Coronary heart disease (CHD) is the second leading cause of cardiovascular death in the Chinese population. It accounts for 22% of cardiovascular deaths in urban areas and 13% in rural areas. Although mortality from CHD in China is relatively low compared with Western levels, the burden of CHD has been increasing. This is partly because of a worsening profile of risk factors, such as an increased prevalence of hypertension, hyperlipidaemia, overweight/obesity, diabetes, etc and partly because of an increase in the aged population. Large-scale, randomised controlled trials on thrombolytic, blood-pressure-lowering, antiplatelet and blood-cholesterol-lowering treatment as well as cardiac intervention have been conducted for Chinese patients with myocardial infarction. The studies provide important information for the prevention and management of chronic CHD and acute myocardial infarction in the Chinese population.

To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III-IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1-23.1%) than in the ATG-10 group (4.5%, CI, 0.7-8.3%, P ¼ 0.005, 95% CI for the difference, À 19.4% to À 3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1-33.5%) than in the ATG-6 group (9.6% (4.0-15.2%), P ¼ 0.001). The 1-year disease-free survival rates were 84.3% (77.3-91.3%) and 86.0% (79.2-92.8%) for the ATG-6 group and ATG-10 groups, respectively (P ¼ 0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD. INTRODUCTIONAntithymocyte globulin (ATG) has been used in the conditioning regimen to prevent severe GVHD in haploidentical hematopoietic SCT (HSCT), and our previous study presented encouraging results. 1 However, the limitations associated with the use of ATG as a regimen for in vivo T-cell depletion (TCD) include the occurrence of delayed immune reconstitution and an increased risk of severe infections, depending on the dose of ATG administered. 2 Several previous studies have suggested suitable doses of ATG in matched unrelated transplantations. 3,4 However, to date, the optimal dose of ATG with respect to the prevention of severe GVHD following the haploidentical transplantation is unknown.In our recently reported retrospective study, we reduced the total dose of ATG from the traditional 10 mg/kg in our classic regimen to 6 mg/kg for refractory/relapsed patients undergoing haploidentical HSCT. We observed that the reduction of the total dose of ATG to 6 mg/kg produced similar rates of engraftment, GVHD and survival compared with the 10 mg/kg dose of ATG. 5 Based on these findings, we set out to extend the use of 6 mg/kg ATG to standard-risk patients. Therefore, we initiated the current prospective randomized study to evaluate the effect of the two different doses of ATG in conditioning regimens on graft failure, GVHD, relapse and survival among standard-risk patients receiving haploidentical HSCT. We postulated that the use of 6 mg/kg ATG might reduce adverse events without increasing the risk of GVHD.

MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.

Genetic polymorphisms of CYP2C9 significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies have been performed on CYP2C9 genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles, *2 and *3, in relatively small sample sizes. To scale up the gene-scanning region and determine relatively precise data on the genetic distribution pattern in Chinese populations, unrelated healthy Han Chinese volunteers from Zhejiang Province (n=1127) and Hebei (n=1000) Province were recruited as subjects for the direct sequencing of all exons of CYP2C9. As a result, 14 previously reported alleles were detected in this work, and 8 of these alleles (*14, *16, *19, *23, *27, *29, *33 and *34) were described for the first time in Chinese populations. In addition, 37 novel mutations were also detected, of which 22 variants were non-synonymous, and 21 new alleles, *36-*56, were designated by the Human CYP Allele Nomenclature Committee. In vitro functional analysis of these 22 novel CYP2C9 variants revealed that 17 mutations had a significant influence on the protein's catalytic activity. Our study provides the most accurate data on CYP2C9 polymorphisms in Han Chinese populations and detects the largest number of novel allelic variants existing to date. These new alleles will greatly enrich the current knowledge of naturally occurring CYP2C9 variants in Chinese populations.

Transient ischemia is a leading cause of cognitive dysfunction. Postischemic ROS generation and an increase in the cytosolic Zn2+ level ([Zn2+]c) are critical in delayed CA1 pyramidal neuronal death, but the underlying mechanisms are not fully understood. Here we investigated the role of ROS-sensitive TRPM2 (transient receptor potential melastatin-related 2) channel. Using in vivo and in vitro models of ischemia–reperfusion, we showed that genetic knockout of TRPM2 strongly prohibited the delayed increase in the [Zn2+]c, ROS generation, CA1 pyramidal neuronal death and postischemic memory impairment. Time-lapse imaging revealed that TRPM2 deficiency had no effect on the ischemia-induced increase in the [Zn2+]c but abolished the cytosolic Zn2+ accumulation during reperfusion as well as ROS-elicited increases in the [Zn2+]c. These results provide the first evidence to show a critical role for TRPM2 channel activation during reperfusion in the delayed increase in the [Zn2+]c and CA1 pyramidal neuronal death and identify TRPM2 as a key molecule signaling ROS generation to postischemic brain injury.