Background Front-line power grid workers are required to face a variety of occupational hazards (such as aerial work), which make them susceptible to psychological problems and further reduce their performance efficiency and safety level. Objective To investigate the mental health status of front-line power grid workers and explore the influence of personality traits on mental health and the potential mediating role of work-family support between them. Methods This study was designed as a cross-sectional study. From January to June 2019, a cluster random sampling method was used to select two of the 20 power supply stations owned by a Guangdong power company. A total of 485 front-line power grid workers were included in the study. Sociodemographic characteristics were investigated, and NEO Five-Factor Inventory, Work-Family Support Scale, and Symptom Checklist 90 (SCL-90) were used in the survey. Spearman correlation analysis was conducted to analyze the correlations between measured variables. Structural equation modeling was used to analyze the relationships of personality traits, work-family support, and mental health, and Bootstrap analysis was used to test the mediating effect of work-family support on the relationship of personality traits and mental health. Results The M (P₂₅, P₇₅) of total SCL-90 score was 134.00 (110.00, 167.00）, and 139 (28.66%) front-line power grid workers showed positive mental health symptoms. The correlation analysis indicated that among the front-line power grid workers, neuroticism score was negatively correlated with work-family support total score (r_s=−0.356, P<0.001), and positively correlated with the total score of SCL-90 (r_s=0.557, P<0.001) as well as all the scores of its sub-dimensions (r_s=0.436-0.550, P<0.001). Openness score was positively correlated with work-family support total score (r_s=0.269, P<0.001), and except for paranoid ideation (P>0.05), openness score was negatively correlated with the scores of all the other sub-dimensions of SCL-90 (r_s=−0.091-−0.147, P<0.05). The scores of the other three personality traits (extroversion, agreeableness, and conscientiousness) were positively correlated with work-family support total score (r_s=0.331-0.466, P<0.001), and negatively correlated with the total score of SCL-90 as well as the scores of all its sub-dimensions (P<0.001). The modified structural equation modeling indicated that the direct effect of work-family support on mental health symptoms was −0.225 (P<0.001). The direct effects of extraversion and openness on work-family support were 0.241 (P<0.001) and 0.123 (P<0.05), respectively, while the effect on mental health symptoms was not statistically significant. The direct effects of neuroticism on work-family support and mental health symptoms were -0.152 (P<0.01) and 0.467 (P<0.001), respectively. The direct effects of conscientiousness on work-family support and mental health symptoms were not statistically significant (P>0.05). The direct effect of agreeableness on work-family support was not statistically significant (P>0.05), while the direct effect on mental health symptoms was −0.180 (P<0.001). Conclusion The front-line power grid workers show a high score of SCL-90. Workers with higher neuroticism are more vulnerable to mental health symptoms. Work-family support fully mediates the effects of extraversion and openness on mental health symptoms, and partially mediates the effects of neuroticism on mental health symptoms, while does not mediate the effects of agreeableness on mental health symptoms. Sufficient work-family support may improve mental health status.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.

Objective:To explore the efficacy of Fuzheng Zhuyu Xiehuo Decoction for the patients with acute pancreatitis (AP) of intermingled blood stasis-toxin syndrome and its influence on peripheral blood inflammatory factors and microcirculation indicators.Methods:A total of 100 patients with AP, admitted to department of spleen and stomach diseases of the First Affiliated Hospital of Hunan University of Chinese Medicine and department of gastroenterology of the Central Hospital of Shaoyang, who met the inclusion criteria between March 2019 and March 2020, were divided into two groups according to the random number table method, with 50 in each group. The control group was given conventional western medicine, while the observation group was treated with Fuzheng Zhuyu Xiehuo Decoction on the basis of the control group. The TCM syndromes were scored before and after treatment, and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) was used to evaluate the severity of the disease, and ELISA was adopted to detect the levels of IL-6, IL-8, TNF-α and thromboxane A2 (TXA2), prostaglandin I 2 (PGI 2) and platelet activating factor (PAF). The abdominal pain, abdominal distension, fever, gastrointestinal function recovery time and hospital stay were observed and the adverse events were recorded. Results:The total effective rate was 96.0% (48/50) in the observation group and that of the control group was 84.0% (42/50) ( χ2=4.00, P=0.045). The scores of abdominal pain, abdominal distension, fever and nausea and vomiting in observation group were significantly lower than those in the control group ( t=7.07, 7.06, 11.47, 10.30, all Ps<0.01), and the recovery times of abdominal pain, abdominal distension, fever and gastrointestinal function and hospital stay in the observation group were significantly shorter than those in the control group ( t=4.52, 4.90, 6.27, 6.55, 7.12, all Ps<0.01). After treatment, the levels of serum IL-6 [(30.15±7.04) μg/L vs. (42.37±8.29) μg/L, t=7.95], IL-8 [(39.36±8.11) μg/L vs. (50.36±10.47) μg/L, t=5.87], TNF-α [(106.28±21.04) μg/L vs. (153.45±30.23) μg/L, t=9.06] in the observation group were significantly lower than those in the control group ( P<0.01). The serum TXA2 [(223.68±40.15) ng/L vs. (257.11±50.32) ng/L, t=3.67] and PAF [(74.86±15.37) ng/L vs. (85.53±15.26) ng/L, t=3.48] in the observation group were significantly lower than those in the control group ( P<0.01) while the level of PGI 2 [(91.43±17.45) ng/L vs. (76.49±15.13) ng/L, t=4.57] in the observation group was significantly higher than those in the control group ( P<0.01). Conclusion:Fuzheng Zhuyu Xiehuo Decoction combined with western medicine can improve clinical symptoms and blood microcirculation status, relieve inflammatory response and enhance clinical efficacy of patients with AP of intermingled blood stasis-toxin syndrome.

With the rapid development of sequencing technology and bioinformatics analysis, the application of high-throughput sequencing (NGS) technology in precision medicine has been deepening, mainly in genetic disease diagnosis, tumor gene detection and concomitant diagnosis, as well as infectious disease detection. Compared with the traditional clinical tests, NGS analysis are more complicated with tedious operation steps and complex workflow, and they have high requirements for data analysis and variant interpretation. NGS approaches were reviewed in clinical diagnosis for constitutional disorders, cancer, infectious diseases as well as current issues in these clinical applications. Finally some suggestions for the quality management of laboratories were discussed.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

Point-of-care testing (POCT) is one of the fastest growing disciplines of clinical laboratory medicine. It serves as a convenient tool for rapid clinical diagnosis. However, the increasing demand for POCT testing and the continuous expansion of the testing field has brought many new challenges to its quality management. This paper would introduce the problems existing in the clinical application of POCT, discuss the corresponding quality improvement suggestions and explore new thinkings for standardizing POCT management.

Objective:To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19).Methods:Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV.Results:Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs.Conclusions:The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.

Objective: To evaluate the external quality assessment (EQA) program for genotyping results of tacrolimus metabolism-related cytochrome P450 family 3 subfamily A member 5 ( CYP3A5 )using plasmid DNA constructed in vitro as quality control samples, discuss the problems in clinical laboratories enrolled in the program and improve the detection quality of CYP3A5 gene. Methods: Recombinant plasmid carrying CYP3A5 *3 (rs776746) AA locus sequence was constructed as wild type sample and plasmid with CYP3A5 *3 GG mutation as mutant type sample. Heterozygous mutant samples were obtained by mixing the two plasmids with equal proportion. Recombinant plasmids DNA were used as the sample panel for EQA scheme. Participating laboratories were asked to test the samples using their routine methods and report the results before deadlines. The scores of each laboratory were calculated based on their results and the overall coincidence of different samples as well as the sensitivity and specificity of different methods. Results: CYP3A5 *3 locus genotypes of the constructed plasmid were verified by Sanger sequencing. The results of 15 and 17 valid laboratories were received respectively in the two EQA programs. The total percentage of 93.33% (14/15) and 100% (17/17) of the laboratories submitted correct results for all the samples. The overall coincidence rates were 96% (72/75) and 100% (85/85) respectively. All the laboratories using digital FISH got full marks in two EQA schemes, while the coincidence rates were 90% (27/30) and 100% (40/40) for Sanger sequencing. Conclusion The recombinant plasmid DNA constructed in this study could effectively detect the performance of reagents with good clinical applicability. The results of EQA programs suggested that the overall accuracy rate of enrolled laboratories was high enough, while the performances in some laboratories still need to be improved. Quality controls in clinical laboratories were essential to assure the accuracy of results.

Objective: To develop a kind of quality control material which simulates clinical specimens for detecting plasma methylated Septin9 (mSEPT9) and investigate the performance for mSEPT9 detection in external quality assessment (EQA) of laboratories. Methods: The cultured Hela and Jurkat cells, known to contain methylated and unmethylated Septin9 gene respectively, were cultured. The genomic DNA of the cells was collected and extracted, and detected by mSEPT9 kit. According to the Ct value, the genomic DNA was diluted into different concentrations of quality control materials with negative plasma. The homogeneity and stability of the quality control materials were evaluated. The panels consisted of 5 blindly coded samples were distributed to EQA participants and the results were summarized and evaluated. Results: The purity and concentration of extracted genomic DNA met with the needs of use and could be used as quality control products for mSEPT9 detection. The homogeneity and stability met with the requirements of China National Accreditation Service for Conformity Assessment. Some of the participating laboratories occurred false positive results and false negative results, and a good linear correlation for the detected results (Ct values) was only observed in about 55.6% of the laboratories. Among the 9 participating laboratories, 7 laboratories (77.8%) performed well, 1 laboratory (11.1%) qualified, and 1 laboratory (11.1%) unqualified. Conclusion The quality control materials for mSEPT9 detection was successfully developed and the application in external quality assessment should be of great significance for evaluating and improving the detection ability of clinical laboratory.