OBJECTIVE To systematically review the pharmacoeconomic evaluation literature about proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia， and to provide a reference for clinical treatment， health decision-making and future follow-up research. METHODS Retrieved from English and Chinese databases such as PubMed and CNKI， the pharmacoeconomic literature about PCSK9 inhibitors （evolocumab and alirocumab） for the prevention of cardiovascular disease in patients with hypercholesterolemia was collected from the establishment of the database to October 8， 2023. The quality of the included literature was assessed with Consolidated Health Economic Evaluation Reporting Standards 2022 （CHEERS 2022） scale. The descriptive analysis was performed for basic information， model structure， related parameters， sensitivity analysis and the results of included studies. RESULTS & CONCLUSIONS A total of 29 literature were included， with overall good quality. The evaluation mainly adopted the Markov model from the healthcare system， payer and societal perspective. The effectiveness and utility data mainly came from the previous studies； the direct cost was mainly considered with a discount rate of 1.5%-5.0% per year， while the willingness-to-pay threshold was often set at 1-3 times the gross domestic product per capita. Most health output indicators were measured in life years and quality-adjusted life years. The sensitivity analysis of most studies demonstrated the robustness and the main influential factor was the drug cost. Most Chinese studies showed that PCSK9 inhibitor was not cost-effective for the prevention of cardiovascular disease in patients with acute coronary syndrome， myocardial infarction and atherosclerotic cardiovascular disease. It was cost-effective to use PCSK9 inhibitors for the prevention of cardiovascular disease only in specific groups， such as patients with triple vessel disease， patients with newly diagnosed acute coronary syndrome and low-density lipoprotein cholesterol≥100 mg/dL. Future research should refer to the CHEERS 2022 scale to improve the design， and strive to select large-scale， high-quality data to enhance the quality of reports and the transparency of health decisions， so as to more accurately assess the cost-effectiveness of PCSK9 inhibitors.

Objective To investigate the effects of cinnamaldehyde,the main active component of cinnamon,on benzene-induced immune injury in mice and the related mechanism.Methods Forty male BALB/c mice were randomly divided into the control group,model group(benzene 500 mg/kg),cinnamaldehyde low,medium and high dose groups(5,25,50 mg/kg),with 8 mice in each group.Except the control group,mice in each group were treated with benzene by intragastric administration daily to induce immune and oxidative stress damage,but the intervention group was treated with cinnamaldehyde 5 times/week for 3 weeks.After medication,peripheral blood was collected 24 h after the last gavage for blood cell count,and the changes in body weight of mice in each group were observed.The pathological structure of the spleen and thymus was observed via hematoxylin-eosin(HE)staining.Peripheral blood mononuclear cells(PBMCs)of mice were extracted and the amounts of reactive oxygen species(ROS)and ATP in mitochondria were measured.Plasma levels of malondialdehyde(MDA)were measured using the barbituric acid method,the activity of glutathione peroxidase(GSH-PX)in plasmawith the dithiodinitrobenzoic acid methodand the activity of total superoxide dismutase(SOD)in plasma using the hydroxylamine method.Results After exposure to benzene,the body weight of the model group became lower(P<0.05).The spleen and thymus were damaged,and the indexes of the spleen and thymus were decreased(P<0.05).Counts of peripheral white blood cells and lymphocyteswere decreased(P<0.05).The activities of GSH and SOD in plasma were decreased(P<0.05),but the content of MDA was increased(P<0.05).The amount of mitochondrial ROS in PBMC was increased,while the ATP content was decreased(P<0.05).The weight of mice increased after treatment with cinnamaldehyde.The spleen and thymus tissues recovered well,and the indexes of the spleen and thymus were increased(P<0.05).Counts of peripheral white blood cells and lymphocytesin the high dose cinnamaldehyde group were increased(P<0.05).The activities of GSH and SOD in plasma were increased,while the content of MDA was decreased(P<0.05).The amount of mitochondrial ROS in PBMC was decreased,but the ATP content was increased(P<0.05).Treatment with cinnamaldehyde could alleviate the damage to the mitochondrial function of PBMC induced by benzene in mice,and 50 mg/kg was the best dose(P<0.05).The therapeutic effect of cinnamaldehyde had a dose-response relationship.Conclusion Cinnamaldehyde can inhibit benzene-induced immune injury and oxidative stress injury in mice by delivering an antioxidant effect and improving mitochondrial enhancement of PBMC.

Objective:To explore the anger emotional state,traits and expression characteristics in patients with schizophrenia with violent behavior in community.Methods:Twenty-five patients with schizopnrenia with a history of violent behavior among the community rehabilitation institutions were selected as the violent behavior group,and 74 patients with schizopnrenia without a history of violent behavior were selected as the nonviolent behavior group.The Brief Psychiatric Rating Scale(BPRS)was used to assess psychiatric symptoms,and the State-Trait An-ger Expression Inventory(STAXI)was used to assess anger characteristics.Results:Compared with the nonviolent behavior group,the violent behavior group had significantly higher scores in the trait of anger(patient dimension score,rational dimension score)and expression of anger(total score,restraint dimension score)[(28.0±23.8)vs.(19.6±13.3),(55.0±30.6)vs.(40.0±21.5),(34.2±11.6)vs.(27.3±10.7),(56.0±26.1)vs.(33.7±21.1),Ps＜0.05].Higher scores of rationality dimension of anger trait(OR=3.69,95％CI:1.43-7.98)and re-straint dimension of anger expression(OR=3.25,95％CI:1.39-7.47)were risk factors for violent behaviors.Conclusion:Compared with patients with schizopnrenia without violent behavior,patients with violent behavior history may show more lack of rationality,and poorer anger restraint.

Objective To construct a prognostic risk model for exploring the prognostic value of copper metabolism related genes(CMRGs)in lung adenocarcinoma(LUAD),thereby providing a reference for personalized treatment of LUAD patients.Methods The RNA-seq data of LUAD tissues and adjacent or normal lung tissues were downloaded from the Cancer Genome Atlas(TCGA)database and Genotype-tissue Expression(GTEx)database.The risk scoring model was established using univariate Cox regression analysis,Lasso analysis and multivariate Cox regression analysis,and the receiver operating characteristic(ROC)curves and nomogram were used to evaluate the model performance.The LUAD data in the Gene Expression Omnibus(GEO),the Tumor Immune Single-cell Hub(TISCH)single-cell sequencing analysis,and the Human Protein Atlas(HPA)immunohistochemistry analysis were used for external validation.Additionally,the immune microenvironment and drug sensitivity of high-and low-risk groups were analyzed.Results A risk model consisting of 6 genes was constructed.The overall survival rate of low-risk group was higher than that of high-risk group(P<0.001).ROC analysis showed that the area under curve of the risk model in training set reached 0.729,0.749 and 0.707 at 1-,3-and 5-year,respectively,and the C index of C-index curve was 0.721(95%CI:0.678-0.764).The immune microenvironment differed significantly between high-and low-risk groups(P<0.001),and the drug sensitivity analysis in high-and low-risk groups revealed that there was statistically significant for gemcitabine,gefitinib,crizotinib and savolitinib(P<0.001).Conclusion The risk model constructed with 6 CMRGs enable the prediction of the prognosis of LUAD patients.The immune microenvironment differs in high-and low-risk group,and high-risk patients are more sensitive to drugs such as gemcitabine,gefitinib,crizotinib and savolitinib,which provide a reference for the personalized treatment of LUAD patients.

Objective To develop a new risk scoring model based on cuproptosis-related lncRNAs (CRLs) to predict the prognosis of lung squamous cell carcinoma (LUSC). Methods Data were obtained mainly from TCGA and GTEx databases. Univariate Cox, Lasso, and multivariate Cox regression analyses were conducted to determine CRLs that affect the prognosis of LUSC and establish a risk scoring model. The ability of risk score characteristics to independently predict LUSC survival was compared with that of clinical characteristics by calculating the area under the ROC curve (AUC). Immune-related functions and immune checkpoint differences were compared between high- and low-risk groups. Results Nine CRLs were selected as independent prognostic lncRNAs for LUSC, and a risk scoring model was developed. Risk score was the influence factor for the prognosis of LUSC. The AUC values predicted by the risk score model for 1-, 3-, and 5-year survival rates of patients with LUSC were 0.710, 0.718, and 0.743, respectively. The high- and low-risk groups were partly statistically different in terms of immune-related functional assays and immune checkpoint assays (P < 0.05). Conclusion The risk scoring model developed based on nine CRLs could predict the prognosis and immune therapy response of patients with LUSC in clinical practice.

Objective:To explore the source of students and the way to understand the policy of public and non-public undergraduate students majoring in preventive medicine.Methods:Using cluster random sampling, a total of 205 students from the first batch of public funded undergraduates and the same batch of non-public funded undergraduates of preventive medicine from Batch 2020 of two medical colleges in Shandong Province were selected as research objects. Questionnaires were issued on the platform of Sojump to investigate the source of students and the way to understand the policy. SPSS 22.0 statistical software was used to analyze the data, and the relative number and composition ratio were used to describe the counting data. Chi-square test was used to compare the characteristics of students and the understanding degree of the policy between government-funded undergraduates and non-government-funded undergraduates. Multiple responses were used to analyze students' understanding of the policy.Results:There were significant differences in the gender ( χ2=10.29, P<0.001), place of household registration ( χ2=5.61, P=0.018), father's educational level ( χ2=9.78, P=0.044) and the way to understand the policy ( χ2=17.19, P<0.001) of the public and non-public funded undergraduates majoring in preventive medicine. And 88.4% of the students knew about the policy of public medical students through their teachers, classmates and family members. Conclusion:There are more female government-funded undergraduates in preventive medicine than male students, and more rural students than urban students, with the spreading way of from mouth to mouth as the main approach to know this policy.

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world, and the current lung cancer screening and treatment strategies are constantly improving, but its 5-year survival rate is still very low, which seriously endangers human health. Therefore, it is critical to explore new biomarkers to provide personalized treatment and improve the prognosis. Cuproptosis is a newly discovered type of cell death, which is due to the accumulation of excess copper ions in the cell, eventually leading to cell death, which has been suggested by studies to be closely related to the occurrence and development of lung adenocarcinoma (LUAD). Based on The Cancer Genome Atlas (TCGA) database, this study explored the association between cuproptosis-related genes (CRGs) and LUAD prognosis, established a prognostic risk model, and analyzed the interaction between CRGs and LUAD immune cell infiltration. METHODS: The RNA-seq data of LUAD tissue and paracancerous or normal lung tissue were downloaded from the TCGA database; the RNA-seq data of normal lung tissue was downloaded from the Genotype-tissue Expression (GTEx) database, and the data of 462 lung adenocarcinoma cases were downloaded from the Gene Expression Omnibus repository (GEO) as verification. T the risk score model to assess prognosis was constructed by univariate Cox and Lasso-Cox regression analysis, and the predictive ability of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Immune-related and drug susceptibility analysis was further performed on high- and low-risk groups. RESULTS: A total of 1656 CRGs and 1356 differentially expressed CRGs were obtained, and 13 CRGs were screened out based on univariate Cox and Lasso-Cox regression analysis to construct a prognostic risk model, and the area under the curves (AUCs) of ROC curves 1-, 3- and 5- year were 0.749, 0.740 and 0.689, respectively. Further study of immune-related functions and immune checkpoint differential analysis between high- and low-risk groups was done. High-risk groups were more sensitive to drugs such as Savolitinib, Palbociclib, and Cytarabine and were more likely to benefit from immunotherapy. CONCLUSIONS The risk model constructed based on 13 CRGs has good prognostic value, which can assist LUAD patients in individualized treatment, and provides an important theoretical basis for the treatment and prognosis of LUAD.
Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/genetics* ; Early Detection of Cancer ; Lung Neoplasms/genetics* ; Prognosis ; Copper ; Apoptosis

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 investigate the application and effect of blended learning in epidemiology course.Methods The 83 nursing undergraduates in one class of grade 2016 were enrolled as experimental group and the 122 nursing undergraduates in another class were enrolled as control group.The undergraduates in the experimental group received blended learning in epidemiology course,and those in the control group received traditional teaching.An anonymous questionnaire survey was performed after the course ended,and the teaching effect was assessed based on the score of a non-standard answer examination and the degree of recognition of comprehensive ability cultivation.SPSS 18.0 was used for data analysis,and the t-test and the chi-square test were used for comparison of data between groups.Results The experimental group had a significantly higher total score than the control group [(85.55 ± 10.49) vs.(80.07 ± 9.47),t=3.897,P=0.000].Compared with the control group,the experimental group had a significantly higher degree of recognition of independent learning ability,cooperative ability,knowledge application,and problem-solving ability after blended learning (P＜0.05).Conclusion Blended learning can be applied in epidemiology course,and its teaching effect is accepted by students.

is one of the most well-known proto-oncogenes. Its gain-of-function mutations occur in approximately 30% of all human cancers. As the most frequently mutated isoform, KRAS is intensively studied in the past years. Despite its well-recognized importance in cancer malignancy, continuous efforts in the past three decades failed to develop approved therapies for mutant cancer. KRAS has thus long been considered to be undruggable. Encouragingly, recent studies have aroused renewed interest in the development of KRAS inhibitors either directly towards mutant KRAS or against the crucial steps required for KRAS activation. This review summarizes the most recent progress in the exploration of KRAS-targeted anticancer strategies and hopefully provides useful insights for the field.