Urinary Bile Acid Profile of Newborns Born by Cesarean Section Is Characterized by Oxidative Metabolism of Primary Bile Acids: Limited Roles of Fetal-Specific CYP3A7 in Cholate Oxidations.

This work aims to investigate how the bile acid metabolism of newborns differs from that of adults along the axis of primary, secondary, and tertiary bile acids (BAs). The total unconjugated BA profiles were quantitatively determined by enzyme digestion techniques in urine of 21 newborns born by cesarean section, 29 healthy parturient women, 30 healthy males, and 28 healthy nonpregnant females. As expected, because of a lack of developed gut microbiota, newborns exhibited poor metabolism of secondary BAs. Accordingly, the tertiary BAs contributed limitedly to the urinary excretion of BAs in newborns despite their tertiary-to-secondary ratios significantly increasing. As a result, the primary BAs of newborns underwent extensive oxidative metabolism, resulting in elevated urinary levels of some fetal-specific BAs, including 3-dehydroCA, 3ß,7α,12α-trihydroxy-5ß-cholan-24-oic acid, 3α,12-oxo-hydroxy-5ß-cholan-24-oic acid, and nine tetrahydroxy-cholan-24-oic acids (Tetra-BAs). Parturient women had significantly elevated urinary levels of tertiary BAs and fetal-specific BAs compared with female control, indicating that they may be excreted into amniotic fluid for maternal disposition. An in vitro metabolism assay in infant liver microsomes showed that four Tetra-BAs and 3-dehydroCA were hydroxylated metabolites of cholate, glycocholate, and particularly taurocholate. However, the recombinant cytochrome P450 enzyme assay found that the fetal-specific CYP3A7 did not contribute to these oxidation metabolisms as much as expected compared with CYP3A4. In conclusion, newborns show a BA metabolism pattern predominated by primary BA oxidations due to immaturity of secondary BA metabolism. Translational studies following this finding may bring new ideas and strategies for both pediatric pharmacology and diagnosis and treatment of perinatal cholestasis-associated diseases. SIGNIFICANCE STATEMENT: The prenatal BA disposition is different from adults because of a lack of gut microbiota. However, how the BA metabolism of newborns differs from that of adults along the axis of primary, secondary, and tertiary BAs remains poorly defined. This work demonstrated that the urinary BA profiles of newborns born by cesarean section are characterized by oxidative metabolism of primary BAs, in which the fetal-specific CYP3A7 plays a limited role in the downstream oxidation metabolism of cholate.

Stereoselective Oxidation Kinetics of Deoxycholate in Recombinant and Microsomal CYP3A Enzymes: Deoxycholate 19-Hydroxylation Is an In Vitro Marker of CYP3A7 Activity.

The primary bile acids (BAs) synthesized from cholesterol in the liver are converted to secondary BAs by gut microbiota. It was recently disclosed that the major secondary BA, deoxycholate (DCA) species, is stereoselectively oxidized to tertiary BAs exclusively by CYP3A enzymes. This work subsequently investigated the in vitro oxidation kinetics of DCA at C-1ß, C-3ß, C-4ß, C-5ß, C-6α, C-6ß, and C-19 in recombinant CYP3A enzymes and naive enzymes in human liver microsomes (HLMs). The stereoselective oxidation of DCA fit well with Hill kinetics at 1-300 µM in both recombinant CYP3A enzymes and pooled HLMs. With no contributions or trace contributions from CYP3A5, CYP3A7 favors oxidation at C-19, C-4ß, C-6α, C-3ß, and C-1ß, whereas CYP3A4 favors the oxidation at C-5ß and C-6ß compared with each other. Correlation between DCA oxidation and testosterone 6ß-hydroxylation in 14 adult single-donor HLMs provided proof-of-concept evidence that DCA 19-hydroxylation is an in vitro marker reaction for CYP3A7 activity, whereas oxidation at other sites represents mixed indicators for CYP3A4 and CYP3A7 activities. Deactivation caused by DCA-induced cytochrome P450-cytochrome P420 conversion, as shown by the spectral titrations of isolated CYP3A proteins, was observed when DCA levels were near or higher than the critical micelle concentration (about 1500 µM). Unlike CYP3A4, CYP3A7 showed abnormally elevated activities at 500 and 750 µM, which might be associated with an altered affinity for DCA multimers. The disclosed kinetic and functional roles of CYP3A isoforms in disposing of the gut bacteria-derived DCA may help in understanding the structural and functional mechanisms of CYP3A.

Past occupational dust exposure, depressive symptoms and anxiety in retired Chinese factory workers: the Guangzhou Biobank Cohort Study.

OBJECTIVE: Few studies have systematically investigated the impact of past occupational dust exposure on mental health. We examined whether retired factory workers exposed to any of the 4 dusts of silica, cement, coal and asbestos had more depressive symptoms and anxiety in southern China, which has experienced rapid economic development. METHODS: We used data from the Guangzhou Biobank Cohort Study phase 3. Exposures, lifestyle, symptoms and medical history of the participants were assessed with a structured interview. Self-reported intensity and duration of past occupational dust exposure were used to derive cumulative exposure. Outcome measures were assessed by the 15-item Chinese version of the Geriatric Depression Scale (score ≥5) and the single-item on anxiety. RESULTS: The results revealed that 359 workers were exposed to at least one of the 4 dusts and that 1,253 were unexposed (controls). After adjustment of multiple confounders, greater risks of depressive symptoms were associated with high exposure to silica (odds ratio (OR) of 3.12, 95% CI of 1.17-8.31) and asbestos (OR of 6.90; CI of 1.29-36.75). Risks of anxiety were higher in those with low or high exposures to dust (OR of 2.01 and CI of 1.04-3.87 and OR of 2.29 and CI of 1.30-4.03, respectively) and cement (OR of 3.20 and CI of 1.27-8.07 and OR of 2.30 and CI of 1.09-4.87, respectively), and those with high exposure to silica (OR of 5.29, CI of 1.76-15.92). CONCLUSIONS: Past occupational exposures to silica, cement, coal and asbestos dusts were associated with adverse mental health outcomes in retired factory workers. The mechanism underlying the relationship between occupational exposures and psychological symptoms in later life needs to be further studied.

[Analysis of influential factors for job burnout among managers in a joint venture in Guangzhou, China].

OBJECTIVE: To investigate the influential factors for job burnout among the managerial staff in a Sino-Japanese joint venture automobile manufacturer in Guangzhou, China. METHODS: A total of 288 managers in a Sino-Japanese joint venture automobile manufacturer were surveyed using the Occupational Stress Indicator, Maslach Burnout Inventory (MBI), Eysenck Personality Questionnaire, Simplified Coping Style Questionnaire, and Social Support Rating Scale. RESULTS: On the depersonalization dimension, the male managers had significantly higher scores than the female managers. The scores of emotion exhaustion and depersonalization of MBI showed significant differences among the managers with different levels of occupational stress. The path analysis showed that occupational stress, neuroticism, and psychoticism had negative effects on emotion exhaustion, while job satisfaction and utilization of social support had direct positive effects on emotion exhaustion. Occupational stress, psychoticism, and passive coping style had direct negative effects on depersonalization, while job satisfaction, objective support, and utilization of social support had positive effects on depersonalization. Job satisfaction and active coping style had positive effects on sense of personal accomplishment, while passive coping style had a negative effect on sense of personal accomplishment. Personality exerted its effect on social support through coping style and thus on job satisfaction and job burnout. CONCLUSION: Male managers have a greater propensity to depersonalization than their female counterparts. High occupational stress is a risk factor for job burnout. Personality, social support, and coping style are influential factors for job burnout.

The relationship between occupational stress, burnout, and turnover intention among managerial staff from a Sino-Japanese joint venture in Guangzhou, China.

OBJECTIVE: The aim of this study was to analyze the associations between occupational stress, burnout and turnover intention and explore their associated factors among managerial staff in Guangzhou, China. METHODS: This cross-sectional study recruited 288 managerial employees from a Sino-Japanese joint venture automobile manufacturing enterprise in Guangzhou. The questionnaire included questions about sociodemographic characteristics, smoking, drinking and physical activity and the Chinese versio ns of the Occupational Stress Indicator (OSI), Maslach Burnout Inventory (MBI), Eysenck Personality Questionnaire (EPQ), Simplified Coping Style Questionnaire (SCSQ) and Social Support Rating Scale (SSRS). The response rate was 57.6%. Stepwise regression analysis was performed to examine the associations between burnout and occupational stress and turnover intention and related factors. RESULTS: The respondents had a high level burnout on the personal accomplishment subscale and had a high prevalence of turnover intention. Neuroticism, psychoticism, job satisfaction, occupational stress and social support were strong predictors of emotional exhaustion. Psychoticism, passive coping, occupational stress, objective support, utilization of support, male gender and job satisfaction were strong predictors of depersonalization. Active and passive coping and job satisfaction were strong predictors of personal accomplishment. Job dissatisfaction and emotional exhaustion were strong predictors of turnover intention. CONCLUSIONS: High occupational stress and low job satisfaction were associated with high burnout, particularly in the emotional exhaustion and depersonalization dimensions. Low job satisfaction and high emotional exhaustion were associated with high turnover intention among employees. Personality traits, social support and coping style were also found to be associated with burnout.

[Epidemiological study of occupational diseases in Guangzhou City, China in 2001 - 2010].

OBJECTIVE: To analyze the epidemiological characteristics of occupational diseases in Guangzhou City, China in 2001 - 2010, and to provide a scientific basis for the prevention and control of occupational diseases. METHODS: Statistical analysis was performed on the reported data on the occupational diseases in Guangzhou from 2001 to 2010. RESULTS: A total of 380 cases of occupational diseases (37 types,8 classes) were diagnosed and reported in 2001 - 2010. The three most frequent diseases were occupational poisonings (48.9%), pneumoconiosis (20.0%), and occupational ear, nose, and throat (ENT) diseases (18.7%). In the cases of occupational poisonings, 25.3% suffered from acute occupational poisonings, especially the poisoning by dichloroethane (19.1%), and 74.7% suffered from chronic occupational poisonings, mainly caused by lead (38.8%), benzene (37.4%), and n-hexane (18.0%). The cases of silicosis accounted for 77.6% of all cases of pneumoconiosis. The cases of noise-induced deafness accounted for 97.2% of all cases of occupational ENT diseases. Patients with occupational diseases were reported in 13 districts of Guangzhou, mostly in Panyu (18.9%), Tianhe (13.2%), Baiyun (12.9%), and Liwan (11.1%). All the cases occurred in 19 industries, mainly including light industry (27.1%) and machinery industry (23.7%). Of all cases, 29.5% were in the public sector, 40.3% in the private sector, and 30.3% in the foreign-funded enterprises and those funded by businessmen from Hong Kong, Macao, and Taiwan. The ratio of male to female cases was 15:4. The mean age of onset was 42.2 ± 10.9 years. The average speed of development of occupational diseases was 134.0%, and the average growth rate was 34.0%. CONCLUSION: The incidence of occupational diseases tends to increase year by year, with younger age of onset and shorter history of exposure in patients. The occupational poisonings caused by lead, benzene, n-hexane, and dichloroethane, silicosis, and noise-induced deafness seem to be the main occupational hazards in Guangzhou, China. Occupational diseases occur in all districts of Guangzhou and in various industries. The private sector and small enterprises should be the focuses of occupational health supervision.

[Influential factors on psychosocial health of the migrant workers in Guangzhou].

OBJECTIVE: To study the influential factors on psychosocial health of the migrant workers in Guangzhou. METHODS: The Symptom Checklist 90 (SCL-90) and Eysenck Personality Questionnaire (EPQ) were used to investigate 518 migrant workers in Guangzhou. RESULTS: The rate of migrant workers with psychosocial problems was 36.5%. The scores of SCL-90 and positive rates in migrant workers with the different personality types had significant difference (P < 0.01). The results of binary logistic regression analysis indicated that the working years, drinking, sex, P scores, E scores and N scores of EPQ were main predictors of the poor physical fitness status. The vocations, working years, P scores and N scores of EPQ were strong predictors of the somatization. he vocations, P scores and N scores of EPQ were strong predictors of the obsessive compulsive symptom. The smoking, P scores and N scores of EPQ were strong predictors of the interpersonal sensitivity. The working years, P scores of EPQ were strong predictors of the depression. P scores of EPQ was strong predictors of the anxiety. P scores, E scores and N scores of EPQ were strong predictors of the hostility. The working years, smoking, P scores, E scores and N scores of EPQ were strong predictors of the phobic anxiety. The working years, P scores of EPQ were strong predictors of the paranoid ideation. The working years, P scores and N scores of EPQ were strong predictors of the psychosis. CONCLUSION: The level of mental health of the migrant workers was significantly associated with the personality. The results of present study indicated that different vocation, sex, working years, smoking and drinking might interfere with the psychological states. The migrant workers with the personality of psychoticism, neuroticism and introversion may have unhealthy mental reaction.

[Personality and occupation stress of workers in processing line in Guangzhou].

OBJECTIVE: To study relationships between personality and occupational stress of workers in processing line in Guangzhou. METHODS: 452 workers in processing line in Guangzhou were investigated by the Eysenck Personality Questionnaire (EPQ) and Occupational Stress Indicator (OSI). RESULTS: N scores and P scores of EPQ were positively correlated with the occupational stress and the poor physical fitness status (r value was 0.196, 0.128, 0.202, 0.218, respectively) (P < 0.01). N scores of EPQ were positively correlated with the type A behavior (r = 0.164) and negatively correlated with the mental well-being level (r = -0.196, P < 0.01). P scores of EPQ were negative correlated with the sense of job satisfaction and the stress coping ability(r value was -0.146, -0.140, respectively) (P < 0.01). E scores and L scores of EPQ were negatively correlated with the type A behavior (r value was -0.159, -0.138, respectively) (P < 0.01). E scores of EPQ were positively correlated with the stress coping ability (r = 0.176, P < 0.01). L scores of EPQ were negatively correlated with the occupational stress, the poor physical fitness status and the explanation to vicinity event (r value was -0.139, -0.140, -0.111, respectively) (P < 0.01, P < 0.05). CONCLUSION: The personality of neuroticism, psychoticism and introversion may be related to the occupational stress, the sense of job satisfaction and unhealthy mental reaction.

[Analysis of the situation of occupational health surveillance and the morbidity of occupational diseases in Guangzhou].

OBJECTIVE: To analyze the situation of occupational health surveillance and the characteristics of occupational diseases in Guangzhou. METHODS: The situation of occupational health surveillance and the morbidity of occupational diseases were studied retrospectively by use of the physical examination data collected from the labour hygienic reports of the city from 1993 to 2002. The data were divided into two groups: the first group from 1993 to 1997, and the second from 1998 to 2002. RESULTS: Annual average of occupational health examination in the past 10 years was over 75%. The data in the second group (1998 - 2002) showed that the number of hearing loss observed subjects, noise surveilled personnels, dust and chemicals contraindicated personnels were significantly higher than those in the 1st group (P < 0.01). The morbidity of chronic occupational disease newly occurred was 91 cases in lst group, and 181 cases in 2nd group (P < 0.05), in which the incidence of chemical poisoning and noise induced hearing loss increased significantly but that of pneumoconiosis between two groups was not significantly different (P > 0.05). In the past 10 years, 581 cases of occupational diseases were diagnosed, of which, 309 cases (53.18%) were acute poisonings, while 272 cases (46.82%) were chronic occupational diseases. Pneumoconiosis, lead and benzene poisoning were common in chronic occupational diseases (16.70%, 16.87% respectively). With the passage of time, the incidence ages of pneumoconiosis, chemical poisoning and total occupational diseases tended towards younger. The difference was statistically significant (P < 0.01) CONCLUSION: A normal system for occupational health surveillance has been developed in Guangzhou. Detectable rates in focused surveillance and contraindication have been obviously increasing. The incidence of occupational disease (mainly including acute occupational poisoning, pneumoconiosis, lead and benzene poisonings) is also going up. The incidence age of chronic occupational diseases tends to be younger accompanied with a shorter work history.