Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion ofbone marrow plasmacytes.It accounts for 10 ％ of all hematological malignancies.The proteasome,an intracellular enzyme complex that degrades ubiquitin-tagged proteins to regulate protein levels within the cell,plays an important role in maintaining cellular homeostasis.Proteasome inhibitors proved to be significantly effective in the clinical treatment of MM.In recent years,the application of the proteasome inhibitor has led to increased survival rates in MM patients.Bortezomib is the first proteasome inhibitor that has been approved by the US Food and Drug Administration due to its ability to reversibly inhibit the 26 s proteasome functions.Despite the fact that Bortezomib improves medical treatment,many patients experience difficulty responding to this drug and some patients who do respond eventually relapse.These results have led researchers to investigate new proteasome inhibitors with mechanisms different from those of Bortezomib.Some drugs that bind to the active site of the proteasome and irreversibly inhibit the complex have recently been developed and are currently being tested in advanced clinical trials.Here,we will elaborate on the proteasome inhibitors targeting MM and focus on newly discovered inhibitors that may overcome the resistance to Bortezomib.

In this last decade,one of the major advances in the management of multiple myeloma has been the introduction of the novel agents thalidomide,bortezomib,and lenalidomide as part of treatment in young patients eligible for high-dose therapy (HDT) and autologous stem cell transplantation (ASCT).These drugs have markedly improved the rate of complete remission both before and after ASCT without substantially increasingly toxicity.The implementation of an ‘optimal strategy’ consisting of novel-agent-based induction,HDT,and the use of novel agents in consolidation and maintenance may result in 5-year survival rate of 80 ％ and cure might be considered in a subset of patients who present with good prognostic features at the time of diagnosis.Nevertheless,the high efficacy of the novel agents has led some groups to test these agents upfront without ASCT.At the end of 2014,preliminary randomized data favor early ASCT plus novel agents over novel agents alone.Therefore,the optimal approach to the treatment of multiple myeloma is still to propose the most effective treatment that should involve the use of frontline ASCT in young patients eligible for HDT.This article reviews the latest research presented at the 56th American Society of Hematology (ASH) annual meeting on the multiple myeloma and its clinical management.

China ; epidemiology ; Hearing Loss, Sudden ; diagnosis ; epidemiology ; Humans

Despite many recent advances in the treatment of multiple myeloma (MM), the course of the disease is characterized by a repeating pattern of periods of remission and relapse as patients cycle through the available treatment options. Evidence is mounting that long-term maintenance therapy may help suppressing residual disease after definitive therapy, prolonging remission and delaying relapse. For patients undergoing autologous stem cell transplantation (ASCT), lenalidomide maintenance therapy has been shown to improve progression-free survival (PFS), however, it is still unclear whether this translates into extended overall survival (OS). For patients ineligible for ASCT, continuous therapy with lenalidomide and low-dose dexamethasone is shown to improve PFS and OS (interim analysis) compared with a standard, fixed-duration regimen of melphalan, prednisone, and thalidomide in a large phase Ⅲ trial. Other trials have also investigated thalidomide and bortezomib maintenance for ASCT patients, and both agents have been evaluated as continuous therapy for those who are ASCT ineligible. However, some important questions regarding the optimal regimen and duration of therapy must be answered by prospective clinical trials before maintenance therapy, and continuous therapy should be considered routine practice. This article reviewed the available data on the use of maintenance or continuous therapy strategies and highlights ongoing trials reported in the 57th American Society of Hematology (ASH) annual meeting that would help to further define the role of these strategies in the management of patients with newly diagnosed MM.

Objective To analyze the oral glucose tolerance test (OGTT) curve characteristics in Chinese women with gestational diabetes mellitus (GDM) or gestational impaired glucose test (GIGT) and to evaluate whether omission of the third-hour plasma glucose measurement of the OGTT could alter the sensitivity of the diagnosis on GDM,and whether there is a close relationship between plasma glucose values of 50 g glucose challenge test (50 g GCT) or OGTT and insulin therapy. Methods A retrospective analysis on medical records of 647 cases with GDM from January 1,1989 to December 31,2002 and 233 cases with GIGT were performed. Among 647 cases of GDM,535 were diagnosed by 75g OGTT. All OGTT (535 with GDM and 233 with GIGT) results were evaluated. Results There were 112 cases of GDM diagnosed by elevated fasting plasma glucose without OGTT performed. Of 535 cases of GDM diagnosed by OGTT,49.2% (263/535) women were with fasting plasma glucose value ≥5.8 mmol/L;90.1% (482/535) women with 1hr plasma glucose values ≥ 10. 6 mmol/L;64.7% (359/535) were with 2 hr plasma glucose levels ≥9.2 mmol/L. There were only 114 cases (21.3%) with abnormal 3 hr plasma glucose levels among 535 women with OGTT,and when 3 hr plasma glucose reached cutoff value,49.1% the other three values of OGTT were abnormal and 34.2% with the other two values of OGTT. Among 233 women with GIGT,only 4 cases with the abnormal 3 hr plasma glucose. We also investigate use of the glucose values for the first 2 hours of OGTT only missed 19 cases of GDM,still discriminated 516 cases. Omission of the third -hour glucose tolerance test value only resulted in failure to diagnose 2.9%(19/647) of GDM cases and 1.72%(4/233) of GIGT cases in Chinese women. Plasma glucose levels ≥11.2 mmol/L following 50 GCT were highly associated with GDM necessitating insulin therapy (75.4%). An elevated fasting plasma glucose level was also associated with insulin therapy (59.7%).Conclusion Omission of the third -hour glucose tolerance test value still yielded a higher sensitivity of 97.1%(628/647) of GDM cases and 98.2%(229/233) of GIGT cases in Chinese women. It is practicable to omit 3-hour post -glucose ingestion value of the OGTT in Chinese women. Plasma glucose levels ≥11.2mmol/L following 50g GCT indicated 75.4% cases of GDM necessitating insulin therapy.

Based on the community-based and family-centered concepts, the Chain Rehabilitation Services for children with cerebral palsy (CP) integrates all kinds of social resources to build the early screening network and community rehabilitation centers, and to enhance the integration of rehabilitation and educational services. This chain model makes it possible to coordinate the related institutes to provide better services for children with CP. Better services and better systematic management of children with CP in Shanghai and surrounding areas has also been achieved through this project.

It is very important to have a clear and widely accepted definition and classification for clinical diagnosis, rehabilitation, research and social support of children with cerebral palsy, as well as in establishing a regional, national and global monitoring database. There are some new changes about the definition, clinical types and function classification of cerebral palsy recently domestic and abroad, which pay more attention to assessments on function and participation in daily life.

Objective To study the correlation of 5 polymorphisms of Han Chinese patients in Sichuan Province with age-related macular degeneration (AMD). Methods The blood samples from 384 Han Chinese patients diagnosed with AMD and another 384 matched controls were collected using case-control study method. The chosen gene single nucleotide polymorphisms (SNPs) were genotyped by SnaPShot classify technology in the patients with AMD and 384 controls of Chinese Han population. Results All of the 5 genetype frequencies of the SNPs were in accordance with Hardy-Weinberg Equilibrium (P > 0.05). There were no statistically significantdifferences between the AMD group and the control group in the rs13117504 G allele frequency (P = 0.037, OR=1.24, 95%CI:1.01~1.53), the rs10033900 C allele frequency (P=0.023, OR=1.27, 95%CI: 1.03 ~1.57) and the rs1003390 frequency in the AMD dominant model (P = 0.039, OR = 0.74, 95%CI: 0.55 ~ 0.99). There were no statistically significant differences between the groups in the rs6822976 A allele frequencies (P =0.158), the rs7438961 G allele frequencies (P = 0.798) and, the rs7671905 T allele frequency (P = 0.909). The rs10033900 in the recessive model of AMD had no significant difference as compared to that in the control group (P = 0.107). The two groups showed no significant differences in both the dominant and recessive model of AMD in terms of the frequencies of rs13117504, rs6822976, rs7438961 and rs7671905 (P > 0.05). Conclusion The rs13117504 and rs10033900 of SNPs near CFI gene upstream has significant association with age-related macular degeneration , while the rs6822976 , rs7438961 , rs7671905 of SNPs have no significant correlations with age-related macular degeneration in Han Chinese population.

Objective To construct the eukaryotic expression vector of pprI gene from Deinococcus radiodurans R1 and investigate its radioresistant effects in eukaryotic cells.Methods A recombinant vector pEGFP-c1-pprI was constructed by DNA recombinant technique.The empty vector pEGFP-c1 and the pEGFP-c1-pprI were transferred into human lung epithelial cells Beas-2B by LipofectamineTM 2000,respectively.Then the infected cells were screened in order to develop a cell line with stable expression of pprI gene.Cell survival rate was tested by clone-forming assay.Cell cycle distribution and apoptosis were detected by a flow cytometry.The fluorescence intensity of reactive oxygen species (ROS) was observed by a fluorescent microscope.γ-H2AX foci in the irradiated cell was detected by immunofluorescence.Results The eukaryotic expression plasmid of pprI prokaryotic gene was constructed and PprI fusion protein was expressed in human lung epithelial cells successfully,and the cell line (2BG) with a stable pprI gene expression was established.After irradiation,the cell survival fraction of 2BG cells was significantly higher than Beas-2B cells so that the value of D0 、Dq and N of the survival curve were increased.Moreover,the fluorescence intensity of ROS and the number of γ-H2AX foci in 2BG cells were also lower than those of B eas-2B cells(F =16.73,19.47,6.94,P ＜ 0.05).Between these two cell lines,the apoptosis rate and cell cycle G2 arrest also had significant difference (F =139.73,237.92,P ＜ 0.05).Conclusions The pprI gene from Deinococcus radiodurans RI can be stably expressed in the eukaryotic cells and it allows the transferred cells to have a radioresistant function.

This paper is to report the polymorphism of raw materials of clopidogrel bisulfate at home and abroad. By the analysis of Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (p-XRD), samples are roughly classified into two groups, except one patent material. And the differential scanning calorimeter (DSC) examination showed more detailed information for these materials. The results of the study could provide comprehensive basis for the quality evaluation of clopidogrel bisulfate.