Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

ObjectiveTo elucidate the expression patterns of CYHR1 in colorectal cancer （CRC） and its regulatory role in tumour cell proliferation and metastasis-related phenotypes. MethodsExpression differences of CYHR1 between colorectal cancer tissues and adjacent normal tissues were analyzed using data from The Cancer Genome Atlas （TCGA） database， and the association between CYHR1 expression and patient survival was evaluated. A CRC cell model with CYHR1 overexpression was established， and changes in the expression of related molecules were verified by quantitative real-time PCR （qRT-PCR）. Cell proliferation and metastatic potential were assessed using MTT assays， colony formation assays， and Transwell migration and invasion assays to evaluate the effects of CYHR1 and MALAT1 on CRC cell proliferation and migration/invasion， including combined intervention experiments. ResultsDatabase analysis revealed that CYHR1 is significantly overexpressed in CRC tissues， and that this overexpression is significantly associated with poorer overall survival. Compared with normal control cells， mRNA expression levels of CYHR1 were markedly elevated in CRC cell lines （HCT116， RKO， etc.） （P=0.002； P=0.006）. Functional experiments demonstrated that CYHR1 overexpression significantly promoted the proliferation （P＜0.001）， colony formation （P＜0.001）， migration （P=0.002） and invasive capacity （P=0.002） of HCT116 cells； whereas knockdown of either CYHR1 or MALAT1 inhibited CRC cell proliferation and reduced their migration （P=0.006） and invasive capacity （P=0.006）. In the context of CYHR1 overexpression， combined knockdown of MALAT1 partially reversed the promotional effect of CYHR1 on CRC cell proliferation， migration and invasion （P＜0.001； P=0.001）. Mechanistic studies further revealed that CYHR1 overexpression upregulates MALAT1 mRNA expression levels （P＜0.001）， whilst CYHR1 knockdown leads to downregulation of MALAT1 expression （P＜0.001）； MALAT1 knockdown likewise downregulates CYHR1 expression， suggesting a mutually reinforcing positive regulatory relationship between the two. Furthermore， CYHR1 can activate the IL-6/STAT3 signalling axis， whilst knockdown of IL-6 or STAT3 inhibited the upregulation of MALAT1 expression by CYHR1 （P=0.031； P=0.006）. ConclusionCYHR1 is abnormally overexpressed in colorectal cancer and is closely associated with poor prognosis. CYHR1 may promote the proliferation， migration， and invasion of colorectal cancer （CRC） cells by activating the IL-6/STAT3/MALAT1 axis.

Recently, the World Health Organization (WHO) R&D Blueprint for Epidemics released the 2024 priority pathogen list. Over 200 scientists around the world evaluated the evidences of transmissions, virulences of 1 652 pathogens and the availability of medical countermeasures in two years. Finally, 33 pathogens that could potentially cause the next pandemic were included in the priority pathogen list. This list introduces the scientific framework of "family-priority pathogen-prototype pathogen", emphasizing the importance of studying entire pathogen family rather than specific pathogen. The list can be used to guide and coordinate the research and development of medical countermeasures, including vaccine, blood product, antibody, antimicrobial or antiviral drug, diagnostic test, and personal protective equipment, thereby improving the global rapid response to unknown infectious disease threats. This article summarizes the scientific background and main contents of the WHO priority pathogen list and the enlightenment for pandemic preparedness in the development of medical countermeasures in China to provide reference for the disease prevention and control in China.

Objective:To analyze the burden and trends of noncommunicable chronic disease(NCD) attributable to metabolic factors in China from 1990 to 2021.Methods:Data from the Global Burden of Diseases(GBD) 2021 database were utilized to describe changes in mortality and disability-adjusted life years(DALYs) of NCD in China from 1990 to 2021. Stratified analyses were conducted by age, sex, sociodemographic index(SDI), and related risk factors. Statistical analyses and predictions were conducted using the age-period-cohort model and the Nordpred model.Results:In 2021, the age-standardized mortality rate and age-standardized DALYs rate of NCD attributable to metabolic factors in China were 227.56 per 100 000 and 4 829.39 per 100 000, respectively. Their average annual percentage changes were -0.76%( P<0.001) and -0.77%( P<0.001). Overall, the burden decreased progressively with higher SDI levels. Analysis using the age-period-cohort model indicated reduced birth cohort and period effects for metabolic factor-attributable NCD, while age effects rose significantly. The minimum relative risk( RR) value was observed in the 15-19 age group( RR=0.01), and the maximum RR value occurred in the 95-99 age group( RR=996.86). The overall rising mortality trend indicated that age effects are the predominant driver at present. Projections estimate that by 2046, deaths from metabolic factor-attributable NCD in China will reach 8 189 563, with an age-standardized mortality rate of 236.95 per 100 000. Conclusions:China continues to face a substantial burden of NCD linked to metabolic factors, with older adults, males, and individuals with hypertension, diabetes, and prediabetes identified as key populations requiring targeted interventions.

Objective To investigate immune characteristics of non-responsive macrolide-resistant Mycoplasma pneumoniae pneumonia(MPP)and macrolide-susceptible Mycoplasma pneumoniae pneumonia(MSMPP),and the clinical significance of serum Mycoplasma pneumonia DNA load and NK cell count in the course of disease were evaluated.Methods A total of 120 MPP patients hospitalized at Hangzhou Children's Hospital from August 2022 to August 2023 were selected as subjects,they were divided into MSMPP group(n=36)and macrolide-unresponsive MPP(MUMPP)group(n=84)based on whether they were effective within 72h of using macrolide antibiotics.Compare various indicators levels in the first 6 hours after admission between two groups.Multivariate analysis of variance was used for independent risk factors and receiver operating characteristic(ROC)curve analysis was used for diagnostic performance.Results CD4+T,NK,and lgMP-DNA were independent risk factors for predicting whether MPP patients were MUMPP.The area under ROC curve for CD4+T,NK,lgMP-DNA,NK+CD4+T,lgMP-DNA+CD4+T,and lgMP-DNA+NK were 0.684,0.753,0.728,0.803,0.779,and 0.813,respectively.Conclusion Decreased peripheral blood NK cells and high MP-DNA load are important clinical features of drug-resistant Mycoplasma pneumonia,and combined detection can provide important clinical value for subsequent diagnosis and treatment.

Objective To investigate the status of management of iodinated contrast media(ICM)extravasation in Henan Province,as well as nurses' knowledge and influencing factors,in order to provide a basis for optimizing management strategies.Methods A self-designed questionnaire was applied,employing convenience sampling,to survey nursing administrators and nurses in the radiology departments of 55 tertiary hospitals across 16 regions of Henan Province,from December 2024 to January 2025.Multiple linear regression analysis was conducted to explore the factors influencing nurses' knowledge.Results A total of 55 nursing administrators and 64 nurses participated,with a valid questionnaire response rate of 100％.The survey results reveal that only 5.45％of radiology depart-ments utilized high-pressure central venous catheters,and 32.73％employed vascular visualization techniques.When setting the high-pressure injection speed for ICM,only 54.55％of radiology departments required an assessment of the type and model of intravenous access.Additionally,only 9.09％of radiology departments mandated an observa-tion for 2 to 4 hours following ICM extravasation.Furthermore,only 50.91％of radiology departments had estab-lished an information system for ICM use.The nurses' knowledge score regarding the prevention and management of ICM extravasation was(90.00±17.59),influenced by years of experience in radiology and professional titles(P＜0.05).Conclusion The prevention and management measures for ICM in radiology departments in Henan Province need further improvement.Nursing administrators should optimize management strategies,improve relevant training systems,and continuously enhance nurses' knowledge and practical abilities.

BACKGROUND:Multiple observational studies have suggested a potential association between telomere length and musculoskeletal diseases.However,the underlying mechanisms remain unclear. OBJECTIVE:To investigate the genetic causal relationship between telomere length and musculoskeletal diseases using two-sample Mendelian randomization analysis. METHODS:Genome-wide association study summary data of telomere length were obtained from the UK Biobank.Genome-wide association study summary data of 10 common musculoskeletal diseases(osteonecrosis,osteomyelitis,osteoporosis,rheumatoid arthritis,low back pain,spinal stenosis,gout,scapulohumeral periarthritis,ankylosing spondylitis and deep venous thrombosis of lower limbs)were obtained from the FinnGen consortium.Inverse variance weighting,Mendelian randomization-Egger and weighted median methods were used to evaluate the causal relationship between telomere length and 10 musculoskeletal diseases.Inverse variance weighting was the primary Mendelian randomization analysis method,and sensitivity analysis was performed to explore the robustness of the results. RESULTS AND CONCLUSION:(1)Inverse variance-weighted results indicated a negative causal relationship between genetically predicted telomere length and rheumatoid arthritis(odds ratio=0.78,95%confidence interval:0.64-0.95,P=0.015)and osteonecrosis(odds ratio=0.56,95%confidence interval:0.36-0.90,P=0.016).No causal relationship was found between telomere length and the other eight musculoskeletal diseases(all P>0.05).(2)Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(all P>0.05).(3)This Mendelian randomized study supports that telomere length has protective effects against rheumatoid arthritis and osteonecrosis.However,more basic and clinical research will be needed to support our findings in the future.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Objective To investigate the role of low-density lipoprotein receptor-related protein 1(LRP1),the key gene of epithelial-mesenchymal transition,in silicosis fibrosis progression,and to preliminarily explore its regulatory mechanisms.Methods Gene set variation analysis(GSVA)was employed on GSE70866 and GSE49072 from Gene Expression Omnibus(GEO)database to assess the activity of the epithelial-mesenchymal transition gene set.LRP1 was screened via Venn diagram intersection.A multivariable Cox proportional hazards regression model(adjusted for age and sex)was constructed to validate the independent prognostic value of LRP1.Patients were grouped based on LRP1 expression,and its function mechanisms in pulmonary were explored through differential analysis,enrichment analysis,correlation analysis,and immune infiltration analysis.The silicosis model was established by a single intratracheal injection of 10 mg SiO2 suspension in C57BL/6J mice,with 100 μL of 0.9%saline administered as the control group.Pathological changes were assessed by hematoxylin-eosin staining in lung tissues.EMT model was induced in A549 cells by TGF-β1 at varying time points.LRP1 mRNA levels were measured by qPCR in lung tissues and A549 cells of TGF-β1-induced EMT model.Protein expression of LRP1,E-Cadherin,α-SMA,collagen I,p-PI3K,PI3K,p-mTOR and mTOR were detected by Western blot in lung tissues and A549 cells.Results The epithelial-mesenchymal transition gene set score was significantly higher in patients than in healthy control,with high-score patients showing reduced survival time(P<0.01).Bioinformatics analysis revealed that LRP1 primarily acts through the mTOR signaling pathway.Immune infiltration analysis demonstrated enhanced activities of activated dendritic cells,effector memory CD4+T cells,and Th17/Th2 cells in LRP1 high-expression patients,suggesting its potential regulatory role in adaptive immune responses.Histopathological observation confirmed obvious silica nodule formation in lung tissues of mouse silicosis model.RT-qPCR and Western blot analyses showed that the expression levels of LRP1 mRNA and protein were significantly downregulated in both silicosis mouse lungs and A549 cells(P<0.05).E-cadherin protein expression was downregulated,while α-SMA and collagen I expression were upregulated(P<0.05).Furthermore,the phosphorylation ratios of PI3K(p-PI3K/PI3K)and mTOR(p-mTOR/mTOR)were significantly increased(P<0.05).Conclusion LRP1 downregulation may activate the PI3K/mTOR signaling pathway,promoting the EMT process and fibrosis in silicosis.Targeting LRP1 regulation might become a new therapeutic strategy for silicosis.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.