The core idea of occupational health risk assessment models is to systematically evaluate occupational health risks according to target hazard characteristics and relevant exposure levels of workers. Occupational exposure assessment is based on concentration, frequency, exposure time, and other indicators that indicate actual exposure of workers to occupational hazards, which is a critical component of health risk assessment. However, the accuracy and comparability of assessment results are affected by differences in parameter assignment for exposure assessment across different studies, as well as insufficient emphasis on multiple occupational hazard exposure. This review aimed to explore the assignment and standardization of exposure assessment parameters for occupational health risk assessment modeling, and systematically sorted out the meaning, assignment methods, and sources of exposure assessment related parameters in commonly used occupational health risk assessment models, with the goal of providing researchers with standardized assessment tools to enhance the scientific rigor and practicality of occupational health risk assessments. Considering the individual differences and temporal fluctuations in occupational exposure, it is recommended that researchers should adopt appropriate sampling strategies, reasonably select sample subjects and time based on the division of similar exposure group (SEG), and conduct statistical inference on the obtained data to derive representative exposure parameters. For combined exposure to chemicals with similar toxic effects, the health risk assessment methods are relatively mature. However, the assessment of combined exposure to hazards with different properties and health effects still lacks scientific authority and needs further research and discussion.

Objective: To investigate the effects and underlying mechanisms of the macrophage migration inhibitory factor(MIF) inhibitor(S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester(ISO-1) on sepsis-induced acute kidney injury(AKI). Methods: Human renal tubular epithelial HK-2 cells were divided into Con group(without any treatment), ISO-1 group(10 μg/ml ISO-1 treatment for 24 h) and LPS group(10 μg/ml LPS treatment for 24 h), LPS+ISO-1 group(10 μg/ml LPS treatment for 24 h followed by 10 μg/ml ISO-1 treatment for 24 h). ELISA was used to measure the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) in the cell supernatants. Reactive oxygen species(ROS) levels were assessed using the 6-carboxyl-2 ′,7′-dichlorodihydrofluorescein diacetate fluorescent indicator(DCFH-DA) method. Apoptosis levels were detected by TUNEL staining, and Western blot was employed to analyze the expression of proteins of Kelch like ECH associated protein 1(Keap1), NFE2 like bZIP transcription factor 2(Nrf2), heme oxygenase-1(HO-1), as well as apoptosis-related proteins Bcl-2, Bax, and cleaved Caspase-3(c-Caspase-3). A sepsis mouse model was established using the cecal ligation and puncture(CLP) method, and the mice were divided into four groups: sham-operated(Sham), ISO-1 control(ISO-1), CLP, and ISO-1 treatment(CLP+ISO-1). After the experiment, mouse kidney tissues were collected for HE staining to observe pathological changes. Blood urea nitrogen(BUN), serum creatinine(Scr), myeloperoxidase(MPO) levels in kidney tissues, glutathione(GSH) and superoxide dismutase(SOD) activities were measured. Western blot was also used to detect the expression of MIF and proteins in the Nrf2/Keap1 signaling pathway and apoptosis-related proteins in kidney tissues. Results: Compared to the Con group, the LPS and LPS+ISO-1 groups showed significantly increased levels of TNF-α, IL-1β, IL-6, TUNEL-positive rates, ROS levels, and protein expressions of Keap1, Bax, and c-Caspase-3 in HK-2 cells(P<0.05), while the expressions of Nrf2, HO-1, and Bcl-2 significantly decreased(P<0.05). The ISO-1 group showed no significant changes(P>0.05). Compared to the LPS group, the LPS+ISO-1 group exhibited significantly decreased levels of TNF-α, IL-1β, IL-6, TUNEL-positive rates, ROS levels, and protein expressions of Keap1, Bax, and c-Caspase-3, while the expressions of Nrf2, HO-1, and Bcl-2 significantly increased(P<0.05). In the mouse experiments, compared to the Sham group, the CLP and CLP+ISO-1 groups showed severe kidney tissue damage, increased levels of serum BUN, Scr, and kidney MIF, Keap1, Bax, and c-Caspase-3 protein expressions(P<0.05), while GSH, SOD activities, and protein expressions of Nrf2, HO-1, and Bcl-2 significantly decreased(P<0.05). The ISO-1 group showed no significant changes(P>0.05). Compared to the CLP group, the CLP+ISO-1 group showed significant improvements in the aforementioned indicators(P<0.05). Conclusion The specific MIF inhibitor ISO-1 can ameliorate sepsis-induced AKI by inhibiting oxidative stress, inflammatory response, and apoptosis bothin vitroandin vivo. The mechanism may be through Nrf2/Keap1 signaling pathway.

Objective Based on the theoretical connotation of"Dredge Du meridian remodeling god"intervention in PSD,two rounds of expert questionnaire were conducted in combination with Delphi survey method to optimize the diagnosis and treatment scheme of massage intervention in PSD,and to develop an optimal operation mode of Tuina for PSD.Methods Experts with rich experience in Tuina intervention in different provinces and cities in China were selected to participate in two rounds of questionnaires.Items were screened after statistical analysis of experts′ basic information,positive degree,coordination coefficient and authority coefficient of the two rounds of questionnaires.Results In the two rounds of Delphi survey,34 and 37 experts were selected for questionnaire survey,and the positive coefficients of experts were 94.44%and 94.47%,respectively.The average expert authority coefficients of the two rounds were 0.65 and 0.74.The expert coordination degree of the two rounds of questionnaires was medium,and Kendall coefficient W>0.4.Conclusion After two rounds of expert research in Delphi,the specific techniques,techniques and treatment frequency were screened and demarcated,and the optimized PSD diagnosis and treatment plan of"Dredge Du meridian remodeling god"Tuina intervention with high expert authority and good consensus was formed,which can be promoted and applied to PSD patients clinically.

Wuhan is the city with the most serious outbreak of corona virus disease 2019 (COVID-19) in China. The outbreak of community has exhausted the current medical resources. With integrating local and support medical resources from other province, Wuhan City has rapidly rebuilt a new emergency medical system of classified treatment, and effectively responded to the overload medical demand after the outbreak in the community.

Objective: To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C. Methods: Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded. Results: 108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin. Conclusion Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

OBJECTIVETo study the role of endoplasmic reticulum stress (ERS) in acute liver failure (ALF) using a mouse model of D-Galactosamine/lipopolysaccharide (D-GalN/LPS)-induced ALF.

METHODSThe ALF model was established by administering intraperitoneal (i.p.) injections of D-Ga1N (700 mg/kg) and LPS (10 mug/kg) to six C57BL/6 mice. Three of the modeled mice were also administered 4-phenylbutyrate (4-PBA; 100 mg/kg i.p.) at 6 hours before the onset of ALF and served as the intervention group. Non-modeled mice served as controls. All mice were analyzed by western blotting and qRT-PCR to determine the expression levels of ERS-related proteins in liver tissue. Liver function was assessed by measuring levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum. Extent of injury to the liver tissue was assessed by hematoxylin-eosin staining and histological analysis. qRT-PCR was also used to detect differences in expression of inflammation-related genes, and western blotting was also used to detect differences in expression of the apoptosis related protein Caspase-3.The extent of apoptosis in liver tissue was assessed by TUNEL assay.

RESULTSThe ERS markers GRP78 and GRP94 showed increased expression at both the gene and protein levels which followed progression of ALF. The ERS effector proteins XBP-1, ATF-6 and IRE 1 a involved in the unfolded protein response were activated in the early stages of ALF, and the ERS-induced apoptosis regulators Caspase-12 and CHOP were activated in the late stage of ALF. Inhibition of ERS by 4-PBA intervention protected against injury to liver tissue and function, as evidenced by significantly lower levels of serum ALT and AST and a remarkably decreased extent of histological alterations. Furthermore, the inhibition of ERS suppressed expression of the proinflammatory cytokines TNFa, IL-6 and IL-1 β, and reduced the extent of hepatocyte apoptosis.

CONCLUSIONERS is activated in the mouse model of D-GalN/LPS-induced ALF. Inhibition of ERS may be protective against liver injury and the mechanism of action may involve reductions in inflammatory and apoptotic factors and/or signaling. Therefore, inhibiting ERS may represent a novel therapeutic approach for treating ALF.

Animals ; Apoptosis ; Disease Models, Animal ; Endoplasmic Reticulum Stress ; Galactosamine ; adverse effects ; Lipopolysaccharides ; adverse effects ; Liver Failure, Acute ; chemically induced ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL

Objective To detect anti-HCV in serum of hepatic disease patients by performing the confirmatory test, and further to confirm HCV infection. Methods Two recombinant immunoblot assays (CWT and CHIRON RIBA HCV 3.0 Strip Immunoblot Assay) were used respectively to detect anti-HCV in 477 human serum samples, which comprised 350 HCV-infected patients' specimens, 7 none-A none-E hepatitis specimens, 30 HBV-infected patients' specimens, 30 hepatitis E virus infected patients'specimens, and 60 specimens drawn from blood donors. The latter three groups served as controls. Results A total of 120 control non-HCV-infected patients' specimens were negative when tested by both assays. Among 350 HCV-infected patients, 341 were positive and 9 were indeterminated by CWT assay; 343 were positive and 7 were indeterminated by CHIRON RIBA HCV 3. 0 SIA. Seven none-A none-E hepatitis specimens tested by both assays turned out to be 2 positive, 4 negative and 1 indeterminate. The consistency rate of these two assays was 99. 16% (Kappa=0.98). Conclusion CWT assay is highly coherent with CHIRON RIBA HCV 3.0 SIA assay in the methodology of anti-HCV antibody detection, which can be applied in the determination of HCV infection among none-A none-E hepatitis patients.

s E in Beijing belong to HEV genotype Ⅳ.

significantly save the time of diagnosis and facilitate the clinical application of large samples.