Hematopoietic stem and progenitor cells (HSPCs) give rise to the blood system and maintain hematopoiesis throughout the human lifespan. Here, we report a transcriptional census of human bone-marrow-derived HSPCs from the neonate, infant, child, adult, and aging stages, showing two subpopulations of multipotent progenitors separated by CD52 expression. From birth to the adult stage, stem and multipotent progenitors shared similar transcriptional alterations, and erythroid potential was enhanced after the infant stage. By integrating transcriptome, chromatin accessibility, and functional data, we further showed that aging hematopoietic stem cells (HSCs) exhibited a bias toward megakaryocytic differentiation. Finally, in comparison with the HSCs from the cord blood, neonate bone-marrow-derived HSCs were more quiescent and had higher long-term regeneration capability and durable self-renewal. Taken together, this work provides an integral transcriptome landscape of HSPCs and identifies their dynamics in post-natal steady-state hemopoiesis, thereby helping explore hematopoiesis in development and diseases.

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only clinical cure for thalassemia major (TM). Graft-versus-host disease (GVHD) and transplant-related mortality (TRM) remain major barriers to clinical outcomes in TM-unrelated donor transplantation (MUD-HSCT). Aims: The role of Basiliximab in preventing acute graft-versus-host disease (aGVHD) after MUD-HSCT in thalassemia major (TM) is still unknown. We performed a prospective, multicenter, open-label, randomized controlled trial (RCT). The study is registered at www.clinicaltrials.gov as #NCT02342145. PATIENTS AND METHODS: Patients with TM with unrelated donor were randomly assigned to a basiliximab group (20 mg/kg basiliximab on days 0 and +4, respectively, plus tacrolimus [FK506], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (FK506, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. Results: From April 2015 and September 2021, a total of 205 TM patients were enrolled. The ratio of male to female was 123 to 82 with a median age of 7 years (range, 2-19 years). Patients were randomly assigned to the basiliximab group of 102 and the control group of 103. Comparison of the basiliximab group and the control group, the cumulative incidence rate of grade 2-4 aGVHD was 24.5% and 29.1%, respectively (P=0.456), and the cumulative incidence rate of grade 3-4 aGVHD was 8.8% and 14.6% (P=0.201); the cumulative incidence rate of moderate or severe chronic GVHD was both 2.9%; median days of neutrophil engraftment were +11.8 and +11.6 days, respectively (P=0.701), platelets Implantation days were +15.4 and +13.5 days (P=0.126); TRM was 3.6% and 7.1% (P=0.249), over survival (OS) was 96.4% and 92.0% (P=0.188), respectively and thalassemia-free survival (TFS) of the two groups was also the same as the OS. There was no significant difference between the basiliximab and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, and transplant-related complications. Subgroup analysis according to the degree of HLA matching showed that the 9/10 mismatch group had significantly lower OS and TFS than the 10/10 matched group (both 82.6% v 96.5%, P=0.004). The 3-year OS and TFS of the entire cohort (205 TM patients ) were 94.1% and 94.0%, respectively(Table 1, Fig 1). CONCLUSION: This first prospective randomized study showed basiliximab at a dose of 20 mg on day 0 and day+ 4 did not reduced the incidence of both aGVHD and cGVHD in patients with TM after MUD-HSCT. The incidence of aGVHD in unrelated donor transplants for TM patients is still high, 9/10 mismatched unrelated donor transplants had poor result when comparing 10/10 matched donor transplants for TM patients. Unrelated donors are still a very good alternative source of donors. The TFS of TM patients treated by unrelated donor transplantation can reach 94.0%. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Hu8F4 is a T cell receptor (TCR)-like antibody with high affinity for leukemia-associated antigen PR1/HLA-A2 epitope. Adapted into a chimeric antigen receptor (CAR) format, Hu8F4-CAR is comprised of the Hu8F4 scFv, the human IgG1 CH2CH3 extracellular spacer domain, a human CD28 costimulatory domain, and the human CD3ζ signaling domain. We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from AML patients in vitro. Previous studies have shown that modification of the Fc domains of IgG4 CH2CH3 spacer regions can eliminate activation-induced cell death and off-target killing mediated by mouse Fc gamma receptor (FcgR)-expressing cells. We generated Hu8F4-CAR(PQ) with mutated Fc receptor binding sites on the CH2 domain of Hu8F4-CAR to prevent unwanted interactions with FcgR-expressing cells in vivo. The primary human T cells transduced with Hu8F4-CAR(PQ) can specifically lyse HLA-A2+ PR1-expressing leukemia cell lines in vitro. Furthermore, both adult donor-derived and cord blood-derived Hu8F4-CAR(PQ)-T cells are active and can eliminate U937 leukemia cells in NSG mice. Herein, we demonstrate that modification of the IgG1-based spacer can eliminate Fc receptor-binding-induced adverse effects and Hu8F4-CAR(PQ)-T cells can kill leukemia in vivo.

OBJECTIVE:To investigate the expression and its relative mechanism of hypoxia-inducible factor-1α(HIF-1α) in bone marrow(BM) of mice during G-CSF mobilization of hematopoietic stem cells (HSC) .METHODS:Flow cytometry was used to detect the proportion of Lin-Sca-1+ c-kit+ (LSK) cells in peripheral blood of C57BL/6J mice before and after G-CSF mobilization. And the expression of HIF-1α and osteocalcin (OCN) mRNA and protein were detected by RQ-PCR and immunohistochemistry. The number of osteoblasts in bone marrow specimens of mice was counted under the microscope.RESULTS:The proportion of LSK cells in peripheral blood began to increase at day 4 of G-CSF mobilization, and reached the peak at day 5, which was significantly higher than that of control group (P<0.05). There was no distinct difference in the expression of HIF-1α mRNA between bone marrow nucleated cells and osteoblasts of steady-state mice (P=0.073), while OCN mRNA was mainly expressed in osteoblasts, which was higher than that in bone marrow nucleated cells (P=0.034). After mobilization, the expression level of HIF-1α increased, but OCN decreased, and the number of endosteum osteoblasts decreased. The change of HIF-1α expression was later than that of OCN and was consistent with the proportion of LSK cells in peripheral blood.CONCLUSION:The expression of HIF-1α in bone marrow was increased during the mobilization of HSC mediated by G-CSF, and one of the mechanisms may be related to the peripheral migration of HSC induced by osteoblasts inhibition.

BackgroundMinimal residual disease (MRD) is an important prognostic factor for survival in adults with acute leukemia. The role of pretransplantation MRD status in myelodysplastic syndrome with excess blasts (MDS-EB) is unknown. This study retrospectively analyzed the relationship between pretransplantation MRD status and long-term survival. Materials and MethodsPatients with MDS-EB who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from March 5, 2005, to November 8, 2020, were included. The relationship between pretransplantation MRD status and long-term survival was analyzed using univariate and multivariate logistic regression models. ResultsOf 220 patients with MDS-EB who underwent allo-HSCT, 198 were eligible for inclusion in this multicenter, retrospective cohort study. Complete remission was attained in 121 (61.1%) patients, and 103 patients underwent detection of MRD pretransplantation, with 67 patients being MRD-positive and 36 patients being MRD-negative. The median follow-up time was 16 months, the median age was 41 years (6-65 years), and 58% of the patients were men. The 3-year disease-free survival (DFS) and overall survival (OS) probabilities for all patients were 70.1% and 72.9%, respectively. For patients in complete remission, the 3-year DFS and OS probabilities were 72.2% and 74.8%, respectively. Further analysis found that the 3-year DFS rates of MRD-negative and MRD-positive patients were 85.6% and 66.5% (p = .045), respectively, whereas the 3-year OS rates were 91.3% and 66.4% (p = .035), respectively. Univariate and multivariate analyses showed that poor pretransplantation MRD clearance was an independent prognostic risk factor for DFS and OS. ConclusionPoor pretransplantation MRD clearance is an independent prognostic risk factor for long-term survival after allo-HSCT for patients with MDS-EB. Plain language summary Poor minimal residual disease clearance pretransplanation is an independent prognostic risk factor for long-term survival after allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome with excess blasts.

This study mainly used The Cancer Genome Atlas (TCGA) RNA sequencing dataset to screen prognostic snoRNAs of acute myeloid leukemia (AML), and used for the construction of prognostic snoRNAs signature for AML. A total of 130 AML patients with RNA sequencing dataset were used for prognostic snoRNAs screenning. SnoRNAs co-expressed genes and differentially expressed genes (DEGs) were used for functional annotation, as well as gene set enrichment analysis (GSEA). Connectivity Map (CMap) also used for potential targeted drugs screening. Through genome-wide screening, we identified 30 snoRNAs that were significantly associated with the prognosis of AML. Then we used the step function to screen a prognostic signature composed of 14 snoRNAs (SNORD72, SNORD38, U3, SNORA73B, SNORD79, SNORA73, SNORD12B, SNORA74, SNORD116-12, SNORA65, SNORA14, snoU13, SNORA75, SNORA31), which can significantly divide AML patients into high- and low-risk groups. Through GSEA, snoRNAs co-expressed genes and DEGs functional enrichment analysis, we screened a large number of potential functional mechanisms of this prognostic signature in AML, such as phosphatidylinositol 3-kinase-Akt, Wnt, epithelial to mesenchymal transition, T cell receptors, NF-kappa B, mTOR and other classic cancer-related signaling pathways. In the subsequent targeted drug screening using CMap, we also identified six drugs that can be used for AML targeted therapy, they were alimemazine, MG-262, fluoxetine, quipazine, naltrexone and oxybenzone. In conclusion, our current study was constructed an AML prognostic signature based on the 14 prognostic snoRNAs, which may serve as a novel prognostic biomarker for AML.

The purpose was to predict the risk of acute kidney injury (AKI) within 100 days after hematopoietic stem cell transplantation (HSCT) in patients with hematologic disease by using a new predictive nomogram. Collect clinical data of patients with hematologic disease undergoing HSCT in our hospital from August 2012 to March 2018. Parameters with non-zero coefficients were selected by the Least Absolute Selection Operator (LASSO). Then these parameters were selected to build a new predictive nomogram model. Receiver operating characteristic (ROC) curve, calibration curve, C-index, and decision curve analysis (DCA) were used for the validation of the evaluation model. Finally, the nomogram was further evaluated by internal verification. According to 2012 Kidney Disease Improving Global Guidelines (KDIGO) diagnostic criteria, among 144 patients, the occurrence of AKI within 100 days after HSCT The rate was 29.2% (42/144). The C-index of the nomogram was 0.842. The C-value calculated by the internal verification was 0.809. The AUC was 0.842, and The DCA range of the predicted nomogram was from 0.01 to 0.71. This article established a high-precision nomogram for the first time for predicting the risk of AKI within 100 days after HSCT in patients with hematologic diseases. The nomogram had good clinical validity and reliability. For clinicians, it was very important to prevent AKI after HSCT.

回顾性分析广西医科大学第一附属医院1例造血干细胞移植(HSCT)受者出现胸膜肺弹力纤维增生症(PPFE)的临床资料，从发病机制、临床表现、肺功能、胸部CT、诊断及治疗方面阐述PPFE的特点。PPFE的治疗尚未达成共识，预后差，药物治疗效果欠佳，肺移植是患者疾病进展至终末期的治疗选择。

The regulatory mechanism of hypoxia-inducible factor-1α (HIF-1α) is complex. HIF-1α may inhibit or promote apoptosis in osteoblasts under different physiological conditions, and induce bone regeneration and repair injury in coordination with angiogenesis. The relationship between H2O2 and HIFs is complex, and this study aimed to explore the role of HIF-1α in H2O2-induced apoptosis. Dimethyloxallyl glycine (DMOG) and 2-Methoxyestradiol (2ME) were used to stabilize and inhibit HIFs, respectively. Cell viability was assessed with CCK8. Apoptosis and ROS levels were detected by flow cytometry, and HIF mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Western blot was performed to detect HIF-1α, HIF-2α, Bax, Bak, Bcl-2, Bcl-XL, caspase-9, and PCNA protein amounts. Our data suggest that both HIF-1α and HIF-2α play a protective role in oxidative stress. HIF-1α reduces H2O2-induced apoptosis by upregulating Bcl-2 and Bcl-XL, downregulating Bax, Bak, and caspase-9, stabilizing intracellular ROS levels, and promoting the repair of H2O2-induced DNA damage to reduce apoptosis.

Objective:To explore the predictive value of peripheral blood CD34-positive cell count for the stem cell mobilization effect of plerixafor in patients with multiple myeloma (MM).Methods:The clinical data of 12 MM patients who used plerixafor for stem cell mobilization in the First Affiliated Hospital of Guangxi Medical University from December 2019 to February 2021 were retrospectively analyzed. The changes of peripheral blood CD34-positive cell count and the collection status of stem cell in all patients before and after the mobilization of plerixafor were analyzed.Results:Twelve patients were included in this study. These patients were in international staging system (ISS) stage Ⅱ-Ⅲ, and the induction therapy was mainly VRD regimen. The CD34-positive cell count was increased after the use of plerixafor in all patients no matter which mobilization strategies were used before plerixafor. The CD34-positive cell count was 3.63/μl (0.72-13.53/μl) and 32.11/μl (8.52-53.68/μl) before and after the use of plerixafor, and the difference was statistically significant ( Z = -0.40, P<0.001); the median increasing time was 11.50 times (1.61-23.71 times). The mobilization failure occurred in 1 patient. The CD34-positive cell count in his blood was less than 1/μl before the use of plerixafor; though increased 11.83 times after the use of plerixafor, the CD34-positive cell count was still less than 10/μl. Pearson analysis showed that among the patients with CD34-positive cell count less than 4/μl before the use of plerixafor, there was a positive correlation in peripheral blood CD34-positive cell count before and after the use of plerixafor ( r = 0.80, P = 0.032). Conclusions:The peripheral blood CD34-positive cell count has a certain predictive value for the stem cell mobilization effect of plerixafor in MM patients.

OBJECTIVE To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT). METHODS The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed. RESULTS Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001). CONCLUSION The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;

Objective: The present study aimed to determine the prognostic value of HOXA cluster antisense RNA2 (HOXA-AS2) in acute myeloid leukemia (AML), and to explore its potential molecular mechanisms. We also screening of potential drugs targeting HOXA-AS2 in AML. Methods: The level 3 raw genome-wide RNA sequencing dataset of AML was download from The Cancer Genome Atlas (TCGA) Data Portal, and the potential molecular mechanisms and drugs prediction of HOXA-AS2 in AML were explored using multiple bioinformatics analysis approaches. Results: TCGA AML cohort dataset indicated that HOXA-AS2 was significantly up-regulated in AML bone marrow tissues, and high HOXA-AS2 expression was related to poor overall survival (log-rank P=0.0284, hazard ratio 1.640, 95% confidence interval 1.046-2.573). Functional enrichment of differentially expressed genes (DEGs) suggested that the difference in prognosis between AML patients with high- and low-HOXA-AS2 expression may be due to differences in biological processes and pathways, including cell adhesion, angiogenesis, mitogen-activated protein kinase, cell differentiation, and other biological processes, and phosphatidylinositol 3 kinase-protein kinase B and Wnt signaling pathways. We also screened out three potential HOXA-AS2-targeted therapeutic drugs for AML, megestrol, carmustine, and cefoxitin, based on these DEGs. Functional enrichment analysis of HOXA-AS2-co-expressed genes revealed that HOXA-AS2 may act a part in AML by regulating nuclear factor-κB transcription factor activity, DNA methylation, angiogenesis, apoptosis, cell migration, Toll-like receptor 4, and Wnt signaling pathways. Conclusion: Our findings suggest that HOXA-AS2 is up-regulated in the bone marrow in patients with AML, and may serve as a novel prognostic biomarker for AML.

None declared. The peer review history for this article is available at https://publons.com/publon/10.1111/odi.13658.

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present prospective study, we aimed to investigate the incidence, management, and outcome of VOD/SOS in patients with thalassemia major (TM) who received allo-HSCT. VOD/SOS was diagnosed and classified based on the modified Seattle criteria. The prophylactic regimen for VOD/SOS was a combination treatment of dalteparin and lipo-PGE1. VOD/SOS was managed through an approach consisting of adequate supportive measures, short-term withdrawal of calcineurin inhibitors (CNIs), and the use of methylprednisolone and basiliximab for graft-versus-host disease prophylaxis. VOD/SOS was found in 54 of 521 patients (10.4%) at a median time of 12 days after allo-HSCT. The cumulative incidence of all-grade and moderate VOD/SOS was 10.4% and 4.2%, respectively. Among the 54 VOD/SOS patients, no patient developed severe grade and died from VOD/SOS. Besides, the cumulative incidence of transplant-related mortality on day 100 for patients with or without VOD/SOS was 0% vs. 4.0% ( P = 0.187), respectively, and the 3-year overall survival rates were 94.3% vs. 93.2% ( P = 0.707), respectively. Collectively, we concluded that appropriate symptomatic therapy and short-term withdrawal of CNIs safely mitigated the mortality of VOD/SOS in TM patients who underwent allo-HSCT.

目的 总结血液病并发革兰阳性菌血流感染患者的临床特点,并分析接受规律治疗的患者的预后影响因素.方法 回顾性分析164例合并革兰阳性菌血流感染的血液病患者的临床资料,按照细菌分离培养时间将病例及其检出病原菌分为A组(2012年6月至2016年5月)及B组(2016年6月至2020年5月).总结两组病原菌的分布和耐药情况、患者的抗菌治疗情况及临床结局.分析接受规律治疗的血液病患者并发革兰阳性菌血流感染后30 d内死亡的影响因素,并评估相关因素预测患者预后的效能.结果 (1)共检出革兰阳性菌172株,包括168株球菌和4株杆菌,检出率位列前四的病原菌依次为凝固酶阴性葡萄球菌、草绿色链球菌、金黄色葡萄球菌及肠球菌.B组的金黄色葡萄球菌检出率高于A组(P<0.05),而两组其他病原体的检出率差异无统计学意义(均P>0.05).(2)耐甲氧西林凝固酶阴性葡萄球菌、耐甲氧西林金黄色葡萄球菌、耐万古霉素肠球菌总检出率分别为83.9％(73/87)、53.8％(14/26)及6.7％(1/15).凝固酶阴性葡萄球菌、金黄色葡萄球菌、草绿色链球菌、肠球菌对万古霉素、替考拉宁、利奈唑胺及替加环素敏感率为93.3％ ～100.0％.(3)初始应用糖肽类抗生素或利奈唑胺者抗生素调整率仅为16.9％,低于初始未应用糖肽类抗生素或利奈唑胺者的62.2％(P<0.05).接受规律治疗的血液病患者并发革兰阳性菌血流感染后30 d内病死率为12.2％.(4)高龄、合并感染性休克、肠球菌血流感染及血流感染当天血清白蛋白<30 g/L是血液病并发革兰阳性菌血流感染患者接受规律治疗后30 d内死亡的独立危险因素(均P<0.05).将4个危险因素作为综合指标,预测血液病并发革兰阳性菌血流感染患者规律治疗后30 d内死亡的曲线下面积为0.943,优于单一危险因素预测的曲线下面积(P<0.05).结论 血液病患者并发革兰阳性菌血流感染时以凝固酶阴性葡萄球菌为主,金黄色葡萄球菌检出率有上升趋势;在完善血培养的同时,早期可经验性应用糖肽类抗生素、利奈唑胺等进行治疗.应重视高龄、合并肠球菌血流感染、感染性休克及血流感染当天血清白蛋白<30 g/L的患者,规律治疗的同时须密切、动态观察病情,以降低病死率.

Background: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for hematological disorders. Tacrolimus is widely used after HSCT, but it has highly interindividual variable pharmacokinetics. Population pharmacokinetics (PPK) researches of tacrolimus in children with β-thalassemia major (β-TM) undergoing HSCT are insufficient. Objective: To establish a PPK model of tacrolimus in children with β-TM and optimize initial dosing regimen for achieving target concentration of 5 to 15 ng/mL. Methods: Data on patients aged <18 years were retrospectively collected from January 2017 to December 2018. PPK analysis and Monte Carlo simulations were performed using nonlinear mixed-effects modeling. Results: A data set of 55 patients with 332 concentrations was included. A 2-compartment model could best describe the pharmacokinetics of tacrolimus. The body surface area and gender were significant covariates in the final model. The typical value of clearance, the distribution volume of the central room, the distribution volume of the peripheral room, and the intercompartmental clearance were 5.05L/h, 4.33L, 155L, and 6.22L/h, respectively. The optimal initial dosing regimen of 0.03, 0.04, 0.05, 0.06, and 0.10 mg/kg were appropriate for female children with a weight (WT) of 50 to 10 kg. The regimen of 0.04, 0.05, 0.06, 0.07, and 0.12 mg/kg is suitable for male children with a WT of 50 to 10 kg. The probability of target attainment (PTA) of each regimen reached 91%. Conclusion and Relevance: A stable PPK model of tacrolimus was established. The proposed dosage regimen reached a good PTA, which could provide a reference for tacrolimus therapy.

What is known and objectives Augmented renal clearance (ARC) is characterized by enhanced renal clearance, which leads to insufficient vancomycin exposure and treatment failure. In haematologic malignancy patients, determination of optimal vancomycin dosage is essential because of high stake of life-threatening bacterial infection and increased clearance. The aim of this study was to describe vancomycin pharmacokinetic parameters in haematologic malignancy with augmented renal clearance children and define the appropriate dosing regimen to achieve an AUC(0-24h)/MIC >= 400. Methods Hematologic malignancy with ARC children was enrolled in this retrospective study. The vancomycin PPK model was established by non-linear mixed-effects modelling programme. Goodness-of-fit (GOF) plots, non-parametric bootstrap, normalized prediction distribution error (NPDE) and visual predictive checks (VPCs) were carried out for internal evaluation of the final model. Monte Carlo simulation method was used to stimulate the optimal dosage regimens. Results Fifty-three patients with 106 samples were included. A one-compartment model with first-order elimination was developed, and the final model was as follows: CL (L/h) = 6.32x(WT/70?(0.75) x e(0.0467); V(L) = 39.6x(WT/70), where WT denotes weight (kg). The internal validation of the model showed a good prediction performance. Monte Carlo simulation results showed that when MIC was 0.5 mg/L or 1 mg/L, the recommended doses to achieve a target of AUC(0-24h)/MIC >= 400 were 25 to 40 and 50 to 75 mg/kg/d, respectively. With decreasing weight, the recommended dosage to achieve an AUC(0-24h)/MIC >= 400 increased. What is new and conclusion A one-compartment vancomycin PPK model was established in haematologic malignancy with augmented renal clearance children with weight with allometric scaling as a significant covariate. When MIC was 1 mg/L, current recommended paediatric dosages were insufficient in haematologic malignancy with augmented renal clearance children and should be increased.

目的 探讨微课联合翻转课堂在留学生血液病学教学中的应用效果.方法 结合留学生的基础知识水平和文化特点,将血液病教学内容用多媒体技术制作成微课(附带有音频或动漫效果的幻灯片或短视频),放置于网络上让学生自主学习;同时课堂上以学生与教师的互动模式为主进行交流或学习.结果 可正确引导留学生课前的学习,帮助学生高效完成课外作业,提高留学生自主学习的效率和临床实践知识的应用能力,教学效果良好,学生满意度高.结论 微课联合翻转课堂能提高留学生血液病学教学水平,调动留学生的学习主动性、积极性,提高留学生的知识应用能力.

血液内科是以血液和造血组织为主要研究对象的医学科学的一个独立分支学科,是一门基础医学、临床医学和先进检验技术高度结合的学科,处于医学发展的最前沿,知识更新日新月异,信息量大.血液内科的这些特点导致传统的以教师授课为主的LBL(lecture-based learning)教学模式无法完全胜任教学需要,导致学生普遍感觉血液内科难学、在参加考试遇到血液内科相关题目不能正确回答、在诊断治疗血液内科患者时面临困难,最终对血液内科的学习产生畏难情绪.为克服LBL教学模式的缺点,各高校均对主流的PBL(problem-based learning)教学模式进行了改革,但在教学中仍存在不少问题.因此,继续研究和改进血液内科教育模式以适应医学迅速发展的需要仍十分迫切.

目的 总结重型地中海贫血异基因造血干细胞移植(allo-HSCT)后并发可逆性后部脑病综合征(PRES)的诊治经验.方法 报告2例地中海贫血患儿在allo-HSCT后并发PRES,并复习文献,分析其临床及影像学特点,总结诊断、治疗方法.结果 2例地中海贫血患儿发生急性移植物抗宿主病后出现高血压、抽搐和意识障碍等症状,结合影像学检查诊断为PRES,给予停用钙调神经磷酸酶抑制剂(CIN),经控制血压、镇静、抗癫痫等对症治疗后病情均获得完全缓解.结论 PRES临床表现及影像学特征鲜明,明确诊断后应停用CNI,及时给予控制血压及镇静对症治疗,以减少中枢神经系统的永久性损害.