OBJECTIVE To evaluate the cost-utility of ciclesonide （CIC） versus budesonide （BUD） for the maintenance treatment of mild to moderate bronchial asthma. METHODS From the perspective of Chinese health service system， a Markov model was established based on the data from a clinical trial in China and some literature. The cycle length was 1 week， the time horizon was 60 years. A discount rate of 5% per year was applied. Cost-utility analysis was performed on therapeutic scheme of CIC and BUD using three times of China’s per capita gross domestic product （GDP） in 2023 as the threshold of willing-to-pay （WTP）. One-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were applied to test the uncertainty of basic analysis. RESULTS Compared with BUD scheme， the incremental cost of the CIC scheme was 9 401.67 yuan， and the incremental quality-adjusted life years（QALYs） were 0.001 3； incremental cost-effectiveness ratio （ICER） was 6 928 868.26 yuan/QALY， far beyond the threshold of WTP 268 074 yuan/QALY. One-way sensitivity analysis showed that the usage， dosage and unit price of CIC and BUD were parameters that had a significant impact on ICER； probabilistic sensitivity analysis showed that the basic analysis results were relatively robust； scenario analysis showed that， when the price of CIC reduced to 159.95 yuan/branch， the probability of CIC scheme having economics was similar to that of BUD scheme. CONCLUSIONS At the current price， CIC is not economical compared with BUD for the maintenance treatment of mild to moderate asthma， using three times of China’s GDP in 2023 as the threshold of WTP.

OBJECTIVE To evaluate the cost-utility of ciclesonide （CIC） versus budesonide （BUD） for the maintenance treatment of mild to moderate bronchial asthma. METHODS From the perspective of Chinese health service system， a Markov model was established based on the data from a clinical trial in China and some literature. The cycle length was 1 week， the time horizon was 60 years. A discount rate of 5% per year was applied. Cost-utility analysis was performed on therapeutic scheme of CIC and BUD using three times of China’s per capita gross domestic product （GDP） in 2023 as the threshold of willing-to-pay （WTP）. One-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were applied to test the uncertainty of basic analysis. RESULTS Compared with BUD scheme， the incremental cost of the CIC scheme was 9 401.67 yuan， and the incremental quality-adjusted life years（QALYs） were 0.001 3； incremental cost-effectiveness ratio （ICER） was 6 928 868.26 yuan/QALY， far beyond the threshold of WTP 268 074 yuan/QALY. One-way sensitivity analysis showed that the usage， dosage and unit price of CIC and BUD were parameters that had a significant impact on ICER； probabilistic sensitivity analysis showed that the basic analysis results were relatively robust； scenario analysis showed that， when the price of CIC reduced to 159.95 yuan/branch， the probability of CIC scheme having economics was similar to that of BUD scheme. CONCLUSIONS At the current price， CIC is not economical compared with BUD for the maintenance treatment of mild to moderate asthma， using three times of China’s GDP in 2023 as the threshold of WTP.

Objective: To explore the relative importance of different food attributes and levels in food decision making of school aged children, and to understand their meal preferences, so as to provide the evidence for formulating precise intervention strategies for dietary behaviours of school aged children. Methods: From May to June 2024, a total of 854 children aged 11 to 15 years old were selected from 2 middle schools (each school in urban and rural areas) in both Hubei Province and Anhui Province by stratified cluster random sampling method to conduct a D-optimal discrete choice experiment. The mixed Logit model was used to analyze children s preference for meal attributes and different levels, and to calculate the relative importance (RI) of attributes and willingness to pay (WTP) in meal choices. Results: The included five food attributes had statistical significance on meal choice of school aged children ( P <0.05). The relative importance of food attributes affecting the meal choices of school aged children in descending order were dining mode ( RI =31.26%), food varieties ( RI =30.56%), cooking method( RI =23.84%), taste( RI =8.06%) and price ( RI =6.27%). Among them, school aged children preferred home cooked meals ( β =0.74) (WTP=86.3 yuan),varied foods(grain/tubers+vegetables+fish, meat, eggs and beans) ( β =0.61) (WTP=71.9 yuan), fried/roasted cooking ( β =0.51) and spicy taste ( β =0.33).Price was negatively correlated with meal choices( β =-0.01) ( P <0.05). Based on residential area and body mass index (BMI), the stratified analysis showed that dining mode was highest in the relative importance for rural children with overweight and obese children ( RI =31.28%,34.17%), both of whom preferred home cooked meals ( β =0.76, 0.91), and meals containing fish, meat, eggs and beans with grain/tubers or grain/tubers and vegetables in terms of food choice (area: β =0.53, 0.53 ; BMI: β =0.55, 0.56) ( P <0.05). Conclusions School aged children have different preferences for different attributes of meals. The quality of school meals should be improved,the cost of buying healthy meals should be reduced,targeted family health education should be carried out,and healthy cooking methods should be advocated.

OBJECTIVE To provide reference for relevant departments to improve the drug provision in children’s hospitals and further implement clinical management practices for rational drug use in pediatric patients. METHODS According to the drug purchasing statistics of four sample class A tertiary children’s hospitals in Jiangsu province from 2012 to 2023， this study systematically reviewed and analyzed the drug provision and utilization in children’s hospitals， including the number of pharmaceuticals procured and used in hospitals， the concentration of drug usage among different hospitals， the situation of drugs recommended by the National Essential Medicine List and children’s clinical diagnosis and treatment guidelines， and the standardization of clinical medication. RESULTS In 2023， the number of commonly used drugs in 4 tertiary children’s hospitals was 922 varieties and 1 401 specifications， which was significantly lower than the total number of currently marketed children’s drugs. However， the concentration of drug usage among different hospitals was not high， with the proportion of drugs supplied and used in only one hospital accounting for approximately 40% and 50% respectively in terms of drug variety and specification. At present， among the drugs procured and used in sample children’s hospitals， the proportion of national essential medicines basically maintained between 30% and 40%， while drugs which could be safely and effectively used for children was about 60%. In addition， around 40% of the drug varieties recommended in pediatric clinical practice guidelines had also been applied in clinical treatment. Nevertheless， about 30% to 40% of prescription behavior was dependent on doctors’ personal experience and the phenomena of drugs prohibited and unsuitable use for children still existed. CONCLUSIONS Although the number of clinical medications for children in China is limited， there are significant differences in the overall medication choices made by hospitals. The scientific， rational and standardized use of clinical medications also needs to be further strengthened.

Background The decline of physical activity in the elderly due to aging may increase the risk of sarcopenia. Currently, there is a lack of evidence from large natural populations on the relationship between PA and sarcopenia. Objective To explore the relationship between PA and sarcopenia in the elderly aged 60 years and above in 10 provinces (autonomous regions) of China. Methods Data were retrieved from the 2022—2023 round of the China Development and Nutrition Health Impact Cohort. Personal basic information and PA data were collected by questionnaire survey. Skeletal muscle mass was measured by bio-electrical impedance analysis, muscle strength was measured using a grip dynamometer, and physical performance was reflected by 6-meter walk speed. The Asian Working Group for Sarcopenia (AWGS) 2019 criteria were used to diagnose sarcopenia. Light physical activity (LPA) duration, moderate-to-vigorous physical activity (MVPA) duration, and total physical activity volume were calculated. A total of 3326 residents aged ≥60 years with complete data were selected as the survey participants. Multiple logistic regression models and restricted cubic splines (RCS) were used to assess the association between PA duration/volume and sarcopenia. Results In 10 provinces (autonomous regions) of China, the prevalence of sarcopenia in the elderly aged 60 years and above was 5.5% (95%CI: 4.7%, 6.2%). The logistic regression analysis showed that compared with the elderly reporting 0-7.0 h·week⁻¹ in LPA duration, the risk of sarcopenia in the elderly with LPA duration of >14.0-21.0 h·week⁻¹ was reduced by 51% (OR=0.49, 95%CI: 0.26, 0.96). Compared with the elderly with total physical activity ≥15.0 metabolic equivalent of task (MET)-h·week⁻¹, those with <7.5 MET-h·week⁻¹ had a 2.24-fold increased risk of sarcopenia (OR=2.24, 95%CI: 1.17, 4.29). The RCS results found that LPA duration and total physical activity volume each showed a nonlinear dose-response relationship with the risk of sarcopenia (P_overall<0.05, P_non-linear<0.05). Compared with the elderly with an LPA duration of 0 h· week⁻¹, the risk of sarcopenia in the elderly with an LPA duration of 12.6 h· week⁻¹ was the lowest (OR=0.42, 95%CI: 0.21, 0.83). Compared with the elderly with a total physical activity volume of 15.0 MET-h· week⁻¹, the elderly with a total physical activity volume of 46.0 MET-h· week⁻¹ had the lowest risk of sarcopenia (OR=0.57, 95%CI: 0.38, 0.84). There was no statistically significant association between weekly MVPA duration and the risk of sarcopenia (P>0.05). Conclusion Increasing weekly LPA duration and total physical activity volume would help to reduce the risk of sarcopenia.

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

Objective To explore the effects of CDP-diacylglycerol synthase 1(CDS1)on autophagy and amyloid deposition in hippocampal neurons of mice and the related mechanism.Methods Congo red and immunohistochemical staining were used to observe the amyloid deposition in hippocampus of amyloid precursor protein(APP)/presenilin 1(PS1)double-transgenic mice.Lentivirus-mediated overexpression of APP was induced in HT22 cells,and Congo red staining was used to observe the amyloid deposition in HT22 cells.The protein expression levels of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ and P62 in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were detected by Western blotting.The differential protein CDS1 was screened based on the hippocampal proteomics results of APP/PS1 double-transgenic mice.The expression of CDS1 protein in hippocampal tissue of APP/PS1 transgenic mice and APP-overexpressed HT22 cells was detected by Western blotting.After lentivirus-mediated APP overexpression in HT22 cells,CDS1 was overexpressed,and the protein expression levels of LC3-Ⅱ and P62 were detected by Western blotting.Results β-amyloid protein(Aβ)was deposited in the hippocampus of APP/PS1 mice and in HT22 cells overexpressing APP.The levels of LC3-Ⅱ and P62 protein in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were significantly increased.A differential metabolic pathway,glycerophospholipid metabolic pathway,was screened by Kyoto Encyclopedia of Genes and Genomes pathway analysis in the proteomic results of APP/PS1 double-transgenic mice,and the differential protein CDS1 was obtained.Compared with wild-type C57BL/6 mice,APP/PS1 double-transgenic mice exhibited a significantly decrease in CDS1 protein expression in the hippocampus(0.46±0.07 vs 1.00±0.25,P＜0.01).Similarly,lentivirus-mediated overexpression of APP in HT22 cells resulted in decreased CDS1 protein levels compared to cells infected with empty viral vector controls(0.68±0.18 vs 1.00±0.13,P＜0.01).The autophagy flow of nerve cells was significantly restored after the CDS1 overexpression in APP-overexpressed HT22 cells(LC3-Ⅱ:1.00±0.15 vs 0.21±0.05,P＜0.01;P62:1.00±0.16 vs 0.67±0.10,P＜0.01),and Aβ deposition was significantly decreased.Conclusion Downregulation of CDS1 expression can induce dysfusion of autophagosome and lysosome,promoting amyloid deposition in hippocampus of mice with Alzheimer's disease.

Objective:To evaluate the consistency of the Chinese three-dimensional anterior visual field analysis system (Scansys), the anterior segment analyzer (Pentacam), the frequency-domain anterior segment optical coherence tomography system (CASIA SS-1000), and a new ultra-high frequency digital ultrasound scanning system (Arcscan Insight100) to measure central vault after implantable collamer lens (ICL) implantation in myopic eyes with crystalline lenses.Methods:A diagnostic test study was conducted.Fifty-six myopic patients (56 eyes) who underwent ICL V4c implantation from June to December 2019 were included.Scansys, Pentacam, CASIA and Arcscan were used to measure the central vault after surgery.The vault measurements were compared.Correlations between the measurements of the four instruments were analyzed using Pearson correlation analysis, and consistency comparisons were analyzed using the Bland-Altman method.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]). Written informed consent was obtained from each subject.Results:The central vault measurements by Scansys, Pentacam, CASIA and Arcscan were (481.8±191.6), (476.4±190.6), (619.3±207.5) and (534.0±221.2)μm, respectively, with a statistically significant overall difference ( F=143.301, P<0.001). The vault measurements by Scansys and Pentacam were significantly lower than CASIA and Arcscan, and Arcscan was lower than CASIA, with statistically significant differences (all at P<0.001). There were strong positive correlations in vault measurements between Arcscan and CASIA, Arcscan and Pentacam, Arcscan and Scansys, CASIA and Pentacam, CASIA and Scansys, Pentacam and Scansys ( r=0.982, 0.933, 0.931, 0.942, 0.941, 0.989; all at P<0.001). Intraclass correlation coefficients of vault measurements by Scansys, Pentacam, CASIA and Arcscan were 0.985, 0.975, 0.998, 0.992, respectively.The 95% limits of agreement of vault measurements differences were -170 to 0, 0 to 280, 0 to 280, -110 to 210, -100 to 220 μm, between CASIA and Arcscan, CASIA and Scansys, CASIA and Pentacam, Arcscan and Scansys, Arcscan and Pentacam, respectively, and the maximum absolute value of the difference was beyond the clinically acceptable range, showing poor agreement.The 95% limits of agreement of vault measurement difference was -60 to 50 μm between Scansys and Pentacam, showing a good agreement. Conclusions:The repeatability of the vault after ICL V4c implantation in myopic eyes measured by the four instruments is good.Among them, the vault measurements of Scansys and Pentacam are smaller, showing good consistency, and their results could be substituted for each other.The measurement of CASIA is the largest, followed by Arcscan, which have a large difference from each other, and their results can not be substituted for each other, which should be comprehensively analyzed with the actual situation in clinical work.

OBJECTIVE To design the implementation path around the key links of the management in the clinical comprehensive evaluation of drug in China， and to provide suggestions for optimizing and perfecting the management in the clinical comprehensive evaluation of drug. METHODS Based on the relevant experience of drug evaluation management in typical countries regions at home and abroad， the discussion was performed and the management mechanism was designed from seven aspects， such as funding source， selection of topics， staff management， information management， data management， evaluation process and quality assessment. RESULTS & CONCLUSIONS In terms of funding sources， the financial department can provide funding guarantees or other alternative forms such as performance evaluations to encourage all parties to undertake the clinical comprehensive evaluation of drug projects. In terms of the selection of topics， a “top-down” or “bottom-up” selection mode can be determined according to the project’s nature and actual situation， and a selection process of “forming alternatives-setting up theme selection list-demonstrating and publishing theme selection list” can be formed. In terms of staff management， the specialty of team members should be specified， and the expert team should be established to provide clinical comprehensive evaluation of drug. In terms of information management， the national/provincial basic informational platform should be established， and the registration system should be established. In terms of data management， a regional health data-sharing platform should be formed and the “application-checking-utilization” mechanism should be conducted. In terms of the evaluation process， the evaluation procedures that concern on project implementation plan demonstration system and project closing review system should be constructed. In terms of quality assessment， quality assessment and reward and punishment mechanism for project completion，that consider the quality of management first while focusing on the technical quality， can be established. The management mechanism based on the standardized implementation of the seven key links will standardize the development of clinical comprehensive evaluation of drugs in China to some extent， and help improve the quality of clinical comprehensive evaluation projects for drugs.

Objective To construct and validate a clinical prediction model for delayed extubation undergoing non-emergency major surgery based on the random forest algorithm.Methods Clinical data of 7 528 patients undergoing non-emergency major surgery under general anesthesia from January 2018 to De-cember 2022 were retrospectively collected.The patients were divided into two groups according to whether extubation was performed within 2 hours after surgery:non-delayed extubation group(≤2 hours)and de-layed extubation group(＞2 hours).All the patients were randomly divided into a training set and a valida-tion set in a ratio of 7 ∶ 3.The predictive factors for delayed extubation after surgery were screened through LASSO regression and Logistic regression.The random forest model was established and verified by random forest algorithm.Results There were 123 patients(1.6%)experienced delayed extubation after surgery.ASA physical status,department,intraoperative use of flurbiprofen ester,dexmedetomidine,glucocorticoid,hypocalcemia,severe anemia,intraoperative blood transfusion,and airway spasm were identified as inde-pendent predictive factors for delayed extubation.The area under curve(AUC)value of the random forest prediction model in the validation set was0.751(95%CI0.742-0.778),and the sensitivity was98.1%,and the specificity was 41.9%.Conclusion The predictive model of delayed extubation undergoing non-e-mergency major surgery based on random forest algorithm has a good predictive value,which may be helpful to prevent delayed extubation undergoing non-emergency major surgery.