Traditional treatment modalities for thalassemia include regular blood transfusions and allogenic hematopoietic stem cell transplantation(allo-HSCT).In recent years,autologous transplantation of gene-modified hematopoietic stem cells has emerged as a new curative strategy for transfusion-dependent thalassemia(TDT),which has the potential to replace conventional treatments,and provide lifelong benefits for patients.There are two existing technical approaches for gene therapy of β-thalassemia:gene addition,which involves transducing exogenous β-globin genes into hematopoietic stem cells(HSCs),and gene editing,which utilizes CRISPR-Cas9 or other editing systems to re-activate the expression of γ-globin gene.This article summarizes the marketed products and research progress in clinical trials,aiming to analyze the respective advantages and limitations of these two approaches,and discusses the effectiveness and safety of current gene therapies for β-thalassemia,as well as the future directions for associated technologies,including ex vivo HSC expansion with maintenance of stemness and vector-mediated in vivo gene modification.In terms of clinical translational medicine,this article provides in-depth insights into promising solutions for contemporary challenges confronted in clinical trials,including process development challenges,clinical trial conduct,regulatory approval processes,commercialization and payment systems.

OBJECTIVE T o verify and compare the values of the different risk assessment scores in prediction of in-fections in the ST elevation myocardial infarction(STEMI)patients undergoing percutaneous coronary interven-tion(PCI)therapy.METHODS A total of 226 STEMI patients who received PCI in The Second Medical Center of Chinese PLA General Hospital from Aug.2019 to Jul.2024 were recruited as the research subjects.The efficien-cies of the six types of risk assessment scores,including age,serum creatinine,or glomerular filtration rate/ejec-tion fraction(ACEF/AGEF)score,Canadian acute coronary syndrome(C ACS)score,embolism risk score 2(CHADS2)score,global register of acute coronary events(GRACE)score and for contrast induced nephropathy(Mehran)scorein prediction of infections and major adverse clinical events(M ACE)were analyzed.RESULTS All of the risk assessment scores showed remarkable discriminating capability in prediction of infections(AUC:0 746 to 0 791)except CHADS2 score[the area under the curve(AUC)=0.682;95％CI=0.652 to 0.712)].All of the risk assessment scores showed the excellent performance in calibration of infections except CACS risk assess-ment score(calibration slope=0.77;95％CI=0.18 to 1.35).The risk assessment scores also showed tremen-dous capability in discriminating MACE during the hospital stay except CHADS2 score,with the AUC ranging be-tween 0.700 and 0.786.All of the six types of risk assessment scores showed the most excellent performance in calibration of MACE during the hospital stay.CONCLUSION ACEF,AGEF,CACS,GRACE and Mehran scores show remarkable discriminating capability and calibration in prediction of infections and MACE.

Traditional treatment modalities for thalassemia include regular blood transfusions and allogenic hematopoietic stem cell transplantation(allo-HSCT).In recent years,autologous transplantation of gene-modified hematopoietic stem cells has emerged as a new curative strategy for transfusion-dependent thalassemia(TDT),which has the potential to replace conventional treatments,and provide lifelong benefits for patients.There are two existing technical approaches for gene therapy of β-thalassemia:gene addition,which involves transducing exogenous β-globin genes into hematopoietic stem cells(HSCs),and gene editing,which utilizes CRISPR-Cas9 or other editing systems to re-activate the expression of γ-globin gene.This article summarizes the marketed products and research progress in clinical trials,aiming to analyze the respective advantages and limitations of these two approaches,and discusses the effectiveness and safety of current gene therapies for β-thalassemia,as well as the future directions for associated technologies,including ex vivo HSC expansion with maintenance of stemness and vector-mediated in vivo gene modification.In terms of clinical translational medicine,this article provides in-depth insights into promising solutions for contemporary challenges confronted in clinical trials,including process development challenges,clinical trial conduct,regulatory approval processes,commercialization and payment systems.

OBJECTIVE T o verify and compare the values of the different risk assessment scores in prediction of in-fections in the ST elevation myocardial infarction(STEMI)patients undergoing percutaneous coronary interven-tion(PCI)therapy.METHODS A total of 226 STEMI patients who received PCI in The Second Medical Center of Chinese PLA General Hospital from Aug.2019 to Jul.2024 were recruited as the research subjects.The efficien-cies of the six types of risk assessment scores,including age,serum creatinine,or glomerular filtration rate/ejec-tion fraction(ACEF/AGEF)score,Canadian acute coronary syndrome(C ACS)score,embolism risk score 2(CHADS2)score,global register of acute coronary events(GRACE)score and for contrast induced nephropathy(Mehran)scorein prediction of infections and major adverse clinical events(M ACE)were analyzed.RESULTS All of the risk assessment scores showed remarkable discriminating capability in prediction of infections(AUC:0 746 to 0 791)except CHADS2 score[the area under the curve(AUC)=0.682;95％CI=0.652 to 0.712)].All of the risk assessment scores showed the excellent performance in calibration of infections except CACS risk assess-ment score(calibration slope=0.77;95％CI=0.18 to 1.35).The risk assessment scores also showed tremen-dous capability in discriminating MACE during the hospital stay except CHADS2 score,with the AUC ranging be-tween 0.700 and 0.786.All of the six types of risk assessment scores showed the most excellent performance in calibration of MACE during the hospital stay.CONCLUSION ACEF,AGEF,CACS,GRACE and Mehran scores show remarkable discriminating capability and calibration in prediction of infections and MACE.

Objective:To study the effects and the related molecular mechanisms of miR-148a-3p on the proliferation,invasion and migration of salivary adenoid cystic carcinoma SACC-LM cells.Methods:miR-148a-3p mimics and inhibitors,siRNA targeting EG-FR and their corresponding controls were transfected into SACC-LM cells.Bioinformatics was used to predict the potential target genes of miR-148a-3p.EGFR and miR-148a-3p mRNA expression levels were examined by qRT-PCR and the protein levels of EG-FR were detected by Western blotting.CCK-8,scratch,and Transwell assays were used to study the proliferation,migration,and invasion of SACC-LM cells,respectively.The direct targeting relationship between miR-148a-3p and EGFR was examined by using the double luciferase reporter gene assay.Statistical analysis of the data was performed by SPSS 22.0 software.Results:Overexpres-sion or inhibition of miR-148a-3p significantly inhibited or promoted the proliferation,invasion and metastasis of SACC-LM cells re-spectively(P＜0.05).Bioinformatics and double luciferase assay showed that miR-148a-3p directly targeted and regulated the expres-sion of EGFR(P＜0.001).Downregulation of EGFR inhibited the proliferation,migration and invasion of SACC-LM cells(P＜0.05)and partially reversed the promoting effect of miR-148a-3p inhibition(P＜0.05).Conclusion:The downregulation of miR-148a-3p leads to the abnormally high expression of its target gene EGFR,and promotes the proliferation,invasion,and migration of salivary adenoid cystic carcinoma cells.

Objective:To investigate the effects of methyltransferases like 3(METTL3)mediated m6A modification of double homology cassette A pseudogene8(DUXAP8)on the proliferation,migration and invasion of salivary adenoid cystic carcinoma SACC-LM cells and its potential molecular mechanisms.Methods:Whole-transcriptome sequencing showed that DUXAP8 was highly ex-pressed in SACC than in para-cancerous tissues(P＜0.05).The m6A modification sites on DUXAP8 were predicted using the SRAMP website,and the mRNA and protein expression of m6A-modified genes and the genes associated with the epithelial-mesen-chymal transition(EMT)was measured by qRT-PCR and Western blot,respectively.METTL3 and DUXAP8 was knocked down or overexpressed in SACC-LM cells,and the proliferation,migration,and invasion of the cells were assessed by CCK-8,scratch and Transwell assays.The correlation between METTL3 and DUXAP8 was evaluated using MeRIP-qPCR.Results:The expression of DUXAP8 in SACC tumor was higher than that in para-cancerous tissues(P＜0.05).Knockdown of DUXAP8 reduced proliferation,migration and invasion of SACC-LM cells,as well as the expression of EMT-related genes(P＜0.05).Multiple m6A modification sites of high confidence were found on DUXAP8.METTL3 was highly expressed in tumor tissues,more than other related genes(P＜0.05)and enzyme-encoding genes in SACC-LM cells(P＜0.05).METTL3 was found to function as a methyltransferase to regulate the expression of DUX-AP8,and downregulation of METTL3 inhibited prolifera-tion,migration and invasion of SACC-LM cells and partially reversed the promotion of these activities induced by DUX-AP8 overexpression(P＜0.05).Conclusion:METTL3-me-diated m6A modification upregulated DUXAP8 expression,which promotes the proliferation,migration and invasion of SACC cells.

Objective To investigate the relationship between disrupted corticospinal tract (CST) and motor recovery after stroke by using diffusion tensor tracking (DTT). Methods From March, 2012 to June, 2013, 15 chronic stroke patients with left subcortical lesions and 15 age- and sex- matched healthy subjects were performed diffusion tensor imaging (DTI) examination. The CST was tracked by DTT technique, and the damaged values of the CST caused by the stroke lesions were quantified using a CST template generated from healthy controls. Furthermore, the correlations of the damaged values of the CST with Fugl-Meyer Assessment (FMA) were performed. Results The range of the damaged values of CST in stroke patients was 0.00% to 29.6%. There were very strong negative correlation between the damaged values of the CST and FMA scores (the wrist, r = -0.660; hand, r = -0.813; wrist plus hand, r = -0.795, respectively, P < 0.01). It also showed strong negative correlation between the damaged values of the CST and FMA scores (upper limb, r = -0.614; upper limb plus lower limb, r = -0.563, respectively, P < 0.05). Whereas, there was no correlation between the damaged values of the CST and FMA scores of lower limb (r = -0.270, P = 0.331). In addition, the lesion volumes of stroke and FMA scores were not significantly correlated (P > 0.05). Conclusion The severity of motor deficit after stroke was closely related to the overlap of lesions with CST. The damaged values of the CST based on DTT may be used as a potential biomarker to assess motor impairments of upper limbs, especially hand and wrist in stroke patients.

Objective To analysis the change of hip joint in healthy infants by ultrasound,and establish the normal reference value of the developmental dysplasia of the hip(DDH). Methods A total of 8 000 healthy infants from 0 to 24 weeks were collected from the Multi-center study of 10 children′s medical centers. Among them,3 855 infants(2 065 females and 1 790 males) with complete data and follow-up were included in this study. All subjects were divided into 6 groups ( ＜4,4～7,8～11,12～15,16～19 and≥20 weeks group). α angle,femoral head length and width,femoral head coverage ratio by acetabulum ( FHC) were measured in the coronal view on the neutral position;distance from pubis to femoral head ( P-H) and distance from ischium to femoral head ( I-H ) were measured in the transverse view on neutral position;distance from femoral head topubis ( H-P) was measured in the posterolateraltransverse view on the flexion position. The results of each group changes with age were analysised. Results ① The α angle of healthy infants from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05),but there was no significant difference between 16～19 and ≥20 weeks group( P ＞0.05). ②The femoral head length and width of all age groups were increased with age,the difference among all the groups was statistically significant( all P ＜0.05). ③ FHC from 0 to 20 weeks were increased with age,the difference among the groups were statistically significant( P ＜0.05) except between 16～19 and ≥20 weeks group( P ＞0.05). ④ The P-H and I-H in all age groups showed no statistically significant ( all P＞0.05). ⑤The H-P of all age groups were increased with age,the difference between the groups were statistically significant(all P ＜0.05).Conclusions The development of hip joints have the certain regular developmental pattern in healthy infants less than 5 months of birth and are relatively constant after birth more than 5 months. The ultrasound normal reference value of the hip joints can be used for the early diagnosis of the DDH.

Objective To determine the reproductive physiology and blood physiological and biochemical characteristics of SPF Yorkshire and Landrace swine.Methods Ten reproductive physiology parameters,19 blood physiological parameters and 18 blood biochemical parameters in SPF Yorkshire and Landrace swine were measured using conventional methods and the differences between population,between age groups and between both sexes were analyzed.Results There were no significant differences(P>0.05) in reproductive physiology parameters and most blood physiological and biochemical parameters of the SPF Yorkshire and Landrace swine.A few of parameters,such as blood physiological indices GRAN,HGB,RDW,PLT,PCT,and blood biochemical indices ALKP,CHOL,TBIL,BUN,showed significant difference(P<0.05) between populations,between age groups and between both sexes,however,the values of difference were rather small,deviated from the normal range.Conclusion The physiological and biochemical characteristics of SPF Yorkshire and Landrace swine are basically stable and there is no significant difference compared with other laboratory miniature pigs.This study will provide valuable basic data for raising velvet yield,establishment of animal models and evaluating the genetic quality of closed colony.

Objective The aim of this study was to investigate the polymorphism of SLA class II genes in Canadian SPF Yorkshire and Landrace pigs.Methods Blood samples were obtained from 15 SPF Yorkshire and 22 Landrace pigs for isolation of peripheral blood mononuclear cells respectively, and the DQB1, DRB1 and DQA genes were amplified by PCR after reverse transcription.SLA class II genes were obtained by analyzing the direct and cloning result.The polymorphism of alleles was analyzed using the DNAsp 5.0 software.Results A total of 25 alleles were identified at three genes, including eight DQB1, ten DRB1 and seven DQA, and three alleles were submitted the complete sequences for the first time.The official allele names were assigned as SLA-DQB1*0212 (KU754590), SLA-DQB1*0203 (KU754591) and DRB1*06:07(KU754601) by the SLA Nomenclature Committee.Three novel DQA alleles were discovered.Five of the 15 amino acids, one of the 16 amino acids and 11 of the 19 amino acids, which bind processing antigens, showed well conserved among the alleles of DQB1, DRB1 and DQA genes in the SPF Yorkshire and Landrace pigs, respectively.Neighbor-joining tree showed that the three genes were divided into two clusters, respectively.There was a close relationship between SPF Yorkshire and Landrace pigs and foreign Yucatan miniature pigs, and it showed no obvious genetic distance with other pigs.Conclusions A total of 25 SLA class II alleles have been identified successfully in this study, and there are more abundant polymorphism for them.There is a widely distribution for SLA class II alleles identified in this study in other pig breeds.It is critical for the eventual future use of SPF Yorkshire and Landrace pigs as classical laboratory animal models.