Objective:To construct a biosafety evaluation index system for major emergency public health events in medical institutions.Methods:Based on previous laboratory biosafety evaluation work, relevant regulations and standards on biosafety in China were collected through literature research and expert consultations. Candidate indicators for constructing the biosafety evaluation system for major emergency public health events in medical institutions were selected, and a framework was established. Two rounds of expert questionnaires were conducted to determine the content of the index system based on experts′ evaluation, and each indicator′s relevance and importance were scored. Finally, two rounds of Delphi consultations were carried out, and the Analytic Hierarchy Process (AHP) was applied to calculate the weights of indicators.Results:The response rates for the total four rounds of questionnaire surveys were all 100%. The first two rounds focused on determining the framework, while the latter two focused on determining the weights for each indicator. The authority coefficients of the expert consultations for the two rounds of weights were 0.65 and 0.70, respectively, indicating the reliability of the research results. In the final round of survey, the Kendall′s coefficients of concordance at each level were all greater than 0.1. Through statistical testing, the P-values were all less than 0.05, indicating good coordination of expert opinions. Ultimately, we established an operational biosafety evaluation system for major emergency public health events in medical institutions, consisting of 4 primary indicators, 26 secondary indicators, and 119 tertiary indicators, with additional deduction items, bonus items, unacceptable items, and monitoring indicators.Conclusions:Based on scientific theory, a biosafety evaluation system for major emergency public health events in medical institutions was constructed, achieving the integration of routine and emergency measures. This system can be used for self-assessment of laboratory biosafety during emergency public health events, addressing the lack of unified standards in biosafety evaluation. Through regular self-assessment, it can enhance the level of biosafety management in medical institution laboratories, to realize the value of application and dissemination.

Objective:To construct a biosafety evaluation index system for major emergency public health events in medical institutions.Methods:Based on previous laboratory biosafety evaluation work, relevant regulations and standards on biosafety in China were collected through literature research and expert consultations. Candidate indicators for constructing the biosafety evaluation system for major emergency public health events in medical institutions were selected, and a framework was established. Two rounds of expert questionnaires were conducted to determine the content of the index system based on experts′ evaluation, and each indicator′s relevance and importance were scored. Finally, two rounds of Delphi consultations were carried out, and the Analytic Hierarchy Process (AHP) was applied to calculate the weights of indicators.Results:The response rates for the total four rounds of questionnaire surveys were all 100%. The first two rounds focused on determining the framework, while the latter two focused on determining the weights for each indicator. The authority coefficients of the expert consultations for the two rounds of weights were 0.65 and 0.70, respectively, indicating the reliability of the research results. In the final round of survey, the Kendall′s coefficients of concordance at each level were all greater than 0.1. Through statistical testing, the P-values were all less than 0.05, indicating good coordination of expert opinions. Ultimately, we established an operational biosafety evaluation system for major emergency public health events in medical institutions, consisting of 4 primary indicators, 26 secondary indicators, and 119 tertiary indicators, with additional deduction items, bonus items, unacceptable items, and monitoring indicators.Conclusions:Based on scientific theory, a biosafety evaluation system for major emergency public health events in medical institutions was constructed, achieving the integration of routine and emergency measures. This system can be used for self-assessment of laboratory biosafety during emergency public health events, addressing the lack of unified standards in biosafety evaluation. Through regular self-assessment, it can enhance the level of biosafety management in medical institution laboratories, to realize the value of application and dissemination.

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

Objective:To compare the comprehensive performance of three Varian on-board image (OBI) image systems (KV-CBCT, KV-planar and MV-EPID) and to explore the value of the combined application of these three systems in daily image-guided radiotherapy for nasopharyngeal cancer.Methods:KV-CBCT, KV-planar and MV-EPID scanning and registration were carried out in the left and right/abdominal and back/head and foot direction on human head and neck phantom. The set-up error, registration time, additional radiation dose and image quality of the three systems were compared by F-test.Results:KV-CBCT, kV-planar and MV-EPID were scanned for 55 times, respectively, and the set-up errors in the left and right/abdominal and back/head and foot direction of the three image-guided systems were (0.00±5.43)/(-0.02±5.49)/(0.02±5.58) mm, (0.04±5.49)/(0.02±5.56)/(0.02±5.54) mm, (0.02±5.22)/(0.11±5.34)/(-0.04±5.33) mm, respectively ( P=0.999, 1.000, 0.989). The average time consuming was (200±45) s, (120±36) s and (115±42) s; the additional radiation dose from low to high was kV-planar, KV-CBCT and MV-EPID; the image quality from low to high was MV-EPID, kV-planar and KV-CBCT. Conclusions:Three image-guided systems can meet the requirements of image-guided radiotherapy for nasopharyngeal cancer. Based on the overall performance of the three systems, 1 CBCT+ 4 kV planar per week is recommended and EPID should be used as a backup system in daily image-guided radiotherapy for nasopharyngeal cancer. This scheme makes full use of the high image quality of CBCT and the low radiation of kV planar to realize the regular detection of nasopharyngeal cancer volume change and the implementation of high-precision radiotherapy.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.

Objective To evaluate the effectiveness of spectral CT with multiple parameters on the diagnosis of ovarian cancer. Methods The data of 22 patients with spectral CT enhanced scan were analyzed retrospectively.The patients were divided into two groups:ovarian cancer group (n=11)and benign tumor group (n=11),according to the pathologic results.CT values at 40 keV,iodine concentration (IC),water concentration(WC)and spectral curve slope (λHU)of arterial phase and venous phase in the tumors of two groups were measured with gemstone spectral imaging(GSI)post-processing software.The independent samples t test was used to compare these multiple parameters above between two groups.Interobserver agreement with regard to various parameters was assessed using Cohen’s Kappa . For the parameters which showed statistically different,the receiver operating characteristic(ROC)curves were further generated to calculate their diagnostic effectiveness respectively.Results CT values at 40 keV,IC andλHUmeasured in arterial and venous phases were higher in ovarian cancer group than those in benign tumor group.There were significant differences between these two groups(P<0.05). While WC had no significant difference in these two groups (P>0.05).Interobserver agreement with regard to various parameters was excellent (Kappa>0.80).CT values at 40 keV,IC andλHUhad high effectiveness on the diagnosis of ovarian cancer according to ROC curves.The optimal parameter among them was IC in arterial phase with AUC of 0.90.Using 10.92 (100 μg/cm3)as a threshold value,the sensitivity and specificity for diagnosis were 90.9% and 90.9%.Conclusion Spectral CT with multiple parameters,including CT values at 40 keV,IC and λHUhave significant differences between benign and malignant ovarian tumors.IC in arterial phase has the highest effectiveness on the diagnosis of ovarian cancer.

Objective To observe the fundus lesions in the unilateral rhegmatogenous retinal detachment (RRD) eyes and contralateral eyes in non-traumatic emmetropia patients,and explore the risks of lateral eyes.Methods This is a retrospective case analysis.A total of 426 patients of unilateral RRD diagnosed by clinical examination were enrolled in this study.There were 273 males and 74 females.The average age of onset was 54.7 years.81.46％ of them (347 patients) were 51-70 years old.The average detachment time was 2.12 months.They were divided into two groups,equal or lesser than 50 years old group and more than 50 years old group.A total of 100 patients (200 eyes) with ocular surface disorders were randomly selected as control.The lattice-like degeneration,cystic degeneration and dry retinal holes were treated with prophylactic laser photocoagulation.Follow-up period was 6 to 24 months.The age,gender,proliferative vitreous retinopathy (PVR) grading,best corrected visual acuity (BCVA),distribution and quantity of retinal holes,and posterior vitreous detachment (PVD) were retrospectively analyzed.The incidence of PVD among different age groups was compared with Chi square.Results Among 426 RRD eyes,there were 239 eyes (56.10％) with PVD.Among them,there were 30 eyes with age equal or lesser than 50 years old (12.55％) and 209 eyes with age more than 50 years old (84.75％).There were 187 eyes (43.90％) without PVD,which including 38 eyes with age equal or lesser than 50 years old (20.32％) and 149 eyes with age more than 50 years old (79.68％).The incidence of PVD among different age groups was statistically significant (x2=4.72,P＜ 0.05).There were 10,254,40 and 5 eyes in class A,B,C and D of PVR,respectively;117 eyes without PVR.The retinal hole was located in superior temporal,inferior temporal,superior nasal,inferior nasal and macular in 305,91,22,4 and 4 eyes,respectively.The number of holes was 1,2,and more than 3 in 297,89 and 40 eyes,respectively.The retinal detachment range of 1,2,3 quadrants and total dissociation were 92,230,71,33 eyes,respectively.The fundus lesion was found in 47 eyes (11.03％) in the lateral eyes.There were 20 RRD eyes in class B of PVR,and 27 RRD eyes in class C of PVR.Retinal degenerated area was found.Among them,the degeneration of 41 eyes was located in the temporal retina,45 eyes involved in a quadrant.There were 16 eyes with peripheral retinal dry holes;the holes diameter was less than 1,1-2,greater than 2 optic-discs in 6,11 and 5 retinal holes.At the end of the follow-up,there were 47 eyes with almost normal visual field,16 eyes with decreased visual acuity,noeyes with retinal detachment.In the control group,4 patients (5 eyes,2.50％) had fundus lesions.Conclusion The unilateral RRD in non-traumatic emmetropia mostly occurs in elderly patients;11.03％ of patients had fundus lesions in the contralateral eyes,higher than the general population.

Objective To investigate the distribution pattern and antimicrobial resistance of the clinical isolates of pathogen.Methods The identification and dug susceptibility tests of the isolates from 2013 to 2015 were performed by using VITEK2-compact system.The susceptibilities of isolates to antimicrobial agents were analyzed with WHONET 5.6 software.Results A Total of 2 991(90.4%) gram-negative bacteria and 317(9.6%) gram-positive bacteria were isolated.Among all of the isolates,the top three pathogens were Klebsiella pneumonia,followed by Pseudomonas aeruginosa and Acinetobacter baumannii.The detection rates of extended-spectrum beta-lactamase(ESBLs)-producing Escherichia coli were 40.4%,48.2% and 38.3% respectively in the three consecutive years,while the detection rates of the ESBLs-producing Klebsiella pneumonia were 16.9%,8.4% and 11.6% respectively.No Escherichia coli resistant to impenem were detected.The resistant rate to impenem of Klebsiella pneumonia was 1.6%.The detection rates of methicillin resistant Staphylococcus aureus(MRSA) and methicillin resistant coagulase-negative staphylococci(MRCNS) in the three years were 53.8%,54.3%,42.9% and 84.5%,82.7%,85.9% respectively.No Staphylococci isolates resistant to linezolid and tigecycline were found.Enterococcus isolates were sensitive to gentamicine,linezolid,tigecycline and vancomycin.Conclusion Carbapenems could remain the best antimicrobials against Enterobacteriaccae.Lnezolid and tigecycline could be effective antimicrobials against Staphylococci isolates.The detection rates of Klebsiella pneumonia and Acinetobacter baumannii increased year by year.The monitoring of drug resistance should be strengthened to control the emergence and spread of multidrug resistant pathogen.

Objective To explore the ability of advanced oxidation protein products (AOPP)in predicting the progression of diabetic retinopathy (DR)in patients with type 2 diabetes mellitus (T2DM). Methods 363 T2DM patients were enrolled in this prospective cohort study. According to the quartile points of baseline AOPP level,patients were divided into four groups (Q1,Q2,Q3 and Q4 ). The progression rate of DR was calculated according to the changes of non-mydriatic fundus photography after a 5-year follow-up. Results With the increase of baseline AOPP level,the rate of progression of DR increased (19.51% vs 28.42% vs 37.36% vs 47.37%,P <0.01). Logistic regression analysis showed that baseline level of AOPP was an independent risk factor for the progression of DR (OR=1.833,95%CI:1.573~1.982,P<0.05).Area under the curve of AOPP in predicting DR is 0.883 (95% CI:0.842~0.924)with the sensitivity 86.1% and specificity 91.9%. Conclusion AOPP may be one of the biomarkers for the prediction of type 2 diabetic retinopathy progression.

Objective To analyze the dose dependent cardiotoxicity of cyclophosphamide and thus establish the mouse models for understanding the underlying mechanisms . Methods Thirty mice ( 7 -8 weeks old) were randomly divided into 6 groups:control of one course group ,control of two courses group , one course of low dose ( 50 mg/kg) group ,two courses of low dose group ,one course of high dose ( 100 mg/kg) group ,two courses of high dose group . The changes of cardiac function and morphology were analyzed at indicated times by ultrasound and histology respectively . Results Compared with the control groups , injection of low dose cyclophosphamide either with one course or two courses ,and injection of high dose with only one course had no in statically significant changes in hair color ,physical activity ,body weight and cardiac function( P > 0 .05) . Treatment of two courses with high dose resulted in significant decrease of physical activity and body weight ( P < 0 .05 ) . Meanwhile ,cardiac systolic function was significantly decreased( P <0 .05) . Histology study revealed robust cardiac hypertrophy and fibrosis . Conclusions Two courses of intraperitoneal injection of cyclophosphamide at high dose result in obvious cardiotoxicity , especially systolic dysfunction .Intraperitoneal injection of two courses of cyclophosphamide serves as a good strategy to induce cardiotoxicity in mice ,which could be applied for future mechanism study .