OBJECTIVE To systematically compare mature experiences of comprehensive drug value assessment in typical countries/regions and to provide decision-making references for China to establish a scientific and standardized comprehensive drug value assessment system for medical-insured drugs. METHODS The literature analysis was used to systematically review drug value assessment frameworks in 11 representative countries/regions， namely the UK， Canada， Italy， Australia， Germany， France， South Korea， Japan， the United States， as well as Taiwan （China） and Hong Kong （China）. Comparisons were made across three dimensions： assessment entities， value dimension， and application of results. RESULTS &CONCLUSIONS In most countries/regions， independent technical assessment institutions have been established as part of the drug value evaluation system， with the involvement of multiple stakeholders （e.g.， the UK， Canada）. The mainstream drug value assessment frameworks have generally transcended the traditional core dimensions of safety， efficacy， and cost-effectiveness， exhibiting two major trends： the continuous expansion of assessment dimensions and stricter evidence requirements. Assessment outcomes are closely integrated with payment policies， ranging from providing technical advice for decision-making （e.g.， Italy， France） to directly determining reimbursement eligibility （e.g.， the UK， Germany）. The following recommendations are proposed for China： first， establish an evaluation mechanism featuring multi-stakeholder participation and separation of evaluation from decision-making. Second， develop a comprehensive evaluation framework integrating clinical， economic， patient， and societal value， emphasizing quantitative indicator exploration and real-world evidence application. Third， promote direct linkage between value-based tiering outcomes and medical insurance reimbursement decisions or access negotiations to balance patient benefits， fund sustainability， and industrial innovation.

Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

Objective: To explore the impact of adverse childhood experiences (ACEs) on health risk behaviors (HRBs) among college students and the mediating role of psychological symptoms, so as to provide a basis for developing intervention strategies. Methods: From March to April 2023, a convenience cluster sample of 1 801 students from 12 universities in Nanning, Liuzhou, Guilin, Wuzhou of Guangxi completed an online survey. A self designed questionnaire, Adverse Childhood Experiences-International Questionnaire (ACE-IQ) and Symptom Checklist-90 (SCL-90) were used for evaluation tools. Binary Logistic regression, structural equation modeling (SEM) and Bootstrap methods were used to analyze the associations and mediating effects. Results: Overall, 71.2% of college students experienced at least one type of ACE, with emotional neglect (40.3%) and emotional abuse ( 25.2 %) having the highest detection rates. The top three HRBs were unhealthy diet (77.8%), physical inactivity (54.1%), and smoking/alcohol use (18.5%). Logistic regression showed that poor family functioning, abuse, and extra familial violence were each associated with an increased risk of smoking/alcohol use ( OR =1.14, 1.11, 1.18) and deliberate self harm ( OR =1.26, 1.19,1.30) (all P <0.05). Experience of abuse increased the risk of high risk sexual behavior and family dysfunction increaded the risk of physical inactivity, respectively ( OR = 1.07 , 1.04, both P <0.05). Mediation analysis revealed that anxiety ( β =0.20) and depression ( β = 0.09 ) partially mediated the pathway from poor family functioning to deliberate self harm; paranoia ( β =0.02) partially mediated the pathway from abuse to high risk sexual behavior; and obsessive-compulsive symptoms ( β =0.26) and depression ( β =0.10) partially mediated the pathway from extra familial violence to deliberate self harm (all P <0.05). Conclusion Psychological symptoms play a mediating role in the association between ACEs and HRBs, and mental health interventions may reduce the risk of HRBs among college students.

OBJECTIVE To investigate the effects of osthole （OST） on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog （SHH） signaling pathway. METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group， OST low-dose， medium-dose and high-dose groups （OST-L group， OST-M group， OST-H group， 20， 30， 40 mg/kg OST）， high-dose OST+SHH inhibitor cyclopamide group （OST-H+cyclopamide group， 40 mg/kg OST+10 mg/kg cyclopamide）， with 12 rats in each group. Another 12 rats were selected as the control group. The wound healing of rats on 1， 7 and 14 days of administration was observed， and the wound healing rate of rats in each group was measured. The pathological changes and collagen deposition in rat wound tissue were observed； the levels of angiopoietin-1 （Ang-1） and basic fibroblast growth factor （bFGF） in wound tissue of rats were detected； the relative expressions of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor-2 （VEGFR-2） mRNA were also detected in wound tissue of rats； the protein expressions of VEGFA， VEGFR-2， SHH and glioma-associated oncogene homolog-1 （GLI1） were determined in wound tissue of rats. RESULTS Compared with Model group， the healing rate of skin wound， relative expression of collagen protein， the levels of Ang-1 and bFGF， the mRNA and protein expressions of VEGFA and VEGFR-2， and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups （P＜0.05）. The wound tissue underwent significant re- epithelialization， with reduced inflammatory cell infiltration and granulation tissue edema， and an increase in the number of new blood vessels. SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats. CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

Transcription factor PU.1, as a core member of the ETS family, plays a pivotal role in the multi-lineage differentiation of hematopoietic stem cells, particularly in the regulation of erythroid differentiation. PU.1 orchestrates the process of hematopoietic stem cell differentiation towards erythroid cells by modulating the transcription of lineage-determining factors and interacting with other key transcription factors in a fine-tuned manner. PU.1 plays an irreplaceable role in the development and function of red blood cells, with its abnormal expression closely related to the occurrence and progression of various blood diseases, including leukemia, myelodysplastic syndromes, and various types of anemia. This article comprehensively analyzes the functional roles and molecular mechanisms of PU.1 in various stages of erythroid differentiation, as well as its potential roles in related blood diseases. This review not only deepens our understanding of the mechanism by which PU.1 regulates erythroid differentiation, but also provides theoretical grounds for blood disease therapies based on PU.1.
Humans ; Proto-Oncogene Proteins/genetics* ; Trans-Activators/genetics* ; Cell Differentiation/physiology* ; Hematologic Diseases/physiopathology* ; Erythroid Cells/cytology* ; Animals ; Erythropoiesis/physiology*

The transcriptome sequencing based on Illumina Novaseq 6000 Platform was performed with the untreated seed embryo(DS), stratified seed embryo(SS), and germinated seed embryo(GS) of Zanthoxylum nitidum, aiming to explore the molecular mechanism regulating the seed dormancy and germination of Z. nitidum and uncover key differentially expressed genes(DEGs). A total of 61.41 Gb clean data was obtained, and 86 386 unigenes with an average length of 773.49 bp were assembled. A total of 29 290 DEGs were screened from three comparison groups(SS vs DS, GS vs SS, and GS vs DS), and these genes were annotated on 134 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways. KEGG enrichment analysis revealed that the plant hormone signal transduction pathway is the richest pathway, containing 226 DEGs. Among all DEGs, 894 transcription factors were identified, which were distributed across 34 transcription factor families. These transcription factors were also mainly concentrated in plant hormone signal transduction and mitogen-activated protein kinase(MAPK) signaling pathways. Further real-time quantitative polymerase chain reaction(RT-qPCR) validation of 12 DEGs showed that the transcriptome data is reliable. During the process of seed dormancy release and germination, a large number of DEGs involved in polysaccharide degradation, protein synthesis, lipid metabolism, and hormone signal transduction were expressed. These genes were involved in multiple metabolic pathways, forming a complex regulatory network for dormancy and germination. This study lays a solid foundation for analyzing the molecular mechanisms of seed dormancy and germination of Z. nitidum.
Zanthoxylum/metabolism* ; Plant Dormancy/genetics* ; Seeds/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Transcriptome ; Gene Expression Profiling ; Germination ; Transcription Factors/metabolism* ; Plant Growth Regulators/genetics* ; Signal Transduction

Objective To screen the anti-CD22-specific nanobodies to provide a basis for immunotherapy agents. Methods The naive phage nanobody library was constructed and its diversity was analyzed. Three rounds of biotinylated streptavidin liquid phase screening were performed by using biotinylated CD22 antigen as the target, and the sequence of nanobodies against CD22 were identified by ELISA and gene sequencing. Results The capacity of the constructed naive phage nanobody library was 3.89×10⁹ CFU/mL, and the insertion of effective fragments was higher than 85%. Based on this library, seven anti-human CD22 nanobodies were screened, and the amino acid sequence comparison results showed that the overall similarity was 70.34%, and all of them were hydrophilic proteins. The results of protein-protein complex docking prediction showed that the mimetic proteins of the five nanobody sequences could be paired and linked to CD22, and the main forces were hydrophobic interaction and hydrogen bonding. Conclusion This study provided a basis for the study of chimeric antigen receptor T cells targeting CD22, successfully constructed the natural phage nanobody library and obtaining five anti-CD22-specific nanobodies.
Camelus/immunology* ; Single-Domain Antibodies/chemistry* ; Peptide Library ; Humans ; Animals ; Sialic Acid Binding Ig-like Lectin 2/genetics* ; Amino Acid Sequence ; Molecular Docking Simulation

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*