Petrogenesis and tectonic implications of the Silurian adakitic granitoids in the eastern segment of the Qilian Orogenic Belt,Northwest China

Geodynamic mechanism responsible for the generation of Silurian granitoids and the tectonic evolution of the Qilian orogenic belt remains controversial. In this study, we report the results of zircon U–Pb age, and systematic whole-rock geochemical data for the Haoquangou and Liujiaxia granitoids within the North Qilian orogenic belt and the Qilian Block, respectively, to constrain their petrogenesis, and the Silurian tectonic evolution of the Qilian orogenic belt. Zircon U–Pb ages indicate that the Haoquangou and Liujiaxia intrusions were emplaced at423 ± 3 Ma and 432 ± 4 Ma, respectively. The Haoquangou granodiorites are calc-alkaline, while the Liujiaxia granites belong to the high-K calc-alkaline series.Both are peraluminous in composition and have relatively depleted Nd isotopic [ε_(Nd)(t) =(-3.9 – + 0.6)] characteristics compared with regional basement rocks, implying their derivation from a juvenile lower crust. They show adakitic geochemical characteristics and were generated by partial melting of thickened lower continental crust. Postcollisional extensional regime related to lithospheric delamination was the most likely geodynamic mechanism for the generation of the Haoquangou granodiorite, while the Liujiaxia granites were generated in a compressive setting during continental collision between the Qaidam and Qilian blocks.

Consensus on the digestive endoscopic tunnel technique

With the digestive endoscopic tunnel technique(DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria(MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal(GI) tract.At present, the tunnel technique application range covers the following:(1)Treatment of lesions originating from the mucosal layer, e.g., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis;(2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc.; and(3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment.The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism,and significance of DETT, prevention of infection and concepts of DETTassociated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract(indications and contraindications, procedures, pre-and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations).

Low WT1 transcript levels at diagnosis predicted poor outcomes of acute myeloid leukemia patients with t(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation

Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous disease.Identifying AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent therapy.This study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on outcomes.Methods:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were included.Patients who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive allo-HSCT.Patients who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 cycles.WT1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were tested.Results:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.001,0.016,and <0.001,respectively) and overall survival(HR = 3.50,2.32,and 4.34;95%CI 1.56-7.82,1.09-4.97,and 1.98-9.53;P = 0.002,0.030,and <0.001,respectively) in all patients.Conclusions:Testing for WTl transcript levels at diagnosis in patients with AML and t(8;21) may predict outcomes in those who achieve remission.A randomized study is warranted to determine whether allo-HSCT can improve prognosis in these patients.

Predictive Value of Dynamic Peri-Transplantation MRD Assessed By MFC Either Alone or in Combination with Other Variables for Outcomes of Patients with T-Cell Acute Lymphoblastic Leukemia

We performed a retrospective analysis to investigate dynamic peri-hematopoieticstem cell transplantation(HSCT)minimal/measurable residual disease(MRD)on outcomes inpatients with T-cell acute lymphoblastic leukemia(T-ALL).A total of 271 patients were enrolledand classified into three groups:unchanged ncgative MRD pre-and post-HSCT group(group A),post-MRD non-increase group(group B),and post-MRD increase group(group C).The patientsin group B and group C experienced a higher cumulative incidence of relapse(CIR)(42%vs.71%vs.16%,P<0.001)and lower leukemia-free survival(LFS)(46%vs.21%vs.70%,P<0.001)andoverall survival(OS)(50%vs.28%vs.72%,P<0.001)than in group A,but there was no significantdifference in non-relapse mortality(NRM)among three groups(14%vs.12%vs.8%,P=0.752).Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR(HR=2.392,95%CI,1.816-3.151,P<0.001),LFS(HR=1.964,95%CI,1.546-2.496,P<0.001)and os(HR=1.731,95%CI,1.348-2.222,P<0.001).We also established a risk scoring system based ondynamic peri-HSCT MRD combined with remission status pre-HSCT and onsct of chronic graft-versus-host disease(GVHD).This risk scoring system could better distinguish ClR(c=0.730)thanthat for pre-HSCT MRD(c=0.562),post-HSCT MRD(c=0.616)and pre-and post-MRD dynamics(c=0.648).Our results confirm the outcome predictive value of dynamic peri-HSCT MRD eitheralone or in combination with other variables for patients with T-ALL.

SUPPRESSION OF CELL ADHESION ON POLYACRYLONITRILE-BASED MEMBRANES BY THE ANCHORING OF PHOSPHOLIPID MOIETIES

In this work, the membrane surface of poly（acrylonitrile-co-2-hydroxyethyl methacrylate） （PANCHEMA） was chemically modified by anchoring of phospholipid moieties. The process involved the reaction of hydroxyl groups on the membrane surface with 2-chloro-2-oxo-1,3,2-dioxaphospholane （COP） followed by the ring-opening reaction of COP with trimethylamine. Chemical differences between the original and the modified membranes were characterized by FT-IR and XPS, It was found that the amount of macrophage adhered on the modified membrane surface is substantially lower than that on polyacrylonitrile （PAN） and PANCHEMA membranes under the same condition, The morphological change of the adherent cell is also suppressed by the generation ofphospholipid moieties on the membrane surface.

Disease Risk Comorbidity Index for Patients Receiving Haploidentical Allogeneic Hematopoietic Transplantation

We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.

Uretero-lumbar artery fistula: A case report

BACKGROUND Uretero-arterial fistula(UAF)is a disease that usually involves the aorta,common iliac artery,external iliac artery,hypogastric artery,and lumbar artery.Among them,uretero-lumbar artery fistula(ULAF)is the most unusual type.So,both in China and around the world,the diagnosis and treatment of ULAF is a big challenge.CASE SUMMARY A 55-year-old female patient with a history of pelvic radiotherapy developed unexplained massive hemorrhage during replacement of the right Resonance metallic ureteral double-J tubes due to a long-standing indwelling ureteral stent for ureteral stricture.Later,we found contrast extravasation from the patient's right L4 artery into the ureter under digital subtraction angiography(DSA)and administered polyvinyl alcohol particle embolic agent and coil embolization;hematuria was controlled.Follow-up investigations at 18 mo showed no sign of recurrence.CONCLUSION DSA is very important in the diagnosis and treatment of UAF,and DSA should be preferred when UAF is suspected.In addition,the use of softer ureteral stents in patients with primary disease and risk factors for UAF should be considered to avoid increasing the risk of the development of the disease;endovascular treatment should be preferred in patients who have developed UAF.

Paratesticular liposarcoma: Two case reports

BACKGROUND Paratesticular liposarcoma accounts for approximately 7%of scrotal tumors.They are rare lesions of the reproductive system with approximately 90%of the lesions originating from the spermatic cord.Surgery,with the goal of complete resection,is the mainstay for treatment of this disease.However,treatment consisting of extended resection to decrease local recurrence remains controversial.CASE SUMMARY We report the cases of two patients with paratesticular liposarcomas who were treated with radical testicular tumor resection without adjuvant therapy.Followup investigations at 9 mo showed no sign of recurrence.CONCLUSION Surgery is the first-line treatment,regardless of whether it is a recurrent or primary tumor.Extended resection carries a higher risk of complications and should not be performed routinely.Preoperative radiotherapy can reduce the local recurrence rate without affecting the overall survival.

Expanded clinical-grade NK cells exhibit stronger effects than primary NK cells against HCMV infection

Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell reconstitution may protect against the development of human CMV (HCMV) infection post-HSCT. Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells. Nevertheless, whether expanded NK cells have stronger anti-HCMV function is unknown. Herein, we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells. Expanded NK cells showed higher expression of activating receptors, chemokine receptors and adhesion molecules;stronger cytotoxicity against HCMV-infected fibroblasts;and better inhibition of HCMV propagation in vitro than primary NK cells. In HCMV-infected humanized mice, expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion. A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection (HR = 0.54, 95% CI = 0.32–0.93, p = 0.042) and refractory HCMV infection (HR = 0.34, 95% CI = 0.18–0.65, p = 0.009) than controls and better NK cell reconstitution on day 30 post NK cell infusion. In conclusion, expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.

Machine learning algorithm as a prognostic tool for Epstein-Barr virus reactivation after haploidentical hematopoietic stem cell transplantation

Epstein-Barr virus(EBV)reactivation is one of the most important infections after hematopoietic stem cell transplantation(HSCT)using haplo-identical related donors(HID).We aimed to establish a comprehensive model with machine learning,which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin(ATG)for graft-versus-host disease(GVHD)prophylaxis.We enrolled 470 consecutive acute leukemia patients,60%of them(n=282)randomly selected as a training cohort,the remaining 40%(n=188)as a validation cohort.The equation was as follows:Probability(EBV reactivation)=1/1+exp(−Y),where Y=0.0250×(age)–0.3614×(gender)+0.0668×(underlying disease)–0.6297×(disease status before HSCT)–0.0726×(disease risk index)–0.0118×(hematopoietic cell transplantation-specific comorbidity index[HCT-CI]score)+1.2037×(human leukocyte antigen disparity)+0.5347×(EBV serostatus)+0.1605×(conditioning regimen)–0.2270×(donor/recipient gender matched)+0.2304×(donor/recipient relation)–0.0170×(mononuclear cell counts in graft)+0.0395×(CD34+cell count in graft)–2.4510.The threshold of probability was 0.4623,which separated patients into low-and high-risk groups.The 1-year cumulative incidence of EBV reactivation in the low-and high-risk groups was 11.0%versus 24.5%(P<.001),10.7%versus 19.3%(P=.046),and 11.4%versus 31.6%(P=.001),respectively,in total,training and validation cohorts.The model could also predict relapse and survival after HID HSCT.We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.

Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia

Aplastic anemia(AA)is a life-threatening disease characterized by bone marrow(BM)failure and pancytopenia.As an important component of the BM microenvironment,endothelial cells(ECs)play a crucial role in supporting hematopoiesis and regulating immunity.However,whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown.In this study,a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA.Nacetyl-L-cysteine(NAC,a reactive oxygen species scavenger)or exogenous EC infusion was administered to AA mice.Furthermore,the frequency and functions of BM ECs from AA patients and healthy donors were evaluated.BM ECs from AA patients were treated with NAC in vitro,and then the functions of BM ECs were evaluated.We found that BM ECs were significantly decreased and damaged in AA mice.Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized,whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice.Consistently,BM ECs in AA patients were decreased and dysfunctional.Furthermore,dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes,which could be repaired by NAC in vitro.The reactive oxygen species pathway was activated,and hematopoiesis-and immune-related signaling pathways were enriched in BM ECs of AA patients.In conclusion,our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA,suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients.

Glucocorticoid and glycolysis inhibitors cooperatively abrogate acute graft-versus-host disease

Although glucorticosteroids(GCs)are the standard first-line therapy for acute graft-versus-host disease(a Gv HD),nearly 50%of a Gv HD patients have no response to GCs.The role of T cell metabolism in murine a Gv HD was recently reported.However,whether GCs and metabolism regulators could cooperatively suppress T cell alloreactivity and ameliorate a Gv HD remains to be elucidated.Increased glycolysis,characterized by elevated 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3),and higher rates of glucose consumption and lactate production were found in Tcells from a Gv HD patients.Genetic upregulation of PFKFB3 induced T cell proliferation and differentiation into proinflammatory cells.In a humanized mouse model,PFKFB3-overexpressing or PFKFB3-silenced T cells aggravated or prevented a Gv HD,respectively.Importantly,our integrated data from patient samples in vitro,in a humanized xenogeneic murine model of a Gv HD and graft-versus-leukaemia(GVL)demonstrate that GCs combined with a glycolysis inhibitor could cooperatively reduce the alloreactivity of T cells and ameliorate a Gv HD without loss of GVL effects.Together,the current study indicated that glycolysis is critical for T cell activation and induction of human a Gv HD.Therefore,the regulation of glycolysis offers a potential pathogenesis-oriented therapeutic strategy for a Gv HD patients.GCs combined with glycolysis inhibitors promises to be a novel first-line combination therapy for a Gv HD patients.

基于个体化机器学习的原发性免疫性血小板减少症危重出血预测模型:一项全国前瞻性队列研究

原发性免疫性血小板减少症(ITP)中少见但至关重要的危重出血事件,给患者的预后、生活质量和治疗决策带来严重影响。尽管有一些研究探讨了ITP中与危重出血相关的风险因素,但目前尚缺乏大样本数据、大规模多中心研究结果以及针对ITP患者致命出血事件的预测模型。本研究首次采用国际血栓与止血学会新提出的ITP致命出血标准,利用大样本数据开发了首个基于机器学习的在线应用,用于预测ITP患者的致命出血.研究中,我们使用中国各地大型多中心数据进行开发,并对全国39家医疗中心进行为期一年的外部测试,得到了较好的训练、验证和测试数据集预测能力该基于新算法的便捷网络工具能够快速识别ITP患者的出血风险,辅助临床决策,有望未来降低不良事件的发生。

A perfect mismatch: haploidentical hematopoietic stem cell transplantation overtakes a bend

Matching for the major histocompatibility complex(MHC)—and more specifically,the human leukocyte antigen(HLA)system—has been the gold standard in transplantation for decades.Selecting an HLA-matched donor is the preferred and straightforward choice for most immunologists,hematologists,and organ transplant specialists.

Dynamic immune profiling identifies the stronger graft-versus-leukemia (GVL) effects with haploidentical allografts compared to HLA-matched stem cell transplantation

Haploidentical stem cell transplantation(haplo-SCT)achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation(MSDT)in treating hematological malignancies.To define the underlying regulatory dynamics,we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple dimension.First,we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility(MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo.We found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia burden.The stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor–α,interferon-γ,pore-forming proteins and CD107a secreted by T cells or natural killer cells.Furthermore,we conducted a prospective clinical trial which enrolled 135 patients with t(8;21)acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or MSDT.The results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with MSDT.Ex vivo experiments showed that,1 year after transplantation,cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same period.Our results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.

The role of collateral related donors in haploidentical hematopoietic stem cell transplantation

A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors(CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs(n = 60) and maternal donors(MDs, n = 296), which were the last choice of donor selection in immediate related donors(IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0%(95% CI, 11.3%–32.7%) versus 17.4%(95% CI, 13.0%–21.8%)(P = 0.455) and 25.0%(95% CI, 13.9%–36.1%) versus 23.1%(95% CI, 18.2%–28.0%)(P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2%(95% CI, 40.4%–66.0%) versus 59.5%(95% CI, 53.8%–65.2%)(P = 0.406) and 56.5%(95% CI,43.8%–69.2%) versus 61.8%(95% CI, 56.1%–67.5%)(P = 0.458) for the CRDs and MDs, respectively.Female donor/male recipient(FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs.

Relationship of Cell Compositions in AIIografts with Outcomes after Haploidentical Transplantation for Acquired Severe Aplastic Anemia： Effects of CD34＋ and CD14＋ Cell Doses

Background： The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation （SCT）. Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT （haplo-SCT） for patients with acquired severe aplastic anemia （SAA）. Methods： A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis. Results： A total of 126 patients （97.7%） achieved neutrophil engraftment, and 121 patients （95.7%） achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease （GVHD） was 32.6%. After a median follow-up of 842 （range： 124-4110） days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14＋ （P = 0.018） and CD34＋ cells （P 〈 0.001） were associated with a successful platelet engraftment. A successthl platelet was associated with superior survival （P 〈 0.001）. No correlation of other cell components with outcomes was observed. Conclusions： These results provide evidence and explain that higher doses ofCD34＋ and CD 14＋ cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.

单倍型相合移植治疗重型再生障碍性贫血长期随访:一项多中心前瞻性研究

近年来,单倍型相合移植治疗重型再生障碍性贫血(再障)取得了很大的进展,但尚缺乏长期随访的数据.本文报道了一项前瞻性、多中心临床研究,聚焦单倍型相合移植作为二线方案治疗重型再障的长期疗效及生活质量,纵向、前瞻性评估了移植前、移植后3年和移植后5年的生活质量(成人应用SF-36量表,儿童应用PedsQL4.0量表).该项研究总共纳入287例病人,存活病人的中位随访时间4.56(3.01~9.05)年.在长期随访中,97.5%病人获得稳定的完全供者嵌合,93.4%病人获得完全造血重建.预计9年总生存率和无失败生存率85.4%±2.1%和84.0%±2.2%.移植时年龄(≥18岁)和体能状态评估(ECOG≥2分)是影响生存的预后因素.再障病人在单倍型移植后3年的生活质量较移植前有明显改善,且在移植后5年时有进一步改善.无论是儿童还是成人,中重度慢性移植物抗宿主病是影响生活质量的不良因素.末次随访时74.0%儿童和72.9%成人已恢复正常学习或工作.该研究提示在没有同胞全合供者的情况下,移植作为治疗重型再障患者的二线方案,单倍型供者可成为常规推荐.

Depression, Anxiety, and Quality of Life in Paroxysmal Kinesigenic Dyskinesia Patients

Background：Paroxysmal kinesigenic dyskinesia （PKD） is a rare movement disorder characterized by recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements.Under the condition of psychological burden,some patients＆#39; attacks may get worsened with longer duration and higher frequency.This study aimed to assess nonmotor symptoms and quality of life of patients with PKD in a large population.Methods：We performed a cross-sectional survey in 165 primary PKD patients from August 2008 to October 2016 in Rui Jin Hospital,using Symptom Check List-90-Revised （SCL-90-R）,World Health Organization Quality of Life-100 （WHOQoL-100）,Self-Rating Depression Scale,and Self-Rating Anxiety Scale.We evaluated the differences of SCL-90-R and WHOQOL-100 scores in patients and Chinese normative data （taken from literature） by using the unpaired Student＆#39;s t-test.We applied multivariate linear regression to analyze the relationships between motor manifestations,mental health,and quality of life among PKD patients.Results：Compared with Chinese normative data taken from literature,patients with PKD exhibited significantly higher （worse） scores across all SCL-90-R subscales （somatization,obsessive-compulsive,interpersonal sensitivity,depression,anxiety,hostility,phobic anxiety,paranoid ideation,and psychoticism;P =0.000 for all） and significantly lower （worse） scores of five domains in WHOQoL-100 （physical domain,psychological domain,independence domain,social relationship domain,and general quality of life;P =0.000 for all）.Nonremission of dyskinesia episodes （P =0.011） and higher depression score （P =0.000） were significantly associated with lower levels of quality of life.The rates of depression and anxiety in patients with PKD were 41.2% （68/165） and 26.7% （44/165）,respectively.Conclusions：Depression,anxiety,and low levels of quality of life were prevalent in patients with PKD.Co-occurrence of depression and anxiety was common among these patients.Regular mental health interventions could set depression and anxiety as intervention targets.Considering that the motor episodes could be elicited by voluntary movements and sometimes also by emotional stress,and that symptoms may get worsened with longer duration and higher frequency when patients are stressed out,intervention or treatment of depression and anxiety might improve the motor symptoms and overall quality of life in PKD patients.

Association of Persistent Minimal Residual Disease with Poor Outcomes of Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo?HSCT). Methods: We retrospectively analyzed 145 consecutive AML patients undergoing allo?HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre?HSCT. Results: In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre?HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 5.547, P = 0.019). In haploidentical SCT (haplo?SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre?HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo?SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo?SCT, those without persistent MRD underwent haplo?SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ2 = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200–2.382, P = 0.003), worse leukemia?free survival (HR = 1.812, 95% CI: 1.168–2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528–3.627, P < 0.001). Conclusion: Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo?SCT settings.