Autophagy generally exists in organisms as a protective mechanism against external pressure, and myocardial autophagy plays a vital role to maintain myocardial function. Early exercise-based rehabilitation improves health-related quality of life and functional capacity after acute myocardial infarction. This paper summarized the role of autophagy in sport rehabilitation for myocardial infarction and possible mechanisms.

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.

Objective: To investigate the role of retinoic acid (RA) in the differentiation, and maturation of dendritic cells (DCs) derived from cord blood monocytes, and its mechanism. Method: Nine cord blood samples were collected from healthy and well nourished newborns. Monocytes were isolated and cultured in vitro. Cells were divided into 4 groups: control group; retinoid acid receptor ? (RAR? )agonist group (RA group); RAR? antagonist group (RO group) and agonist plus antagonist group (RA+RO group). Part cells were collected in D9, and the surface markers on cells were detected by flow cytometer. The mixed lymphocyte reaction (allo-MLR) was used to evaluate the ability of DC to induce proliferation of T cells and the influence by RA and RAR?. Th cytokines were measured in protein level by ELISA and in mRNA levels by RT-PCR to decipher the effect of RA and RAR? in the regulation of Th1/Th2 balance by DCs. Results: The differentiation and maturation of DCs were inhibited significantly in RA group compared with control group. When RO was added into the culture, the effects of RA can be reversed. After MLR , the suppression effect of RA on allo-T cell proliferation was inversed by RO. During the influence of DC on Th cell polarization, RO could inhibit the down-regulation of Th1 cytokine (IFN-?) as well as the up- regulation of Th2 cytokines (IL-4, IL-10) by RA, whether on protein levels or on mRNA levels. Conclusion: Retinoic acid inhibited the differentiation and maturation of DC derived from cord blood monocytes, reduced the ability to stimulate allo-T lymphocytes proliferation by DCs, and made immune response bias to Th2. RAR? plays a very important role in the regulation of RA on DCs.

Objective: To investigate the effects and mechanisms of vitamin A on tracheal mucosal immunity. Method: The rat model with vitamin A deficiency (VAD) was established. By use of immunohistochemical, RT-quantity PCR and ELISA methods, the number of dendritic cells (DCs, OX-62 positive cells), the maturation of DCs (the positive areas of CD80 and CCR7), the pathogen recognition receptors (the positive areas of TLR2 and of TLR4) and TLRs signal transduction (the mRNA level of MyD88), as well as cytokines production in tracheal mucous membrane were detected. Results: In VAD rats, the number of DCs in trachea was increased, but the expressions of CD80 and CCR7 were similar with control group. The TLR2 and MyD88 mRNA levels were up-regulated, and IL-12 production was also raised. However, Th2 cytokines IL-4 and IL-6 were reduced significantly in protein and mRNA levels, and the production of IL-10 protein was declined compared with the control. Conclusion: In VAD rats, the number of DCs, receptors of pathogens recognition, and cytokines production in trachea mucosa were significantly changed. The affection of VAD on DCs may play important role in the impaired mucosal immunity of trachea.

Objective To evaluate the surgical procedures and both oncological and functional outcome in patients with bone tumors of the shoulder girdle.Methods Seventy-one patients including 61.pts with malignant tumor and 10 pts with giant cell tumors of the shoulder girdle treated in our department from July 1998 to July 2006 were studied retrospectively.According to the location,there were 15 pts with scapula tumor and 56 pts with proximal humeral tumor.Forty-two male pts and 29 female pts were included in this study with an average age of 36.5 years old ranging from 11.to 62 years old.Surgical procedures:forequarter amputation in 10 pts;Scapulectomy in 3 pts;Scapulectomy and artificial scapular replacement in 3pts;partial scapulectomy and proximal humerus resection with prosthetic reconstruction in 8 pts;proximal humerus resection and prosthesis replacement in 47 pts.Results Due to adequate soft tissue was preserved,the mean functional score was 28 for the pts with giant cell tumor according to MSTS functional scoring system,compared with the functional score 23 for the pts with malignant tumor because the deltoid muscle insertion was resected in the latter group.Among the thirty-seven patients with osteosarcoma,local recurrence occurred in four cases(10.8%),lung metastasis in five and bone metastasis in two.The seven patients died of disease.One patient iagnosed of malignancy in giant cell tumor died after distal metastasis.thtee patients with Ewing sarcoma died of the disease.No recurrence Wag observed in both five humeral chondrosarcoma and five scapular chondrosarcoma.Conclusion Tumot resection and proximal humeral prostbesis replacement is the optimal method for the sarcoma of shoulder girdle in term of preservation of elbow and hand function.Preservation of abductor insertion is necessary for good abduction function.The metastatic rate of proximal humeral osteosarcoma was lower than that of lower extremities.also the prognosis of oncological outcome.Intra-articular and extra-atticular tumor resection produced similar local recurrence rate in the present study,which suggested intra-articular resection may be an altemafive procedure.

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 evaluate the effects of sedation with propofol or dexmedetomidine on volume responsiveness in critically ill patients with acute circulatory failure. Methods Ninety?one critically ill patients with acute circulatory failure, aged 20-90 yr, weighing 40-80 kg, requiring sedation with propofol or dexmedetomidine, of Acute Physiology and Chronic Health Evaluation Ⅱ scores 12-47, of Sequential Organ Failure Assessment scores 1-18, and of NYHA Ⅰ or Ⅱ, were included. The patients were randomly divided into 2 groups using a random number table: propofol group ( n = 45 ) and dexmedetomidine group ( n=46) . Before and after propofol or dexmedetomidine sedation, when Richmond Agitation Sedation Scale score reached -2 or -1 ( BIS value 60-75) ( after sedation) , passive leg?raising (PLR) test was performed to evaluate volume responsiveness. An increase in cardiac index (ΔCI) ≥10% after PLR was considered to be a positive response, whereas ΔCI<10% after PLR was considered to be a negative response. The patients who presented with negative responses before sedation served as negative volume responsiveness subgroups ( N subgroups ) , that was PN subgroup and DN subgroup. Results The positive rates of volume responsiveness were 64% ( 14 cases) and 25% ( 5 cases) in PN and DN subgroups, respectively. The positive rates of volume responsiveness were significantly higher after sedation than before sedation in PN and DN subgroups. Compared with DN subgroup, the positive rates of volume responsiveness were significantly increased after sedation in PN subgroup. Conclusion For the critically ill patients with acute circulatory failure, both propofol and dexmedetomidine sedation can improve volume responsiveness, and propofol provides better efficacy than dexmedetomidine.

Objective To review the long-term oncologic and functional outcomes of surgical treatment for pelvic chondrosarcoma at a single institution to further delineate surgical strategy of resection and function reconstruction.Methods All of 165 patients with pelvic chondrosarcoma that had been surgically treated between July 2000 and Dec 2013 were reviewed retrospectively.There were 102 male and 63 female patients who had a mean age of 43.5 (range,13 to 75) years.The resection type included Type T 16,type Ⅱ 18,type Ⅲ 11,type Ⅰ+Ⅱ 19,type Ⅱ+Ⅲ 63,type Ⅰ+Ⅳ 15,type Ⅰ+Ⅱ+Ⅲ 10 and type Ⅰ+Ⅱ+Ⅳ 13 cases.The pathology diagnosis was grade Ⅰ in 15,grade Ⅱ in 88,grade Ⅲ in 20,dedifferentiated in 28,mesenchymal in 12 and clear cell chondrosarcoma in 2 patients.Nine cases were secondary lesion following multiple exostoses.114 patients received no previous treatment while others were referred due to recurrent tumor.En bloc resection was achieved in 142 patients and intralesional resection in 23 cases.Twelve patients had a hemipelvectomy to achieve local tumor control,whereas 153 patients underwent a limb-salvage procedure.Spinal screw-rod system was used to reconstruct anterior pelvic ring after ilium resection.Modular hemipelvic endoprosthesis was utilized to reconstruct periacetabular defect after tumor resection while no reconstruction was performed after ischium and pubis resection.Results The median duration of follow-up was 54.1 (range,l0 to 159) months.147 (89.1％) patients were alive at the final follow-up,seven of which were alive with tumor.The estimated 5-year survival was 81.5％.Thirty-three patients (20％) had local recurrence,and twenty (12.1％) had lung metastasis.Recurrent case,sacroiliac joint involvement and intralesional resction were three risk factors for postoperative recurrence.Patients who received type Ⅱ+Ⅲ resection and reconstruction had a mean functional score of 23 according to MSTS 93.The mean MSTS 93 for patients with type Ⅰ+Ⅱ and type Ⅰ+Ⅱ+Ⅳ resection and reconstruction was 18.The wound complication rate was 15.8％.Two aseptic loosening and 2 pubic connection plate breakage were observed in hemipelvic endoprosthesis reconstruction.Conclusion Tumor grade correlates with overall or disease-free survival.For low-grade chondrosarcoma,adequate surgical margin can provide long-term local control while for high-grade cases,distant metastasis is the main case of treatment failure.Adequate surgical margin can be achieved in cases with acetabulum involved.However,aggressive surgical resection of pelvic chondrosarcoma still remains as a challenge for orthopaedic oncologists when the tumor invades the iliosacral joint,which necessitates careful preoperative plan and skilled surgical techniques.

Objective To observe the intervention with electroacupuncture(EA) through regulating protein kinase(MAPK/ERK) pathway for cerebral ischemia rats.Methods SD rats were randomized into pseudo-operation group,model group and EA group.And the three groups were divided into 2-hour,one-day and 3-day subgroups according to the observation time.Focal cerebral ischemia(FCI) rat models were established by middle cerebral artery occlusion(MCAO) with heat-coagulation method.EA group received EA on Baihui(GV20) and Dazhui(GV14),qd,for 2 hours,one day and 3 days respectively.The learning and memory abilities of the rats in Y maze test and their neuroethological score were observed.Immunohistochemical method was used to observe the expression of phosphorylated extracellular signal-regulated kinase(p-ERK) after ischemia in CA1 area and CA3 area.Results In the model group,the neuroethological score was markedly increased,time for arriving the safe area in Y maze was prolonged(P