The research progresses of iron homeostasis and the diagnosis of hereditary iron overload in the 56th American Society of Hematology (ASH) annual meetings were reviewed.Over the last 2 decades,the discovery of mutations in genes leading to hereditary disorders of iron overload,iron deficiency,and iron maldistribution had accelerated our understanding of human iron homeostasis.This article provided an updated overview of the human iron cycle,regulation of iron homeostasis,how perturbations in these homeostatic mechanisms led to iron overload disease and strategies for the diagnosis of hereditary iron overload.

Progress of guidelines for quantifying iron overload in the 56th American Society of Hematology (ASH) annual meetings was reviewed.This article reviewed the use of historical data,serological measures,and MRI to estimate somatic iron burden.Before chelation therapy utilization,transfusional volume was an accurate method for estimating liver iron burden,whereas transferrin saturation reflected the risk of extrahepatic iron deposition.Liver biopsy was invasive and plagued by sampling variability.In the current study,we recommended annual liver iron concentration to be measured by MRI for all patients on chronic transfusion therapy.And it was important to measure cardiac T2* by MRI every 6-24 months depending on the clinical risk of cardiac iron deposition.Recent validation data for pancreas and pituitary iron assessments was also presented,while the further confirmatory data was suggested before these techniques could be recommended for routine clinical use.

New progresses of timing of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and aplastic anemia in the 56th ASH annual meetings were reviewed.Allo-HSCT for MDS was a potentially curative procedure,but it was associated with a significant risk of morbidity and mortality.With the recent approval of disease-modifying agents,the appropriate timing of alloHSCT needed to be addressed.For low and intermediate-1 IPSS risk groups,the decision to delay HSCT from the time of diagnosis maximized overall survival.For patients with intermediate-2 and high-risk disease,immediate HSCT at the time of diagnosis was associated with a greater number of life-years than HSCT at a delayed time point.The methods that underwent HSCT were after azacitidine,leukemia-type induction chemotherapy,or both.for severe aplastic anemia (SAA),HSCT was a proven cure,but HLA-matched sibling donors were found in fewer than 25 ％ of newly diagnosed patients.The use of early unrelated donor HSCT was an evolving concept that will became more accepted as improvements in HSCT outcomes continued.Moving forward,HLA-matched related and unrelated donor HSCT will likely become the treatment of choice for most patients with higher-risk MDS and newly diagnosed SAA.

New progress of guidelines for novel targets to iron overload in the 56th American Society of Hematology (ASH) annual meeting was reviewed.β-thalassemia and hereditary hemochromatosis disorders,and inappropriately low levels of the liver hormone hepcidin are responsible for the increased iron absorption,leading to toxic iron accumulation in many organs.Several studies have shown that targeting iron absorption could be beneficial to reducing or preventing iron overload in these 2 disorders.New approaches target Tmprss6.Additional strategies in β-thalassemia are showing beneficial effects in ameliorating ineffective erythropoiesis and anemia.The goal of this review is to discuss the major factors controlling iron metabolism and erythropoiesis and to discuss potential novel therapeutic approaches to reduce or prevent iron overload in these 2 disorders and ameliorate anemia in β-thalassemia.

Objective To investigate chemokine receptor CX3CR1 gene T280M polymorphism in patients with ischemic cerebrovascular disease(ICVD) and its frequency.Methods 165 patients with ICVD(cerebral infarction 85 cases,lacunar infarction 40 cases,transient ischemic attack 40 cases) and 150 age- and sex-matched healthy controls(normal control group) were involved in this study.The polymorphism of T280M was analyzed by multiplex polymerase chain reaction-restriction fragment length based(PCR-RFLB),the gene frequency was compared between two groups and each ICVD subgroups.Results There were TT and TM genotypes in normal control group,and TT,TM and MM genotypes in ICVD group.The genotype were significant differences between the two groups(P0.05).Conclusions There is MM genotype in the chemokine receptor CX3CR1 gene T280M in the patients with ICVD,and their M allele frequency obviously increase.It suggests that CX3CR1 gene T280M polymorphism may be associated with ICVD.

New progress of guidelines for established and novel agents for myelodysplastic syndromes (MDS) in the 56th American Society of Hematology (ASH) annual meetings was reviewed.MDS was the most commonly diagnosed myeloid malignancy.According to prognostic scoring systems,the MDS patients were divided into lower-risk and higher-risk group.The goal of treatment for lower-risk patients is transfusions minimization and life quality optimization,while the goal of treatment for higher-risk patients is transformation to acute leukemia delay and life prolongation.The lower-risk patients with isolated cytopenia are treated with erythropoiesis-stimulating agents or growth factors.For patients with the del (5q) cytogenetic abnormality or those who were failure in these initial treatment,lenalidomide or experimental agents may be administrated.Lower-risk patients with multiple cytopenia may be treated with immunosuppressive drugs or low-dose hypomethylating agents.For patients with higher-risk disease,hypomethylating agents are the preferred initial treatment approach,with evaluation for hematopoietic cell transplantation at diagnosis.

Objective To investigate the expression of C/EBP homology protein(CHOP) in rat brain tissue after focal cerebral ischemia-reperfusion,as well as to observe the influence of the shenxiong injection on the expression of CHOP.Methods One hundred forty four male rats were randomly divided into three groups:the sham-operation group,operation group,shenxiong group.Focal cerebral ischemia and reperfusion rat models were established by using suture.Zea Longa method was introduced to evaluate neurologic behavioral changes.The levels of mRNA and protein of CHOP were measured with methods of immunohistochemistry and reverse transcription polymerase chain reaction.The neuronal apoptosis was detected by the method of terminal deoxynucleotidy1 transferase-mediated dUTP-biotin nick end labeling.Results The expression of CHOP was up-regulated in per-infarction after cerebral ischemia-reperfusion in rats.CHOP mRNA and protein levels peaked at the 12th h and 24th h after reperfusion,respectively.The apoptosis cell counting increased gradually after cerebral ischemia-reperfusion and peaked at the 24th h after reperfusion.Compared with the saline control group,treatment with shenxiong injection could reduce the neuronal apoptosis at the 6th,12th,24th,and 72nd h after reperfusion (P ＜0.01).Compared with the saline control group,treatment with shenxiong injection could decrease CHOP mRNA and protein expression at the 6th,12th,24th,and 72nd h after reperfusion (P ＜0.01).Conclusions Shenxiong Injection may prevent neurocyte from apoptosis by inhibition of the expression of CHOP induced by endoplasmic reticulum stress.

Objective To observe the effect of Shenxiong injection on the changes of brain X-box binding protein 1 (XBP1) gene expression following cerebral ischemia-reperfusion in rats and to investigate its neuroprotective effect and mechanisms. Methods One hundred forty-four male SD rats were randomly assigned to sham-operation, saline control and Shenxiong groups. A rat model of middle cerebral artery occlusion was induced using the suture method. Shenxiong injection 33.3 ml/kg was injected intraperitoneally during the reperfusion in the Shenxiong group. The same volume of saline was injected intraperitoneally in the saline control group. The animals were sacrificed at 6, 12, 24, and 72 hours after the reperfusion.Meanwhile, immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) were used respectively to detect the expressions of XBP1 protein and mRNA in the cerebral ischemic areas. TUNEL was used to detect neuronal apoptosis. Results The levels of XBP1 protein and mRNA increased after the reperfusion, and it reached the peak at 12 hours; both the numbers of apoptotic cells and neurological scores in the Shenxiong group were lower than those in the saline control group at 6, 12, 24, and 72 hours after the reperfusion (all P ＜0.01); the levels of XBP1 and mRNA at 6, 12, and 24 hours after the reperfusion were alsosignificantly lower than those in the saline control group (all P ＜ 0.01). Conclusions Shenxiong injection may have certain inhibition on the endoplasmic reticulum stress activated XBP1 pathway induced by cerebral ischemia-reperfusion.

New progress of treatment of low-risk myelodysplastic syndromes (MDS) reported in the 58th American Socienty of Hematology (ASH) Annual Meetings was reviewed. Anemia is a single common symptom of low-risk MDS, and erythropoietic-stimulating agents (ESA) may be effective. The dose and duration of erythropoietic-stimulating agents (ESA) are critical to determine efficacy. If the treatment of ESA failed, the available options may include lenalidomide (approved for del5q positive cases), hypomethylating agents and a rather large number of experimental agents. The choice for the second-line treatment must consider the biologic, cytogenetic and molecular-identified characteristics of individual patient, as well as frailty and comorbidities. Other cytopenias rarely appear alone. Thrombomimetic agents for thrombocytopenia has been proposed in clinical trials, but there were some safety issues. Although neutropenia is targeted symptomatically with growth factor supportive care, the immunosuppressive therapy is indicated mainly for pancytopenic and hypoplastic low-risk MDS. Finally, hematopoietic stem cell transplantion is the curative option also for low-risk MDS, but it should be carefully evaluated to balancing toxicity and the possibility of survival advantage.

Research progress of somatic mutations and the response to the treatment of de novo myelodysplastic syndromes (MDS) patients in the 57th American Society of Hematology (ASH) annual meetings was reviewed. The optimal methods and therapy time for patients with high-risk de novo MDS remained an area of ongoing investigation. The clinical prognostic scoring system does not include the molecular genetic abnormalities and DNA metlylation of histone/nuclear chromatin modifications, which may predict the effect of hypomethylation (HMA). Treatment of HMA may change the expression of genes related with prognosis, and the response rate to the HMA treatment was significantly increased for TET2-mutated patients with high-variant allele frequencies. The overall grade of recommendation for choosing HMA therapy over induction chemotherapy in high-risk MDS based on molecular genetic mutations was 2C, according to less-associated toxicity and increased responses primarily in TET2-mutated disease. Further prospective studies are needed to evaluate the long-term effects of HMA therapy, particularly in TET2-mutated patients.