Ideal cardiovascular health and mortality: pooled results of three prospective cohorts in Chinese adults / 中华医学杂志(英文版)

BACKGROUND@#Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps.@*METHODS@#A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis.@*RESULTS@#During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed.@*CONCLUSIONS@#ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents / 医学前沿

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents / 医学前沿

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Self-Rated Health Status and Risk of Incident Stroke in 0.5 Million Chinese Adults: The China Kadoorie Biobank Study / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Self-rated health (SRH) is a consistent and strong predictor of all-cause and cardiovascular mortality in various populations. However, the associations between SRH measures and risk of first-ever or recurrent stroke were rarely explored. We thus aim to prospectively investigate the associations between SRH measures and risk of total and subtypes of stroke in Chinese population. METHODS: A total of 494,113 participants from the China Kadoorie Biobank without prior heart diseases or cancer (486,541 without stroke and 7,572 with stroke) were followed from baseline (2004 to 2008) until December 31, 2013. General and age-comparative SRH were obtained from baseline questionnaires. First-ever stroke or recurrent events were ascertained through linkage to disease registry system and health insurance data. RESULTS: We identified 27,662 first-ever stroke and 2,909 recurrent events during an average of 7.0 years of follow-up. Compared with excellent general SRH, the hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever stroke associated with good, fair, and poor general SRH were 1.04 (1.00 to 1.08), 1.19 (1.15 to 1.23), and 1.49 (1.42 to 1.56) in the multivariate model, respectively. Compared with better age-comparative SRH, the HRs (95% CIs) of same and worse age-comparative SRH were 1.13 (1.10 to 1.17) and 1.51 (1.45 to 1.58), respectively. The relations of SRH measures with ischemic stroke, hemorrhagic stroke, and recurrent stroke were similar to that with total first-ever stroke. However, the magnitude of associations was much stronger for fatal stroke than for non-fatal stroke. CONCLUSIONS: This large-scale prospective cohort suggests that self-perceived health status is associated with incident stroke, regardless of stroke subtype.

Analysis of prevalence and related factors of osteoporosis in retired population based on Dongfeng-Tongji Cohort / 中华预防医学杂志

Objective@#To investigate the prevalence and related factors of osteoporosis among retired population in Dongfeng-Tongji cohort.@*Methods@#27 009 retired participants were recruited from Dongfeng Motor Corporation in Hubei Province in 2008 and followed up from April to October in 2013. newly retired participants also were recruited. Data were collected by using questionnaire, physical examination, serum hepatase detection and bone densitometry. Totally, 30 916 participants were included for data analysis after excluding participants with severe bone metabolic diseases, taking hormone drugs, incomplete follow-up data and who were under 45 years old. Age-standardized prevalence of osteoporosis was calculated according to data of the 2010 Sixth National Population Census. Multivariate logistic regression analysis was applied to explore the associated factors of osteoporosis.@*Results@#Prevalence of osteoporosis was 42.3% (13 083/30 916) and age standardized prevalence was 40.7%: 35.0% (4 854/13 878) and 34.8% for males; 48.3% (8 229/17 038) and 47.1% for females. Significantly associated factors with osteoporosis for both males and females included: older age (male: OR=1.67, 95%CI: 1.40-1.99; female:OR=3.34, 95%CI: 2.70-4.13), lower BMI (male: OR=1.70, 95%CI: 1.40-2.06; female: OR=1.27, 95%CI: 1.04-1.53), exercise (male: OR=0.69, 95%CI: 0.61-0.78; female: OR=0.87, 95%CI: 0.80-0.96), abnormal elevated serum alkaline phosphatase (ALP) (male: OR=1.12, 95%CI: 1.01-1.24; female: OR=1.15, 95%CI: 1.06-1.25), γ-glutamyltransferase (γ-GT) (male: OR=1.16, 95%CI: 1.02-1.30; female: OR=1.13, 95%CI: 1.03-1.24) and aspartate transaminase/alanine aminotransferase (AST/ALT) (male: OR=1.15, 95%CI: 1.05-1.25; female: OR=1.28, 95%CI: 1.19-1.38). Smoking (OR=1.27, 95%CI: 1.07-1.39) and drinking (OR=1.11, 95%CI: 1.08-1.16) were associated factors for males while menopausal (OR=1.67, 95%CI: 1.47-1.89) for females. There were positive dose-response correlation relationships of serum levels of ALP, γ-GT and AST/ALT with osteoporosis (all P values<0.05).@*Conclusion@#Osteoporosis was relatively common among retired population in Dongfeng-Tongji cohort. In addition to known factors such as older age, lower BMI and exercise, abnormal elevated serum ALP, γ-GT and AST/ALT were also associated with osteoporosis.

Association of alcohol use and incidence of type 2 diabetes mellitus in the middle-aged and elderly male population: a prospective cohort study / 中华预防医学杂志

Objective@#To investigate the association between alcohol use and incidence of type 2 diabetes mellitus (T2DM) in the middle-aged and elderly male population.@*Methods@#All participants were from Dongfeng-Tongji cohort, 27 009 retired employees from Dongfeng Motor Corporation in Hubei Province were enrolled in the Dongfeng-Tongji cohort baseline survey in 2008. In baseline study, information of alcohol use and other covariates were collected by semi-structured questionnaire and all participants completed physical examination including the test of fasting glucose and blood lipid levels. A total of 6 784 male participants from Dongfeng-Tongji cohort who were without diagnosis of diabetes, coronary heart disease, stroke, or cancer in baseline study were enrolled in this study. We completed the first follow-up in 2013 and the outcome of disease or death was retrieved based on health-care medical records according to the unique medical insurance ID. Cox proportional hazard regression model was used to estimate the association between alcohol use and incidence of type 2 diabetes mellitus (T2DM), by drinking features and patterns.@*Results@#Out of the 6 784 participants, 3 541 participant were defined as non-alcohol drinkers and there were 15 852.2 person-years of follow-up; among which 270 new cases of T2DM were diagnosed withthe crude incidence density of non-alcohol drinkers at 1 703.2/100 000 person-years. The other 3 243 subjects were classified as alcohol drinkers and there were 14 509.8 person-years of follow-up; and among which 258 new cases of T2DM were diagnosed, with the crude incidence density of T2DM at 1 778.1/100 000 person-years. Multivariate COX proportional hazard regression model indicated that there was no significantly increased risk of T2DM incidence between alcohol drinkers and non-alcohol drinkers(HR(95% CI): 1.09 (0.91- 1.30)). However, participants who averagely consumed >20 g/d or>7 times/week had a significantly increased risk of T2DM compared with non-alcohol drinkers, and the value of HR(95%CI) was 1.27 (1.02- 1.58) and 1.35 (1.00- 1.83), respectively. Among men who consumed alcoholic beverages more than 7 times/week, HR (95%CI) for T2DM incidence in the subjects who consumed 0.01 to 40 g and > 40 g once a time were 1.48 (1.05- 2.09) and 1.27 (0.80- 2.10), respectively.@*Conclusion@#Although we found no relationship between alcohol use and T2DM incidence overall, alcohol use more than 20 g/d or more than 7 times/week would increase the risk of T2DM.

Analysis on the association of single nucleotide polymorphism in the promoter region of pre-miR-320b-2 with coronary heart disease risk and factors influencing circulating microRNA-320b level / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of rs10916581, a common single nucleotide polymorphism (SNP) located in the promoter region of pre-miR-320b-2, on coronary heart disease (CHD) risk and circulating microRNA-320b (miR-320b) level. To explore potential factors influencing circulating miR-320b level.</p><p><b>METHODS</b>Rs10916581 was genotyped in a case-control study with 1 507 CHD cases and 1 379 age- and sex-frequency-matched controls. The cases were consecutively recruited from 3 hospitals (Tongji Hospital, Union Hospital, and Wugang Hospital) in Wuhan city (Hubei, China) between May 2004 and October 2009 and all the controls resided in Wuhan communities. A subgroup of 174 CHD cases and 181 non-diabetes controls without acute infection were randomly selected and their circulating miR-320b levels were detected using quantitative reverse transcriptase polymerase chain reaction assays. The association of rs10916581 with CHD susceptibility was analyzed with multivariable logistic regression model. Generalized linear regression model was used to explore the associations of rs10916581 and some other factors with circulating miR-320b level.</p><p><b>RESULTS</b>In single-factor logistic regression analysis, no association was found between rs10916581 and CHD risk. After adjustment for age, sex, BMI, smoking status, hypertension, diabetes, total triglyceride, total cholesterol/high density lipoprotein (TC/HDL-C), the result did not materially alter(compared with CC genotype, the OR (95%CI) of CHR in the subjects carried CT, TT, CT+TT genotypes were 0.94 (0.76-1.15), 0.99 (0.74-1.33) and 0.95 (0.78-1.16) ). No significant interactions were observed between the conventional risk factors of CHD (age, gender, smoking status, BMI, hypertension, diabetes, CHD family history) and rs10916581 on CHD risk (P > 0.05). Rs10916581 showed no significant association with circulating miR-320b level in cases, controls or total population (β(95%CI) was -0.028 (-0.495-0.440), 0.250 (-0.226-0.727) and 0.134 (-0.218-0.486) respectively, P > 0.05). However, circulating miR-320b level was negatively associated with BMI (β (95%CI) was -0.140 (-0.261--0.020), P = 0.022) while positively associated with TC/HDL(β (95%CI) was 0.620 (0.261-0.979), P = 0.001) in cases, and in total population, its circulating level tended to be lower in diabetes or hypertension patients (β(95%CI) was -1.025 (-1.696--0.354) and -0.594 (-1.138--0.049) respectively, P = 0.003, 0.033 respectively) and was positively associated with TC/HDL-C (β(95%CI) was 0.108 (0.027-0.190), P = 0.009).</p><p><b>CONCLUSION</b>The common SNP (rs10916581) in the promoter region of pre-miR-320b-2 might have little contribution to the CHD predisposition in Chinese Han population, and it might not affect circulating miR-320b level. Conventional CHD risk factors (BMI, TC/HDL-C, hypertension and diabetes) might have effects on its circulating level.</p>

Association between urinary polycyclic aromatic hydrocarbon metabolites and elevated serum uric acid levels in coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and serum uric acid levels in coke oven workers and to provide new clues to the pathogenic mechanism of PAHs.</p><p><b>METHODS</b>A total of 1302 coke oven workers were divided into four groups, namely control group and low-, intermediate-, and high-dose exposure groups. The concentrations of ambient PAHs at each workplace were determined by high-performance liquid chromatography. The detailed information on the occupational history and health of workers was collected by questionnaire survey and physical examination, and so were their blood and urine samples. Serum uric acid and creatinine levels were measured using a Hitachi 7020 automatic biochemical analyzer. Ten urinary PAH metabolites were detected by gas chromatography-mass spectrometry.</p><p><b>RESULTS</b>Serum uric acid levels were the highest in the high-dose exposure group, followed by the intermediate- and low-dose exposure groups, and were the lowest in the control group. There were significant correlations between serum uric acid levels and the quartiles of 1-hydroxynaphthalene and 1-hydroxyphenanthrene (P < 0.05). After adjustment for PAH metabolite-related relationship, only urinary 1-hydroxyphenanthrene was significantly correlated with serum uric acid levels (P = 0.001). After adjustment for confounding factors and using the 1st quartile of 1-hydroxyphenanthrene as a reference, the odds ratio for hyperuricemia in subjects with the 2nd, 3rd, and 4th quartiles of 1-hydroxyphenanthrene were 1.55, 1.57, and 2.35, respectively.</p><p><b>CONCLUSION</b>Urinary 1-hydroxyphenanthrene is associated with a dose-response increase in serum uric acid levels in coke oven workers, and exposure to phenanthrene in PAHs may be a risk factor for hyperuricemia.</p>

Association of rs501120 and rs17465637 gene polymorphisms with coronary heart disease in the Chinese Han population / 中国医师杂志

Objective To investigate the rs501120 and rs17465637 gene polymorphisms,and their relationship with the risk of coronary heart disease(CHD)in Chinese Han population.Methods 775 CHD without treatment and 775 age and gender matched controls were selected for this study,the genotypes of two single nucleotide polymorphisms(SNP)rs501120 and rs17465637 were tested with TaqMan-MGB probes.Results There was no significant difference in the frequency of genotypes of the 2 SNPs between CHD group and control group(P ＞0.05).Stratified analysis showed that SNP rs501120 had significant protection with CHD in people younger than 60 years old(OR 0.4,95% CI 0.2-0.9,P ＜ 0.05)or people with diabetes(OR0.3,95%CI0.1-0.7,P ＜0.05).Conclusions The results suggested that rs501120 was tightly associated with CHD in people younger than 60 years or had diabetes.

Expression of Hsp27 and Hsp70 in lymphocytes and plasma in healthy workers and coal miners with lung cancer / 华中科技大学学报（医学）（英德文版）

In coal mines, main occupational hazard is coal-mine dust, which can cause health problem including coal workers' pneumoconiosis and lung cancer. Some heat shock proteins (Hsps) have been reported as an acute response to a wide variety of stressful stimuli. Whether Hsps protect against chronic environmental coal-mine dust over years is unknown. It is also interesting to know that whether the expression of Hsp27 and Hsp70 proteins as a marker for exposure is associated risk of lung cancer among coal miners. We investigated the association between levels of Hsp27 and Hsp70 expression in lymphocytes and plasma and levels of coal-mine dust exposure in workplace or risk of lung cancer in 42 cancer-free non-coal miners, 99 cancer-free coal miners and 51 coal miners with lung cancer in Taiyuan city in China. The results showed that plasma Hsp27 levels were increased in coal miners compared to non-coal miners (P<0.01). Except high cumulative coal-mine dust exposure (OR=13.62, 95%CI=6.05-30.69) and amount of smoking higher than 24 pack-year (OR=2.72, 95% CI=1.37-5.42), the elevated levels of plasma Hsp70 (OR=13.00, 95% CI=5.14-32.91) and plasma Hsp27 (OR=2.97, 95% CI=1.40-6.32) and decreased expression of Hsp70 in lymphocytes (OR=2.36, 95% CI=1.05-5.31) were associated with increased risk of lung cancer. These findings suggest that plasma Hsp27 may be a potential marker for coal-mine dust exposure. And the expression of Hsp27 and Hsp70 levels in plasma and lymphocytes may be used as biomarkers for lung cancer induced by occupational coal-mine dust exposure.

Cohort mortality study in three ceramic factories in Jingdezhen in China / 华中科技大学学报（医学）（英德文版）

To investigate the health impacts of crystalline silica mixed dust and other potential occupational hazards on workers in ceramic factories, a cohort study of 4851 workers registered in the employment records in 3 ceramic factories in Jingdezhen city of China between 1972 and 1974 was identified. The cohort mortality was traced throughout 2003 with an accumulation of 128970.2 person-years, revealed 1542 deaths. Standardized mortality ratios (SMRs) were calculated for the main causes of death by using Chinese national mortality rates as reference. The mortality from all causes in three ceramic factories was 12.0 per thousand and the cumulative mortality was 31.8%. Malignant neoplasm, cardiovascular diseases, respiratory diseases, infectious diseases were the first four illnesses that threaten workers' life, and they accounted for 73.2% of all deaths. The results of this study showed that the standardized mortality ratio for all subjects was 1.02, which is very close to that expected on the basis of the China national mortality rates. Statistically significant mortality excesses for respiratory disease (SMR=1.36), pneumoconiosis (SMR=37.34), infectious disease (SMR=5.70) and pulmonary tuberculosis (SMR=3.88) were observed. The mortality of 2938 dust-exposed workers was higher than that of 1913 non dust-exposed workers. Except for pneumoconiosis, the mortality from lung cancer, non-malignant respiratory diseases and pulmonary tuberculosis in dust-exposed workers were significantly increased as compared with that in non-exposed workers, and the relative risks (RRs) were 1.86 (1.16-2.99), 2.50 (1.84-3.40), 1.81 (1.34-2.45). The exposure-response relationships between cumulative dust exposure level and mortality from all causes, colorectal cancer, lung cancer, respiratory diseases, and pulmonary tuberculosis were also identified. The findings indicated that silica mixed dust in ceramic factories has harmful impact on the workers' health and life span in ceramic factory.

Association of G+1688A Polymorphism of Platelet Endothelial Cell Adhesion Molecule-1 Gene with Myocardial Infarction in the Chinese Han Population / 华中科技大学学报（医学）（英德文版）

In order to investigate the association of G+1688A (Ser563Asn) polymorphism of platelet endothelial cell adhesion molecule-1 (PECAM-1) gene with myocardial infarction (MI) in the Chi- nese Han population, the G+1688A polymorphism in PECAM-1 gene was detected by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method among 502 subjects, including 218 patients with MI and 284 controls. The results showed that there was significant dif-ference in AA frequencies of genotype G+1688A polymorphism between case and control groups (39% vs 24%, P<0.001). A similar trend was observed on the allele frequencies (A/G: 62% vs 49%, P<0.001). Among the subjects with high serum total cholesterol level or high systolic blood pressure level, the variant AA genotype was associated with high risk of MI (adjusted OR, 2.13; 95% CI, 1.08-4.41 and adjusted OR, 2.53; 95%CI, 1.63-3.63). The single nucleotide polymorphism (SNP) at position +1688 in the exon 8 of PECAM-1 gene was associated with MI and the allele A might be a risk factor for MI in the Chinese Han population.

ANP T2238C, C-664G gene polymorphism and coronary heart diseasein chinese population / 华中科技大学学报（医学）（英德文版）

The association between atrial natriuretic peptide (ANP) polymorphism and coronary heart disease (CHD) was studied in Chinese population. The genotypes of ANP T2238C and ANP C-664G were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods in 158 consecutive CHD patients and 165 controls. It was found that the distribution of A2A2 genotype in CHD group was significantly higher than that in control group (P0.05). The results suggest that A2A2 T2238C genotype could be one of the risk factors for CHD (P<0.05, OR: 1.80, 95 % CI: 1.03-3.15).

ANP T2238C, C-664G Gene Polymorphism and Coronary Heart Diseasein Chinese Population / 华中科技大学学报（医学）（英德文版）

The association between atrial natriuretic peptide (ANP) polymorphism and coronary heart disease (CHD) was studied in Chinese population. The genotypes of ANP T2238C and ANP C-664G were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods in 158 consecutive CHD patients and 165 controls. It was found that the distribution of A2A2 genotype in CHD group was significantly higher than that in control group (P＜0.05). Stepwise Logistic regression analysis revealed that male, smoking, history of hypertension,history of diabetes, family history of hypertension, high level of serum cholesterol, and ANP T2238C polymorphism were the possible risk factors in patients with CHD (P＜0.05). However, there was no significant difference between the patients with CHD and the control group in the distribution of ANP C-664G polymorphism (P＞0.05). The results suggest that A2A2 T2238C genotype could be one of the risk factors for CHD (P＜0.05, OR: 1.80, 95% CI:1.03-3.15).

Effects of benzo[a]pyrene and lead either in separation or in combination on neuronal survival rate and nuclear DNA damage in vitro / 中国组织工程研究

BACKGROUND: Benzo[a]pyrene injures central and peripheral nerves at a certain degree. The study is at an initial phase concerning to the neurotoxicity of benzo[a]pyrene allied with other toxic objects.OBJECTIVE: Molecular biological technique integrated with neuron culture were applied in the study of benzo[a]pyrene and lead applied separately or in combination on neurotoxicity and nuclear DNA damage in vitro.DESIGN: Repeated measure.SETTING: Teaching-Research Room of Labor and Hygiene of Chongqing Medical University and Laboratory of Thermobiology and Molecular Toxicology of Occupation Medical Institute of Tongji Medical College of Huazhong University of Science and Technology.MATERIALS: The experiment was performed in Laboratory of Thermobiology and Molecular Toxicology of Occupation Medical Institute of Tongji Medical College ofHuazhong University of Science and Technology from June to September 2003. Ten SD rats of 8-day old were employed and their brain tissues were prepared as primary cell culture object, which were divided into 10 culture groups, 5 culture dishes in each group. The managements were as follows in each group: [1] blank control; [2] solvent control[parallel management with equivalent dimethyl sulfoxide (DMSO) +liver microsome enzyme]; [3] lead group of low concentration (acetic lead 5 μmol/L) (No. 1 group); [4] lead group of high concentration (acetic lead 50 μmol/L) (No. 2 group); [5] benzo[a]pyrene group of low concentration (benzo[a]pyrene 5 μmol/L + liver microsome enzym) (No. 3 group); [6]benzo[a]pyrene group of high concentration (benzo[a]pyrene 50 μmol/L +liver microsome enzym) (No. 4 group); [7] lead of low concentration +benzo[a]pyrene of low concentration group (No. 5 group); [8] lead of low concentration + benzo[a]pyrene of high concentration group (No. 6 group);[9] lead of high concentration + benzo[a]pyrene of low concentration group (No.7 group); [10] lead of high concentration + benzo[a]pyrene of high concentration group (No. 8 group).METHODS: After stained poisoning for 90 minutes, trypsin digestion method was used for sample collection and trypan blue staining method was applied to assay cell survival rate in each group. Single-cell gel electrophoresis (SCGE) was used to determine the damage of nuclear DNA in each group.MAIN OUTCOME MEASURES: Neuronal survival rate and damage rate of nuclear DNA in poisoning with benzo[a]pyrene and lead either in separation or in combination.RESULTS: [1] Cell survival rates in various groups poisoned with benzo [a]pyrene and lead of two concentrations either in separation or combination were lower than the controls [poisoning group (44.14±4.80)% to(82.40±2.70)%, the controls (88.44±2.53)% to ( 90.12±2.23)%, P ＜ 0.05to 0.01]. [2] Degrees of nuclear DNA damage in single poisoning group with benzo[a]pyrene of high concentration, lead of low concentration + benzo[a]pyrene of high concentration, lead of high concentration + benzo[a]-pyrene of low concentration and lead of high concentration + benzo[a]pyrene of high concentration were higher than the controls [63% (19/30), 87%(26/30), 80% (24/30), 97% (29/30), 13% (4/30), 20% (6/30), P ＜ 0.01].CONCLUSION: Both benzo[a]pyrene and lead present neurotoxicity in vitro and coordinate with each other. The damage of benzo[a]pyrene is worse than lead in neuronal nuclear DNA cultured in vitro.

Neurotoxicity of benzo [a] pyrene and its effects on heat stress protein 70 and heat stress protein 90β in brain tissue of mice / 中国组织工程研究

BACKGROUND: Benzo[a] pyrene(BaP) is kind of polyaromatic hydrocarbon which is a chemical pollutant extensively existing in living and productive environments. It is found overseas that it has neurotoxic effects under certain conditions.OBJECTIVE: To study the neurotoxicity of BaP and its effects on expression of two heat stress proteins(HSPs) HSP70 and HSP90β in brain tissue of mice.DESIGN: Randomized case control study of experimental animals.SETTING: Laboratory of thermobiology and molecular toxicology of a unversity, department of preventive medicine of a university.MATERIALS: The experiment was conducted in the Thermobiology and Molecular Toxicity Laboratory, Tongji Medical College, Huazhong Science and Technology University. Fifty male Kunming mice were randomly divided into 5 groups with each of 10 mice including 3 administrated groups, 1 vehicle group and 1 control group. All mice in 3 exposed groups were intraperitoneally administrated BaP dissolved in corn oil at dose levels of 7.8mg/kg, 3.2 mg/kg and 1.3 mg/kg respectively for four times per week. The mice in vehicle group received an equal volume of com oil and the mice in control group received no additional treatment.METHODS: The signs of neurotoxicity in each group were examined and recorded during the administration. At the end of 8-week administration, the brains were excised to calculate brain tissue organ coefficient. Western blot method was used to assay the HSP70 and HSP90β.MAIN OUTCOME MEASURES: Effects of BaP on HSP70 and HSP90βin brain tissue of mice.Bap exposure groups was much lower than that of control group( P ＜ 0. 01,P ＜ 0. 001 ) while the organ coefficient of high dose group was much of HSP70 was characterized by greatly increased expression in low dose group while the relative expression of HSP90β was increased in middle and high dose groups.CONCLUSION: BaP has certain neurotoxic effects. With the increase of toxic dose, the expression of HSP90β increases which can be used as signal of toxic damage under certain conditions.

Expression of Heat Shock Protein 70 and 27 in Non-small Cell Lung Cancer and Its Clinical Significance / 华中科技大学学报（医学）（英德文版）

The heat shock proteins (HSPs) 70 and HSP 27 expression in patients with non-small cell lung cancer (NSCLC) was studied and the relationship between HSP 70 and HSP 27 with the clinicopathological features of NSCLC was investigated. The expression of HSP 70 and HSP 27 was detected in tumor tissues from 60 patients with NSCLC by S-P immunohistochemistry. The findings were analyzed in combination with the histological types, histopathological differentiation, lymph node metastasis, patients' clinical stages, smoking history and gender. The results showed that of the 60 NSCLC tissue specimens studied, the immunoreactivity of HSP 70 and HSP 27 was detected in 47 (78.3 %) and 43 (71.7 %) specimens, respectively. A positive correlation was found between the overexpression of HSP 70 and HSP 27. The histopathological differentiation, lymph node metastasis, clinical stages and smoking history were correlated to the expression of HSP 70, but not to the expression of HSP 27. No statistical significance was observed in histological types and gender with respect to both HSP 70 and HSP 27 expression. It is suggested that the HSP 70 expression is a powerful and significant prognostic indicator and is related to histopathological differ entiation, lymph node metastasis, patients' clinical stages, smoking history, whereas HSP 27 expression is not.

Expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation / 华中科技大学学报（医学）（英德文版）

In order to investigate the changes in the expression of extracellular signal-regulated kinase (ERK1/ERK2) and angiotensin-converting enzyme (ACE) in the patients with atrial fibrillation (AF), 52 patients with rheumatic heart diseases were examined. Nineteen patients had chronic persistent AF (AF > or = 6 months, CAF), 12 patients had paroxymal AF (PAF) and 21 patients had no history of AF. The ERK expression was detected at the mRNA level by reverse transcription polymerase chain reaction, at the protein level by Western blotting and at atrial tissue level by immunohistochemistry. ERK-activating kinases (MEK1/2) and ACE were determined by Western blotting techniques. The expression of ERK2-mRNA was increased in the patients with CAF (74 +/- 19 U vs sinus rhythm: 32 +/- 24 U, P < 0.05). Activated ERK1/ERK2 and MEK1/2 were increased to more than 150% in the patients with AF compared to those with sinus rhythm. No significant difference between CAF and PAF was found. The expression of ACE was three-fold increased in the patients with CAF compared to those with sinus rhythm. Patients with AF showed an increased expression of ERK1/ERK2 in atrial interstitial cells and marked atrial fibrosis. An ACE-dependent increase in the amounts of activated ERK1/ERK2 in atrial interstitial cells may be one of molecular mechanisms for the development of atrial fibrosis in the patients with AF. These findings may have important impact on the treatment of AF.

Expression of HSP70 in peripheral lymphocytes of the patients with allergic rhinitis / 华中科技大学学报（医学）（英德文版）

The expression levels of heat shock protein 70 (HSP70) from peripheral lymphocytes of the patients with allergic rhinitis (AR) and the clinical implication were investigated. In the morning, 3 ml of fasting venous blood was taken out. The lymphocytes were isolated by using Ficoll-Hypaque and the expression of HSP70 in the lymphocytes was detected by using Western blot. In the AR patients the HSP70 level (41.49 +/- 15.77 integrated optical density, IOD) were significantly higher than that in the control group (23.89 +/- 10.13 IOD, P < 0.05). Western blot demonstrated that HSP70 bands in AR patients were more intensive than those in the control group. It was concluded that the elevated HSP70 level in peripheral lymphocytes of the AR patients might contribute to the development of AR.

Expression of HSP70 in peripheral lymphocytes of the patients with allergic rhinitis / 华中科技大学学报（医学）（英德文版）

The expression levels of heat shock protein 70 (HSP70) from peripheral lymphocytes of the patients with allergic rhinitis (AR) and the clinical implication were investigated. In the morning, 3 ml of fasting venous blood was taken out. The lymphocytes were isolated by using Ficoll-Hypaque and the expression of HSP70 in the lymphocytes was detected by using Western blot. In the AR patients the HSP70 level (41.49 +/- 15.77 integrated optical density, IOD) were significantly higher than that in the control group (23.89 +/- 10.13 IOD, P < 0.05). Western blot demonstrated that HSP70 bands in AR patients were more intensive than those in the control group. It was concluded that the elevated HSP70 level in peripheral lymphocytes of the AR patients might contribute to the development of AR.