Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To establish a simple model for arteriosclerosis(AS)screening to provide a viable tool for the timely identification of AS risk among residents aged 40～65 years.Methods Data were obtained from the Sleep and Chronic Diseases Program in Fuquan City.The original dataset was divided into a training subset and a validation subset(80%:20%).LASSO and logistic regression models were used to screen variables,perform multivariate regression analyses.Internal validation was performed using the Bootstrap method.Nomogram Plot was constructed,and risk score thresholds were determined based on ROC curves to classify high-risk populations.Results RS Model was established to include age,gender,napping,sleep efficiency,sleep disorders,hyperten-sion and diabetes,with AUC=74.80%and a model risk score threshold=84.20.PHC Model was established to include age,gender,napping,sleep efficiency,systolic blood pressure,fasting blood glucose,and pulse variables,with AUC=82.80%and a risk score threshold of 78.00.Decision curves showed that both models performed well in terms of calibration and actual benefits for health management.Conclusion The two AS screening models exhibit acceptable accuracy and differentiation.Therefore,it can be applied in residents'self-health management and in primary care organizations'screening work in a large scale.

Objective:To analyze the association between body health score and the risk of hypertension among health examination population aged 40-65 years.Methods:This study was a cross-sectional study, and 1 104 people aged 40-65 years who underwent physical examination at the Physical Examination Centre of the First People′s Hospital of Fuquan City from March to November 2022 were selected. Clinical data, such as general information, physical examination, body composition and history of hypertension diseases, were collected. The body health score was reported by the Xiaomi Body Fat Scale′s accompanying exercise health software, and was calculated by combining body fat, water and other body composition data. The association between body health score and the risk of hypertension was analyzed using restricted cubic spline regression models, while a sensitivity analysis and sex-stratified analyses were performed. Multivariate logistic regression combined with stratified analysis was used to explore the association between dimensions of body composition and the risk of hypertension.Results:The body health score was significantly lower in hypertensive patients than in non-hypertensive patients among the 1 104 health examination population [52.0(30.0) vs 69.0(35.8) points] ( Z=-8.547, P<0.001). The lower the body health score, the higher the risk of hypertension ( χ2=18.48, PNonlinear<0.001). In the total population, high body mass index was associated with an increased risk of hypertension ( OR=1.744, 95% CI: 1.104-2.765), high protein content was associated with a reduced risk of hypertension ( OR=0.587, 95% CI: 0.344-0.982) (both P<0.05). Gender-stratified analyses showed that high protein content was associated with a reduced risk of hypertension only in men ( OR=0.233, 95% CI: 0.080-0.592) ( P=0.004). High body mass index was positively associated with the risk of hypertension when the body health score was ≥60 points ( OR=2.378, 95% CI: 1.255-4.542) ( P=0.008). High visceral adiposity index (VAI) was positively associated with the risk of hypertension when the body health score was <60 points ( OR=4.395, 95% CI: 1.466-13.620), and high protein content was negatively associated with the risk of hypertension ( OR=0.255, 95% CI: 0.091-0.638) (all P<0.05). Conclusions:Health examination population aged 40-65 years with lower scores of physical health are more likely to have a risk of hypertension. Men should pay attention to the impact of body protein in hypertension risk prevention and control. The effect of body mass index should be noted when body health scores are ≥60 points, and the effect of VAI and body protein should be considered when body health scores are <60 points.

Objective To establish and validate an individualized risk prediction nomogram model for the occurrence of gestational diabetes mellitus in pregnant women with hypothyroidism. Methods A total of 160 pregnant women with hypothyroidism were selected as the study subjects, including 85 patients with gestational diabetes mellitus (observation group) and 75 patients with normal blood glucose levels (control group). The age, gravidity, parity as well as pre-pregnancy body mass index, thyroid peroxidase antibody (TPOAb), homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta-cell function (HOMA-β), free thyroxine (FT4), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) were compared between the two groups. Multivariable analysis was used to analyze the risk factors for gestational diabetes mellitusin pregnant women with hypothyroidism. The nomogram model was used to predict the risk of gestational diabetes mellitus in pregnant women with hypothyroidism. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the nomogram model for gestational diabetes mellitus in pregnant women with hypothyroidism. Results The age, gravidity, parity as well as pre-pregnancy body mass index, TPOAb, HOMA-IR and HOMA-β were higher in the observation group than in the control group, while pre-pregnancy FT4, FT3 and TSH were lower (P < 0.05). Multivariable analysis showed that older age, gravidity, parity as well as pre-pregnancy body mass index, TPOAb, HOMA-IR and HOMA-β, and lower pre-pregnancy FT4, FT3 and TSH were risk factors for gestational diabetes mellitusin pregnant women with hypothyroidism. The nomogram model prediction showed that older age (28 to 31 years), gravidity (more than 2 times), parity (more than 1 time) as well as pre-pregnancy body mass index (above 24.00 kg/m²), TPOAb (> 421.33 IU/mL), HOMA-IR (> 2.21) and HOMA-β (> 115.66), and lower pre-pregnancy FT4 (< 0.33 ng/dL), FT3 (< 1.65 pg/mL) and TSH (< 0.26 mIU/mL) were risk factors for gestational diabetes mellitus in pregnant women with hypothyroidism. ROC curve analysis showed that the area under the curve of the nomogram model for predicting gestational diabetes mellitus in pregnant women with hypothyroidism was 0.785, indicating good predictive performance. Conclusion The risk prediction nomogram model has high value in individualized prediction of gestational diabetes mellitus in pregnant women with hypothyroidism.

Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment, yet their mechanism of action and individual components contributing to such actions remain to be delineated. Here, we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8⁺ T cell responses and mediating anti-tumor immunity. Mechanistically, both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells. Stimulation of interferon-β expression is exclusively dependent on STING, and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene. Thus, the mRNA vaccine elicits STING-dependent antitumor immunity.

Objective:To explore clinical value of nucleic acid detection for hepatitis B virus (HBV) screening in hospitalized patients.Methods:This cross-sectional study collected and analyzed plasma samples from patients admitted to 10 domestic medical institutions from July 2021 to December 2021. Serological immunoassay and nucleic acid screening were used to simultaneously detect hepatitis B markers such as hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e Antigen (HBeAg), hepatitis B e antibody (HBeAb), hepatitis B core antibody (HBcAb),and HBV DNA. Statistical analysis was performed on the serology, nucleic acid test results and clinical information of the patients.Results:Of the 8 655 collected samples, HBsAg was positive in 216 (2.50%) samples,HBV DNA was positive in 238 (2.75%) samples ( P>0.05); 210 (2.43%) samples were positive for both HBsAg and HBV DNA, 28 (0.32%) were HBsAg negative and HBV DNA positive, 6 cases (0.07%) were HBsAg positive and HBV DNA negative. Conclusion:These results indicate that the HBV DNA testing is equally effective as hepatitis B virus serological detection for hepatitis B virus screening in hospitalized patients.

Objective:This multi-centre study was conducted to assess the efficacy of various preoperative/pre-transfusion screening methods for blood transmitted disease.Methods:From July 2021 to December 2021, plasma samples of patients admitted to 10 hospitals were collected for screening preoperative/pre-transfusion blood transmitted disease. Nucleic acid detection technology was used to detect hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA and human immunodeficiency virus (HIV)(1+2) RNA, and the results were compared with the immuno-serological methods. χ 2 test and Kappa test were used to analyze the efficacy of these two methods. Results:A total of 8 655 valid specimens were collected from 10 hospitals. There was a statistically significant difference in the positive detection rate of HCV between the two methods ( P<0.001). There was no significant difference in the positive detection rate of HBV and HIV assessed by the two methods ( P>0.05), but the number of positive cases detected by HBV DNA and HIV RNA (218 and 4 cases) was significantly higher than the corresponding serological results (216 and 2 cases). At the same time, there were HBV, HCV and HIV immuno-serological omissions by the immuno-serological methods, among which 28 cases were HBsAg negative and HBV DNA positive, 2 cases were HCV antibody negative and HCV RNA positive, and 2 cases were HIV antigen/antibody negative and HIV RNA positive. In addition, in the 66 samples with inconsistent results from the two detection methods, 83.3% (55/66), 68.2% (45/66), 63.6% (42/66) and 62.1% (41/66) of patients aged was>45 years, tumor, surgery and male, respectively. Conclusions:Compared with immuno-serological tests, nucleic acid tests have the advantage in terms of sensitivity on detecting HBV, HCV and HIV infection and could reduce missed detection. The risk of transmission can be reduced by adding HBV, HCV, and HIV nucleic acid tests to preoperative/pre-transfusion immuno-serological tests screening for patients over 45 years of age and tumor patients.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Objective:To construct an evaluation system for clinical nurse research ability training based on the Kirkpatrick model, and provide methods and strategies for clinical nurse research ability training.Methods:Based on literature review and group discussion, the item pool of an evaluation system for clinical nurse research training was constructed using the Kirkpatrick model as the theoretical framework. Using the Delphi method, two rounds of expert consultation were conducted on 17 experts to determine the final evaluation system.Results:In both rounds of expert consultation, 17 questionnaires were distributed, and 17 valid questionnaires were collected. The effective recovery rate of the questionnaires was 100%. After two rounds of expert consultation, the significance tests for the Kendall coordination coefficients of the first, second, and third level indicators were all P<0.05. The expert authority coefficients for the first and second rounds of expert consultation were 0.840 and 0.895, respectively. The evaluation system for clinical nurse research ability training established after two rounds of consultation included four first-level indicators, 11 second-level indicators, and 40 third-level indicators. Conclusions:The evaluation system for clinical nurse research ability training based on the Kirkpatrick model has reliable results, and experts have high levels of enthusiasm, coordination, and authority. It can be used as a tool for evaluating clinical nurse research ability training.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^pro) and papain-like protease (PL^pro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^pro and PL^pro with IC₅₀ values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC₅₀ of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL^pro, and K157, E167 and A246 of PL^pro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.