OBJECTIVE To evaluate the cost-effectiveness of tafolecimab in patients with hypercholesterolemia， and provide support for optimizing management strategies for hypercholesterolemia and healthcare resource allocation. METHODS From the perspective of the Chinese healthcare system， an 11-state mutually exclusive Markov cohort model was developed to simulate disease progression and prognosis in the target population. The model cycle was set to one year， with a 30-year time horizon. Transition probabilities between health states were derived from the CREDIT series of clinical trials， while health utility values and medical cost parameters were sourced from the statistical yearbook and published literature. Quality-adjusted life years （QALYs） were used as the measure of health outcomes. Cost-effectiveness analysis was employed to calculate the incremental cost- effectiveness ratio （ICER） for three dosing regimens of tafolecimab [150 mg every 2 weeks （q2w）， 450 mg every 4 weeks （q4w）， and 600 mg every 6 weeks （q6w）] in combination with statins compared with control therapy （statins）. Using 1-3 times the per capita gross domestic product （GDP） of China in 2024 as willingness-to-pay threshold（WTP）， with a discount rate of 5%. Model robustness was assessed through one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis. RESULTS The 150 mg q2w regimen of tafolecimab yielded an ICER of 235 827.73 yuan/QALY， which was below the WTP （287 100 yuan/ QALY）， indicating that the regimen was cost-effective. In contrast， the ICERs for the 450 mg q4w and 600 mg q6w regimens were 329 498.24 and 318 630.51 yuan/QALY， respec-tively， both exceeding the WTP and thus not cost-effective.One-way sensitivity analysis identified the discount rate as a key influencing factor. Probabilistic sensitivity analysis showed that under the WTP set in this study， the probabilities of cost-effectiveness for the 450 mg q4w and 600 mg q6w regimens were 15.3% and 22.4%， respectively， while the 150 mg q2w regimen had an 85.2% probability of being cost-effective. The situational analysis revealed that， over a simulated time horizon of 5 to 30 years， the ICER of tafolecimab was progressively reduced compared with the control regimen. When the price of tafolecimab was lowered by more than 20%， all three dosing regimens were demonstrated to be cost-effective.CONCLUSIONS Under the current Chinese healthcare system， compared with statin monotherapy， tafolecimab （150 mg q2w） combination improves health outcomes in patients with hypercholesterolemia， and is cost-effective given the current WTP.

•A strategy for in situ metabolically synthesized active drug-based probes was proposed.•The potential purgative targets of SA were successfully hooked and identified.•The work provided a new insight for studying the direct targets of unstable active drugs.

Thyroid-associated ophthalmopathy(TAO)is a progressive eye disease characterized by immune-mediated inflammation of the extraocular muscles and orbital connective tissue.TAO tends to have complex and diverse symptoms and signs,with the features of diversity and concealment,which seriously affect the quality of life of patients.The pathogenesis of TAO is closely associated with thyroid autoimmunity.This article reviews the pathogenesis,clinical features,and treatment of TAO.

BACKGROUND:In recent years,functional near-infrared spectroscopy has shown extensive research significance and application potential in the fields of cognitive neuroscience,clinical medicine,and engineering technology due to its portability,low cost,non-invasiveness,and high temporal resolution.OBJECTIVE:To analyze the research progress,hot issues,and frontier trends of functional near-infrared spectroscopy in the past 10 years.METHODS:Web of Science database was searched for articles related to functional near-infrared spectroscopy published from January 1,2013 to November 30,2023.CiteSpace and VOSviewer software was used to conduct a visual analysis of publication statistics,journals,countries,institutions,authors,and keywords.RESULTS AND CONCLUSION:This article included a total of 2 714 documents,showing an overall upward trend in the volume of literature concerning functional near-infrared spectroscopy over the past decade.The 2 714 documents selected for this article were authored by 9 171 researchers from 2 400 institutions across 68 countries in 495 kinds of journals.The United States and University College London are representative countries and institutions,while Ehlis and Fallgatter are two influential authors in this research field.The journal NeuroImage ranks first with the highest citation rate.Functional near-infrared spectroscopy research primarily comes from University College London in the UK,Beijing Normal University in China,and the University of Tübingen in Germany.The keyword co-occurrence network map generated using VOSviewer 1.6.20 reveals six research clusters.By analyzing the specific keywords of each cluster,we further understand the research hotspots in this field.The burst analysis of keywords uncovers the research frontiers and development trends,providing important guidance for future research directions of functional near-infrared spectroscopy.

BACKGROUND:In recent years,functional near-infrared spectroscopy has shown extensive research significance and application potential in the fields of cognitive neuroscience,clinical medicine,and engineering technology due to its portability,low cost,non-invasiveness,and high temporal resolution.OBJECTIVE:To analyze the research progress,hot issues,and frontier trends of functional near-infrared spectroscopy in the past 10 years.METHODS:Web of Science database was searched for articles related to functional near-infrared spectroscopy published from January 1,2013 to November 30,2023.CiteSpace and VOSviewer software was used to conduct a visual analysis of publication statistics,journals,countries,institutions,authors,and keywords.RESULTS AND CONCLUSION:This article included a total of 2 714 documents,showing an overall upward trend in the volume of literature concerning functional near-infrared spectroscopy over the past decade.The 2 714 documents selected for this article were authored by 9 171 researchers from 2 400 institutions across 68 countries in 495 kinds of journals.The United States and University College London are representative countries and institutions,while Ehlis and Fallgatter are two influential authors in this research field.The journal NeuroImage ranks first with the highest citation rate.Functional near-infrared spectroscopy research primarily comes from University College London in the UK,Beijing Normal University in China,and the University of Tübingen in Germany.The keyword co-occurrence network map generated using VOSviewer 1.6.20 reveals six research clusters.By analyzing the specific keywords of each cluster,we further understand the research hotspots in this field.The burst analysis of keywords uncovers the research frontiers and development trends,providing important guidance for future research directions of functional near-infrared spectroscopy.

This paper applied gas chromatography-mass spectrometry (GC-MS), network pharmacology and nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) metabolomics techniques to study the material basis and mechanism of action of Ning Shen Essential Oil in anti-insomnia. The main volatile components of Ning Shen Essential Oil were analyzed by gas chromatography-mass spectrometry (GC-MS), and the insomnia-related targets were predicted using the Traditional Chinese Medicine Systematic Pharmacology Database and Analytical Platform (TCMSP) and the databases of GeneCards, OMIM and Drugbank. The insomnia model of rats was replicated by intraperitoneal injection of 4-chloro-DL-phenylalanine (PCPA). Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDUTCM20221025010). The modulating effect of Compound Ning Shen Essential Oil on anxiety behavior of rats was evaluated by behavioral related indexes. The serum levels of corticotropin-releasing hormone (CRH), adrenotropic corticotropic hormone (ACTH) and melatonin (MT) were measured by enzyme-linked immunoassay (ELISA). Rat serum and hippocampus were taken for nuclear magnetic resonance (¹H NMR) metabolomics to detect the changes of endogenous metabolites in rat serum hippocampus, to designate the differential metabolites and to construct metabolic pathways. The results showed that the exercise distance in the open field experiment and the number of times and time to enter the open arm in the elevated cross maze experiment of the rats in the model group were significantly reduced (P < 0.05, P < 0.01). The behavioral indexes of rats improved to different degrees after the administration of Ning Shen Essential Oil. The serum CRH and ACTH levels of rats in the model group increased significantly (P < 0.05, P < 0.01), and the MT level decreased significantly (P < 0.01); After the intervention, serum CRH and ACTH levels were reduced to different degrees, and MT levels could be regressed. ¹H NMR metabolomics screened 10 potential biomarkers related to insomnia, which involved in 6 potential metabolic pathways. A total of 35 components of Ning Shen Essential Oil were detected by GC-MS, the main component targets of Ning Shen Essential Oil and insomnia disease targets were intersected, a total of 172 intersecting genes were screened, and 26 core targets were identified. The study demonstrated that Ning Shen Essential Oil had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of the hypothalamic-pituitary-adrenal axis (HPA) related hormones and metabolism of amino acids, lipids and choline.

【Objective】 To investigate the mechanisms of chelerythrine on the treatment of breast cancer based on network pharmacology and molecular docking. 【Methods】 The targets corresponding to chelerythrine and breast cancer were obtained from Mala Cards and Swiss Target Prediction databases. Chelerythrine-related and breast cancer-related targets were found and then combined to get an intersection, which represented potential anti-breast cancer targets of chelerythrine. A protein-protein interaction (PPI) network was constructed from the STRING database and key genes were screened using the topological analysis. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of targets were conducted using metascape database. The relationship between the expressions of key target genes and the survival curve was analyzed using the Kaplan-Meier Plotter database. Molecular docking analysis was performed by AutoDock Vina to verify whether chelerythrine has a definite affinity with key targets. 【Results】 A total of 37 potential targets were obtained in chelerythrine against breast cancer. The result of the topology analysis included 8 key targets. The GO enrichment analysis included 317 GO items. The KEGG pathway analysis included 80 pathways, which were closely related to the PI3K/AKT signaling pathway, the ErbB signaling pathway, VEGF signaling pathway, and others. The results of the survival curve analysis showed that the expression levels of CHEK1, PIK3CA, mTOR and PTGS2 genes were related to the survival time of breast cancer patients. The results of molecular docking proved that the combined activity of chelerythrine with key targets was excellent. 【Conclusion】 Chelerythrine may play an anti-breast cancer role via the PI3K/AKT signaling pathway and has the potential to be developed into a clinical drug for breast cancer.

Objective: To understand knowledge, attitude and behavior toward Coronavirus disease 2019 (COVID 19) among middle school students in Wuhan, in the phase of normalized control and prevention of COVID 19, so as to provide evidence for further health education. Methods: In January 2021, cluster random sampling method was used to select one middle school from Hongshan and Dongxihu District, as well as Donghu high tech zone, respectively. By using the "questionnaire star" platform, questionnaire QR code were sent to students through QQ or wechat by schools. A total of 4 531 middle school students were investigated. Results: Preventive knowledge and behavior rate was 71.5% (3 238) and 56.0% (2 537), respectively. Preventive behaviors towards COVD 19 was reported in 56.0% (2 537) of participants. Students with parents as health care workers reported higher preventive behaviors(P<0.05).Girls had a higher rate of possession of health knowledge for prevention and control than boys. Compared with "essentially no concern about the epidemic","students with less concern about the epidemic" and "those with similar concern as 2020" were more likely to have higher awareness of health knowledge for prevention and control. Compared with the first-year junior middle school students, high school students were less likely to have the rates of knowledge for prevention and control health [OR(95%CI）=1.24（1.09-1.43）,2.56(1.54-4.25),3.30(1.99-5.48),0.49(0.39-0.62),0.45(0.36-0.57),0.63(0.46-0.88)].In terms of health behavior rate, middle school students whose mothers are undergraduates, whose incomes were more than 8 001-15 000 and 15 000 yuan, "whose attention to epidemic situation has declined" , "whose attention is the same as that in 2020" , "who did not plan to study medicine before" , "who are determined to study medicine, and who plan to study medicine more firmly after epidemic situation " were more likely to have health behavior,[OR(95%CI)=1.29(1.04-1.60),1.39（1.07-1.82）,1.74(1.32-2.29),1.77(1.06-2.96),3.47(2.08-5.81)] ,The grade-2 high middle school students had lower probability of preventing and controlling health behaviors [OR(95%CI)=0.74(0.60-0.90)](P<0.05). Preventive knowledge and behaviors towards COVID 19 are mainly from school education, communication with parents and mobile learning. Conclusion Preventive knowledge and behaviors towards COVID 19 among Wuhan middle school students are needed to be improved and targeted health education should be implemented accordingly.

Objective:To explore the relationship between the expression level of micro RNA-133a(miR-133a) and the indexes of heart failure in patients with ischemic heart failure and its clinical application value.Methods:From January 2018 to September 2019, the clinical data of 80 patients diagnosed as ischemic heart failure in Shenyang Fourth People′s Hospital were analyzed prospectively.According to the classification of New York Heart Association(NYHA), 20 cases were divided into NYHA class Ⅰ group, class Ⅱ group, class Ⅲ group and class Ⅳ group, and 20 healthy people in the same period were selected as the healthy control group.The concentration of brain natriuretic peptide (BNP) in peripheral blood was detected by automatic immune analyzer, the indexes of cardiac function were detected by echocardiography, the expression of miR-133a in serum was detected by qRT-PCR, the difference of expression concentration of miR-133a in different functional grades was compared, and the correlation between the concentration of miR-133a and BNP and the indexes of echocardiography was analyzed.Results:The expression of miR-133a in healthy control group(0.167±0.024), NYHA Ⅰ group(0.289±0.012), NYHA Ⅱ group (0.415±0.034), NYHA Ⅲ group(0.981±0.217) and NYHA Ⅳ group(1.238±0.249) was statistically significant( F=106.4, P<0.001). Pearson correlation analysis showed that miR-133a was positively correlated with BNP in NYHAⅡ, Ⅲ and Ⅳ grade( r=0.815, 95% CI: 0.582-0.924, P<0.001; r=0.465, 95% CI: 0.029-0.753, P<0.05; r=0.749, 95% CI: 0.459-0.895, P<0.001). MiR-133 was negatively correlated with EF( r=-0.811, 95% CI: -0.875--0.719, P<0.001), positively correlated with LVPW, LV and EDV( r=0.331, 95% CI: 0.120-0.513, P<0.01; r=0.845, 95% CI: 0.764-0.896, P<0.001; r=0.705, 95% CI: 0.572-0.803, P<0.001). Conclusion:The expression of miR-133a in patients with ischemic heart failure is increased, which is related to the index of cardiac dysfunction, and has certain diagnostic and prognostic value.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.