Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy(CAR–T)cell immunotherapy

Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer treatment.However,the challenges associated with implementing this novel targeted cell therapy are increasingly significant.Particularly in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy.These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach.In this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its efficacy.Furthermore,we aim to identify existing solution strategies and explore their current research status.Through this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.

MT_1-MMP和Factor Ⅷ在人脑胶质瘤中表达差异及其意义

目的探讨膜型基质金属蛋白酶-1(MT1-MMP)和FactorⅧ在人脑胶质瘤中的表达及两者之间的关系。方法用免疫组织化学SP法检测45例人脑胶质瘤组织和10例正常人脑组织中MT1-MMP和FactorⅧ的表达。结果正常人脑组织中无MT1-MMP表达,高级别脑胶质瘤组织(Ⅲ、Ⅳ)中MT1-MMP和FactorⅧ的阳性表达率显著高于低级别胶质瘤组织(Ⅰ、Ⅱ),并且两者的表达呈显著正相关性。结论MT1-MMP在高级别脑胶质瘤组织中高表达,其表达与脑胶质瘤的进展和侵袭密切相关,可作为脑胶质瘤恶性表型的有用指标。MT1-MMP可能在脑胶质瘤的血管生成中发挥重要的调控作用。

Ki-67和Factor Ⅷ在人脑胶质瘤中表达的相互关系及意义

目的探讨Ki-67和FactorⅧ在人脑胶质瘤中的表达及两者之间的关系。方法用免疫组织化学S-P法检测38例人脑胶质瘤组织和7例正常人脑组织中Ki-67和FactorⅧ的表达。结果正常人脑组织中无Ki-67表达,高度恶性胶质瘤(Ⅲ～Ⅳ级)中Ki-67和FactorⅧ的阳性表达率显著高于低级别胶质瘤组织(I～Ⅱ级),并且两者的表达呈显著正相关性。结论Ki-67在恶性胶质瘤组织中高表达,与胶质瘤的进展和侵袭密切相关,可作为胶质瘤恶性表型的有用指标。Ki-67可能在胶质瘤的血管生成中发挥重要的调控作用。

Risk factors for intraocular metastasis of primary liver cancer in diabetic patients:Alpha-fetoprotein and cancer antigen 125

BACKGROUND In rare instances,primary liver cancer can be associated with intraocular metastasis(IOM).AIM To investigate the correlation between a diverse range of clinical characteristics and IOM in diabetic patients with primary liver cancer,and to determine potential risk factors in predicting IOM.METHODS We recruited a total of 722 diabetic patients with primary liver cancer.The differences between the IOM and non-intraocular metastasis(NIOM)groups in these patients were assessed using the chi-squared test and Student’s t-test.Binary logistic regression analysis was subsequently used to determine risk factors.Finally,the diagnostic value of IOM in this cohort with primary liver cancer was analyzed by receiver operating characteristic(ROC)curve analysis.RESULTS In all,13 patients had IOM.There were no remarkable intergroup differences with respect to age,sex,histopathological sub-types,or blood biochemical parameters.However,the IOM group had significantly higher alpha-fetoprotein(AFP)and cancer antigen 125(CA125)values than the NIOM group.Binary logistic regression identified AFP and CA125 to be significant risk factors for IOM in diabetic patients with primary liver cancer.ROC curve analysis showed that the area under the curve values for AFP and CA125 were 0.727 and 0.796,with the cut-off values of 994.20 ng/mL and 120.23 U/mL,respectively.The sensitivity and speci
city for AFP were 92.3%and 59.9%,while those for CA125 were 84.6%and 70.1%,respectively.CONCLUSION Elevated AFP and CA125 represent significant risk factors for IOM in diabetic patients with primary liver cancer.

von Willebrand factor antigen as a therapeutic target of portal hypertension in cirrhosis

Increased thrombotic potential within the liver sinusoids due to local endothelial production of von Willebrand factor antigen macromolecules could represent an additional therapeutic target of portal hypertension in patients with cirrhosis. In this case, anti-inflammatory and antithrombotic drugs could modulate portal pressure by preventing the formation of intrahepatic platelet-induced microthrombi.

Proliferating cell nuclear antigen clamp associated factor,a potential proto-oncogene with increased expression in malignant gastrointestinal tumors

Gastrointestinal(GI)cancers,including malignancies in the gastrointestinal tract and accessory organs of digestion,represent the leading cause of death worldwide due to the poor prognosis of most GI cancers.An investigation into the potential molecular targets of prediction,diagnosis,prognosis,and therapy in GI cancers is urgently required.Proliferating cell nuclear antigen(PCNA)clamp associated factor(PCLAF),which plays an essential role in cell proliferation,apoptosis,and cell cycle regulation by binding to PCNA,is a potential molecular target of GI cancers as it contributes to a series of malignant properties,including tumorigenesis,epithelial-mesenchymal transition,migration,and invasion.Furthermore,PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer.In addition to GI cancers,PCLAF is also involved in other types of cancers and autoimmune diseases.Several pivotal pathways,including the Rb/E2F pathway,NF-κB pathway,and p53-p21 cascade,are implicated in PCLAF-mediated diseases.PCLAF also contributes to some diseases through dysregulation of the p53 pathway,WNT signal pathway,MEK/ERK pathway,and PI3K/AKT/mTOR signal cascade.This review mainly describes in detail the role of PCLAF in physiological status and GI cancers.The signaling pathways involved in PCLAF are also summarized.Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.

Reliability of Plasma Von Willebrand Factor Antigen in Prediction of Esophageal Varices in Patients with Liver Cirrhosis

Background: Bleeding esophageal varices (OVs) due to portal hypertension are one of the major complications with high mortality in liver cirrhosis. So, early detection and management are mandatory. Aim: To evaluate the role of Von Willebrand factor (VWF) in predicting the presence of OVs. Patients and Methods: 62 patients with liver cirrhosis representing different Child-Pugh classes were included. The diagnosis of liver cirrhosis was based on the combination of clinical, laboratory and US examinations. All included patients underwent the following investigations: complete blood count, liver function tests (ALT, AST, serum bilirubin, albumin and total protein, prothrombin time (PT) and concentration (PC), INR and serum alkaline phosphatase), serum creatinine, Von Willebrand factor antigen (VWF-Ag) measurement and abdominal US. Upper endoscopic evaluation was done to detect presence or absence of varices (esophageal or gastric) and/or PHG. Results: 38 males and 24 females with their mean age (46 ± 12 years old) were included. Plasma Von Willebrand factor-Ag level was significantly higher in patients with OVs than those without varices (P value = 0.000). Also, its level was significantly higher in patients with higher grade of OVs, G3 than those with G1 or G2 (P value = 0.000). Patients with large OVs including those with G2 and G3 showed significantly higher values of VWF than those with small OVs (NO and G1) (P value = 0.000). VWF was independent predictor for detecting the presence of OVs with good sensitivity (90), specificity (77.3) and accuracy (85.5) at a cutoff value of 1.74 U/ml. Also it was an independent predictor for detecting the presence of large OVs with good sensitivity (91.2), specificity (85.7) and accuracy (88.7) at a cutoff value of 2.16 U/ml. Conclusion: VWF-Ag could be used as a non invasive laboratory independent predictor for the detection of OVs.

Milk fat globule epithelial growth factorⅧ(MFG-E8)sustains survival of cancer cells by prompting tumor angiogenesis and suppressing host immunities

Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.

Change of Coagulation Factor Ⅷ and Antithrombin Ⅲ Activity in Bank-Stored Blood

Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank stored blood can be used to replenish antithrombin Ⅲ, while bank stored blood in one day can be used to replenish FⅧ.

In vitro and in vivo analyses of a genetically-restricted antigen specific factor from mixed cell cultures of macrophage, T and B lymphocytes

An immunostimulatory factor was identified to be secreted by antigen-pulsed maorophages. This factor was able to induce the generation of antigen specific T helper lymphocytes in vitro as well as in vivo. Further in vitro experiments testing for the genetic restriction of this factor indicated that it is a genetically-restricted antigen specific factor (ASF). The Cunningham plaque assay was used to quantify the generation of T helper lymphocytes by measuring the number of plaque forming cells after sequential incubations of antigen-pulsed maorophages with T lymphocytes, and then spleen cells, and finally the TNP-coated sheep red blood cells.

The effect of Chinese herbal medicine“heche assisted pregnancy recipe”on endometrial estrogen and progesterone receptor,proliferating cell nuclear antigen and vascular endothelial growth factor in the patients with infertility

Objectives:To investigate the effect of Chinese herbal medicine"heche assisted preg-nancy recipe (HCAPR)" on estrogen receptor(ER), progesterone receptor (PR), pro-lifierating cell nuclear antigen(PCNA) and vascular endothelial growth factor (VEGF)in endometrium of infertile women.Methods: The S-P immunohistochemical assay was used to observe expression ofER, PR , PCNA and VEGF in late proliferative phase before and after the HCAPR treat-ment.Results: After the treatment, the expression of ER,PR,PCNA and VEGF in nucleiof glandular epithelium and stromal cells was significantly stronger (all P＜0. 001) re-spectively than that before treatment , especially the expression of PCNA and VEGF.Conclusions: These results suggest that traditional Chinese medicine HCAPR oftonifying kidney and regulating menstruation increased the synthesis of ER,PR, PCNAand VEGF, which may promote normal growth and development of the endometrium ,improve the micro-environment of the endometrium, and enhance uterine receptivity.The evidence may provide theoretical basis for therapy infertility with Chinese herbalmedicine.

Analysis of Intron 22 Inversion Mutation of Factor Ⅷ Genein the Patients with Hemophilia A in J&K State of India

Objective Hemophilia A,an X-linked bleeding disorder,affecting 1 in 5 000 males is caused by heterogeneous mutations in factor Ⅷ gene.Inversion mutation in intron 22 of F8C gene remains its leading cause.The aim of this study was to evaluate the frequency and distribution of the intron 22-inversion mutation in the patients and in the family members in the region.Methods 29 hemophilia A patients from Jammu and Kashmir(20 severe,8 moderate and 1 mild) were analyzed for intron 22-inversion mutation.Results 11(38%) were positive for the distal type of inversion mutation.The mutation was found in 9/20(45%) patients with severe factor Ⅷ deficiency and 2/8(25%) with moderate severity hemophilia A,whereas the patient with mild hemophilia A was found to be negative for inversion mutation.Evaluation of twenty-six female relatives from 11 families of inversion mutation positive patients identified one mother and one sister from one family to be the carrier,suggesting its origin in the mother. Conclusion The present study confirms the intron-22 inversion mutation in F8C gene as the major cause of hemophilia A in the population from Jammu and Kashmir with a higher frequency of inversion mutation in sporadic cases compared to the familial cases.

Psoriatic arthritis: clinical patterns, rheumatoid factor, anti-cyclic citrullinated peptide and human leukocyte antigen risk alleles

Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.Both rheumatoid factor and anti-cyclic citrullinated peptide antibodies positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Symmetrical polyarthritis pattern was predominant(42%)among clinical pattern of psoriatic arthritis.Among 10 rheumatoid factor positive patients,8(80%)patients had symmetrical polyarthritis pattern and out of 7 anti-cyclic citrullinated peptide antibody positive patients,7(100%)patients had symmetrical polyarthritis pattern.Association of anti-cyclic citrullinated peptide(P=0.008)and rheumatoid factor(P=0.006)showed statistical significance with symmetrical polyarthritis pattern.Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Background:Psoriatic arthritis is an inflammatory arthritis associated with psoriasis.It is usually seronegative in nature but a small percentage of patients may be positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Anti-cyclic citrullinated peptide and rheumatoid factor are highly specific for rheumatoid arthritis but their role is not clear in psoriatic arthritis.The prevalence and prognostic value of anti-cyclic citrullinated peptide antibody and rheumatoid factor in psoriatic arthritis patients is not well known.The aim of this study was therefore to investigate the prevalence of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in psoriatic arthritis patients and assess their clinical associations and also to see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Methods:Fifty patients with psoriatic arthritis were tested for the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Polymerase chain reaction was done with sequence specific primer for detection of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Data on five clinical patterns of rheumatological manifestations of psoriatic arthritis patients were collected prospectively on all patients and statistically compared between anti-cyclic citrullinated peptide,rheumatoid factor positive and negative patients by chi-square test.We also see the distribution of human leukocyte antigen-B and human leukocyte antigen-C locus antigens in anti-cyclic citrullinated peptide antibody and rheumatoid factor positive psoriatic arthritis patients.Results:Among 50 psoriatic arthritis patients,rheumatoid arthritis test was positive in 10(20%)patients and anti-cyclic citrullinated peptide was positive in 7(14%)patients.Symmetrical polyarthritis pattern is predominant among clinical pattern of psoriatic arthritis which was found in 21(42%)patients.Among 7 anti-cyclic citrullinated peptide positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 7(100%)patients.Among 10 rheumatoid factor positive psoriatic arthritis patients,symmetrical polyarthritis pattern is predominant and it was found in 8(80%)patients.In this study,symmetrical polyarthritis pattern is statistically associated with anti-cyclic citrullinated peptide positive psoriatic arthritis patients(P=0.008)and rheumatoid factor positive psoriatic arthritis patients(P=0.006).Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 were predominantly found in rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients.Conclusion:Both rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients may be in risk for development of symmetrical polyarthritis pattern.Among rheumatoid factor and anti-cyclic citrullinated peptide positive psoriatic arthritis patients,Human leukocyte antigen-B*07,*38 and human leukocyte antigen-C*07 alleles were more frequently found alleles.

冷损伤对培养的血管内皮细胞合成因子Ⅷ相关抗原的影响

本实验用流式细胞术测定了冷损伤对体外培养的大鼠主动脉血管内皮细胞(VEC)合成因子Ⅷ相关抗原(ⅧR:Ag)的影响。结果表明,冷损伤后的大鼠VEC平均荧光强度增强,说明冷损伤可明显影响VEC合成ⅧR:Ag的功能,这在冷损伤的病理过程中具有重要作用。

骨折端Ⅷ因子相关抗原与血流量的实验研究

目的 研究骨折愈合过程中骨折端Ⅷ因子相关抗原和血流量变化的规律及其相关性。方法 选用 35只大耳白兔制作左侧桡骨骨折动物模型 ,分别于伤后 8、2 4、72h ,1、3、5、8周利用单光子放射计算机断层显像术 (SinglePhotonEmissionComputerizedTomography ,SPECT)测定骨折端血流量变化 ,之后取骨折端标本提取蛋白样本定量检测Ⅷ因子相关抗原。结果 骨折端血流量在致伤后 8h开始上升 ,1周时达顶峰 ,高血流量状态一直维持到第 3周 ,第 5和第 8周基本恢复到正常水平 ;骨折端Ⅷ因子相关抗原在伤后 2 4h开始增高 ,骨折后 3天达到较高的水平 ,该状态一直维持到骨折后的第 3周 ,到第 5周时开始出现较明显的回落 ,第 8周时基本恢复到正常水平。结论 伤后 72h骨折端血流量增高与骨折端血管生成有关 ,早期的血流量增加可能与骨折后的创伤反应有关。

大黄虫丸对难治性肾病综合征Ⅷ因子抗原及纤维蛋白原的影响

目的 :探讨大黄虫丸对特发性膜性肾炎 ( MGN)肾病综合征 ( NS) 因子抗原 ( R:Ag)、纤维蛋白原 ( Fbg)的作用。方法 :选择 MGN— NS患者 60例 ,用美国 IL公司生产 ACT- 2 0 0自动凝血机检测 R:Ag、Fbg的变化。并随机分为治疗组和对照组 ,治疗组用大黄虫丸 ,对照组用潘生丁干预治疗。观察大黄虫丸对 MGN- NS患者血 R:Ag、Fbg的影响。结果 :实验组 R:Ag、Fbg水平较正常对照组显著增高 ( P<0 .0 0 1 ) , R:Ag、Fbg与 BUN呈显著正相关 ( P<0 .0 0 1 ) ,Fbg与白蛋白 ( ALB)呈显著负相关 ( P<0 .0 1 )。经用大黄虫丸治疗后 ,MGN- NS患者血 R:Ag、Fbg显著降低 ( P<0 .0 1 ,P<0 .0 5 ) ,明显优于潘生丁 ( P<0 .0 5 )。结论 :大黄虫丸能显著降低 MGN- NS患者 R:Ag、Fbg含量 ,改善高凝状态。

VEGF在骨折愈合过程中对Ⅷ因子相关抗原表达变化影响的实验研究

目的 研究血管内皮生长因子 (VEGF)在骨折愈合过程中骨折端对Ⅷ因子相关抗原含量变化的影响 ,以确定VEGF对骨折端血管重建中的作用。方法 用 10 5只大耳白兔制作桡骨骨折模型 ,随机分为对照组、应用VEGF组、拮抗VEGF组 ,分别于伤后不同时间利用Westernblot方法测定各组动物骨折端Ⅷ因子相关抗原含量变化。结果 应用外源性VEGF后 ,骨折端Ⅷ因子相关抗原含量明显增加 ;拮抗VEGF则使骨折端Ⅷ因子相关抗原含量明显下降。结论 VEGF对骨折愈合过程中的血管重建具有重要作用 。

CD105和Ⅷ因子相关抗原对大肠癌新生血管标记的研究

目的探讨CD105和Ⅷ因子相关抗原(F8RAg)在大肠癌的表达意义,并将二者对大肠癌新生血管的标记作用进行对比。方法采用鼠抗人CD105单克隆抗体和鼠抗人F8RAg原单克隆抗体,应用免疫组化技术对40例大肠癌手术切除的新鲜标本及40例正常对照组的微血管进行定量检测,计数100倍视野下5个血管丰富视野的微血管密度(MVD),取其均值。结果大肠癌组织与正常对照组的MVD间的差异具有非常显著性(P<001);以CD105和F8RAg为新生血管标记物测得的大肠癌微血管密度间的差异具有非常显著性(P<001);以CD105标记的大肠癌微血管密度与大肠癌的淋巴结转移、远处转移及临床分期有关(P<001);而以F8RAg为标记物测得的MVD与淋巴结转移、远处转移及临床分期无关(P>005)。结论大肠癌新生血管形成与肿瘤的生长、转移及预后有关,CD105和F8RAg均在大肠癌有良好表达,但CD105在标染肿瘤新生血管上比F8RAg更具有特异性。

血友病A患者因子Ⅷ抑制物的检出率及抑制物产生的环境因素

目的调查血友病A（HA）患者因子Ⅷ（FⅧ）抑制物的检出率,初步探讨抑制物产生的环境因素。方法以2003年4月-2007年4月在北京协和医院就诊的107例HA患者及在院外征集的158例HA患者（共265例）为研究对象,采用一期法检测FⅧ：C活性,Bethesda法检测FⅧ抑制物。结果265例HA患者中,22例（8.3%）抑制物检测为阳性,其中86.4%（19/22）为低反应者（抑制物滴度≤5 000 BU/L）,13.6%（3/22）为高反应者（抑制物滴度〉5 000 BU/L）。年龄〉50岁患者的抑制物检出率为50%,明显高于其他年龄组（P=0.000）。在158例临床治疗资料较完整的新征集患者中,FⅧ制剂输注频率大于12次/年者的抑制物阳性率为12.8%,而输注频率小于12次/年者为5.8%,两组相比差异无统计学意义（P=0.156）。有短时间内持续输注FⅧ史者的抑制物阳性率明显高于无持续输注FⅧ史的患者（28.5%vs.1.6%,P=0.000）。应用多种品牌和单一品牌FⅧ制剂患者的抑制物阳性率分别为9.3%和3.9%,两组相比差异无统计学意义（P=0.229）。结论HA患者抑制物的生成可能与患者年龄、短时间内持续输注FⅧ史等因素有关。

中国血友病A患者因子Ⅷ抑制物形成特征及随访研究

目的随访研究中国血友病A患者因子Ⅷ(FⅧ)抑制物发生率和特征。方法 215例血友病A患者在24月(2007年6月至2009年6月)的连续随访中,监测FⅧ抑制物发生、变化及转归,并观察患者临床特征。结果 215例血友病A患者随访24月FⅧ抑制物累积发病率为11.6%(25/215);其中低滴度者占72%(18/25),高滴度者占28%(7/25);FⅧ抑制物阳性发生时的中位年龄为25岁(6～59岁)、累积中位暴露日为150日;15/25(60%)低滴度阳性者(中位滴度1.25BU/ml)在自然情况下于6～15月(中位10月)转为阴性,5/25(20%)高滴度抑制物者(中位滴度100BU/ml)则随访24月持续阳性,另外5/25(20%)FⅧ抑制物阳性无变化;25例FⅧ抑制物阳性者出血频率较其阴性时显著增加(P=0.025);18/25例继续应用FⅧ者,FⅧ产品用量(IU/kg·月)较前显著增加(P=0.015),但靶关节数目在24月随访期间并无增加(P=0.329)。结论我国血友病A患者FⅧ抑制物发病率和特征与欧美等国家存在差异。