Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation (HSCT), characterized by microangiopathic hemolytic anemia, thrombocytopenia, microthrombosis, and multi-organ dysfunction. Mortality rates range from 50% to 90%, with higher rates observed in high-risk patients. The pathogenesis of TA-TMA involves abnormal activation of the complement system—particularly of the alternative pathway—resulting in endothelial injury and microthrombosis. We present the case of a 17-year-old man with high-risk TA-TMA who achieved a favorable outcome following the oral administration of the factor B inhibitor iptacopan. The patient exhibited significant improvements in laboratory markers, including reductions in lactate dehydrogenase, urine protein/creatinine ratio, and C5b-9 levels, along with recovery of platelet counts and haptoglobin levels. This case highlights the potential efficacy of iptacopan in the management of TA-TMA, particularly in high-risk patients, and suggests that complement factor B inhibition may offer a promising therapeutic strategy for this challenging condition.

目的 探讨去甲基化药物阿扎胞苷联合Bcl-2抑制剂维奈克拉(Venetoclax)治疗难治复发急性髓系白血病(AML)的有效性及安全性.方法 回顾性分析2018年10月至2020年3月本院收治的5例难治复发AML患者的临床特征、包括骨髓在内的检查结果及诊治经过,并回顾相关文献.结果 所有患者均顺利完成至少4个疗程的化疗.5例患者中,完全缓解(CR)2例,骨髓缓解伴血象不完全恢复(CRi)1例,疾病稳定(SD)2例;所有患者均合并肺部感染,其中1例合并感染性休克.患者总生存时间558(234～1430)d,目前所有患者均存活.结论 对于难治复发AML,阿扎胞苷联合Bcl-2抑制剂Venetoclax治疗安全、有效.

近年来出现不少急性髓系白血病(acute myeloid leu-kemia,AML)的治疗新药,其中对于年龄＜60岁的复发AML,《中国复发难治性急性髓系白血病诊疗指南》(2021年版),建议可选择BCL-2抑制剂Venetoclax(维奈克拉)联合去甲基化的治疗方案,但由于BCL-2抑制剂在国内尚未正式获批,导致临床使用率并不高,我们现报道1例中年女性复发AML患者使用该方案后得到完全缓解的个案,为以后临床上该方案得到广泛应用提供指导.

血液系统疾病行造血干细胞移植术后并发红细胞增多症罕见,其发生机制目前尚不清楚,国内尚鲜见此类报道.该文报道了1例年轻男性再生障碍性贫血患者行异基因造血干细胞移植后1年余发生红细胞增多症临床表现.同时回顾相关文献进行分析总结,以期提高对该疾病的认识和诊治.

目的:探讨骨髓增生异常/骨髓增殖性肿瘤伴环形铁粒幼细胞和血小板增多（MDS/MPN-RS-T）合并骨髓纤维化患者的临床特点及治疗。方法:回顾性分析南方医科大学深圳医院2018年5月收治的1例伴SF3B1及JAK2基因突变的MDS/MPN-RS-T合并骨髓纤维化患者的临床资料，并进行相关文献复习。结果:患者以头晕、乏力为主要症状，诊断为伴SF3B1及JAK2基因突变的MDS/MPN-RS-T合并骨髓纤维化，予羟基脲降细胞治疗及芦可替尼靶向治疗，效果良好。结论:MDS/MPN-RS-T是血液肿瘤系统新定义的克隆性造血干细胞疾病，具有两种疾病的双重特点，不易鉴别，易漏诊，其有效的治疗选择仍有待探索。

Hemophagocytic lymphohistiocytosis (HLH) is a high-fatality disease caused by hereditary or acquired immune dysfunction, and is characterized by pathological inflammatory response. Primary HLH (pHLH) has hereditary genetic defects, and secondary HLH (sHLH) is caused by a variety of underlying diseases. Here, we report the case of a patient with aggressive natural killer cell leukemia and HLH-related gene defects who achieved long-term survival after treatment. A 20-year-old man presented to our hospital with symptoms of fever and fatigue. Investigations revealed splenomegaly, cytopenia, hyperferritinemia, hypofibrinogenemia, elevated levels of soluble CD25 ( sCD25), and hemophagocytosis in bone marrow. Bone marrow flow cytometry showed 23.4% abnormal natural killer cells, the cells were CD2, CD7, CD16, CD94, NKG2A positive, met the diagnosis of aggressive NK-Cell leukemia. Investigation of the patient's pedigree revealed that mutations of pHLH-related genes (LYST and UNC13D) were inherited from his father and mother, but neither of the parents had the disease. The patient received hematopoietic stem-cell transplantation (HSCT), after which he achieved complete remission. As of 2020-10-19, the patient's survival has exceeded 3 years, and he has returned to his normal life. A variety of factors contribute to the onset of HLH, and this case gives greater insight into the etiology of HLH. Allogeneic HSCT is a key treatment for HLH patients with underlying genetic mutations.

纯红细胞再生障碍性贫血(PRCA)是一种少见的疾病,是一组选择性影响骨髓中红系祖细胞生长和分化的临床综合征.这种疾病可能是先天性的,也可能与潜在疾病有关.获得性PRCA可继发于各种感染性疾病,包括人类微小病毒B19、大颗粒淋巴细胞白血病和其他淋巴细胞增殖性疾病、胸腺瘤等.目前认为,免疫因素是导致慢性PRCA的主要原因,另外,还有病毒或化学毒物暴露史等非免疫的可能机制.

BackgroundThe aim of this study was to investigate the association between telomerase reverse transcriptase (TERT) gene polymorphisms and acute myeloid leukemia (AML) susceptibility in a Chinese Han population.MethodsA total of 102 AML patients and 108 healthy controls were enrolled in this case-control study. TERT gene rs2853669 and rs2736100 polymorphisms were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Chi-square test was applied to compare polymorphism distributions between case and control groups. The strength of the association between TERT gene polymorphisms and AML susceptibility was evaluated utilizing odds ratio (OR) with corresponding 95% confidence interval (CI).ResultsCC genotype and C allele of rs2736100 polymorphism were more frequent in AML patients (P<0.05), and individuals carrying CC genotype showed higher risk of suffering from AML (OR=2.632, 95% CI 1.129-6.133). But for rs2853669 polymorphism, no significant differences were detected in either genotype or allele distributions between groups (P>0.05).ConclusionsThis study suggested a positive association between TERT gene rs2736100 polymorphism and AML susceptibility in Chinese Han population.

由伯氏立克次氏体(柯克斯体Coxiella burnetii)引起的Q热是一种发热性人畜共患病,在世界范围内分布.该病具有多种表现,包括急性自限性流感样综合征、急性肺炎或肝炎和慢性感染(主要表现为心内膜炎)[1 ].噬血细胞综合征,更恰当地称为噬血细胞性淋巴组织细胞增多症(HL H ) ,是单核吞噬细胞系统的反应性疾病,其特征在于过度的组织细胞增殖和活化,具有显著的噬血细胞增多表现.噬血细胞综合征由原发性和继发性HLH组成,可能与感染、恶性肿瘤、自身免疫性疾病或药物有关[2-6 ].本文报告1例急性Q热伴罕见的噬血细胞综合征、EB病毒感染、嗜血细胞综合征、肝肾功能衰竭病例.

Background This study aimed to investigate the effects of microRNA19a (miR-19a) antisense oligonucleotide (ASODN) on the proliferation and apoptosis of acute myeloid leukemia cells (HL60). Methods In experiment 1, HL60 cells were divided into the blank control group, the blank transfection group, the scrambled oligonucleotide (SODN) group and the ASODN group. MiR-19a ASODN and SODN were independently transferred into HL60 cells. The miR-19a expression was detected by real-time quantitative RT-PCR (qRT-PCR) after 48-h and 72-h transfection; CCK8 assay was used to detect the proliferation inhibition rate at 48 and 72 h; Hoechst 33258 staining was performed to examine apoptotic cells at 48 h; the apoptosis rate was detected by flow cytometry after AnnexinV/PI staining at 48 and 72 h; the protein expression of E2F1 and Bim was detected by Western blotting at 48 h. In experiment 2, cells were divided into the Ara-C group, the SODN + Ara-C group and the ASODN + Ara-C group. The cell proliferation inhibition rate at 48 and 72 h and apoptosis rate at 72 h were assessed as mentioned above. Results MiR-19a expression in the miR-19a ASODN group was lower than in the SODN group and the blank control group (P<0.05). MiR-19a ASODN significantly inhibited the growth of HL60 cells (P<0.05) and increased their apoptosis, and the apoptosis rate peaked at 48 h. The protein expression of E2F1 and Bim in the ASODN group was higher than in the blank control group, blank transfection group and SODN group. In addition, Ara-C further inhibited the growth and induced the apoptosis of miR-19a ASODN-transfected cells (P<0.05) in a time dependent manner. The growth inhibition rate and apoptosis rate in the ASODN + Ara-C group were higher than the sum of those in both Ara-C group and ASODN group. Conclusions miRNA-19a ASODN can inhibit the proliferation and induce apoptosis of HL60 cells and may exert synergistic effects with Ara-C on HL60 cells.

目的 探讨硼替佐米对老年多发性骨髓瘤(MM)病人白细胞介素-6(IL-6)、C反应蛋白(CRP)和β2-微球蛋白(β2-MG)水平的影响及疗效观察.方法 选取60例老年MM病人,随机分为观察组(n=30)和对照组(n=30),对照组采用常规化疗治疗,观察组在常规化疗的基础上联合硼替佐米治疗,比较2组治疗前后IL-6、CRP、β2-MG、M蛋白、血红蛋白水平和骨髓瘤细胞比例的变化,观察2组临床疗效及不良反应发生情况.结果 治疗前2组IL-6、CRP、β2-MG、M蛋白、血红蛋白水平和骨髓瘤细胞比例差异无统计学意义(P>0.05).治疗后2组IL-6、CRP、β2-MG、M蛋白水平和骨髓瘤细胞比例低于治疗前,血红蛋白水平高于治疗前,且与对照组比较,差异均有统计学意义(P<0.05).观察组治疗总有效率为93.33％,明显高于对照组(70.00％)(P<0.05).2组间不良反应发生率比较差异无统计学意义(P>0.05).结论 在常规化疗基础上联用硼替佐米治疗老年MM,能有效降低炎性应激反应,增强疗效,值得进一步研究.

BACKGROUND The objective of this study was to detect the association between ERCC excision repair 2, TFIIH core complex helicase subunit (ERCC2) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) susceptibility. MATERIAL AND METHODS This study used a case-control design. ERCC2 gene rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) both in DLBCL patients and healthy controls. The association between ERCC2 gene polymorphisms and DLBCL risk was assessed by χ² test. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to address the association strength. Subgroup analyses were also performed to investigate the genetic effects of ERCC2 polymorphisms on clinical characteristics of DLBCL patients. RESULTS A significant association was discovered between the rs1799793 A allele and increased DLBCL risk (P=0.031, OR=1.928, 95% CI=1.052-3.534). The C allele of rs13181 was obviously associated with elevated DLBCL susceptibility (P=0.047, OR=1.820, 95% CI=1.002-3.305). The subgroup analysis demonstrated that rs1799793 and rs13181 polymorphisms had no relationship with serum lactate dehydrogenase level, nidus number, B-symptoms, Ann Arbor stages, or immunological types in DLBCL cases (P>0.05 for all). CONCLUSIONS Minor allele carriers of ERCC2 gene rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms had higher susceptibility to DLBCL.

目的:探讨不同剂量利妥昔单抗注射液治疗难治性免疫性血小板减少症(rITP)的疗效及对凝血指标的影响.方法:选取2015年1月-2017年5月南方医科大学深圳医院及宜昌市第一人民医院收治的rITP患者80例.采用随机数字表法将其分为标准剂量组(n=40)和小剂量组(n=40).两组患者均采用利妥昔单抗注射液治疗,标准剂量组患者用药剂量为375 mg/m2,小剂量组患者用药剂量为100 mg/m2.比较两组患者临床疗效、治疗前后的凝血指标及治疗过程中不良反应发生情况.结果:小剂量组患者治疗总有效率为67.5％,高于标准剂量组的55.0％,但比较差异无统计学意义(P>0.05);治疗后,两组患者PLT水平高于治疗前,PT、APTT水平均低于治疗前,比较差异均有统计学意义(P<0.0.5);但治疗前后,两组患者PLT、PT、APTT比较,差异均无统计学意义(P>0.05);小剂量组不良反应发生率为12.5％,低于标准剂量组的32.5％,比较差异有统计学意义(χ2=4.588,P=0.032).结论:小剂量利妥昔单抗注射液与标准剂量临床效果相似,对凝血指标具有显著的改善作用,且安全性更好.

Objective: The effects of microRNA-20a (miR-20a) antisense oligonucleotides (ASODNs) on the proliferation and apoptosis of K562 cells were investigated, and the effects of these ASODNs in combination with imatinib on K562 cells were preliminarily observed. Methods: miR-20a ASODNs and scrambled oligonucleotides (SODNs) were chemically synthesized, and the later was used as the control. miR-20a ASODNs were transfected into K562 cells using Lipofectamine 2000 transfection reagent, and the expression of miR-20a was detected using real-time quantitative RT-PCR (qRT-PCR). The CCK8 assay was performed to detect the inhibition of the cell growth rate. The cells were stained by Hoechst 33258 to detect apoptotic cell morphology. Annexin V/PI double staining was used to detect the cell apoptosis rate using flow cytometry. The protein expression levels of E2F1, P21, and Bim in the K562 cell line were detected using western blotting. Results: The qRT-PCR results showed that the expression level of miR-20a in K562 cells transfected with miR-20a ASODNs was lower than those in the normal control, SODN and blank transfection groups (p < 0.05). miR-20a ASODNs significantly inhibited the growth of K562 cells as compared to the controls (p < 0.05). The Hoechst staining results showed morphological changes, suggesting apoptosis. The cell apoptosis rates in the ASODN group was (13.9 ± 1.5)%, which was significantly higher than that in the normal control group (1.84 ± 0.21)%, blank transfection group (3.21 ± 0.32)%, and SODN group (3.72 ± 0.44)% (p < 0.05). The protein expression of E2F1 and P21 in K562 cells transfected with miR-20a ASODNs were higher, while the level of Bim protein was significantly lower than that in the control groups. When miR-20a ASODNs were combined with imatinib, the growth of K562 cells was significantly inhibited as compared to the ASODN treatment alone, imatinib alone, and SODN+imatinib groups (p < 0.05). Conclusions: miR-20a ASODNs could induce apoptosis and inhibit the proliferation of K562 cells. In addition, imatinib combined with miR-20a ASODNs can increase the inhibitory effect on K562 cell proliferation.

再生障碍性贫血-阵发性睡眠性血红蛋白尿综合征(AA-PNH综合征)是一种多能造血干细胞疾病,既有一系或多系血细胞减少,又有溶血表现,病情较为凶险.目前,骨髓间充质干细胞(BMSCs)已广泛用于血液病的治疗,对于耐药且近期无法行异基因造血干细胞移植(allo-HSCT)的难治性患者是有效的治疗手段之一.