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ObjectiveTo analyze the exposure-response relationship of peripheral whole blood chromium level and lung function as well as genetic toxicity indicators in workers exposed to hexavalent chromium [Cr(Ⅵ)] compounds, and to propose a biological exposure limit of whole blood chromium for soluble Cr(Ⅵ) compounds-exposed workers. Methods A total of 515 workers from a dynamic occupational Cr(Ⅵ) compounds-exposed cohort in an enterprise from 2010 to 2017 were selected as the research subjects using a retrospective cohort study. A total of 918 followed-up results of research subjects and baseline data of a cohort were analyzed based on bibliometric analysis. The results include lung function tests, whole blood chromium level detected by inductively coupled plasma-mass spectrometry, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) detected by high performance liquid chromatography-tandem mass spectrometry, peripheral micronuclei frequency (MNF) detected by cytokinesis-block micronucleus assay, and mitochondrial DNA copy number (mtCN) detected by real-time fluorescence quantitative polymerase chain reaction. Results The results of bibliometric analysis showed that domestic and foreign studies on biological monitoring of Cr(Ⅵ) compounds increased year by year in the past 30 years, and whole blood chromium levels had a good correlation with the occupational Cr(Ⅵ) compounds exposure. The geometric mean of whole blood chromium levels in males and females among the occupational Cr(Ⅵ) compounds exposure cohort was 2.77 and 1.79 μg/L, respectively. A turning point appeared in 6.00 μg/L chromium in whole blood of the exposure-response curve of whole blood chromium levels with lung function indicators and genetic toxicity indicators. For each unit increase in the natural logarithm-transformed whole blood chromium level, the forced expiratory volume in one second (FEV1) decreased by 0.05 L, the FEV1/forced-vital-capacity decreased by 0.67%, the peak expiratory flow decreased by 0.15 L/s, the maximal mid-expiratory flow decreased by 0.09 L/s, the MNF increased by 0.149‰, the urinary 8-OHdG increased by 0.090 μg/g, and the mtCN increased by 0.013. When the whole blood chromium level was >6.00 μg/L, there was a significant increase in urinary 8-OHdG, MNF, and mtCN (all P<0.01). Conclusion The level of whole blood chromium can be used as a biomarker for occupational exposure to soluble Cr(Ⅵ) compounds. The preliminary biological exposure limit is set at 6.00 μg/L for whole blood chromium in workers exposed to soluble Cr(Ⅵ) compounds.

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Mutations in the spike glycoprotein of SARS-CoV-2 allow the virus to probe the sequence space in search of higher-fitness states. New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with such mutations. Interestingly, the sites of mutation in these sublineages vary between the VOCs. Whether such differences reflect the random nature of mutation appearance or distinct evolutionary spaces of spike in the VOCs is unclear. Here we show that each position of spike has a lineage-specific likelihood for mutations to appear and dominate descendent sublineages. This likelihood can be accurately estimated from the lineage-specific mutational profile of spike at a protein-wide level. The mutability environment of each position, including adjacent sites on the protein structure and neighboring sites on the network of comutability, accurately forecast changes in descendent sublineages. Mapping of imminent changes within the VOCs can contribute to the design of immunogens and therapeutics that address future forms of SARS-CoV-2.

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The spike protein of SARS-CoV-2 is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The variation between infected individuals in domain specificity of the antibodies and in their relative neutralization efficacy is still poorly characterized. To this end, we tested serum and plasma samples from 85 COVID-19 convalescent subjects using 7 immunoassays that employ different domains, subunits and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. We observed strong correlations between the levels of NTD- and RBD-specific antibodies, with a fixed ratio of each type to all anti-spike antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects, and was not associated with the overall amount of anti-spike antibodies produced. Accordingly, the ability of immunoassays that use RBD, NTD and different forms of S1 or S1/S2 as capture antigens to estimate the neutralizing efficacy of convalescent samples was largely similar. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCEInfection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD, NTD and S2. Different infected individuals generate vastly different amounts of anti-spike antibodies. By contrast, as we show here, there is a remarkable similarity in the properties of the antibodies produced. Different individuals generate the same proportions of antibodies against each domain of the spike protein. Furthermore, the relationship between the amount of anti-spike antibodies produced and their neutralization efficacy of SARS-CoV-2 is highly conserved. Therefore, the observed variation in the neutralizing activity of the antibody response in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or relative antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.

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OBJECTIVE: To evaluate the genetic damage induced by occupational chromate exposure, and to analyze the association between human 8-oxoguanine-DNA N-glycosylase 1(hOGG1) polymorphisms and genetic damage in population with chromate exposure. METHODS: A total of 136 chromate exposed workers were recruited as exposure group by judgmental sampling method, and 156 workers without chromate and other occupational hazard factors exposure were recruited as control group. The whole blood chromium(WB-Cr) level was measured by inductively coupled plasma mass spectrometry. Urinary 8-hydroxy-2′-deoxyguanosine(8-OHdG) was determined by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms of hOGG1 gene were genotyped by the matrix assisted laser desorption ionization/time of flight mass spectrometry. RESULTS: The WB-Cr level was higher in the exposure group than that in the control group(meclian: 3.41 vs 0.90 μg/L, P<0.01). The urinary 8-OHdG level was higher in the exposure group compared with that in the control group(meclian: 6.02 vs 4.72 μg/g·creatinine, P<0.01). In study subjects(exposure group and control group), after adjusting the potential influencing factors such as age, body mass index(BMI), gender, smoking and drinking, chromate exposure might be a risk factor for increasing urinary 8-OHdG level(P<0.05), and the recessive models of rs293796 and rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05). In chromate exposure group, the additive and recessive models of rs293796 and the recessive model of rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05), while the dominant model of rs3219008 was protective factor of increasing urinary 8-OHdG level(P<0.05), after adjusting the potential influencing factors such as age, BMI, gender, smoking, drinking. However, after multiple Bonferroni correction tests, only the recessive model of rs293796 was the risk factor of increasing urinary 8-OHdG level in the exposed group(P<0.01). There was significant interaction between chromate exposure and rs293796 on urinary 8-OHdG(P<0.01). CONCLUSION: The rs13096551 and rs293796 of hOGG1 were associated with the alteration of urinary 8-OHdG level induced by chromate. There was interaction between rs294796 of hOGG1 and chromate exposure on urinary 8-OHdG level.

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To evaluate the intervention effects of randomized controlled trials (RCT) involved in theoretical efficacy and actual clinical outcome (effectiveness). Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) is a tool to help researchers make decisions in study design which is consistent with the intended purpose of their trial which can be used in the design of RCT to balance the internal validity and external validity. The role of PRECIS has been gradually recognized in the practice of designing clinical trials. To ensure that the design choices are concordant with the intention and the facilitation of use set by patients, clinicians and policy makers, a new PRECIS-2 tool has been developed by mangy international team experts under modification and upgrading the existing PRECIS. The PRECIS-2 tool mainly focuses on trial design choices which determining the applicability of a trial. PRECIS-2 has nine domains, with each of them intends to help the researchers consider the consequences of that design decision in terms of the applicability of the results under particular setting. The purpose of this paper is to introduce the development, basic principle, characteristics and application of PRECIS-2 for the designers and decision makers when working on clinical trials.

Asunto(s)

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Biomonitoring can be applied to assess internal exposure and environmental exposure by exposure markers with providing internal exposure to biological characterization and individual exposure information, which is a key tool to evaluate the risk exposure to disease by biological alternation information. With the development of high throughput, broad spectrum and high efficiency screening and detection technology, biomonitoring is defined as traditional biological monitoring (targeted monitoring) and non targeted monitoring analysis (exposomic approaches). An exposomic approach differs from traditional biomonitoring in that it can theoretically include all exposures of potential health significance, whether they are derived from exogenous sources. Both traditional and nontraditional biomonitoring methods should be used to understand the complexity of exposures faced throughout the lifespan. Through hybrid approaches, emerging techniques and the integration of bioinformatics, and developing the detection methods for low abundance chemicals, improving the differentiation ability between endogenous and exogenous chemical, the health outcomes and exposures can be widely recognized and characterized, which can finally contribute to improving the precise prevention and intervention for diseases under the new exposomic model.

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To evaluate the intervention effects of randomized controlled trials (RCT) involved in theoretical efficacy and actual clinical outcome (effectiveness).Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) is a tool to help researchers make decisions in study design which is consistent with the intended purpose of their trial which can be used in the design of RCT to balance the intemal validity and external validity.The role of PRECIS has been gradually recognized in the practice of designing clinical trials.To ensure that the design choices are concordant with the intention and the facilitation of use set by patients,clinicians and policy makers,a new PRECIS-2 tool has been developed by mangy international team experts under modification and upgrading the existing PRECIS.The PRECIS-2 tool mainly focuses on trial design choices which determining the applicability of a trial.PRECIS-2 has nine domains,with each of them intends to help the researchers consider the consequences of that design decision in terms of the applicability of the results under particular setting.The purpose of this paper is to introduce the development,basic principle,characteristics and application of PRECIS-2 for the designers and decision makers when working on clinical trials.

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Objective@#To investigate the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate.@*Methods@#A dynamic cohort study was conducted of chromate-exposed workers (343 cases) and non-chromate-exposed workers (73 cases) at a chromate production enterprise who were selected according to specific inclusion and exclusion criteria from 2010 to 2015. Personal information and chromate exposure information were obtained by questionnaire. A generalized estimating equation was employed to analyze the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate, controlling for age, gender, smoking, alcohol consumption and body mass index.@*Results@#The mean ages and working ages of those entering the cohort study were 36.67 ±6.78 and 38.47 ± 7.18, respectively, for the exposure group and 8.39 ± 6.02 and 12.86 ± 8.34, respectively, for the control group. The erythrocyte content [(4.73±0.46), (4.81±0.53), (4.41±0.45)]×1012/L in the peripheral blood in the chromate exposure group was lower than that [(4.76±0.42), (4.95±0.45), (4.47±0.39)]×1012/L in the control group for the years 2010, 2011, 2012 and 2014 (t values were 0.38, 1.96, 0.92 and 1.21; P values were 0.703, 0.051, 0.358 and 0.227, respectively). The correlations between the years 2010 and 2011, 2011 and 2012, 2012 and 2014, and 2014 and 2015 were 0.667, 0.464,-0.070 and 0.020, respectively (P<0.001). The RR for males and those that consumed alcohol were 0.661 (95% CI: 0.616-0.709) and 0.910 (95% CI: 0.811- 1.201), respectively. Compared with the control group, the risk of reduced erythrocyte levels in the peripheral blood was increased by 0.915 (95% CI: 0.852- 0.982) in the chromate-exposed group.@*Conclusions@#The erythrocyte content of peripheral blood was reduced after long-term exposure to chromate. Maleness and alcohol consumption were factors that increased the risk of reduced peripheral blood erythrocytes in the chromate-exposed population.

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Randomized controlled trial (RCT) can be designed as explanatory trial and pragmatic/practical trial (PCT) for clinical effect evaluation.The pragmatic/practical trial reflects the intervention effect under actual clinical condition,which has relatively good extrapolation,but its internal validity is relatively poor.In contrast,explanatory trials conducted under ideal conditions have better inner validity but inferior external validity.However,in the design of RCT,PCT and explanatory trials are not always opposite.Many RCTs have the properties of the two designs at the same time,Pragmatic-explanatory continuum indicator summary (PRECIS) can be used in the design of RCT for the balance between internal validity and external validity.There are few available reports about the application of PRECIS in China at present,so this paper summarizes the basic principles,characteristics of PRECIS and the application of PRECIS in order to provide reference for the clinical trial design in China.

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Objective: To prevent the error of overcharging fees, missing fees and mistaken identity fees, check the inpatient expense rationality with using the self-developed software system. Methods:With extracting data from HIS and other systems, check and audit the inpatient expense, such as billing classification, red account records, logic checks, integrity checks, etc, according to pre-established rules. Results:Using the auditing software can greatly improve the work efficiency and the accuracy of inpatient expense, reduce the incidence of billing dispute issue. Conclusion:This system has valuable reference and be worth generalizing because it can bring the social benefit to hospital.