlation between Ct value and the logarithm of original concentration was favorable. Conclusion: The expression of RRM1 mRNA in non-small cell lung cancer tissues and peripheral blood was successfully detected by using SYBR Green I fluorescence real-time quantitative PCR assay. There is no significant difference between the two sources of samples. The detection method has relatively higher sensitivity and specificity and can be used in clinical analysis.

Research Progress on Biosynthetic Pathway of Terpenoids Containing Ginsenoside and the HMGR / 中国生物工程杂志

As a model terpenoid,the ginsenoside is one of Panax ginseng’s main effective components.An overview of biosynthetic pathway of terpenoids and the HMG-CoA reductases was presented.The massive research materials indicated that the HMG-CoA reductases is the first key enzyme of the regulation of the mevalonic acid way,which has some reference value to promote the research on the biosynthetic pathway and the regulation of ginsenoside.

Effect of antisense oligodeoxynucleotide of small subunit component of human ribonucleotide reductase on human choriocarcinoma cell line in vitro / 中华妇产科杂志

Objective To study effect of the antisense oligodeoxynucleotide (ASODN) of small subunit of human ribonucleotide reductase (RRM2) mRNA on cell line of human choriocarcinoma in vitro. Methods Two 20-mer gapmer ASODNs with a full phosphorothioate backbone were artificially synthesized, which were complementary to nucleotides 626-645 (a coding region) and 1572-1591 (a 3′untranslated region) of RRM2, respectively. ASODNs were transfected into JAR cells through oligofectamine. The survival rate was assessed by methyl thiazolyl tetrazolium (MMT) assay, and RRM2 expression was detected by immunoblot and reverse transcriptase polymerase chain reaction (RT-PCR) methods. Results Antisense oligodeoxynucleotide one (ASODN1) targeting the coding region significantly inhibited growth of JAR cells in a dose- and time-dependent manner and downregulated RRM2 expression in a time-dependent manner. ASODN1 at 100 nmol/L could inhibit significantly cell growth ( P =0.000), and the effects of ASODN1 on JAR cell proliferation were enhanced with increase of ASODN1 concentration and reached the peak point at 400 nmol/L concentration ( P =0.000). Cell growth was significantly inhibited by 200 nmol/L of ASODN1 after 24 h of treatment ( P =0.000). The effect of ASODN1 was at the maximum at 48 h ( P =0.000), and began to decrease at 72 h of treatment. RRM2 expression started to reduce after ASOND1 treatment for 12 hours, and was obviously downregulated at 24 h of treatment, and decreased to the lowest level at 48 h ( P