Objective: To explore the effects of personality and sleep quality with psychological distress of junior and senior high school stduents, so as to provide a reference basis for precise interventions of junior and senior high school students mental health. Methods: In October 2023, a convenience sampling method was used to select 9 034 students aged 12-17 from Shiyan City as the study subjects. The Pittsburgh Sleep Quality Index (PSQI) and Kessler Psychological Distress Scale (K10) were used to collect information on sleep quality and psychological distress of junior and senior high school stduents. Between group comparison was conducted by using t-test and Chi-square test. Generalized linear models were employed to analyze the interaction and joint effects of personality and sleep quality on psychological distress. Results: The generalized linear model analysis showed that the interaction between personality and sleep quality on psychological distress was statistically significant of junior and senior high school students(effect size=0.80, P <0.01). The general linear model analysis indicated that, after adjusting for variables such as age, gender, screen time, and daily sitting time with the extroverted and good sleep quality group as the reference, the introverted and poor sleep quality group had the largest mean difference in psychological distress scores (difference=0.51, P <0.05). When stratified by sleep quality, psychological distress scores were higher in the introverted and neutral personality groups with both poor and good sleep quality compared to the extroverted group (poor sleep quality: introverted difference=3.71, neutral difference=1.14; good sleep quality: introverted difference=2.23, neutral difference=0.57, all P < 0.05). When stratified by personality, psychological distress scores were higher in the poor sleep quality groups for introverted, neutral, and extroverted individuals compared to their good sleep quality counterparts (differences=8.66, 7.83, 7.34, all P < 0.05 ). Conclusions Personality and sleep quality have interactive and joint effects on psychological distress of junior and senior high school stduents. Personalized psychological interventions should be developed based on personality and sleep quality.

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.

BACKGROUND:Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury;however,the specific mechanism is still not clear.Therefore,revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE:To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats. METHODS:Allen's impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group.The serum of rats of each group was collected.H9c2 cells were divided into a blank control group,a sham operated rat serum group,a spinal cord injury rat serum group and a luteolin pretreatment group.The cells in blank control group were only cultured with ordinary culture medium.The cells in the sham operated rat serum group were treated with medium containing 10%serum from sham operated rat.The cells in the spinal cord injury rat serum group were treated with medium containing 10%serum from spinal cord injury rat.The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10%rat serum from spinal cord injury rat.After 24 hours of culture,the survival rate of each group of H9c2 cells was measured by CCK-8 assay.Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group. RESULTS AND CONCLUSION:Compared with the blank control group,there was no significant change in cell survival rate in the sham operated rat serum group(P>0.05).Compared with the sham operated rat serum group,the cell survival rate(P<0.01)and the expression of LC3 protein(P<0.05)in spinal cord injury rat serum group was significantly reduced,and the expression of p62 protein was significantly increased(P<0.05).Compared with the spinal cord injury rat serum group,the survival rate of cells in the luteolin pretreatment group significantly increased(P<0.000 1);the expression of LC3 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05).The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy.

AIM: To investigate the influence of relevant inflammatory markers in peripheral blood on the progression of neovascular glaucoma(NVG)secondary to diabetic retinopathy(DR)patients.METHODS: Retrospective case-control study. Patients were categorized into two groups based on the presence or absence of NVG: those with proliferative diabetic retinopathy(PDR)alone(PDR group, n=148)and those with NVG secondary to PDR(NVG secondary to PDR group, n=142). Peripheral blood inflammatory markers were evaluated, including white blood cell-related indices, neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), monocyte-to-lymphocyte ratio(MLR), and systemic immune-inflammation index(SII). The distinctions in peripheral blood inflammatory markers between the two groups of patients and their relationships with NVG secondary to PDR were analyzed.RESULTS:No statistically significant differences were observed in basic characteristics between the two groups, confirming their comparability. However, significant differences were found in eosinophil percentage and MLR between the PDR group and the NVG secondary to PDR group(all P<0.05), with both values being significantly higher in the NVG secondary to PDR group. Multivariate Logistic regression analysis revealed that the eosinophil percentage and the MLR were factors influencing the development of patients with NVG secondary to PDR.CONCLUSION: Eosinophil percentage and MLR may be associated with the progression of PDR to NVG, and could serve as potential predictive markers for NVG development in PDR patients.

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.

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

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 discuss the suitable concentration of D-galactose(D-gal)and modeling period,and establish its induced aging-related cognitive dysfunction model in the mice,and perform a comprehensive evaluation.Methods:Fifty C57BL/6J mice were randomly divided into control group and 100,200,400,and 800 mg·kg-1 D-gal groups,with 10 mice in each group.The mice in various D-gal groups were subcutaneously injected with the corresponding concentration of D-gal once daily;the mice in control group were injected with an equal volume of normal saline.The body mass and water consumption of the mice in various groups were monitored;forelimb grip strength test and experiment on the ability of pole climbing sports were used to evaluate the motor coordination ability of the mice in various groups;novel object recognition test,Y maze test,and Morris water maze test were used to evaluate the cognitive function of the mice in various groups;HE staining and Nissl staining were used to observe the pathomorphology of brain tissue of the mice in various groups;immunohistochemistry method was used to detect the expression of β-galactosidase(β-gal)protein in brain tissue of the mice in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),IL-18,and IL-4 in hippocampus tissue of the mice in various groups;Western blotting method was used to detect the expression levels of β-gal,p53,and p16 proteins in hippocampus tissue of the mice in various groups.Results:The body mass growth trends of the mice in control group and various D-gal groups were consistent and there was no statistically significant difference(P>0.05),and there was no statistically significant difference in water consumption(P>0.05).After 8 weeks of subcutaneous injection of D-gal,compared with control group,the forelimb grip strength values of the mice in 200 and 400 mg·kg?1 D-gal groups were significantly decreased(P<0.05 or P<0.01);the pole-climbing time of the mice in 200 mg·kg?1 D-gal group was significantly prolonged(P<0.05);the recognition indexes of the mice in 200 and 400 mg·kg?1 D-gal groups were significantly decreased(P<0.01);the spontaneous alternation rate of the mice in 100,200,400,and 800 mg·kg?1 D-gal group was significantly decreased(P<0.05 or P<0.01),the escape latency was significantly increased(P<0.05).Spatial probe test showed that compared with control group,the escape latency of the mice in 200 mg·kg?1 D-gal group was significantly increased(P<0.05).The HE staining and Nissl staining results showed that compared with control group,the hippocampus neurons of the mice in 200 mg·kg-1 D-gal group were arranged disorderly,with obvious nuclear pyknosis,nuclear condensation,and abnormal morphology and structure,and the number of Nissl staining positive cells was significantly decreased.The immunohistochemistry results showed that compared with control group,the β-gal expressions in CA1 region,CA3 region,and cortex region of hippocampus tissue of the mice in 200 mg·kg?1 D-gal group were strongly positive.The RT-qPCR results showed that compared with control group,the expression levels of IL-1β,IL-18,and TNF-α mRNA in hippocampus tissue of the mice in 200 mg·kg?1 D-gal group were significantly increased(P<0.05 or P<0.01),and the expression level of IL-4 mRNA was significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of β-gal,p53,and p16 proteins in hippocampus tissue of the mice in 200 mg·kg?1 D-gal group were significantly increased(P<0.05 or P<0.01).Conclusion:The aging-related cognitive dysfunction model in the mice can be established by subcutaneous injection of 200 mg·kg?1 D-gal daily for 8 weeks.

In the context of medical insurance payment reform,the sample hospital has implemented performance management optimization to effectively address the challenges posed by diagnosis-intervention packet(DIP)payment.Reform measures focused on disease quality,rational diagnosis and treatment,operational management,medical technological value,and policy orientation,and they have significantly optimized service ability and performance evaluation indexes of the hospital.Main achievements included a reduction in the cost consumption index and an increase in the clinical performance index,with the overall DIP payment rate increasing from 88.86%to 103.23%and a marked improvement in operational management.The quality control and operational efficiency of the hospital have been effectively enhanced by choosing proper DIP payment evaluation indexes and improving performance management,and provided strong support for the high-quality development of the hospital.