Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin^®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin^®. BAT1706 and Avastin^® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin^® are highly similar in terms of in vitro functional activities.

OBJECTIVETo observe the effects of lithium chloride combined with human umbilical cord blood mesenchymal stem cell (hUCB-SCs) transplantation in the treatment of spinal cord injury in rats.

METHODSEighty female SD rats with complete T9 spinal cord transaction were randomized into 4 groups (n=20), namely the control group (group A), lithium chloride group (group B), hUCB-SCs group (group C) and hUCB-SCs(+) lithium chloride group (group D). On days 1 and 3 and the last days of the following weeks postoperatively, the motor function of the hindlimb of the rats were evaluated according to the BBB scores. At 8 weeks, all the rats were sacrificed and the spinal cords were taken for morphological observation. The spinal cord tissues at the injury site were observed with Brdu nuclear labeling to identify the survival and migration of the transplanted SCs. The regeneration and distribution of the spinal nerve fibers were observed with fluorescent-gold (FG) spinal cord retrograde tracing.

RESULTSBrdu labeling showed that the transplanted hUCB-SCs survived and migrated in the spinal cord 8 weeks postoperatively in groups C and D. FG retrograde tracing identified a small amount of pyramidal cells that migrated across the injury site in groups C and D. The BBB scores of the hindlimb motor function 8 weeks postoperatively were 4.11∓0.14, 4.50∓0.15, 8.31∓0.11 and 11.15∓0.18 in groups A, B, C and D, respectively.

CONCLUSIONLithium chloride can promote the survival and differentiation of hUCB-SCs into neural cells at the injury site. Lithium chloride combined with hUCB-SCs transplantation may accelerate functional recovery of the hindlimbs in rats with complete transection of the spinal cord.

Animals ; Cord Blood Stem Cell Transplantation ; Female ; Humans ; Lithium Chloride ; therapeutic use ; Rats ; Spinal Cord Injuries ; therapy

Objective To determine the changes of cerebrospinal fluid(CSF) ?-endorphin(?-EP) and C-reactive protein(CRP) in children with central nervous system(CNS) infection.Methods Sixty-five children suffered from CNS infection were determined the plasma and CSF ?-EP and CRP concentration during the acute and recovering stage with radioimmunoassay, which included 48 viral encephalitis, 12 purulent meningitis and 5 tuberculou meningitis,and 24 non-CNS disease children were as control group.Results The concentrations of plasma and CSF ?-EP of every experimental group were obviously higher than those of control group during the early stage of CNS infection and these were obviously lower during the recovering stage. The serum concentration of CRP during acute stage was significantly higher than that during recovering stage. No change of serum and CSF CRP concentration was determined during either the acute or recovering stage in the other two experimental groups.Conclusions Determining the plasma and CSF ?-EP is mea-(ningful) in early diagnosis of CNS infection,and determining the serum CRP at the same time may be helpful in differentiating septic and inseptic infection.

In this study, daphnetin and its major metabolites in the intestinal wall of rats were identified by liquid chromatography and quatrupole-time of flight mass spectrometry. Perfusion fluid of duodenum, jejunum, ileum and colon were collected separately for 2 hours from the rat intestine following perfusion with daphnetin. The metabolites of daphnetin in the perfusion fluid of different intestine segments were analyzed by the liquid chromatography and quatrupole-time of flight mass spectrometry. It is shown that the parent drug daphnetin and four metabolites were found in the perfusion fluid of duodenum, jejunum and ileum. However, no metabolites were found in the colon. Among the four metabolites, two daphnetin sulfates (m/z 257) were first discovered as the phase II metabolites of daphnetin in rats, which revealed a new way of daphnetin metabolism in rats.
Animals ; Chromatography, High Pressure Liquid ; Colon ; metabolism ; Duodenum ; metabolism ; Ileum ; metabolism ; Intestines ; metabolism ; Jejunum ; metabolism ; Male ; Perfusion ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; Umbelliferones ; metabolism ; pharmacokinetics

OBJECTIVETo test the efficacy of kyphoplasty using an enhanced balloon expander in restoring the height of vertebral compression fractures (OVCF).

METHODSFifteen lumbar vertebral bodies (L1-L5) were harvested from 3 young male fresh cadavers and separated into individual vertebral bodies with the bilateral pedicles of the vertebral arch removed. Before operation, plain X-ray films of all the vertebral bodies were obtained. All the vertebral bodies were compressed lengthwise to approximately 80% of their original heights using a universal material-testing machine to result in compression fractures. Post-compression vertebral bodies were then repaired using an enhanced balloon expander, and the delivery of the bone cement into the vertebral bodies was observed. The heights of the anterior and posterior borders of the vertebral bodied were measured before and after compression as well as after kyphoplasty.

RESULTSThe inflation of the balloon expander averaged 2.95-/+0.18 ml and the pressure was 122.67-/+27.89 psi (1 psi=6895 Pa). Kyphoplasty resulted in significant restoration of the vertebral body height lost due to the compression (P<0.01).

CONCLUSIONKyphoplasty using an enhanced balloon expander may restore vertebral body height damaged by compression and correct the kyphotic deformity. The balloon expander can be a effective and economic choice for kyphoplasty for its relatively low cost.

Adult ; Bone Cements ; Cadaver ; Catheterization ; Fractures, Compression ; etiology ; surgery ; Humans ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Spinal Fractures ; complications ; surgery ; Tissue Expansion Devices ; Vertebroplasty ; instrumentation ; methods

OBJECTIVETo investigate the effects of mechanical vibration on the morphology of the acellular scaffold for the spinal cord and establish a procedure to construct an acellular rat spinal cord allograft retaining intact matrix fibers for repairing spinal cord injuries.

METHODSFifteen segments of rat spinal cord were divided randomly into 3 groups and subjected to mechanical vibration at the frequency 80 r/min (group A, n=5), 120 r/min (group B, n=5), and 160 r/min (group C, n=5) respectively. The spinal cord was treated with Triton X-100 and sodium deoxycholate at room temperature and washed with distilled water. The specimens were observed microscopically with HE staining, and the ultrastructure was observed using scanning electron microscope.

RESULTSIn group A, the spinal cord specimens contained numerous cells and neural sheaths. Vibration at 120 and 160 r/min (in groups B and C) resulted in depletion of all the cells, axons and neural sheaths from the spinal cord after treatment with Triton X-100 and sodium deoxycholate. The acellular spinal cord consisted of a meshwork of the matrix fibers in longitudinal arrangement. In group C, however, obvious disruption of both the spinal dura mater and the matrix fiber occurred in the acellular spinal cord.

CONCLUSIONAll the cells, axons and neural sheaths in the spinal cord can be removed by chemical extraction with Triton X-100 and sodium deoxycholate. Mechanical vibration at suitable frequency may cell preserve the 3-dimensional structure of the matrix fibers. The acellular spinal cord scaffold may serve as an ideal material for constructing tissue-engineered spinal cord.

Animals ; Cell Separation ; methods ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; anatomy & histology ; cytology ; Spinal Cord Injuries ; therapy ; Tissue Engineering ; methods ; Vibration

OBJECTIVE: To examine the normal range of the width of posterior cranial fossa (WPCF) in the second and third trimester by ultrasonography, and to investigate its relationship with fetal congenital and chromosome abnormality. METHODS: WPCF of 2484 fetus (gestational age from 14 to 41 weeks) was measured by ultrasonograph routinely, and the infants were followed up. RESULTS: In 2848 fetus, 2772 were normal and 76 were abnormal. WPCF increased before 32 weeks, decreased after 33 weeks, the largest value of WPCF was 13.4 mm. The occurrence rate of WPCF> or =8 mm in normal fetus was 8.84%, and that in abnormal fetus was 17.46%. Most fetuses with chromosome abnormality had normal WPCF in the second trimester, but some fetuses with remarkable broadening in the late stage. Some abnormal fetuses (such as water head, Dandy-Walker's syndrome etc) showed significant extension of WPCF. CONCLUSION WPCF increases before 32 weeks, decreases after 33 weeks;and can be easily measured during 29 - 32 weeks. WPCF of some fetus with chromosome abnormality or with congenital abnormality is remarkably broadened in the late stage. The fetus of WPCF> or =10 mm should be followed up closely, and antenatal diagnosis should be done if WPCF is more than 14 mm.
Adult ; Cranial Fossa, Posterior ; abnormalities ; diagnostic imaging ; Female ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Pregnancy Trimester, Third ; Ultrasonography, Prenatal

OBJECTIVETo acquire sufficient PDGF-BB protein and provide the basis for the further studies of its role on the fracture healing and trauma reconstruction and its clinical applications.

METHODSConstructed the prokaryotic expression vector pQE-PDGF-B with the gene rearrangement technique, and the monomeric form of recombinant PDGF-B expressed in E. coli M15.

RESULTSPDGF-B mature peptide gene was inserted into prokaryotic expression vector pQE30, which was confirmed by PCR, enzyme digestion and sequencing identification; the expressed products of pQE-PDGF-B in E. coli showed a single protein on SDS-PAGE, and their expression level was about 15% of the total bacterial protein. The molecular weight of the purified PDGF-B protein was about 15 KDs on SDS-PAGE.

CONCLUSIONSThe construction of recombinant plasmid and preparation of the monomeric protein of PDGF-B provides a solid foundation for further studying the function of PDGF-BB and producing biologically PDGF-BB protein.

Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; Humans ; In Vitro Techniques ; Platelet-Derived Growth Factor ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-sis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection

OBJECTIVETo express human platelet-derived growth factor (hPDGF) B chain mature peptide gene in a prokaryotic expression system and detect the bioactivity of the expressed protein.

METHODShPDGF B chain mature peptide gene was amplified and expressed in E. coli, and the recombinant protein, rhPDGF-BB, was purified and renatured in GSSG/GSS system. The bioactivity of rhPDGF-BB in vitro was evaluated with SD rat osteoblasts.

RESULTSThe full-length PDGF-B mature peptide gene was obtained and verified, and successfully expressed in E. coli. Bioactivity detection results showed that the expressed rhPDGF-BB obviously promoted the proliferation and DNA replication of SD rat osteoblasts in vitro (P<0.01).

CONCLUSIONhe PDGF-B chain mature peptide cDNA has been successfully cloned and the PDGF-B precursor highly expressed in E. coli, and renatured rhPDGF-BB displays high bioactivity as shown by MTT assay and flow cytometry. This success provides the basis for production of functional PDGF-BB and facilitates further studies of its role in fracture healing and trauma reconstruction.

Animals ; Cell Proliferation ; Cells, Cultured ; DNA Replication ; Escherichia coli ; genetics ; Genetic Vectors ; Humans ; Osteoblasts ; metabolism ; Proto-Oncogene Proteins c-sis ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; biosynthesis ; genetics

Objective To understand the changing trends of non-communicable diseases (NCDs) in Xinjiang Production and Construction Corps from 1998 to 2008.Methods A stratified-cluster random sampling based cross-sectional NCDs survey was carried out in 2008,and using the data of NCDs from the health service surveys in 1998 and 2004,in Xinjiang Production and Construction Corps.The prevalence rate of NCDs was standardization according to age proportion of the population being surveyed in 1998.Results In 1998,2004 and 2008,the prevalence rates of NCDs in Xinjiang Production and Construction Corps were 17.26%,25.61%,24.85% while the Standardized rates of NCDs were 17.26%,23.54% and 20.49% respectively.The prevalence rates of NCDs were statistically significant different in 35-,45-,55- and over 65 age groups in 1998,2004 and 2008 which showed an consecutive upward trend.The prevalence rates of hypertension,diabetes,cerebrovascular disease,coronary heart disease and chronic obstructive pulmonary disease increased significantly from 1998 to 2008.The prevalence rate of hypertensive disease among 25- age group,diabetes among 35- age group,cerebrovascular disease and coronary heart disease among 45- age groups showed an increasing trend.Conclusion Cardiovascular and cerebrovaseular diseases,together with diabetes were the fastest increasing ones over the past 10 years and becoming the major diseases,making the Xinjiang Production and Construction Corps an aging population.NCDs should be prioritized in the health development plan.Targeted health education should be carried out in the whole population,together with other interventions as well as management programs on chronic diseases to reduce the prevalence of NCDs.