Objective To study effects of backpack gravity center position on kinetics and kinematics of lower-extremity joints in parachuting landing and evaluate the injuries. Methods Seven participants performed parachuting landing with backpack gravity center on three positions: low-back (position 1), upper-back (position 2) and abdomen (position 3). Results The peak vertical ground reaction force (GRF) with backpack on position 2 was significantly lower than that on position 1. The joint moment on sagittal plane of the hip with backpack on position 2 was significantly higher than that on position 1 and position 3. The joint energy absorption of the hip with backpack on position 2 was significantly higher than that on position 1. The angular displacement of the hip on sagittal plane with backpack on position 2 was significantly higher than that on position 1 and was significantly lower than that on position 3. The angular velocity of the hip on sagittal plane with backpack on position 2 was significantly lower than that on position 3. Conclusions Different positions of backpack gravity center could significantly influence kinetic and kinematic parameters of the hip. Backpack gravity center on upper-back position could decrease the lower-extremity injuries. The results can provide evidences for evaluating backpack gravity center and decreasing injuries in parachuting landing.

Objective:To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) .Methods:This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle.Results:In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion:The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

Objective:To explore the effect of intervention of E-cadherin (E-cad) and B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) mediated by transcription activator-like effector nuclease (TALEN) on the biological behaviors ofnasopharyngeal carcinoma cells.Methods:Multi-locus gene targeting vectors pUC-DS1-CMV-E-cad-2A-Neo-DS2 and pUC-DS1-Bmi-1 shRNA-Zeo-DS2 were constructed,and the E-cad and Bmi-1 targeting vectors were transferred with TALEN plasmids to CNE-2 cells individually or simultaneously.The integration of target genes were detected by PCR,the expressions of E-cad and Bmi-1 were detected by Western blot.The changes of cell proliferation were detected by cell counting kit-8 (CCK-8) assay.T-he cell cycle and apoptosis were detected by flow cytometry.The cell migration and invasion were detected by Transwell assay.Results:The E-cad and Bmi-1 shRNA expression elements were successfully integrated into the genome of CNE-2 cells,the protein expression level of E-cad was up-regulated,and the protein expression level of Bmi-1 was down-regulated.The intervention of E-cad and Bmi-1 didn't affect the proliferation,cell cycle and apoptosis of CNE-2 cells,but it significantly inhibited the migration and invasion ability of CNE-2 cells.Furthermore,the intervention of E-cad and Bmi-1 together significantly inhibited the migration ability of nasopharyngeal carcinoma cells compared with the intervention of E-cad or Bmi-1 alone (all P＜0.01).Conclusion:The joint intervention of E-cad and Bmi-1 mediated by TALEN can effectively inhibit the migration and invasion of nasopharyngeal carcinoma cells in vitro,which may lay the preliminary experimental basis for gene therapy of human cancer.

Objective To analyze the expression of hsa-miR-10b in three cervical cancer cell lines , and to find the target genes of hsa-miR-10b.Methods PCR was applied to measure expression levels of hsa-miR-10b in C-33A, HeLa and CaSki .The relative studies on hsa-miR-10b were retrieved from PubMed .The sequence and genome char-acteristics of hsa-miR-10b were analyzed on line by miRbase and NCBI .The target genes of hsa-miR-10b were searched by TargetScan , PicTar and miRanda , and then demonstrated by Gene Ontology and Pathway Enrichment analysis.Results Compared with C-33A, the expression of hsa-miR-10b significantly reduced in HeLa and Caski (P<0.01).Current studies showed that hsa-miR-10b was related with multiple tumorigenesis .hsa-miR-10b was lo-cated in human chromosome 2q31.1 and highly conserved among different species .The target genes were enriched in the biological processes of transcription , gene expression regulation , cell proliferation and etc .(P<0.05).Pathway analysis showed that these target genes were responsible for biochemical erents mediated by to the signaling pathways of cancer, cell cycle, ARF and etc.(P<0.05).Conclusions hsa-miR-10b may have extensive functions , and closely related with the occurrence and development in cervical cancer .Prediction of target genes provides a theoreti-cal basis for the further study .

Increased understanding of the role of incretin hormones in maintaining glucose homeostasis has enabled the development of pharmacotherapies that target deficient incretin activity in type 2 diabetes mellitus.lncretin-based therapies could be classified into 2 categories with different mechanisms of action:glucagon-like peptide 1 ( GLP-1 ) receptor agonists ( e.g.liraglutide,exenatide twice daily,and exenatide once weekly),and the dipeptidyl peptidase 4 ( DPP-4 ) inhibitors ( e.g.sitagliptin,linagliptin,saxagliptin,and vildagliptin),which inhibit the breakdown of endogenous GLP-1.Both categories share some specific characteristics,such as glucose-dependent insulin stimulation and low incidence of hypoglycemia.But there are also different profiles in efficacy between these 2 classes.This article reviews the pharmacokinetics and clinical aspects of efficacy and safety of these 2 classes of incretin-based therapies and elucidates their roles in treating type 2 diabetes mellitus.

Incretins ale gut hormones,which stimulate insulin secretion after meal.One of the incretin hormones,glucagon-like peptide-1(GLP-1),contributes to glucose homeostasis by stimulation of insulin secretion,suppression of glucagon secretion(both in a glucose dependent manner),slowing of gastric emptying,and induction of satiety.It could also improve beta cell function in type 2 diabetes.However,due to its short biological half-life,GLP-1 itself is not practical for type 2 diabetes therapy.Exenatide is a peptide found in the lizard Heloderma suspectum and has a high similarity to GLP-1.It has a much longer biological half life than GLP-1 and is a GLP-1 receptor agonist that Can be used for therapeutic purposes by twice daily injection.Clinical studies with exenatide have shown a significant reduction in HbA_(1C),fasting and postprandial glucose,and body weight in type 2 diabetic patients.Animal studies revealed an improvement of beta cell funotion and an increase in beta cell mass after exenatide treatment.Due to its special therapeutic efficacy,GLP-1 receptor agonist,such as exenatide,is now included in the recently published guidelines for the treatment of type 2 diabetes mellitus.

BACKGROUND: Previous studies have confirmed that embryonic stem cells call be induced to differentiate into insulin-producing cells, but the induction process takes a long time. Most of the processes take about one month.OBJECTIVE: Activin A, all-trans retinoic acid (ATRA), basic fibroblast growth factor (bFGF) and nicotinamide were applied in vitro in combination to observe whether mouse embryonic stem cells could be induct to differentiate into insulin-producing cell in a relatively short time.DESIGN: Cell observation experiment.SETTING: Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.MATERIALS: This study was performed at Shanghai Institute of Endocrine and Metabolic Diseases from October 2004 to February 2006. Two mice of clean grade and of 12.5-14.5 days of gestational age were provided by Shanghai SLAC Laboratory Animal Co., Ltd (Permission No. 2004A034). The protocol was performed in accordance with ethical guidelines for the use and care of animals. Mouse embryonic stem cell lines were supplied by Dr Changxian Zhang (CNRS UMR5641, France). Activin A was the product of the R & D Corporation. ATRA and nicotinamide were supplied by the Sigma Corporation, USA. BFGF was supplied by Gibco Corporaion. METHODS: Head and viscera were removed from embryos of the pregnant mouse. The remaining tissues were cut into pieces and digested with trypsin. Cell suspension was centrifuged and inoculated at 3×108L-1. The cells could be used as mouse feeder layer after 2-3 times of passage. The mouse embryonic stem cells (ESCs) were inoculated onto the feeder layer in knockout Dulbecco's modified Eagle medium (DMEM) supplemented with leukemia inhibitory factors (LIF). ESCs were passaged at 1:3-1:6 after 2-3 days of culture. Culture medium with serum was added into the culture dishes to terminate the digestion. Cell fluid was centrifuged and supernatant was discarded. The sediments were prepared into suspension and inoculated at 2.5×104 with LIF-free culture medium. After 24-48 hours, embryonic bodies (EBs) were collected and replated in 1% Matrigel-coated dishes. When began to adhere to the dishes, EBs were cultured in 10% FBS/DMEM supplemented with 100μg/L activin A for 24 hours. Then EBs were switched to 10% FBS/DMEM for 6-8 hours as an interval. After this interval. EBs differentiated were cultured in 10% FBS/DMEM with 10<-6mol/L RA for another 24 hours followed by culture in 10% FBS/DMEM supplemented with 10μg/L bFGFs for 3-5 days. Finally, EBs differentiated were cultured in DMEM/F12 supplemented with N2 supplement, B27 supplement, 1μg/L laminin, 10μg/L bFGFs, and 10mmol/L nicotinamide for 3-5 days. Dithizone (DTZ) staining, inununofluorescent staining and reverse transcription-polymerase chain reaction (RT-PCR) were applied to detect insulin expression in the differentiated cells.MAIN OUTCOME MEASURES: Induction of ESCs, DTZ staining and immunofluorescent staining as wel as RT-PCR detection.RESULTS: Mouse ESCs growing on a feeder layer formed many colonies with clear boundary and dense structure. However, there was no obvious outer limit between these ESCs. EBs began to adhere to the dishes, which were coated with matrigel, on the 2nd day. After activin A and ATRA interval induction, EBs spread, and most of the living cells were epithelial cell-like when cultured in 10% FBS/DMEM supplemented with 10μg/L bFGFs. After culturing in DMEM/F12 supplemented with N2, B27, nicotinamide, bFGFs and laminin, the cells formed small clusters. The insulin-producing cells were stained dark red with DTZ, and the cells stained with primary antibody to insulin were insulin-positive. After 2 weeks of induction of activin A, ATRA, bFGFs and nicotinamide, the insulin-producing cells expressed insulin 2, Pdxl, Nkx6.1, Nkx2.2, PP, IAPP, Glut2, Somastatin, Hnf3β and Neuro D mRNA but did not express insulin 1 mRNA.CONCLUSION: Mouse ESCs call be induced to differentiate into insulin-producing cells by activin A, ATRA, bFGFs and nicotinamide in vitro. Induction time call be shortened to 2 weeks.

Glucagon-like poptide-1 (GLP-1) is an incretin secreted by the enteroendocrine L cells of the gut. Upon the activation of GLP-1 receptor, adenylyl cyclase is activated and cAMP is generated, leading to the activation of protein kinase A and Epac signal pathway. GLP-1 could also activate calcium/calmodulin pathway as well as mitogen-activated protein kinases and phosphatidyl inositol-3 kinase pathway. GLP-1 not only stimulates the phase 1 and phase 2 insulin secretion, but also increases insulin synthesis. GLP-1 also stimulates proliferation and differentiation of islet β-cells, and protects β-cell from apoptosis and modulates endoplasmic reticulum stress response leading to promotion of β-cell adaptation and survival.

Betacellulin (BTC) is one of "islets regeneration factors" which received more and more attention these years. BTCe is the C-terminal 50-residue region of mature BTC protein and can bind with erbB-1?erbB-4 receptor. It has the same mitogenic activity on cells as the whole section. BTC and BTCe can improve the level of glucose-stimulated insulin secretion (GSIS) during islets culture in vitro though they had no effect on the acute insulin secretion. BTCe also effectively ameliorated the hyperglycemia of STZ-induced diabetic rats by a single plasmid injection into muscle of rats. It is supposed that BTCe promote the proliferation of PDX-1 positive cells or repair some signal transduction pathway. Perhaps the latter is more important.

Objective To study the association of glucagon like peptide 1 receptor (GLP1R) gene polymorphism with type 2 diabetes in Han population in Shanghai. Methods In the study, 360 type 2 diabetic patients and 313 normal control subjects were enrolled. Diabetic patients were further subdivided into insulin treated non obese patients (BMI28, 192 subjects). A single nucleotide polymorphism (SNP) rs 2268657 was genotyped in all the subjects enrolled in the study using allele specific real time PCR and its association with type 2 diabetes was examined. Results The frequencies of AA,AG, GG genotype incontrol group were0.086,0.447, 0.466 respectively, 0.155, 0.375, 0.470 in non obese diabetic patient group respectively, and 0.109, 0.500, 0.391 in obese diabetic patient group respectively. There was significant difference of the frequency of genotype AA between control group and non obese diabetic patient group (OR=1.939, P