Resveratrol (Res), a natural polyphenolic compound, exhibits multiple antitumor activities against acute myeloid leukemia (AML), though its mechanisms remain incompletely understood. In this study, CCK-8 assay, CFSE flow cytometry, Transwell assays, and flow cytometry assessed proliferation, invasion, migration, and programmed cell death in MV4-11 and MOLM-13 leukemic cell lines. Western blotting examined cell death regulatory factors (Cleaved-caspase 3/caspase 3, Bax, Bcl-2), aerobic glycolysis proteins (GLUT1, HK2, LDHA, PKM2), cuproptosis-related proteins (FDX1, DLAT, Lip-DLAT, DLST, Lip-DLST, HSP70, SDHB), and PI3K/AKT pathway proteins (p-PI3K/PI3K, p-AKT/AKT). Intracellular Cu2⁺ levels were measured colorimetrically, while glucose uptake, lactate, and ATP levels were quantified to evaluate cellular metabolism. Mechanistic investigations utilized PFKFB3 overexpression, PI3K activator (740 Y-P), and inhibitor (LY294002) intervention experiments. The antitumor efficacy of Res was validated in an AML xenograft mouse model. Res significantly inhibited AML cell proliferation, invasion, and migration while promoting apoptosis. It markedly downregulated FDX1, Lip-DLAT, Lip-DLST, and SDHB while upregulating HSP70 and intracellular Cu2⁺, inducing cuproptosis—an effect reversible by the cuproptosis inhibitor TTM. Res reduced glucose uptake, lactate production, ATP generation, and downregulated GLUT1, HK2, LDHA, and PKM2, thereby suppressing aerobic glycolysis-a process reversed by PFKFB3 overexpression. Furthermore, Res inhibited PI3K and AKT phosphorylation; the PI3K activator 740 Y-P counteracted Res-mediated effects while the PI3K inhibitor LY294002 enhanced them. In vivo experiments confirmed that Res treatment markedly diminished tumor size and mass, lowered Ki-67 proliferation marker, enhanced programmed cell death, suppressed PI3K/AKT signaling, decreased glycolytic enzyme levels, and elevated copper-dependent cell death mediators. Res exerts anti-AML effects by inhibiting the PI3K/AKT pathway while coordinately regulating aerobic glycolysis and cuproptosis in AML cells. Resveratrol effectively suppresses tumor progression by inhibiting the PI3K/AKT axis, downregulating aerobic glycolysis, and promoting cuproptosis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is the major cause of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Xenopax, a novel and the only available humanized interleukin-2 (IL-2) receptor antagonist, has been approved as a category 2 biological product by the National Medical Products Administration. This study aims to evaluate the efficacy, safety, and prognostic factors of xenopax treatment for SR-aGVHD in real-world settings. This was a multicenter, retrospective analysis that included SR-aGVHD patients who received xenopax at 17 hospitals across China. The data were collected from the electronic medical records in transplant databases. The primary endpoint was the 28-day overall response rate (ORR), encompassing both partial and complete responses. This study also included independent historical SR-aGVHD cohorts treated with best available treatments (BATs, n = 1009) as controls. In total, 172 SR-aGVHD patients were included in this study. Xenopax was administered either as monotherapy (n = 60) or in combination with other second-line treatments (n = 112). The ORR was 64.5

Acute myeloid leukemia (AML) is a malignant tumor of blood cells, which seriously interferes with the generation of normal cells. Although miR-186-5p is diminished in AML, its exact mechanism is not well understood. miR-186-5p and PD-L1 levels in AML cells (HL-60, KG-1, TF-1a, MOLT-3) and subcutaneous tumor tissue were discovered through qRT-PCR and Western blot. miR-186-5 p and PD-L1 combining sites were foreseen by the database and verified by dual luciferase and immunoprecipitation experiments. AML cells with miR-186-5p overexpression or knockdown and PD-L1 overexpression were cocultured with CD4+ and CD8+ T cells. The proliferation, migration, invasion and apoptosis of AML cells, CD8+ and CD4+ T cell growth and apoptosis, and activated markers (Perforin and Granzyme B) and secreted cytokines (IFN-γ, IL-4 and TNF-α) levels were detected by CCK8, Transwell, flow cytometry, CFSE, Western blot and ELISA, respectively. Subcutaneous xenograft magnitude and mass in nude mice were measured. Ki67 level was identified through immunohistochemistry. CD4+ and CD8+ T cell level and infiltration were detected by immunofluorescence and flow cytometry. miR-186-5p was downregulated, and PD-L1 was boosted in AML cells and subcutaneous tumor tissues (p < 0.05), while miR-186-5p targeted down-regulate PD-L1. miR-186-5p upregulation hindered AML cell multiplication, migration, invasion and facilitate cell death, and enhanced the proliferation activity, activation markers (Perforin and Granzyme B) and secreted cytokines (IFN-γ, IL-4, TNF-α) of CD8+ and CD4+ T cells, inhibited apoptosis, and inhibited immune escape (p < 0.05). Knockdown of miR-186-5p can promote AML progression, but PD-L1 upregulation weakens the antitumor impact of miR-186-5p overexpression (p < 0.05). Transplanted tumor mice experiments also found that miR-186-5p hindered PD-L1 and tumor growth (p < 0.05). In conclusion, miR-186-5p can target inhibit PD-L1, suppress AML cells multiplication, movement, invasion and immune escape, and then reduce AML, aiming to provide support and basis for the pathological mechanism and prevention and treatment strategy of AML.

Objective: To evaluate the value of enhanced magnetic resonance imaging (MRI) on the assessment of synovial hyperplasia and International Prophylaxis Study Group (IPSG) score of hemophilic arthropathy (HA). Methods: This was a retrospective case series study. Briefly, 54 joints of 46 male patients with hemophilia type A and diagnosed with HA in Henan Provincial People's Hospital from August 2016 to September 2017 were selected. Plain and enhanced MRI were performed at the same time. The IPSG score of synovial hyperplasia and the total joint before and after enhancement were calculated, and the enhancement rate of the synovium and muscles at the same level were also calculated. The differences in synovial hyperplasia and joint total IPSG scores before and after enhancement were compared by paired rank sum test. The correlation between enhancement joint total IPSG score, synovial IPSG score, synovial enhancement rate, total joint bleeding number, course of disease, and Hemophilia Joint Health Score (HJHS) score were analyzed by Spearman's correlation analysis. Results: Enhanced MRI could more clearly show synovial hyperplasia and ensure better accuracy of joint total IPSG score (Z=-2.24, P=0.025). The enhancement extent of synovial hyperplasia was higher than that of the same level muscle. There was no correlation between synovial enhancement rate and total number of joint bleeding, course of disease, and HJHS score. After enhancement, the joint total IPSG score was highly positively correlated with the total number of joint bleeding and the disease course (r=0.96, 0.84, P<0.001) and moderately positively correlated with the HJHS score (r=0.58, P<0.001). The enhanced synovial IPSG score showed a low positive correlation with the total number of joint bleeding and the disease course (r=0.37, 0.36, P=0.006, 0.008), but no correlation with HJHS score. Conclusion: Enhanced MRI can provide accurate imaging of synovial hyperplasia of HA and make joint IPSG score more accurate.

OBJECTIVE:To investigate the value of serum free light chain (sFLC) and serum calcium ion in the diagnosis and prognosis of multiple myeloma (MM). METHODS:Forty patients with MM treated in Henan Provincial People's Hospital from January 2018 to January 2022 were selected as the observation group, and 40 healthy volunteers were selected as the control group. The differences of sFLC-κ、sFLC-λ、sFLC-κ/λ, serum calcium ions, etc between the two groups were compared. Meanwhile, the differences of sFLC-κ、sFLC-λ、sFLC-κ/λ, serum calcium ions, etc in different international staging systems (ISS), chemotherapy efficacy and prognosis patients were analyzed. RESULTS:The levels of sFLC-κ［(98.39±21.19) vs (12.01±4.45) mg/L］, sFLC-λ［(210.20±45.54) vs (14.10±5.11) mg/L］ and proportions of hypocalcemia （65% vs 0） in the observation group were significantly higher than those in the control group (P < 0.05), while sFLC-κ/ λ ratio［（0.44±0.10） vs (0.87±0.12)］ and serum calcium ions ［（1.98±0.46） vs （2.42±0.40）mmol/L］ were significantly lower than those in the control group (P < 0.05). The sFLC-κ, sFLC-λ, the proportion of hypocalcemia and the course of hypocalcemia in ISS stage III patients in the observation group were significantly higher than those in stage I and II patients (P < 0.05), while sFLC-κ/λ ratio, and serum calcium ions were significantly lower than those in stage I and II patients (P < 0.05). The levels of sFLC-κ ［（107.76±21.22） vs （94.67±20.11）mg/L］, sFLC- λ［（245.54±41.12） vs （205.54±50.22）mg/L］ of patients with hypocalcemia in the observation group was significantly higher than those without hypocalcemia (P < 0.05), while the sFLC-κ/λ ratio was significantly lower than those without hypocalcemia ［（0.42±0.04） vs （0.47±0.06）；P < 0.05］. The levels of sFLC-κ ［(107.29±20.14） vs （ 91.11±18.92）mg/L］, sFLC-λ［（247.98±42.26） vs （179.29±39.32）mg/L］ in patients with ineffective chemotherapy were significantly higher than those in patients with effective chemotherapy (P < 0.05), while the sFLC-κ/λ ratio was significantly lower than those in patients with effective chemotherapy ［(0.43±0.10) vs (0.50±0.09)；P < 0.05）］. The area under the ROC curve for sFLC-κ, sFLC-λ, sFLC-κ/λ predicting ineffective chemotherapy was 0.803, 0.793 and 0.699 respectively, P < 0.05. There was no significant difference in sFLC-κ, sFLC-λ, sFLC-κ/λ ratio, serum calcium ion, hypocalcemia ratio and hypocalcemia course between survival and death patients (P >0.05). CONCLUSION:sFLC and serum calcium are related to ISS stage of MM patients. sFLC level has a certain value to predict the curative effect of chemotherapy in MM patients. However, the prognostic values of sFLC and serum calcium are not yet confirmed for MM patients.

目的 探讨外周血淋巴细胞亚群及MRI特征与乳腺癌Luminal分型的相关性.方法 回顾性分析 253例Luminal型乳腺癌外周血淋巴细胞亚群及其MRI特征,以ER阳性/HER-2 阴性/Ki-67<20%/PR>20%作为Luminal A型乳腺癌分型标准将患者分成Luminal A型和B型两组.分析临床病理、外周血淋巴细胞亚群及乳腺MRI等特征在两组患者中的差异,用Logistic回归分析乳腺癌Luminal B型的独立影响因素及其预测效能.结果 (1)253 例Luminal型乳腺癌患者中Luminal A型61 例,Luminal B型192 例;病理SBR分级高、腋窝淋巴结转移及脉管侵犯的患者更易出现在Luminal B型中,且差异均有统计学意义(P值均<0.05).(2)Luminal B型乳腺癌辅助T淋巴细胞绝对数的中位数较Luminal A型乳腺癌的低(691 vs 773),且差异有统计学意义(P =0.033).(3)MRI上病灶越大、BI-RADS分类越高及腋窝淋巴结转移的患者易出现在Luminal B型乳腺癌患者中,且差异均有统计学意义(P值均<0.05).(4)Logistic回归分析结果表明病理SBR 3 级及MRI上病灶≥20 mm是Luminal B型乳腺癌的独立影响因素,其OR值分别为22.182 和1.981;基于病理分级及MRI上病灶大小及二者联合预测Luminal B型乳腺癌的曲线下面积分别为0.678、0.623 和0.740.结论 乳腺癌的临床病理、外周血淋巴细胞亚群及MRI特征与Luminal分型有一定的相关性,且病理分级及MRI上病灶大小是Luminal B型乳腺癌的独立影响因素.

Introduction Immunosuppressive therapy (IST) for acquired hemophilia A (AHA) results in remission within days to months in 60% to 80% of patients. However, little is known regarding the predictors of response. Aim This study aimed to identify the factors that influence response to treatment. Methods The data of 42 patients with AHA from three hospitals were retrospectively analyzed. Results All 42 AHA patients received IST; complete treatment data were available for 34 patients. The response rate was 60% among the 5/34 (14.7%) patients who received steroids alone, 70.8% among the 24/34 (70.6%) patients who received steroids plus cyclophosphamide, and 80% among the 5/34 (14.7%) patients who received steroids plus cyclophosphamide and rituximab. Overall, 29/34 (85.3%) patients achieved CR; 4/34 (13.8%) of them relapsed after a median time of 410 (21–1279) days. Adverse events occurred in 14/34 (41.2%) patients: 13/34 (38.2%) had infections and 1/34 (2.9%) developed pancytopenia. In univariate and multivariate Cox regression analyses, FVIII inhibitor titer ≥20 BU/mL was the only significant prognostic factor affecting time to CR. No variable had significant effect on OS. Conclusion FVIII inhibitory antibody titer ≥20 BU/mL appears to be an important predictor of time to complete response in patients with acquired hemophilia A treated with immunosuppressive therapy.

Background: FRSW 107, a novel homodimer recombinant factor VIII (rFVIII) Fc fusion protein, is the first domestic extended half-life (EHL) rFVIII under development in China，and is currently at stage of Biologics License Application (BLA) in NMPA for the prophylaxis and treatment of bleeding episodes in adolescent and adult (≥12 yr) with hemophilia A (HA). Aims: This phase III (NCT04456387, CTR20201212), open-label, non-randomized, multicenter trial aimed to evaluate the pharmacokinetics (PK), safety, and clinical efficacy of FRSW 107 for prophylaxis and treatment of bleeding in previously treated HA patients ≥12 yr. Methods: Eligible patients included male severe HA (FVIII:C< 1%) ≥12 yr, previous treatment with FVIII concentrates for ≥150 exposure days (EDs), and absence of FVIII inhibitors (＜0.6 Bethesda Units/mL). A total of 119 patients received FRSW 107 for prophylaxis treatment (n=83) or on-demand treatment (n=36). The patients in the prophylaxis group were administered one dose of 50 IU/kg of FRSW 107 every three days for at least 50 EDs for a minimum period of 6 months, and the primary efficacy endpoint was annualized bleeding rate (ABR). The patients in the on-demand treatment group received 30 to 50 IU/kg of FRSW 107 over 6 months, according to the severity and location of the bleeding, and the primary efficacy endpoint was hemostatic effect (excellent, good). The single-dose and repeat dose PK parameters of 15 patients in the prophylaxis group were analyzed at ED1 and ED35, respectively. Results: In the prophylaxis group, the mean and median annualized bleeding rate (ABR) were 1.61±3.74 and 0.00 (IQR, 0.00-2.02), decreased by 95.01% versus the baseline 32.24±23.98 and 26.00 (IQR, 16.00-46.00), and 56 (67.5%) patients had no bleeds during the trial. Detailed ABR data for prophylaxis group was included in the table below. In the on-demand treatment group, hemostatic efficacy was rated as "excellent” or "good” for 98.9% of bleeds. 97.9% of 721 reported bleeds were treated with ≤2 injections. No FVIII inhibitors have been reported in this study. Drug-related adverse events (AEs) occurred in 10.1% of the patients. No SAE was judged to be related to FRSW107 treatment. No thromboembolic events were reported, and there are no unexpected safety concerns. The terminal half-life of FRSW 107 ranged between 20 to 22 hours. The incremental recovery (IR) was approximately 2.14 (IU/dL)/(IU/kg). The PK parameters and profiles remained consistent between ED1 and the repeated dosing at ED35. Conclusions: The data indicate that FRSW 107 was safe and effective for prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult HA patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

背景:环孢素联合4次短程甲氨蝶呤方案仍是目前公认的、经典的预防急性移植物抗宿主病方案,以往研究显示在同胞全相合移植后第11天是否应用甲氨蝶呤对于急性移植物抗宿主病的发生率没有影响,但减少第11天甲氨蝶呤对单倍体造血干细胞移植患者急性移植物抗宿主病发生率的影响仍不清楚.目的:探讨移植物抗宿主病预防方案中去除第11天甲氨蝶呤的应用对单倍体造血干细胞移植患者发生急性移植物抗宿主病的影响.方法:回顾性分析2017年1月至2019年12月接受单倍体造血干细胞移植治疗的63例恶性血液病患者的临床资料,移植物抗宿主病预防方案为环孢素联合甲氨蝶呤15 mg/m2(第1天),10 mg/m2(第3,6,11天).在第11天时发生严重口腔黏膜炎(Ⅲ-Ⅳ级)的患者,取消第4次甲氨蝶呤应用,归为观察组,共19例;在第11天时发生轻度口腔黏膜炎(0-Ⅱ级)的患者,按标准方案继续第4次甲氨蝶呤应用,归为对照组,共44例.对两组植入情况、急性移植物抗宿主病发生率、总体生存率及复发率进行分析.结果 与结论:①中位随访时间30(3-54)个月,两组患者中性粒细胞全部植活,中位植入时间分别为12(9-29)d和12(8-25)d,差异无显著性意义(P=0.682);观察组1例血小板植入不良,对照组4例血小板植入不良,可分析数据两组中位植入时间分别为12(9-18)d和13(9-31)d,差异无显著性意义(P=0.71);②急性移植物抗宿主病总体发生率为44.4％,Ⅱ-Ⅳ度急性移植物抗宿主病为28.6％;观察组及对照组Ⅱ-Ⅳ度急性移植物抗宿主病发生率分别为31.5％,27.3％,差异无显著性意义(P=0.728);③结果 表明,对于单倍体造血干细胞移植,与标准甲氨蝶呤预防方案比较,去除第11天甲氨蝶呤的应用并不引起急性移植物抗宿主病发生率升高.

目的:探讨外周血淋巴细胞亚群及病灶磁共振成像(magnetic resonance imaging,MRI)特征与乳腺癌腋窝淋巴结(axillary lymph node,ALN)转移的相关性及其辅助提高ALN转移诊断准确度的价值.方法:回顾并分析348例乳腺癌外周血淋巴细胞亚群及其MRI特征,根据患者ALN外科评价结果将其分为ALN转移组和无转移组.分析临床病理学、外周血淋巴细胞亚群及乳腺MRI特征在两组患者中的差异,采用logistic回归分析乳腺癌ALN转移的独立影响因素,并采用受试者工作特征(receiver operating characteristic,ROC)曲线评价其诊断效能.结果:348例乳腺癌患者中ALN转移者103例和无转移者245例;多发病灶、人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阳性、Ki-67增殖指数>20％及淋巴管血管侵犯的患者易出现ALN转移(P<0.05).总T淋巴细胞绝对数和细胞毒性T淋巴细胞绝对数在转移组患者中明显减低,且差异均有统计学意义(P分别为0.044和0.023).MRI上病灶越大的患者越易发生ALN转移,且在两组患者中差异有统计学意义(P<0.001);按照MRI形态学诊断标准,本研究中共检出可疑ALN转移患者146例(42.0％),其诊断的灵敏度、特异度和准确度分别为77.7％、73.1％和74.4％.临床病理学特征及病灶MRI特征、淋巴结MRI形态学特征及两者联合3种方法诊断ALN转移的AUC分别为0.761、0.755和0.851.结论:外周血淋巴细胞亚群及病灶MRI特征与乳腺癌ALN转移有一定的相关性;临床病理学特征及病灶的MRI特征有助于提高乳腺癌ALN转移诊断的准确度.

Acute myeloid leukemia (AML) is as a highly aggressive and heterogeneous hematological malignancy. MiR-20a-5p has been reported to function as an oncogene or tumor suppressor in several tumors, but the clinical significance and regulatory mechanisms of miR-20a-5p in AML cells have not been fully understood. In this study, we found miR-20a-5p was significantly decreased in bone marrow from AML patients, compared with that in healthy controls. Moreover, decreased miR-20a-5p expression was correlated with risk status and poor survival prognosis in AML patients. Overexpression of miR-20a-5p suppressed cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis in two AML cell lines (THP-1 and U937) using CCK-8 assay and flow cytometry analysis. Moreover, miR-20a-5p overexpression attenuated tumor growth in vivo by performing tumor xenograft experiments. Luciferase reporter assay and western blot demonstrated that protein phosphatase 6 catalytic subunit (PPP6C) as a target gene of miR-20a-5p was negatively regulated by miR-20a-5p in AML cells. Furthermore, PPP6C knockdown imitated, while overexpression reversed the effects of miR-20a-5p overexpression on AML cell proliferation, cell cycle G1/S transition and apoptosis. Taken together, our findings demonstrate that miR-20a-5p/PPP6C represent a new therapeutic target for AML and a potential diagnostic marker for AML therapy.

[13] Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification[J]. J Clin Oncol, 2014, 32(27): 30593068. DOI: 10.1200/JCO. 2013.54.8800. [14] Lok AS, Liang RH, Chiu EK, et al. Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy. Report of a prospective study[J]. Gastroenterology, 1991, 100(1):182188. DOI: 10.1016/0016-5085(91)90599-g. [15] Chen J, Wang J, Yang J, et al. Concurrent infection of hepatitis B virus negatively affects the clinical outcome and prognosis of patients with non-Hodgkin's lymphoma after chemotherapy[J]. PLoS One, 2013, 8(7): e69400. DOI: 10.1371/journal.pone. 0069400. [16] Deng L, Song Y, Young KH, et al. Hepatitis B virus-associated diffuse large Bcell lymphoma: unique clinical features, poor outcome, and hepatitis B surface antigendriven origin[J]. Oncotarget, 2015, 6(28): 2506125073. DOI: 10.18632/ oncotarget.4677. [17] Dong HJ, Ni LN, Sheng GF, et al. Risk of hepatitis B virus (HBV)reactivation in non-Hodgkin lymphoma patients receiving rituximabchemotherapy: a metaanalysis[J]. J Clin Virol, 2013, 57(3): 209-214. DOI: 10.1016/j.jcv.2013.03.010. [18] Koutsianas C, Thomas K, Vassilopoulos D. Prevention of HBV reactivation in patients treated with biologic agents[J]. Expert Rev Clin Pharmacol, 2016, 9(4): 579589. DOI: 10.1586/ 17512433.2016.1143773. [19]张令, 袁晓莉, 姜丽, 等. 非霍奇金淋巴瘤合并HBV感染患者 的临床特征及预后相关因素分析[J]. 中华血液学杂志, 2018, 39(7): 563568. DOI: 10.3760/cma.j.issn.02532727.2018. 07.007. [20] Su WP, Wen CC, Hsiung CA, et al. Longterm hepatic consequences of chemotherapyrelated HBV reactivation in lymphoma patients[J]. World J Gastroenterol, 2005, 11(34): 52835288. DOI: 10.3748/wjg.v11.i34.5283. (收稿日期:2021-01-26) (本文编辑:律琦)

Objective:To explore the correlation between the expression of signaling lymphocyte activation molecule family 6 (SLAMF6) on peripheral blood CD8 +T cells and perforin and granzyme B and the clinical significance in patients with newly diagnosed severe aplastic anemia(SAA). Methods:The indicators of blood routine and bone marrow and peripheral blood samples of 32 newly diagnosed SAA patients admitted to Henan Provincial People′s Hospital from January 2016 to June 2019 were collected for retrospective analysis. Flow cytometry was used to detect the expression of SLAMF6, perforin and granzyme B on samples CD8 +T cell before therapy and 6 months after therapy (11 cases received transplantation, 21 cases received immunosuppressive therapy [IST]). Spearman correlation analysis was performed to determine the association between clinical indicators and laboratory test results. The expression of SLAMF6, perforin and granzyme B was also detected in 10 healthy people (normal group) and 13 myelodysplastic syndromes/paroxysmal nocturnal hemoglobinuria (MDS/PNH) patients (MDS/PNH group). Results:(1) At diagnosis: the expression of SLAMF6 was significantly lower in the SAA group than that in the normal group and the MDS/PNH group ([56.40±6.37]% vs [84.34±5.81]% and [82.24±4.98]% (both P<0.001]). The expression of perforin was significantly higher in the SAA group (32.73±8.46) than that in the normal control group (23.75%±5.10%), and the MDS/PNH group (26.12%±5.53%) (both P<0.05). The expression of granzyme B was also significantly higher in the SAA group (36.23%±7.94%) than that in the normal control group (21.67%±5.05%) and the MDS/PNH group (21.79%±5.10%) (both P<0.001). The expression of SLAMF6 was positively correlated with the hemoglobin ( r=0.804), and reticulocyte absolute values ( r=0.656) in peripheral blood, percentage of granulocytes ( r=0.643) and erythrocytes ( r=0.622) in bone marrow of SAA patients (all P<0.05). Expression of SLAMF6 was negatively correlated with perforin ( r=-0.792) and granzyme B ( r=-0.908) on CD8 +T cells in patients with SAA (both P<0.001). (2) After treatment: the expression of SLAMF6 in peripheral blood CD8 +T cells of 30 surviving patients was higher than pre-treatment ([79.19±12.69]% vs [56.40±6.37]%, P<0.001). The expressions of perforin and granzyme B were lower than pre-treatment level (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 11 transplanted patients was higher than before transplantation ([86.54±3.75]% vs [56.40±7.35]%, P<0.001). The expressions of perforin and granzyme B were lower than before transplantation (both P<0.05). The expression of SLAMF6 on CD8 +T cells in 12 IST-respond patients was higher than that before treatment, while the perforin and granzyme B levels were lower than pre-treatment (all P<0.05). The post-treatment expressions of SLAMF6, perforin and granzyme B were similar as before treatment levels in 7 IST-unrespond patients (all P>0.05). Conclusion:SLAMF6 is significantly down-regulated on CD8 +T cells in newly diagnosed SAA, negatively correlated with the effective factors of CD8 +T cells, which might participate in the immune regulatory of CD8 +T cells as a negative regulatory factor in patients with SAA. The SLAMF6 is significantly up-regulated after hematopoietic recovery, while there is no significant change in treatment-unrespond patients, which could thus serve as an useful diagnostic and therapeutic index of patients with SAA.

Objective:To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase.Methods:From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy.Results:The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) ( P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy ( P<0.001) and longer duration of imatinib therapy ( P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions:Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

目的 探讨超声及MELCHIORRE评分在儿童血友病性膝关节病诊断中的价值.方法 对35例临床确诊的血友病患儿的35个靶关节进行超声检查,观察受检关节的声像图特点,行MELCHIORRE评分,并同期行MRI增强检查,根据关节病变程度将患儿分为两组,并比较两种检查方法对两组患儿各阳性病变检出情况及评分的一致性.结果 早期软组织病变16例,另19例合并骨、软骨病变,随着出血次数增加,超声评分明显增加(F=0.824,P＜0.01).超声与MRI对16例早期软组织病变(关节积液、滑膜增厚、含铁血黄素沉积)检出的一致性好至优秀(K=0.636～0.818,P＜0.01),两种方法对关节病变评分的一致性好(K=0.747,P＜0.0l);对19例晚期骨软骨病变各阳性病变(关节积液、滑膜增厚、含铁血黄素沉积、软骨破坏)检出的一致性中等至好(K=0.441～0.642,P＜0.05);而对(骨侵蚀、关节下囊肿)检出的一致性差(K=0.224～0.313,P＜0.05),两种方法对关节病变评分的一致性差(K=0.272,P＜0.01).结论 超声与MRI在诊断儿童血友病性膝关节早期软组织病变方面有较好的一致性,超声能够动态监测疾病的活动性,应作为儿童血友病关节随访的首选检查,MELCHIORRE评分适用于早期软组织病变的评估,可作为临床治疗、随访提供依据.

Objective: To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide β(β-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). Methods: From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5b、β-CTX、PINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. Results: After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, β-CTX and vitamin D3 were decreased significantly (P<0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (t=-1.871, P=0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (t=-8.272, P<0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, P=0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, P=0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,t=5.762, P<0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) μg/L vs (15.6±5.5) μg/L, t=-2.478, P=0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, P=0.044). There was no significant difference in the serum concentration of TRACP-5b and β-CTX between two groups. Conclusion: After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, β-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.

OBJECTIVE:To investigate the long-term clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with human herpes virus 8 (HHV8)-positive multicentric Castleman's disease (MCD).METHODS:A 17-year-old female patient was admitted to Henan Provincial People's Hospital with the complaint of febrile for half a month, headache, and enlarged superficial lymph nodes on October 5, 2010. HHV8-positive mixed cellular Castleman's disease was found by pathological diagnosis of lymph nodes biopsy. After the administration of CHOP and Hyper-CVAD-B, the patient was still febrile, we administrated the followed COAP, two courses of VAD(Vincristine, Adriamycin, Dexamethasone), the patient received CR. Six months after CR, the patient relapsed, we administrated VAD and two courses of bortezomide+dexamethasone chemotherapy, and then the patient received PR. After that, the patient underwent allo-HSCT from his human leukocyte antigen (HLA)-matched unrelated donor after conditioning with Bu/Cy+Etoposide+Smoustin.graft-vs-host disease (GVHD) prophylaxis, which consisted of ATG (7.5 mg/kg, qd, ivdrip) from d-5 to d-2, cyclosporine (3 mg/kg/d, qd, ivdrip, for 24 h) started from day-1, MMF(0.5 g, tid, po.) started from day+1 to +28, and MTX (15 mg per time, ivdrip, d+1,+4,+7,+11). She received 3.5×106/L CD34+cells and 8.1×108/LMNC.RESULTS:Granulocyte engraftment occurred on day+12, platelet engrafted on day+14. Bone marrow biopsy showed normalization of trilineage hematopoiesis on day+33, chimerism: 97.6%. The transplantation was successful and followed up for 7 years with CR.CONCLUSION:Allo-HSCT might cure patients with refractory/relapsed HHV8+ MCD.

Daunorubicin (Dnr) is at the forefront of acute myeloid leukemia (AML) therapy, but drug resistance poses a major threat to treatment success. MicroRNA (miR)-9 has been shown to have a pivotal role in AML development. However, little is known about the role of miR-9 in Dnr resistance in AML. We explored the potential role of miR-9 in Dnr resistance in AML cells and its mechanism of action. AML cell lines with high half-maximal inhibitory concentration to Dnr in vivo had significantly low miR-9 expression. miR-9 overexpresssion sensitized AML cells to Dnr, inhibited cell proliferation, and enhanced the ability of Dnr to induce apoptosis; miR-9 knockdown had the opposite effects. Mechanistic studies demonstrated that eukaryotic translation initiation factor 5A-2 (EIF5A2) was a putative target of miR-9, which was inversely correlated with the expression and role of miR-9 in AML cells. miR-9 improved the anti-tumor effects of Dnr by inhibiting myeloid cell leukemia-1 (MCL-1) expression, which was dependent on downregulation of EIF5A2 expression. These results suggest that miR-9 has an essential role in Dnr resistance in AML cells through inhibition of the EIF5A2/MCL-1 axis in AML cells. Our data highlight the potential application of miR-9 in chemotherapy for AML patients.

In this study, we aimed to study the effect of miR-33b in regulating sensitivity to daunorubicin (DNR) in acute myelocytic leukemia (AML). We used quantitative real-time polymerase chain reaction and Cell Counting Kit-8 assay to detect the level of miR-33b and cell viability. Cell apoptosis and the expression of eIF5A-2 and MCL-1 protein were detected by flow cytometry analysis and Western Blot analysis, respectively. MiR-33b mimic increased sensitivity of AML cells against DNR, while miR-33b inhibitor had the opposite effect. Furthermore, the results showed that the eIF5A-2 gene was a direct target of miR-33b, and miR-33b regulated eIF5A-2 mRNA and protein expression. Silencing of eIF5A-2 by RNA interference increased the sensitivity of AML cells against DNR. We also found that MCL-1 contributed to the regulation of DNR sensitivity, which was dependent on downregulation of eIF5A-2. Finally, knockdown of eIF5A-2 eliminated the effects of miRNA-33b mimic or inhibitor on DNR sensitivity. These findings indicate that miR-33b maybe as a new therapeutic target in AML cells.