Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Clinical characteristics and surgical treatment of ganglioneuroma in spine / 中国骨伤

<p><b>OBJECTIVE</b>To summarize the clinical manifestation and diagnosis of ganglioneuroma in spine and investigate the clinical effect of surgical treatment.</p><p><b>METHODS</b>The clinical data of 6 patients underwent a surgery for ganglioneuroma in spine from January 2008 to January 2015 were retrospectively analyzed. There were 4 males and 2 females, aged from 2 to 63 years old with an average of 34.6 years. The courses of disease were from 3 days to 17 years. Five patients complicated with superficial hypesthesia in correlative level of tumor, and the muscle strength under tumor plane had decreased at different levels, with the strength of grade II-IV. Two cases complicated with hypermyotonia and positive bilateral Hoffmann's and Babinski sign. Five cases were sporadic lesion in correlative spinal canal and one case complicated with the giant occupying lesion in thoracic cavity.</p><p><b>RESULTS</b>Six operations had been performed including 5 en bloc and 1 subtotal resection. Postoperative pathological results showed tumor cells scattered or fasciculated inserted into Schwann cells in the stroma. In 2 patients complicated with radiculalgia before operation, 1 case was relieved and 1 was invariant after operation. All 4 patients with preoperative dyscinesia in the limbs obtained improvement after operation. All the patients were followed up from 0.3 to 6.8 years with an average of 2.5 years. At the final follow-up, according to ASIA grade, 5 cases were good and 1 case was invariant. During the follow-up, only 1 patient experienced chemoradiation because of merging ganglioneuroblastoma and receiving subtotal resection. No recurrence in other 5 cases.</p><p><b>CONCLUSION</b>Ganglioneuroma is a benign and rare tumors in spine. Clinically, radicular pain and sensory-motor disorders are the main manifestations. Its diagnosis depends on pathological examination. Prognosis of surgical treatment is good.</p>

Current situation and progression of induced pluripotent stem cells in treating spinal cord injury / 中国骨伤

Spinal cord injury is a difficult medical problem and current therapeutic methods could not obtain satisfactory results. Recent 20 years, stem cell technology developed rapidly, embryonic stem cells and adult stem cells were used for treating neurological disease and nerve injury of animal models and the clinical results were confirmed. It provided a new prospect for the treatment of nerve injury at the cellular level. However,due to technical and ethical problems, it is difficult to obtain the appropriate cells that can be applied to the human being. Recently, induced pluripotent stem cells were developed as a new method for the treatment of spinal cord injuries by the autologous transplantation. Starting from this work, the purpose of this review is to assess the differentiate ability of induced pluripotent stem cells into neurocyte and review the latest developments in this area.

Green fluorescent protein as marker in chondrocytes overexpressing human insulin-like growth factor-1 for repair of articular cartilage defects in rabbits / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To label the primary articular chondrocytes overexpressing human insulin-like growth factor (hIGF 1) with green fluorescent protein (GFP) for repair of articular cartilage defects in rabbits.</p><p><b>METHODS</b>GFP cDNA was inserted into pcDNA3.1 hIGF 1 to label the expression vector. The recombinant vector, pcGI, a mammalian expression vector with multiple cloning sites under two respective cytomegalovirus promoters/enhancers, was transfected into the primary articular chondrocytes with the help of lipofectamine. After the positive cell clones were selected by G418, G418-resistant chondrocytes were cultured in medium for 4 weeks. The stable expression of hIGF 1 in the articular chondrocytes was determined by in situ hybridization and immunocytochemical analysis and the GFP was confirmed under a fluorescence microscope. Methyl thiazolyl tetrazolium (MTT) and flow cytometer methods were employed to determine the effect of transfection on proliferation of chondrocytes. Gray value was used to analyze quantitatively the expression of type II collagen.</p><p><b>RESULTS</b>The expression of hIGF 1 and GFP was confirmed in transfected chondrocytes by in situ hybridization, immunocytochemical analysis and fluorescence microscope observation. Green articular chondrocytes overexpressing hIGF 1 could expand and maintain their chondrogenic phenotypes for more than 4 weeks. After the transfection of IGF 1, the proliferation of chondrocytes was enhanced and the chondrocytes could effectively maintain the expression of type II collagen.</p><p><b>CONCLUSIONS</b>The hIGF 1 eukaryotic expression vector containing GFP marker gene has been successfully constructed. GFP, which can be visualized in real time and in situ, is stably expressed in articular chondrocytes overexpressing hIGF 1. The labeled articular chondrocytes overexpressing hIGF 1 can be applied in cell-mediated gene therapy as well as for other biomedical purposes of transgenic chondrocytes.</p>

Biomechanical study on pullout strength of thoracic extrapedicular screw fixation / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To identify the biomechanical feasibility of the thoracic extrapedicular approach to the placement of screws.</p><p><b>METHODS</b>Five fresh adult cadaveric thoracic spine from T1 to T8 were harvested. The screw was inserted either by pedicular approach or extrapedicular approach. The result was observed and the pullout strength by pedicular screw approach and extrapedicular screw approach via sagittal axis of the vertebrale was measured and compared statistically.</p><p><b>RESULTS</b>In thoracic pedicular approach, the pullout strength of pedicle screw was 1001.23 N+/-220 N (288.2-1561.7 N)ls and that of thoracic extrapedicular screw approach was 827.01 N+/-260 N when screw was inserted into the vertebrae through transverse process, and 954.25 N+/-254 N when screw was inserted into the vertebrae through the lateral cortex of the pedicle. Compared with pedicular group, the pullout strength in extrapedicular group was decreased by 4.7% inserted through transverse process (P larger than 0.05) and by 17.3% inserted through the lateral cortex (P less than 0.05). The mean pullout strength by extrapedicular approach was decreased by 11.04% as compared with pedicular approach (P less than 0.05).</p><p><b>CONCLUSIONS</b>It is feasible biomechanically to use extrapedicular screw technique to insert pedicular screws in the thoracic spine when it is hard to insert by pedicular approach.</p>

Labeling of human insulin-like growth factor-I eukaryotic expression vector with green fluorescent protein / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To label human insulin-like growth factor-I (hIGF-I) eukaryotic expression vector with green fluorescent protein (GFP) for the repair of articular cartilage defects.</p><p><b>METHODS</b>GFP cDNA was inserted into pcDNA(3.1)-hIGF-1 to construct the co-expression vector with two multiple cloning sites mammalian expression vector under two cytomegalovirus promoters/enhancers respectively. Recombinant pcGI was transfected into NIH 3T3 cells with the help of lipofectamine.</p><p><b>RESULTS</b>Enzyme digestion and agarose gel electrophoresis analysis revealed that pcGI vector contained correct GFP and hIGF-I cDNA. Expression of hIGF-1 and GFP was confirmed in transfected NIH 3T3 cells by immunocytochemical analysis and fluorescence microscopy.</p><p><b>CONCLUSIONS</b>hIGF-I eukaryotic expression vector has been successfully labeled with GFP.</p>

Radiographic verification of pedicle screw pilot hole placement in thoracic spine using Kirschner wires versus spiral wires / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the feasibility of the pedicle screw pilot holes placement in thoracic spine using the spiral wires as the guide pin.</p><p><b>METHODS</b>The pedicle screw pilot holes were drilled within the center of the pedicle and the lateral and medial pedicle walls were violated in 9 human dried thoracic vertebrae. Kirschner wires or spiral wires were separately placed in the holes, and then the posteroanterior and lateral radiographs were taken. The radiographs were evaluated by 3 experienced spine surgeons and 3 young orthopedists. After radiographs were shown to these observers, they combined the posteroanterior and lateral radiographs in each place and determined whether the pedicle screw pilot hole violated the pedicle cortex or not. The results were analyzed by a statistical software.</p><p><b>RESULTS</b>Sensitivity, specificity and accuracy of the method using spiral wires to detect pedicle pilot hole placement were significantly higher than those of using Kirschner wires. With a true posteroanterior radiograph, the sensitivity, specificity and accuracy of the method using spiral wires approximated or attained 100%.</p><p><b>CONCLUSIONS</b>The method of intrapedicular pilot hole placement verification using spiral wires is effective for guiding the accurate placement of pedicle screws.</p>