APOE ε4 allele modifies the associations of toxic metals and their mixture with cognitive impairment among older adults.

BACKGROUND: The evidence of interactive effect of the toxic metal (TM) mixture and apolipoprotein E (APOE) ε4 gene on cognitive impairment in older adults is scarce. We aimed to explore whether the associations of single TMs and their mixture with cognitive impairment depend on APOE ε4 in Chinese community-dwelling older people. METHODS: A total of 1148 older adults from a subset of the baseline survey of a cohort study were included. Blood arsenic (As), cadmium (Cd), lead (Pb), strontium (Sr), and vanadium (V) were detected by inductively coupled plasma mass spectrometry. APOE gene (rs429358, rs7412) polymorphisms were analyzed by the Polymerase Chain Reaction instrument. Mixed effects logistic regression was applied to estimate the relationships of single TMs and APOE genotype with cognitive impairment. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to examine joint impacts of the TM mixture, as well as the interaction of the TM mixture with APOE ε4 genotype on cognitive impairment. RESULTS: Pb displayed a significant linear association with an increased odds of cognitive impairment after adjustment for covariates (Ptrend = 0.045). While APOE genotype did not show a significant correlation with cognitive impairment. WQS showed that the TM mixture was associated with an increased risk of cognitive impairment by 31.0% (OR=1.31, 95% CI: 0.92, 1.87) while no significance was found. BKMR exhibited a significant linear association between the TM mixture and cognitive impairment. Moreover, both WQS and BKMR indicated that Pb contributed the most to cognitive impairment within the mixture. Significant interactions of Pb or the TM mixture and APOE genotype on cognitive impairment were observed, contributing to 38.1% and 38.2% of total effects, respectively. CONCLUSIONS: APOE ε4 allele amplifies the associations of single Pb or the TM mixture with cognitive impairment. These findings may help to develop precision prevention.

Social support, psychological capital, multidimensional job burnout, and turnover intention of primary medical staff: a path analysis drawing on conservation of resources theory.

BACKGROUND: Job burnout is a prevalent and emerging challenge in the primary medical system, causing mass turnover, especially of primary medical staff. Little attention has been paid to the different dimensions of job burnout (emotional exhaustion, personality disintegration, and reduced sense of achievement), which may hinder efforts to tackle high turnover intention among primary medical staff. From the perspective of conservation of resources theory, social support and psychological capital are basic resources with potential to diminish job burnout and thus lower turnover intention. However, there is insufficient research evidence on the relationships between social support, psychological capital, and the three dimensions of job burnout within the primary medical system. OBJECTIVES: Focusing on primary medical staff, this study conducts a path analysis to examine the correlations between two types of resources (social support and psychological capital) and the three dimensions of job burnout, and to test the impact of the latter on turnover intention. Based on the results, effective management strategies to improve the work stability of primary medical staff are proposed. METHODS: Multi-stage cluster random sampling was used to select participants in Anhui Province, China. Data were collected using a self-administered questionnaire containing measures of the main variables and demographic questions. In total, 1132 valid questionnaires were returned by primary medical staff. Structural equation modeling was used for path analysis of the data. RESULTS: Social support was negatively associated with emotional exhaustion (ß = - 0.088, P = 0.020), personality disintegration (ß = - 0.235, P < 0.001), and reduced sense of achievement (ß = - 0.075, P = 0.040). Moreover, psychological capital was negatively associated with emotional exhaustion (ß = - 0.079, P = 0.030), personality disintegration (ß = - 0.156, P < 0.001), and reduced sense of achievement (ß = - 0.432, P < 0.001). All three dimensions of job burnout positively affected turnover intention (emotional exhaustion: ß = 0.246, P < 0.001; personality disintegration: ß = 0.076, P = 0.040; reduced sense of achievement: ß = 0.119, P = 0.001). CONCLUSIONS: The results highlight the importance of social support and psychological capital for diminishing the three dimensions of job burnout for primary medical staff and, in turn, lowering their turnover intention. Accordingly, to alleviate job burnout and improve staff retention, material and psychological supports from leaders, colleagues, family, relatives, and friends are essential, as are measures to improve the psychological energy of primary medical staff.

Associations of toxic metals and their mixture with hyperuricemia in Chinese rural older adults.

Previous studies have related single toxic metals (TMs) to hyperuricemia (HUA) among the general population, however, the association of the TM mixture with HUA, especially in older adults, remains poorly understood. We aimed to examine the relationships between individual TMs and their mixture and HUA in Chinese rural older adults. This study consisted of 2075 rural older adults aged 60 years or over. Blood concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), gallium (Ga), mercury (Hg), lead (Pb), thallium (Tl), and uranium (U) were detected using inductively coupled plasma mass spectrometry. The associations of single TMs with HUA were assessed using logistic regression and restricted cubic spline (RCS) models, and the association of TM mixture with HUA was explored using the elastic net with environmental risk score (ENET-ERS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted logistic regression model showed that Cs (OR = 1.65, 95% CI 1.37-1.99) and Pb (OR = 1.46, 95% CI 1.28-1.67) were positively related to HUA, and RCS model exhibited a positive linear association of Cs and Pb with HUA. ENET-ERS and QGC models quantified a positive correlation between the TM mixture and the odds of HUA, with estimated ORs of 1.15 (95% CI 1.11-1.19) and 1.84 (95% CI 1.37-2.47), respectively, and Cs and Pb had the most weight. BKMR model demonstrated a significant linear association between the TM mixture and increased odds of HUA, with the posterior inclusion probabilities (PIPs) of both Cs and Pb being 1.00. Moreover, we observed a positive interaction between Cs and Pb on HUA. The TM mixture is associated with increased odds of HUA in rural older adults, which may mainly be driven by Cs and Pb. Subsequent studies are warranted to confirm these findings and clarify the mechanisms linking multiple TMs with HUA.

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people.

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

Urinary antibiotic exposure and low grip strength risk in community-dwelling elderly Chinese by gender and age.

Emerging studies have shown that environmental contaminants were related to decreased handgrip strength. Nevertheless, no prior research has investigated the relationship of exposure to environmental antibiotics with grip strength. Thus, we explored the relationship between urinary antibiotic burden and grip strength among the elderly in China. This study consisted of 451 men and 539 women from the baseline survey of a cohort study. Commonly used antibiotics for humans and animals were detected in 990 urine samples through a biomonitoring method. Grip strength was measured by an electronic dynamometer. We examined the associations of antibiotic exposure with low grip strength (LGS), grip strength, and grip strength index, respectively. Results suggested that 34.9% of participants developed LGS, and 93.0% of individuals were exposed to 1-10 antibiotics. Among women, oxytetracycline (Quartile 2: odds ratio: 2.97, 95% confidence interval: 1.36-6.50), florfenicol (Quartile 3: 2.60 [1.28-5.27]), fluoroquinolones (Quartile 4: 1.88 [1.07-3.30]), and chloramphenicols (Quartile 3: 2.73 [1.35-5.51]) could enhance LGS risk. Among men, ofloxacin (Quartile 2: 3.32 [1.45-7.59]) increased LGS risk, whereas tetracycline (Quartile 2: 0.31 [0.11-0.88]) was implicated in reduced LGS risk. In participants < 70 years, ofloxacin (Quartile 2: 3.00 [1.40-6.42]) could increase LGS risk. For participants who were 70 years of age or older, veterinary antibiotics (Quartile 3: 1.73 [1.02-2.94]) were linked to a 73% increased risk of LGS. Our findings suggested that antibiotics mainly pertained to LGS, and there were gender and age disparities in associations between antibiotic exposure and muscle strength indicators in the elderly Chinese population.

Low Abundance of Lactococcus lactis in Human Colorectal Cancer Is Associated with Decreased Natural Killer Cells.

A limited number of studies have demonstrated the role of Lactococcus lactis (L. lactis) in human colorectal cancers (CRCs). The association of L. lactis abundance with the density of natural killer (NK) cells has not been investigated before. In this study, the L. lactis abundance in 60 CRC specimens, 20 adenoma (AD) specimens, and 29 normal colorectal tissues (NCs) specimens was investigated using the fluorescence in situ hybridization of 16S ribosomal RNA. The density of NK cells was detected using immunofluorescence in 28 CRC specimens, 12 AD specimens, and 22 NC specimens. The presence of L. lactis in NCs (48.28%) was detected significantly higher than that in the AD (20.00%, P = .044) and CRC (23.33%, P = .018) specimens. The abundance of L. lactis in NCs (32.73 ± 7.24) was also found to be significantly higher than that in AD (8.91 ± 5.89, P = .029) and CRC (5.63 ± 1.67, P = .003) specimens. In addition, the density of NKp30+ NK cells in NCs (51.14 ± 4.84) was significantly higher than that in the AD (6.10 ± 1.31) and CRC (1.72 ± 0.40) specimens (P < .001). Moreover, a positive association of L. lactis abundance with NKp30+ NK cells density in the colorectal samples (P < .001) was observed. The low abundance of L. lactis in the CRC tissues was associated with the decreased NK cells, which suggested that this might contribute to the progression of CRC by decreasing the number of NK cells.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1944649.

The association between essential trace element mixture and cognitive function in Chinese community-dwelling older adults.

BACKGROUND: The evidence about the effect of essential trace element (ETE) mixture on cognitive function amongst older adults is limited. This study aims to evaluate the associations of single ETEs and ETE mixture with cognitive function using a representative sample of community-dwelling older adults in China. METHODS: A total of 3814 older adults were included in the study. Urinary concentrations of selenium (Se), vanadium (V), cobalt (Co), strontium (Sr), and molybdenum (Mo) were detected by inductively coupled plasma mass spectrometry. Cognitive function in older adults was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Linear regression and Bayesian kernel machine regression (BKMR) were performed to explore the associations of single ETEs and ETE mixture with cognitive function, respectively. RESULTS: Linear regression showed that urinary levels of Se and V were positively associated with MMSE scores in the adjusted single-element models. BKMR also showed marginally positive associations of Se and V with MMSE scores. Moreover, higher urinary levels of ETE mixture were significantly associated with increased MMSE scores in a dose-response pattern, and Se was the most important contributor within the mixture. Both Se and V demonstrated positive additive effects on the associations of other ETEs with MMSE scores, whereas Co had a negative additive effect. CONCLUSIONS: V and Se are positively associated with cognitive function, individually and as a mixture. ETE mixture exhibits a linear dose-response association with improved cognitive function, with Se being the most important component within the mixture. Mixture analyses rather than single ETE analyses may provide a real-world perspective on the relationship between ETE mixture and cognitive function. Further cohort studies are needed to clarify the association of multiple ETEs with cognitive function.

High-rate partial denitrification via effluent residual nitrate controlling and microbial mechanism of nitrite accumulation by carbon dosage optimization.

The high-rate partial denitrification (PD) via effluent residual nitrate controlling by carbon dosage optimization was investigated based on the analysis of microbial mechanism of nitrite accumulation in this study. When the COD/N was changed from 4.0 to 1.8 and the effluent nitrate was above 8.48 mg/L, the nitrate accumulation ratio (NAR) and nitrate removal ratio (NRR) achieved 60 and 90%, respectively. With the electron donor starvation (EDS) strategy, nitrite accumulation was increased, which is related to the reduced utilization of carbon sources. In addition, the rapid increase of Thauera (0.21% to 53.29%) and inhibition of Others and Unclassified (96.93% to 16.99%), and the significantly different expression between reductase genes contributed to nitrite production (narG, 1,727.44 copies/mg) and nitrite reduction (nirS, 208.27 copies/mg; nirK, 203.94 copies/mg) commonly involved in PD start-up and stable operation. Another reactor can be quickly started by controlling effluent residual nitrate within 19 days.

Current status and related factors of turnover intention of primary medical staff in Anhui Province, China: a cross-sectional study.

BACKGROUND: The shortage of primary medical staff is an important issue in the management of health human resources, and it is also a problem that all countries in the world need to face together. Since 2009, China has implemented a new series of medical system reforms and the shortage and loss of primary medical staff have been alleviated accordingly. However, China has a large population and it is difficult to distribute health human resources evenly across regions. This study aimed to explore the current status of turnover intention and its relationship with psychological capital, social support, and job burnout, as well as how these factors influence turnover intention of primary medical staff in Anhui province, China. METHODS: Using structured questionnaires to collect data, including demographic characteristics, turnover intention, psychological capital, social support, and Chinese Maslach Burnout Inventory scale. A total of 1152 primary medical workers of Anhui were investigated. Data were analyzed by t-test, analysis of variance (ANOVA), Pearson correlation analysis, and multiple linear regression model. RESULTS: Total scores of turnover intention, psychological capital, social support, and job burnout of subjects were 14.15 ± 4.35, 100.09 ± 15.98, 64.93 ± 13.23 and 41.07 ± 9.437, respectively. Multiple linear regression showed the related factors of turnover intention were age, job position, work unit, and scores of job burnout. Pearson correlation showed psychological capital and social support were negatively correlated with turnover intention, while the score of job burnout was positively correlated with turnover intention. CONCLUSION: The improvement of psychological capital and social support and the reduction of job burnout may play an important role in reducing turnover intention of primary medical staff. Primary medical managers should strengthen the humanistic care for primary medical staff, optimize the incentive mechanism, and improve internal management of medical institutions for stability.

Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells.

Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.

Mediation role of perceived social support and burnout on financial satisfaction and turnover intention in primary care providers: a cross-sectional study.

BACKGROUND: Turnover intention is a major cause of reduced team morale and low work efficiency. It hinders work performance and reduces the quality of medical services. This study aimed to investigate the relationship between financial satisfaction and turnover intention and its mediators among primary care providers. METHODS: Multi-stage random cluster sampling was used to select 1241 participants from four counties and three districts in Anhui province, China. Data were collected using a self-administered questionnaire. Turnover intention was assessed with a turnover intention assessment scale. Perceived social support and burnout were measured with the 12-item Perceived Social Support Scale and the Chinese version of the Maslach Burnout Inventory, respectively. Structural equation modeling was used for data analysis. RESULTS: The findings showed high turnover intention among primary care providers (mean score 14.16 ± 4.337), and most providers reported low financial satisfaction (mean score 2.49 ± 0.990). The mean perceived social support score was 64.93 ± 13.229, and only 6.1% of primary care providers reported no burnout. Compared with participants with high financial satisfaction, those with low financial satisfaction were more likely to report higher turnover intention (ß = - 0.216, p < 0.001), less perceived social support (ß = 0.181, p < 0.001), and more severe burnout (ß = - 0.123, p < 0.05). Turnover intention may be related to perceived social support (ß = - 0.147, p < 0.001) and burnout (ß = 0.239, p < 0.001). Furthermore, the effect of financial satisfaction on turnover intention was significantly mediated by perceived social support (ß = - 0.027, p < 0.001) and burnout (ß = - 0.029, p < 0.05). CONCLUSIONS: Turnover intention is associated with financial satisfaction, with this association mediated by perceived social support and burnout. A reasonable mechanism needs to be established to improve financial satisfaction and perceived social support and reduce burnout among primary care providers.

[Associations of hyperlipidemia and its subtypes with blood lead levels in Lu'an City community older adults in 2016].

OBJECTIVE: To explore associations of hyperlipidemia and its subtypes with blood lead levels in community older adults. METHODS: From June to September, 2016, a rural and an urban community in Lu'an City, Anhui Province were randomly selected. Older adults aged 60 years old or over in two communities were recruited to participate, receiving a questionnaire interview(including gender, age, region, education, occupation, marital status, lifestyle, and chronic medical history, etc. ), physical examinations(height, weight, and blood pressure) and laboratory tests(blood glucose, blood lipid, and blood lead levels). A total of 1080 older adults volunteered to participate, of which 1008 had completedata. Inductively coupled plasma mass spectrometry was used to measure concentrations of blood lead. The interquartile range was used to divide the distribution of lead in blood. Logistic regression model was used to examine associations of hyperlipidemia and its subtypes with blood lead levels. Restrictive cubic splineswere used to further determine potential dose-response relationships. RESULTS: Of 1008 older adults, the mean age was(71.9±6.5) years old, 459(45.5%)were male, and 557(55.3%) were from the rural community. The prevalence of hyperlipidemia was 51.2%(n=516). The detection rate and geometric mean of blood lead were 100% and 28.08 µg/L(ranged from 7.89 to 278.33 µg/L), respectively. Univariate analysis showed that older adults in the highest quartile group of blood lead(≥75%) had higher odds of hyperlipidemia(OR=1.42, 95%CI 1.00-2.02) and two subtypes(high total serum cholesterol(OR=1.83, 95%CI 1.25-2.68)and mixed hyperlipidemia(OR=1.49, 95%CI 0.83-2.67)) compared to counterparties in the lowest quartile group(≤25%). After adjustment for gender, age, region, education, occupation, marital status, smoking, drinking, exercise conditions, diet, high blood pressure, diabetes, and body mass index, the ORs for hyperlipidemia and mixed hyperlipidemia in the highest quartile group of blood lead were 1.55(95%CI 1.02-2.36) and 2.87(95%CI 1.44-5.70). The restricted cubic spline curves showed approximate linear relationships between blood lead levels and ORs of hyperlipidemia and mixed hyperlipidemia. CONCLUSION: Linear associations of blood lead levels with hyperlipidemia and mixed hyperlipidemia were found in community older adults.

Phosphorylation of eIF2α mitigates endoplasmic reticulum stress and hepatocyte necroptosis in acute liver injury.

INTRODUCTION AND OBJECTIVES: Necroptosis and endoplasmic reticulum (ER) stress has been implicated in acute and chronic liver injury. Activated eukaryotic initiation factor 2 alpha (eIF2α) attenuates protein synthesis and relieves the load of protein folding in the ER. In this study, we aimed to analyze the impact of eIF2α phosphorylation on hepatocyte necroptosis in acute liver injury. MATERIALS AND METHODS: Male BALB/c mice were injected with tunicamycin or d-galactosamine, and LO2 cells were incubated with tunicamycin to induce acute liver injury. 4-Phenylbutyric acid (PBA) and salubrinal were used to inhibit ER stress and eIF2α dephosphorylation, respectively. We analyzed the eIF2α phosphorylation, ER stress, and hepatocyte necroptosis in mice and cells model. RESULTS: Tunicamycin or d-galactosamine significantly induced ER stress and necroptosis, as well as eIF2α phosphorylation, in mice and LO2 cells (p<0.05). ER stress aggravated tunicamycin-induced hepatocyte necroptosis in mice and LO2 cells (p<0.05). Elevated eIF2α phosphorylation significantly mitigated hepatocyte ER stress (p<0.05) and hepatocyte necroptosis in mice (34.37±3.39% vs 22.53±2.18%; p<0.05) and LO2 cells (1±0.11 vs 0.33±0.05; p<0.05). Interestingly, tumor necrosis factor receptor (TNFR) 1 protein levels were not completely synchronized with necroptosis. TNFR1 expression was reduced in d-galactosamine-treated mice (p<0.05) and cells incubated with tunicamycin for 12 and 24h (p<0.05). ER stress partially restored TNFR1 expression and increased necroptosis in tunicamycin-incubated cells (p<0.05). CONCLUSIONS: These results imply that ER stress can mediate hepatocyte necroptosis independent of TNFR1 signaling and elevated eIF2α phosphorylation can mitigate ER stress during acute liver injury.

Antibiotic exposure across three generations from Chinese families and cumulative health risk.

Extensive antibiotic exposure in the general population has been documented by bio-monitoring, but data regarding antibiotic burden across three generations in families living in the same household are lacking. We investigated the distribution of antibiotics and the potential health risk among the three generations by selecting 691 participants from 256 households in Fuyang city, China. A total of 45 antibiotics and two metabolites were screened in urine samples through liquid chromatography electrospray tandem mass spectrometry. In total, 34 antibiotics were found in the samples with an overall detection frequency of 92.0%, and the detection frequencies of individual antibiotic ranged from 0.3% to 28.7%. Specifically, the concentrations of seven antibiotics (azithromycin, amoxicillin, oxytetracycline, levofloxacin, norfloxacin, trimethoprim and sulfamethoxazole) were extremely high (i.e., above 10, 000 ng/mL). The detection rates of tetracyclines were significantly different among the three generations, with parents having the highest detection rate. Penicillin V, chlortetracycline, doxycycline, enrofloxacin, and ciprofloxacin showed a higher detection frequency in parents, whereas tetracycline, danofloxacin, and ofloxacin were more likely to be found in grandparents. The proportions of the sum of the daily exposure dose of VAs and PVAs more than 1 µg/kg/d in children, parents, and grandparents were 31.6%, 39.5%, and 26.5%, respectively. A hazard index (HI) greater than 1 was observed in 14.7% children, which was less than the 23.6% in parents and slightly higher than the 11.8% in grandparents. Ciprofloxacin was the biggest contributor to HI among the three generations. Collectively, these findings indicate that households are widely exposed to various antibiotics in Fuyang city, where parents had the highest health risk associated with the disturbance of gut microbiota.

Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury.

AIM: To investigate the impact of alpha subunit of eukaryotic initiation factor 2 (eIF2α) phosphorylation on liver regeneration. METHODS: Male BALB/c mice were intraperitoneally injected with carbon tetrachloride (CCl4) to induce liver injury. Human hepatocyte LO2 cells were incubated with thapsigargin to induce endoplasmic reticulum (ER) stress. Salubrinal, integrated stress response inhibitor (ISRIB), and DnaJC3 overexpression were used to alter eIF2α phosphorylation levels. RESULTS: CCl4 administration induced significant ER stress and eIF2α phosphorylation, and increased hepatocyte proliferation proportionally to the extent of injury. Inhibiting eIF2α dephosphorylation with salubrinal pretreatment significantly mitigated liver injury and hepatocyte proliferation. In LO2 cells, thapsigargin induced significant eIF2α phosphorylation and inhibited proliferation. Inhibiting eIF2α dephosphorylation partly restored cell proliferation during ER stress. CONCLUSIONS: In acute liver injury, inhibiting eIF2α dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation.

The relationship between demands for lung cancer screening and the constructs of health belief model: a cross-sectional survey in Hefei, China.

The aim of investigation is to explore the relationship between demands for lung cancer screening (LCS) and the constructs derived from the health belief model (HBM) in Hefei. The study collected data about socio-demographics, health beliefs in and demands for LCS during early June to later July 2015. By constructing a LCS demands HBM constructs, it calculated indices of demands for LCS (DSI) and HBM constructs, which include perceived risk (PR) and seriousness (PS) of the cancers; and perceived effectiveness (PE), benefits (PB) and difficulties (PD) of the screening. It also performed descriptive and multivariate regression analysis of the demands and the HBM constructs. The amount of 823 respondents participated and completed the survey. 6.4% of them had ever undertaken LCS, whereas 60.1% of them expressed willingness to accept the service of LCS if it is free. In multiple regression analysis which used weights in calculating the HBM construct indices, education displayed significant positive associations with DSI (p = .044), and most of HBM constructs indices (PSI, PRI, PBI, and PDI) were statistically significant with DSI (p < .05). HBM-based constructs regarding LCS have important effects on demands for the service, and may provide effective paths to cancer screening promotion.

[Relationship between waist circumference, waist-to-hip ratio, waist-to-height ratio and hypertriglyceridemia in elderly in Lu'an City in 2016].

OBJECTIVE: To explore the relationship between waist circumference( WC), waist hip ratio( WHR), waist-to-height( WHtR) and hypertriglyceridemia( HTG) in older adults in Lu'an City. METHODS: In total, 1029 participants aged ≥ 60 years using cluster sampling method from two communities in Jin' an District and Yu' anDistrict of Lu'an City were invited to participate in this community-based study from June to September 2016. A questionnaire was used to collect the information of demographic characteristics, disease history, lifestyles, etc. Height, waist circumference, hip circumference, and blood triglyceride levels were measured. Binary logistic regression analysis was conducted to analysis the association between WC, WHR, WHtR and hypertriglyceridemia. The receiver operating characteristic( ROC) curve was used to evaluated the distinguishable effect of three indices on HTG. RESULTS: Prevalence of HTG was 19. 7%( 14. 0% in male, 24. 5% in female, χ~2= 17. 71, P < 0. 001). After controlling the confounding factors, including area, gender, age, family history, educational level, sedentary time, physical exercise, smoking, alcohol consumption, diet habits, binary Logistics regression analysis showed that the risk of HTG was higher in the elderly with high WC, high WHR, high WHtR, the ORs were 5. 18( 95% CI 2. 81-9. 57), 3. 69( 95% CI 1. 95-6. 95) and 4. 93( 95% CI 2. 72-8. 91), respectively. The area under ROC curves of WC, WHR and WHtR were 0. 67, 0. 67 and 0. 69, respectively. CONCLUSION: WC, WHR and WHtR are closely related with the prevalence of HTG. WC and WHR were significant than others for male HTG and female HTG.

The decreased frequency of SIGIRR-positive CD4+ T cells in peripheral blood of patients with SLE and its correlation with disease activity.

Recently, many studies have shown that Single immunoglobulin interleukin-1 receptor related protein (SIGIRR), a member of the IL-1R family acting as a negative regulator of TLR/IL-1R signaling, affects autoimmune responses in animal model of systemic lupus erythematosus (SLE). However, the role of SIGIRR in the pathogenesis of human SLE has not been widely explored. In this study, we analyzed the frequency of SIGIRR-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) of SLE patients and its correlation with disease activity as well as the clinical data. Circulating SIGIRR-positive CD4+ T cells were quantified in 51 SLE patients and 38 healthy controls by using flow cytometer. Results showed that the percentages of SIGIRR-positive CD4+ T cells were decreased in the PBMCs of SLE patients compared with healthy controls (Z = -5.49, P < 0.001). The frequency of SIGIRR-positive CD4 + T cells were also significantly decreased in SLE patients with nephritis than those without nephritis (Z = -3.71, P < 0.001). In addition, there was significant correlation between the percentages of SIGIRR-positive CD4+ T cells and SLEDAI score (r s = -0.74, P < 0.001), 24-hour urine protein (r s = -0.62, P < 0.001), Scr (r s = -0.65, P < 0.001), ESR (r s = -0.60, P < 0.001), C3 (r s = 0.53, P < 0.001) as well as C4 (r s = 0.52, P < 0.001). However, there was no correlation between the proportion of SIGIRR-positive CD4+ T cells and glucocorticoid dose (P = 0.59). In summary, decreased numbers of SIGIRR-positive CD4+ T cells in SLE patients and its correlation with SLEDAI score as well as the clinical data suggest that SIGIRR may be involved in the pathogenesis of SLE.

Lack of association between the polymorphisms of hypoxia-inducible factor 1A (HIF1A) gene and SLE susceptibility in a Chinese population.

Hypoxia-inducible factor 1 (HIF-1) introduced the immune imbalance between Th17 and Treg cells, which may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of the present study was to determine whether the HIF1A gene influences the susceptibility to SLE. A study on this relationship has not been conducted to date. A total of 3,793 subjects (1,497 SLE patients and 2,296 controls) were included in this study. The genotyping of five single-nucleotide polymorphisms (SNPs) (rs11549465, rs12434438, rs1957757, rs1951795, rs7143164) was determined by Sequenom MassARRAY technology. The statistical analysis was conducted using chi-square test. Odds ratio (OR) with 95% confidence interval (CI) was calculated using unconditional logistic regression with adjustment of age and sex. The allele frequencies were not associated with the disease. No significant differences in genotype frequencies existed between the patients with SLE and the controls in all five SNPs. It is worth mentioning that the allele T at rs11549465, located at the exon sequence, revealed a trend but no significant difference towards the more frequent allele T in SLE than in controls (C versus T: OR=1.206, 95 % CI=0.972-1.495, p =0.088). The genotype effects of recessive, dominant, and codominant models were observed; however, no significant evidence for association was detected. Our findings suggest that the gene polymorphisms of HIF1A might not contribute to SLE susceptibility in the Chinese population. However, further studies are needed on an independent cohort from different genetic backgrounds to confirm HIF1A as an SLE genetic factor.

Prevalence of systemic lupus erythematosus and risk factors in rural areas of Anhui Province.

Systemic lupus erythematosus (SLE) is a severe complex rheumatic disease, but good estimate of its prevalence and risk factors is lacking in China. The aim of the study was to explore the prevalence of SLE and risk factors in rural areas of Anhui Province of China. Eleven counties were randomly selected in Anhui Province, and then, 15% of the villages in selected counties were randomly sampled as study sites. Patients with SLE were identified through two phases. Based on the cases identified, a population-based case-control study was designed to examine risk factors associated with SLE. A total of 1,253,832 individuals and identified 471 SLE cases were surveyed. Crude and age-standardized prevalence were estimated at 37.56 and 36.03 per 100,000 persons, respectively. Gender difference in the prevalence of SLE was significant (P = 4.62 × 10(-76)), and the age-standardized prevalence was 6.17 for males and 67.78 for females per 100,000 persons. The distribution of SLE prevalence was significant by age group (P = 1.78 × 10(-53)), and the peak prevalence was observed at 40-50 years. Multiple environmental factors were associated with SLE, including birth conditions, sweet food, cooking oil, taste, fruit consumption, sunlight exposure, quality of sleep, physical activities, drinking water, residence, negative life events, hepatitis B vaccine, age of menarche, and age at birth of first child (P < 0.05). Our large population-based epidemiological survey estimated the prevalence of SLE at 37.56 per 100,000 persons. Multiple environmental factors were associated with the development of SLE.