ObjectiveTo explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. MethodsClinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. ResultsThe frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut (P=0.07) and KMT2Dwt BTG2wt (P=0.05). On the contrary, patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2DmutBTG2mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). ConclusionDLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

We report the case of a 54-year-old healthy Han Chinese male presenting with fever, pallor, erythematous subcutaneous nodules on the limbs, and significant anemia as indicated by routine blood tests, with no response to antimicrobial therapy. Initial skin biopsy was inconclusive. The erythematous subcutaneous nodules on the limbs rapidly progressed to widespread subcutaneous nodules across the body, with worsening anemia. Bone marrow biopsy revealed multifocal fibroblastic proliferation with focal fibrosis, classified as MF-2, and positive for the JAK2V617F mutation alongside SRSF2 positivity. Whole-body PET-CT scans did not reveal any lymph nodes or suspect lesions with high SUV uptake. A subsequent skin biopsy identified the condition as nodular panniculitis (NP), leading to a final diagnosis of primary myelofibrosis(PMF)with NP. The patient initially received treatment with oral ruxolitinib and prednisone acetate, resulting in normalization of body temperature, resolution of erythematous nodules, and normalization of blood parameters.

Background: Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a breakdown of immune tolerance; in ITP, the body's immune system mistakenly attacks and destroys platelets. This study aims to investigate the role and underlying mechanisms of FOXP3 in chronic ITP. Methods: Flow cytometry was used to detect the proportion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in CD4+CD25+ T lymphocytes from 20 patients with chronic ITP (CITP), 20 acute ITP (AITP) controls, and 20 healthy individuals. CD4+CD25+ Treg cells were isolated from peripheral blood of patients with CITP using magnetic beads and then treated with phosphate-buffered saline solution or decitabine (a methylation inhibitor) for 48 h. The levels of interleukin-2 (IL-2), IL-10, and transforming growth factor-beta1 (TGF-β1) in the plasma and CD4+CD25+ Treg cells were assessed by Enzyme-linked-immunosorbent serologic assay and quantitative real-time polymerase chain reaction (qRT-PCR). FOXP3 level was measured by qRT-PCR and Western blot analysis. Methylation-specific PCR (MS-PCR) was adopted to detect the status of FOXP3 methylation. Results: The number of Treg cells and the contents of IL-2, IL-10, and TGF-β1 decreased in patients with CITP, compared to the AITP control group and normal group. FOXP3 expression was reduced and FOXP3 methylation increased in patients with CITP, compared to the AITP control group and normal group. Hypermethylation of FOXP3 promoter led to decrease in FOXP3 level in Treg cells. Inhibition of FOXP3 promoter hypermethylation promoted the secretion of IL-2, IL-10, and TGF-β1 in Treg cells. Conclusion: The number of Treg cells in CITP patients decreased, and the hypermethylation of FOXP3 promoter led to reduction of its expression in Treg cells, thus affecting the immune functioning of Treg cells.

目的:探讨达雷妥尤单抗方案治疗复发难治性多发性骨髓瘤(RRMM)的临床疗效及安全性,并分析影响疾病缓解的相关因素.方法:回顾性分析2019年1月～2022年9月新疆维吾尔自治区人民医院血液科收治的接受达雷妥尤单抗治疗的50例RRMM患者临床资料.结果:治疗后患者血红蛋白(Hb)、乳酸脱氢酶(LDH)、β2微球蛋白(β2-MG)、血肌酐(Scr)水平均较治疗前明显改善义(P＜0.05).临床总有效率(ORR)为70.9％,无进展生存期(PFS)为11月.两组在年龄、复发次数、溶骨性病变比例上比较有统计学意义(P＜0.05),而在性别、免疫分型、HRCA、贫血、肾损害、髓外病变比例上比较无统计学意义(P＞0.05).疾病缓解组与未缓解组在年龄、复发次数、溶骨性病变比例上比较有统计学意义(P＜0.05),而在性别、免疫分型、HRCA、贫血、肾损害、髓外病变比例上比较无统计学意义(P＞0.05).多因素Logistic回归分析显示,复发次数是影响达雷妥尤单抗方案治疗缓解率的危险因素(P=0.019,OR=1.956).结论:含达雷妥尤单抗方案治疗RRMM具有较好的疗效及安全性,其疗效可受到复发次数的影响.

国家大力发展教育事业的近些年,创新教学模式层出不穷,成为教师革新课堂和达成既定教学目标的重要助力,PLB联合信息化模式就是其中一种,近来被越来越多教师应用于血液病教学中,这一举措为学生主观能动性的发挥奠定坚实基础,如何将这一教学模式发挥出应有的作用和效果,成为教师着重探究的问题.本研究着重站在理论层面剖析和论述PBL联合信息化教学模式,明确该模式对师生综合素质的要求,引申出该模式在血液病教学中的应用策略,仅供参考.

The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. , and mutations predict worse survival in the patients with the aaIPI high-risk group.

The molecular landscapes of diffuse large B-cell lymphoma (DLBCL) remained to be comprehensively investigated with an urgent need to identify novel prognostic biomarkers guiding prognostic stratification and disease monitoring. Baseline tumor samples of 148 DLBCL patients were analyzed using targeted next-generation sequencing (NGS) for mutational profiling, whose clinical reports were retrospectively reviewed. In this cohort, the subgroup of old DLBCL patients (age at diagnosis > 60, N = 80) exhibited significantly higher Eastern Cooperative Oncology Group scores and International Prognostic Index than their young counterparts (age at diagnosis ≤ 60, N = 68). As revealed by the NGS results, PIM1 (43.9%), KMT2D (31.8%), MYD88 (29.7%), and CD79B (27.0%) were identified as the most frequently mutated genes. Aberrations of genes of the immune escape pathway were significantly enriched in the young subgroup, while the altered epigenetic regulators were more abundant in the old patients. FAT4 mutation was identified as a positive prognostic biomarker, associated with longer progression-free survival and overall survival in the entire cohort and the old subgroup, using the Cox regression analyses. However, the prognostic function of FAT4 was not reproduced in the young subgroup. We comprehensively analyzed the pathological and molecular characteristics of old and young DLBCL patients and demonstrated the prognostic value of FAT4 mutation, which requires further validation with sizable cohorts in future research.

目的 探讨弥漫性大B细胞淋巴瘤(DLBCL)ITPKB突变变异等位基因频率(VAF)与预后的相关性.方法 纳入2014年6月—2020年12月在新疆维吾尔自治区人民医院初次诊断的155例DLBCL患者,获取石蜡包埋的肿瘤组织标本.提取肿瘤组织DNA,应用二代测序技术检测包括ITPKB在内的475种热点基因,分析高频突变基因VAF与无进展生存(PFS)和总生存(OS)的关系.结果 ITPKB的突变频率为18.71％,ITPKB突变患者的PFS较未突变患者的PFS明显缩短,但差异无统计学意义(37.00 vs.108.00个月;HR=1.643,95％CI:0.920～2.934,P=0.093).通过基于R语言的网页工具探寻可区分患者预后的最佳VAF截断值,将患者依据VAF值分成对应的两组(高VAF组 vs.低VAF+野生型组),ITPKB最佳VAF的截断值为27.48％(HR=3.48,95％CI:1.70～7.13,P=0.00027),纳入年龄、性别、COO分型、IPI、LDH等临床指标行多因素Cox分析,结果显示PFS与高ITPKB VAF(≥28％)相关(HR=3.592,95％CI:1.738～7.425,P<0.001),是PFS独立的不良预测因素.结论 ITPKB突变高负荷为DLBCL患者PFS的独立危险因素,ITPKB突变的VAF在DLBCL患者中具有预后预测价值.

Cases of disseminated visceral Kaposi's sarcoma (KS) after allogenic hematopoietic stem cell transplantation (HSCT) are very rare worldwide, and disseminated visceral KS is often rapidly progressive and life-threatening, especially in paediatric patients. Here, the case of a 6-year-old female patient with disseminated visceral KS after allogeneic HSCT for treating severe aplastic anaemia is presented. The authors encountered difficulties in making the diagnosis due to lack of experience, but the diagnosis was achieved relatively quickly and accurately using metagenomic next-generation sequencing. After tapering and withdrawal of immunosuppressant drugs, the patient's condition was controlled. In conclusion, although HSCT-related KS is very rare, it should be considered during differential diagnosis.

Objective To retrospectively analyze the clinical manifestations, related laboratory examinations and gene mutation of 20 patients with congenital Fibrinogen disorders (CFD) admitted to our hospital from February 2017 to December 2021, so as to improve the understanding of CFD diagnosis. Methods Clinical characteristics and laboratory examination of 20 CFD patients were collected, and common secondary hypoFibrinemia factors were excluded. Gene sequencing was performed on all exons and flanks of FGA, FGB and FGG genes of 20 patients to find gene mutation sites. The peripheral blood genomic DNA was collected from the family members of two CFD patients, and the genes of the corresponding mutation sites of the proband were detected. Results The 20 CFD patients had no history of bleeding; 11 female patients had no history of spontaneous abortion; all 20 patients had reduced Fib and prolonged thrombin time (TT). There were 13 gene mutations of different types in 20 patients, among which 90% (18/20) were missense mutations, 5% (1/20) was deletion mutation, and 5% (1/20) was frameshift mutation. Seven patients (35%) had Arg35His mutation at site 104 of the FGA chain, among which 3 new gene mutations have not been reported in China. Conclusion Most CFD patients with mild or asymptomatic symptoms can be diagnosed by genetic testing and screening. FGA chain Arg35His is a mutation hotspot in this region, and all of them are Uyghur. Whether the mutation of this site is related to ethnicity needs to be confirmed by further studies.

目的 研究循环肿瘤DNA(ctDNA)作为弥漫大B细胞淋巴瘤(DLBCL)患者早期预后预测指标的可行性.方法 选取新疆维吾尔自治区人民医院血液病科2020年1月-2021年12月收入的50例DLBCL患者为观察组,另选同期50例健康体检者为对照组.采集空腹静脉血测定血浆ctDNA并对比,采用Spreaman相关性分析法检验血浆ctDNA与DLBCL患者Ann Anbor分期、分型、C-MYC测定结果的相关性,绘制受试者操作特征曲线(ROC)评价ctDNA检测早期预测DLBCL患者预后的价值.结果 观察组与对照组比较,观察组内不同Ann Anbor分期、分型、C-MYC测定结果、治疗时间段、疗效患者的血浆ctDNA差异均具有统计学意义(P<0.05);Spreaman相关性分析结果显示,血浆ctDNA与DLBCL患者Ann Anbor分期、分型、C-MYC测定结果均呈正相关关系(r=0.74、0.80、0.85,P<0.05);ROC显示,血浆ctDNA预测DLBCL患者预后的截断值为8.88 ng/mL,曲线下面积、灵敏度、特异度分别为0.945、93.18％、83.33％.结论 在DLBCL患者早期预后预测中血浆ctDNA可作为重要预测指标加以推广使用.

Objective: To detect the chromosomal abnormalities in patients with multiple myeloma (MM) by fluorescence in situ hybridization (FISH) and to explore their correlation with clinical significance and prognostic value.Methods: 83 MM patients who were treated in our hospital from April 2015 to January 2017 were selected as the observation group, and 12 patients with non-hematological malignant diseases who provided bone marrow specimens were selected as the control group. The IGH, 1q21, RB1, D13S319, and p53 probes were used to detect FISH in MM patients and observe chromosomal abnormalities. Correlation with clinical data (age, R-ISS stage, bone loss, white blood cells, platelets, hemoglobin, erythrocyte sedimentation, creatinine, globulin, albumin, and C-reactive protein (CRP)), clinical significance, and prognostic value were analyzed.Results: Among 83 patients with MM, 64 (77.11%) had chromosomal abnormalities, and 19 patients had negative test results. Among those with abnormalities, 8 cases (12.50%) had all four of the chromosomal abnormalities tested for via FISH, 17 cases (26.56%) had three kinds of abnormalities, and 16 cases (25.00%) had two kinds of abnormalities. There were 23 cases (35.94%) with only one chromosome abnormality. We found that IGH rearrangement was related to bone damage and albumin, 1q21 amplification was related to CRP, and 13q14 deletion was related to hemoglobin, albumin and globulin levels, and R-ISS stage. 17p13 deletion was significantly correlated with albumin, platelet, albumin, and globulin levels and R-ISS stages. Among the positive and negative FISH test results, the CR, PR, SD, and PD patients were significantly different in the T-VAD group (P<0.05), but not significantly different in the PAD group (P>0.05). Among the patients with chromosomal abnormalities, the treatment effect was worse than that of patients with negative results. Patients with IGH rearrangement and 17p13 deletion had significantly lower survival time. Patients with normal chromosomes had a significantly negative correlation with prognosis (P<0.05), while 1q21 amplification and 13q14 deletion had no significant correlation with patient prognosis. IGH rearrangement and 17p13 deletion are independent risk factors that affect the prognosis of this group of MM patients.Conclusions: Most patients with MM have chromosomal abnormalities, which are related to some specific clinical measurements. FISH test can identify patients with these abnormalities, who have poorer treatment effect and poor prognosis.

目的 回顾性分析2016年2月～2020年1月就诊于本院的凝血因子Ⅻ缺乏症7例病例患者临床表现、实验室特征,以提高对此类疾病诊治方法的认识.方法 对7例病例凝血因子Ⅻ缺乏患者的临床资料进行分析,并复习相关文献.结果 7例患者均以APTT明显延长为主要表现,无出血、血栓表现,有1例有阳性家族史,有1例为肿瘤继发的获得性凝血因子Ⅻ缺乏症.结论 临床工作中APTT延长但无出血表现患者需全面筛查相关内外源凝血因子和获得性因素非常必要,以避免漏诊,误诊以及过度治疗.

MicroRNAs (miRNAs) function as post-transcriptional mediators for genes involved in cancer progression, including chronic lymphocytic leukemia. MiR-582-5p has been identified as a tumor suppressor in various tumors. The antioncogenic role of miR-582-5p was then validated in this study. Mononuclear cells were isolated from peripheral blood samples of patients with chronic lymphocytic leukemia and healthy donors. Expression of miR-582-3p in the mononuclear cells was examined by qRT-PCR. CCK8 assay was performed to detect cell viability, and cell cycle and apoptosis were evaluated by flow cytometry. Dual luciferase activity assay was performed to determine the targeting relationship between miR-582-3p and HNRNPA1, and western blot was performed to unravel the mechanism. MiR-582-5p was reduced in mononuclear cells of patients with chronic lymphocytic leukemia compared to healthy donors. Forced miR-582-5p expression reduced cell viability, and promoted apoptosis of chronic lymphocytic leukemia cells. Cell cycle was arrested in G0/G1 phase via miR-582-5p mimic. MiR-582-5p bound to HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1) and down-regulated its expression. Silence of HNRNPA1 decreased cell viability, promoted apoptosis, and blocked cell cycle at G0/G1 phase through up-regulation of IκBα (IkappaBalpha). Moreover, HNRNPA1 silencing attenuated the promotive effect induced by miR-582-5p inhibitor on the progression of chronic lymphocytic leukemia. MiR-582-5p demonstrated anti-proliferative and pro-apoptotic roles in chronic lymphocytic leukemia cell growth via down-regulation of HNRNPA1 and up-regulation of IκBα, thus inactivating NF-κB.

目的:对地西他滨联合CAG、微移植治疗老年急性髓系白血病进行临床分析.方法:将2015年1月至2016年7月我院收治的80例老年急性髓系白血病患者随机分为观察组与对照组,各40例,其中对照组接受地西他滨联合CAG治疗,观察组在对照组基础上联合微移植治疗.对比两组临床疗效、不良反应发生率、生存率、微小残留病及WT1基因含量.结果:观察组治疗总有效率为75.0％,对照组为50.0％,两组患者临床疗效差异具有统计学意义(x2=6.572,P=0.0374).观察组不良反应发生率为27.50％,对照组为22.50％,两组患者不良反应发生率比较差异无统计学意义(x2=0.2667,P=0.6056).观察组与对照组的2年无白血病生存率分别为49.8％和25.2％ (P=0.044),2年总生存率分别为54.2％和31.7％(P=0.069).观察组低水平微小残留病例数及WT1基因低表达病例数均多于对照组,且差异具有统计学意义(P＜0.05).结论:地西他滨联合微移植是一种安全有效的巩固方案,适用于老年急性髓系白血病患者.

Aim: To investigate the targets of miR-181b in patients with chronic lymphocytic leukemia (CLL). Materials & methods: The bioinformatic softwares were used to indicate the key target genes associated with miR-181b, and the results were verified in CLL patient samples and 293T cells. Results:CARD11 is a potential target gene of miR-181b, an inverse relationship was revealed between the expression of CARD11 and miR-181b in 104 CLL patients, and it was confirmed in vitro with luciferase assays and western blotting. Kaplan-Meier analysis showed that CLL patients with high CARD11 expression demonstrated poor survival. Conclusion:CARD11 is a novel target of miR-181b that is upregulated, which could be a poor prognostic indicator for CLL patients.

Chidamide has demonstrated significant clinical benefits for patients with relapsed/refractory (R/R) PTCL in previous studies. This multi-center observational study was aimed to evaluate the objective response rate (ORR), overall survival (OS), and safety of chidamide. From February 2015 to December 2017, 548 patients with R/R PTCL from 186 research centers in China were included in the study. Among the 261 patients treated with chidamide monotherapy, ORR was 58.6% and 55 patients (21.1%) achieved complete response (CR). Among the 287 patients receiving chidamide-containing combination therapies, ORR was 73.2% and 73 patients (25.4%) achieved CR. The median OS of all patients was 15.1 months. The median OS of patients receiving chidamide monotherapy and combination therapies was 433 and 463 days, respectively. These results demonstrate a significant survival advantage of chidamide treatments as compared with international historical records. Common adverse effects (AEs) were hematological toxicities. Most AEs in both monotherapy and combined treatments were grade 1–2. No unanticipated AEs occurred. In conclusion, chidamide-based therapy led to a favorable efficacy and survival benefit for R/R PTCL. Future studies should explore the potential advantage of chidamide treatment combined with chemotherapy.

[目的]探讨吉西他滨联合奥沙利铂治疗复发或难治性非霍奇金淋巴瘤(NHL)的临床疗效.[方法]回顾性分析2015年7月至2018年7月在本院诊治的86例复发或难治性NHL患者的临床资料,根据治疗方法不同分为对照组(采用长春瑞滨联合奥沙利铂治疗)和观察组(采用吉西他滨联合奥沙利铂治疗),每组43例.比较两组患者临床疗效和不良反应发生率.[结果]治疗后,观察组患者临床总有效率为72.09％(31/43),与对照组的62.79％(27/43)比较,差异无统计学意义(χ2=0.847,P=0.357);治疗后,两组KPS评分高于治疗前(P<0.05),但两组间比较差异无统计学意义(P>0.05);观察组血小板减少、胃肠道反应、周围神经症状发生率低于对照组(P<0.05);随访12个月,观察组无进展生存率、总生存率分别为58.14％(25/43)、81.40％(35/43),与对照组的55.81％(24/43)、76.74％(33/43)比较,差异均无统计学意义(χ2=0.047,P=0.827;χ2=0.281,P=0.596).[结论]奥沙利铂联合吉西他滨或长春瑞滨治疗复发或难治性NHL的疗效相当,且前者毒副反应更少.

OBJECTIVE:To explore the value of CpG-oligonucleotide(CpG-ODN) immunostimulatory method in chromosome culture of chronic lymphocytic leukemia (CLL) cells and to compare the differences between related studies at home and abroad, so as to improve the success rate of CLL karyotype culture and the detection rate of abnormal karyo-types.METHODS:Bone marrow samples from 82 CLL patients were collected and cultured with phytohemagglutinin (PHA), CpG-oligonucleotide plus interleukin-2 (CpG-ODN DSP30+IL-2) for 72 hours. Chromosomes were prepared and analyzed by conventional cytogenetics (CC). Meanwhile, D13S25, Rb1, ATM, p53 and CSP12 probes were used for interphase fluorescence in situ hybridization (iFISH) test. The differences of chromosome culture and iFISH test results between two cell stimulants were compared.RESULTS:The success rate of karyotype culture in PHA and CpG-ODN DSP30+IL-2 immunostimuli (analyzable mitotic t >20) was 90.2% (74 cases), 68.3% (56 cases) respectively, and the detection rate of abnormal karyotype was 13.5% (10 cases) and 46.4% (26 cases), respectively. The success rate of karyotype culture in PHA group was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.01). The detection rate of abnormal karyotypes in CpG-ODN DSP30+IL-2 group was significantly higher than that in PHA group, and the difference was statistically significant (P=0.003). The detection rate of abnormal karyotypes in iFISH group was 74.4% (61 cases), which was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.000). iFISH detection could verify the abnormalities detected by CC analysis.CONCLUSION:Application of CpG-ODN DSP30+IL-2 immunostimulation method in culture of CLL cells can enhance the detection rate of abnormal karyotypes, especially the detection of various translocations suggesting poor prognosis.