OBJECTIVETo identify the proteins involved in osteogenic differentiation of beagle dog bone marrow mesenchymal stem cells (BMSCs) and explore its possible regulation mechanism of osteogenic differentiation of BMSCs.

METHODSCultured beagle dog BMSCs were induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) for 7 days. The differentially expressed proteins between cells with osteogenic differentiation and control cells were identified by proteomics analysis based on two-dimensional gel electrophoresis. Q-PCR and Western blotting were used to verify the interested protein of LASP1, ferritin light chain and heavy chain.

RESULTSOsteogenic differentiation was induced successfully in the BMSCs. Twenty differentially expressed proteins were identified by proteomic analysis, including 9 down-regulated and 11 up-regulated ones. Q-PCR and Western blotting demonstrated a significant reduction of LASP1 expression and significant up-regulation of ferritin in the BMSCs after a 7-day induction with rhBMP-2.

CONCLUSIONLASP1, which plays an important role in the regulation of the activity of the cytoskeleton, and ferritin, an important molecule in cellular iron homeostasis, can be critical in the osteogenic differentiation of beagle dog BMSCs induced by rhBMP-2.

Adaptor Proteins, Signal Transducing ; metabolism ; Animals ; Bone Marrow Cells ; cytology ; drug effects ; Bone Morphogenetic Protein 2 ; pharmacology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Cytoskeletal Proteins ; metabolism ; Dogs ; Down-Regulation ; Ferritins ; metabolism ; LIM Domain Proteins ; metabolism ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Osteogenesis ; drug effects ; Proteomics ; Recombinant Proteins ; pharmacology ; Transforming Growth Factor beta ; pharmacology ; Up-Regulation

Objective To study the newborn screening program,morbidity,laboratory findings,gene mutations,treatment and follow-up of neonatal propionic academia (PA) in Xuzhou City.Method From September 2015 to September 2018,the blood sample of neonates from newborn screening program in Xuzhou were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) method to examine the blood acylcarnitine level.The diagnosis was confirmed by urine gas chromatography mass spectrometry (GC-MS) and gene analysis.The clinical manifestation,laboratory findings,gene analysis,treatment and prognosis were retrospectively analyzed.Result A total of 297 610 live birth infants blood samples were screened using MS/MS,and 8 cases were diagnosed with PA,with a prevalence of 1∶37 201.Among the 8 patients,7 had no clinical symptoms before the diagnosis and one already had symptoms including recurrent vomiting,drowsiness,tachypnea and hypotonia.Gene analysis revealed that 6 cases carried propionyl-CoA carboxylase α (PCCA) gene mutations and 2 cases carried propionyl-CoA carboxylase β (PCCB) gene mutations.A total of 10 types of PCCA gene mutations were detected,including 5 missense mutations,4 splicing mutations and 1 synonymous mutation,among which 7 were de-novo mutations.A total of 4 types of PCCB gene mutations were detected,including 2 missense mutations,1 frameshift duplication and 1 splicing mutation,among which 3 were de-novo mutations.1 patient died after refusing treatments.The other 7 cases showed significant decline of the blood propionyl-carnitine level,the ratio of propionyl-carnitine to acetylcarnitine,3-OH-propionate and methylcitrate level in urine after treatment.4 cases had normal growth and development,and 3 cases showed various psychomotor retardation on follow-up.Conclusion Newborn screening using LC-MS/MS method is important for early diagnosis of PA.The incidence of PA is relatively high in Xuzhou City.The major clinical manifestations of PA were neurological symptoms.The main cause is PCCA gene defects and missense mutation is most common.

Objective To explore the clinical effect of endoscope assisted suction-cutter removal of apocrine sweat glands in treatment of osmidrosis.Methods This study generalized and analyzed the curative effects of 30 patients with axillary osmidrosis,treated with endoscopy assisted suction-cutter removal of apocrine sweat glands.The efficacy was evaluated according to the postoperative results and complications.Results In all the 30 patients,wound healed 7 to 10 days after operation,and they resumed almost normal life after treatment.From May 2015 to April 2017,the follow-up visits showed that none of them had relapse,infection or skin necrosis.Surgical scar was slight,and in all the patients,symptoms disappeared.Conclusions The operation of endoscopy assisted suction-cutter removal of apocrine sweat glands is a minimally invasive surgery.The advantages include direct vision,radical operation,well preserved dermal vascular network and lower risk of complications.

Objective: To investigate the prevalence of sleep problems and influencing factors among preschoolers, so as to provide a reference for healthy sleep behaviors among preschoolers. Methods: From December 2017 to June 2018, a questionnaires study was administered to parents of 8 456 preschoolers from kindergartens in Yangzhou, Zhenjiang and Xuzhou by using random cluster sampling method. Demographic characteristics, screen time, sleep patterns and the Children s Sleep Habits Questionnaire (CSHQ) were colleted. Results: The average night sleep duration was (9.91±0.64)h, the rate of sleep deprivation was 51.7%, which increased with age ( χ 2 trend =34.19, P <0.01). The total scores of CSHQ were (49.46±5.02), and the prevalence of sleep problems was 95.0%, with the prevalence of specific sleep problems ranged from 2.3% to 76.4%. Multivariate Logistic regression analysis showed that only child, mothers age, parental education, and household economic status was significantly associated the sleep problems ( P <0.05). Conclusion The prevalence of sleep problems among preschool children is more prominent, varies by only child, parental education and household economic status. Parents and society should raise awareness of sleep problems.

Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.
Animals ; Antibodies, Bispecific ; immunology ; Antibodies, Monoclonal ; immunology ; pharmacokinetics ; CD3 Complex ; metabolism ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; ErbB Receptors ; metabolism ; Female ; Humans ; Lymphocyte Activation ; immunology ; Mice, SCID ; Neoplasms ; immunology ; pathology ; Rats, Sprague-Dawley ; T-Lymphocytes, Cytotoxic ; immunology