Objective: To observe the correlation between Nε-carboxymethyl-Lysine (CML), the main component of advanced glycation end products and the calcification of the anterior tibial artery plaque in patients with diabetic foot post foot amputation. Methods: Sixty patients hospitalized for foot amputation operation due to diabetic foot from June 2012 to June 2016 in the Department of Orthopedics, Affiliated Hospital of Jiangsu University were prospectively recruited.The patients were categorized into mild stenosis (0n=20), moderate stenosis (50%≤stenosis<70%, n=20) and severe stenosis (70%≤stenosis≤100%, n=20) based on the color Doppler ultrasound assessed severity of anterior tibial artery stenosis.The baseline clinical data of patients were collected and anterior tibial artery was isolated.Then, HE staining, O-Cresolphthalein Complexone method, enzymic method and ELASA analysis were then performed to detect the evolution of calcification, arterial calcium content, alkaline phosphatase activity and serum CML concentration, respectively. Results: The results from both color Doppler ultrasound scan before amputation and HE staining after amputation showed that echo intensity as well as spotty blue calcium particles of anterior tibial artery plaque increased significantly in proportion to degree of stenosis and destructed elastic plate of the arterial wall was evidenced in patients with severest stenosis.The content of calcium ((2.3±0.9), (3.9±1.3), (6.6±1.7) μmol/mg, respectively, P<0.001), ALP activity ((102.4±39.4), (202.3±73.4), (483.7±117.9) U/mg, respectively, P<0.001) and serum CML level ((28.9±4.4), (37.9±5.3), (57.3±7.1)μg/L, respectively, P<0.001) increased significantly in proportion to stenosis severity.Pearson correlation analysis showed that serum CML level was positively correlated with the content of calcium (r=0.749, P<0.001) and ALP activity (r=0.923, P<0.001), respectively. Conclusions Serum CML level is positively correlated with the calcification of anterior tibial arterial plaque in patients with diabetic foot and could be used to evaluate the calcification of anterior tibial arterial plaque and stenosis degree of anterior tibial arterial in these patients.

Objective To investigate the clinical significance of children bronchial asthma detection by using negative expiratory pressure (NEP) technique.Methods The children with bronchial asthma admitted to Department of Pediatrics of Zhejiang Provincial Integrated Traditional Chinese and Western Medicine Hospital from March 2016 to March 2018 were enrolled.They were divided into mild group (0-4 scores) and severe group (5-12 scores) according to asthma clinical scoring criteria.The children undergoing physical examination at the same period were served as healthy control group.NEP technique and tidal volume (VT) were detected by the pulmonary function instrument.Respiratory flow-volume curves (F-V curves) without NEP were compared with tidal F-V curves after NEP application to assess expiratory flow limitation (EFL).EFL index was calculated according to the percentage of expiratory VT after EFL and expiratory VT when NEP was not used.Pearson correlation method was used to analyze the relationship between EFL index and severity of bronchial asthma.Receiver operating characteristic (ROC) curve was plotted to analyze the value of EFL index in evaluating the severity of bronchial asthma in children.Results A total of 86 children with bronchial asthma were enrolled in the study,and 84 patients completed the test and 2 children withdrew due to other diseases.Finally,84 patients were included in the final analysis,including 41 mild and 43 severe children.Forty-two healthy children in the same period were served as healthy control group.There was no significant difference in gender or age among the groups,and no adverse reactions occurred during the test.The EFL index of children with bronchial asthma was significantly higher than that of the healthy control group,and it was increased with the severity of the disease [mild group compared with healthy control group:(30.60± 6.03)％ vs.(6.64 ± 2.37)％,severe group compared with healthy control group:(33.70 ± 5.41)％ vs.(6.64 ± 2.37)％,both P ＜ 0.05].There was no significant difference in respiratory rate (RR) or VT between mild group or severe group and healthy control group [RR (times/min):31.45 ± 4.18,32.81 ± 4.07 vs.31.97 ± 4.01,VT (mL/kg):6.29 ± 1.14,5.96 ± 0.90 vs.6.30 ± 1.20,all P ＞ 0.05].It was shown by the correlation analysis that EFL index was positively correlated with the severity of asthma (r =0.836,P =0.000).It was shown by ROC curve analysis that the area under ROC curve (AUC) of EFL index for predicting the severity of bronchial asthma in children was 0.801 [95％ confidence interval (95％C/) =0.725-0.878];when the best cut-off value of EFL index was 29.21％,the sensitivity was 85.7％,the specificity was 69.2％,the positive predictive value was 75.1％,and the negative predictive value was 60.2％.Conclusions The EFL index measured by NEP technology was closely related to the severity of bronchial asthma.The higher the EFL index,the more serious of the condition.The severity of bronchial asthma could be early judged by EFL index,which provided a basis for the evaluation and treatment of bronchial asthma.

OBJECTIVE：To provide reference for impro ving the quality of programmed cell death protein 1 （PD-1）/ programmed cell death 1 ligand（PD-L1）inhibitors in the treatment of non-small cell lung cancer related pharmacoeconomic studies in China. METHODS ：Retrieved from Embase ，PubMed，Medline，Cochrane Library ，CNKI，Wanfang database ，VIP and other Chinese and English database ，cost-utility studies about PD- 1/PD-L1 inhibitors in the treatment of non-small cell lung cancer published during Jan. 2016-Jan. 2021 were collected. The data of the included studies were extracted. After the quality of the included studies was evaluated by using the Consolidated Health Economic Evaluation Reporting Standards list ，the relevant data were summarized and compared from the aspects of model framework ，model parameters and uncertainty analysis. RESULTS & CONCLUSIONS：A total of 17 studies were finally included ，the overall quality of them was high but the differences in methodology were great. Markov model or partition survival model based on three states was adopted for 16 studies. The time horizon ranged from 5 years to lifetime ；the cycle length ranged from 1 week to 6 weeks. A total of 8 studies used the standard parameter distribution method for parameter fitting ，and 7 studies additionally adopted other parameters estimation methods as KM curves or spline models. Eleven studies performed the validation of model extrapolation. All studies considered the direct medical costs and reported the incremental cost-effectiveness ratio using quality-adjusted life years as the health outcome. Sixteen studies conducted the deterministic sensitivity analysis and probabilistic sensitivity analysis to improve the stability of the model. It is suggested that studies should keep the integrity of the report ； format，choose the appropriate positive comparators ，selectthe health economic model and construct reasonable assumptions according to the available data format ， use Cholesky decomposition to explore the uncertainty of the parameter fitting ， perform the validation of extrapolation combined with external data and use the appropriate indirect comparison in the absence of the head-to-head clinical trials to improve the quality of related pharmacoeconomic studies in China.

OBJECTIVE To ev aluate the economical efficiency of nivolumab versus everolimus in the second-line treatment of metastatic clear cell renal cell carcinoma. METHODS From the perspective of China ’s health system ，cost-effectiveness analysis of the two therapies was carried out by developing a three-state partitioned survival model. The clinical parameters were from the updated CheckMate 025 study，and the cost and health utility were from relevant websites and published literatures. The model adopted a 2-week cycle and a lifetime research time. The robustness of the results was verified by sensitivity analysis. The economical efficiency of two therapy schemes were evaluated in the scenario of model simulation time of 80 months and charitable drug donation scheme. RESULTS The results of basic analysis showed that compared with everolimus ，the incremental cost-effectiveness ratio （ICER）of nivolumab was 586 982.60 yuan/quality-adjusted life year （QALY），which was far higher than 3 times of China ’s per capita gross domestic product （GDP）in 2020. The results of single-factor sensitivity analysis showed that the 3 parameters that had the greatest impact on the economic evaluation results were the cost of nivolumab ，the utility value of nivolumab group and everolimus group in progressive disease state. The results of probability sensitivity analysis verified the robustness of the basic analysis results. Results of scenario analysis showed that in the first scenario analysis ，in which model simulation time lasted for 80 months，ICER of nivolumab was 417 204.52 yuan/QALY；in the second scenario analysis ，in which nivolumab charitable drug donation program for low-income people was considered ，ICER of nivolumab was 124 988.58 yuan/QALY. CONCLUSIONS Under the threshold of 1-3 times of China ’s per capita GDP in 2020，compared with everolimus ，it is not economical to use nivolumab as the second-line treatment for metastatic clear cell renal cell carcinoma ； nivolumab is economical when considering its charitable drug donation program for low-income people.