Pharmacokinetics，Tissue Distribution and Target Evaluation of Hydroxycamptothecin Nanoparticles in Rats / 中国药房

OBJECTIVE：To study the pharmacokinetics and tissue distribution characteristics of Hydroxycamptothecin （HCPT） nanoparticles in rats ，and to investigate their targeting. METHODS ：Male SD rats were randomly divided into 2 groups，with 6 rats in each group. They were given HCPT nanoparticles and HCPT injection （4 mg/kg based on HCPT ）via tail vein respectively. 500 μL fundus venous plexus blood were sampled at 5，30，60，120，240，360，480，600 and 720 min after administration. The plasma concentration of HCPT in rats were measured by HPLC at different time points. The pharmacokinetic parameters were calculated by DAS 3.0 software. Male SD rats were randomly divided into two groups ，with 24 rats in each group. They were given HCPT nanoparticles and HCPT injection （0.6 mg/kg based on HCPT ）via tail vein ，respectively. Blood was immediately taken from the abdominal aorta ，and heart ，liver，spleen，lung，kidney and brain were removed at 30，60，120，240 min after administration. The plasma and tissue concentration of HCPT in rats were measured by HPLC. The distribution of HCPT ineach tissue and targeting were investigated. RESULTS ：HCPT nanoparticles and its injection conformed to a two-compartment model in rats. Compared with HCPT injection ，AUC0-720 min andAUC0- ∞ increased by 1.89 and 1.87 times respectively ， MRT0-720 min and MRT 0- ∞ increased by 2.74 and 3.00 times respectively， t1/2 β increased by 2.75 times，with statistical significance（P＜0.05）. At 30 min after administration ，HCPT nanoparticles and HCPT injection had the highest concentration in lung；with the passage of time ，the drug gradually accumulated in the liver and reached the highest concentration at 60 min. The relative liver uptake rate of HCPT nanoparticles was the highest （6.28）. Taking liver ad target organ ，and the targeting efficiencies of it in heart ，spleen，lung，kindey，brain and plasma were higher than those of HCPT injection. The selectivity index of HCPT nanoparticles in heart ，lung（except for 30 min after administration ），kidney，brain and plasma were significantly higher than those of HCPT injection at 30-120 min after administration. CONCLUSIONS ：HCPT nanoparticles extend the half-life of the drug ， increase its plasma concentration ，and prolong its action time in vivo ，with significant liver targeting.

Application of Preoperative CT/MRI Image Fusion in Target Positioning for Deep Brain Stimulation / 中国医学科学杂志(英文版)

<strong>Objective</strong> To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.<strong>Methods</strong> We retrospectively analyzed the clinical data and images of 79 cases (68 with Parkinson's disease, 11 with dystonia) who received preoperative CT/MRI image fusion in target positioning of subthalamic nucleus in deep brain stimulation. Deviation of implanted electrodes from the target nucleus of each patient were measured. Neurological evaluations of each patient before and after the treatment were performed and compared. Complications of the positioning and treatment were recorded.<strong>Results</strong> The mean deviations of the electrodes implanted on X, Y, and Z axis were 0.5 mm, 0.6 mm, and 0.6 mm, respectively. Postoperative neurologic evaluations scores of unified Parkinson's disease rating scale (UPDRS) for Parkinson's disease and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) for dystonia patients improved significantly compared to the preoperative scores (P<0.001); Complications occurred in 10.1% (8/79) patients, and main side effects were dysarthria and diplopia.<strong>Conclusion</strong> Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.

Progress and application prospects of glutamine synthase in plants / 生物工程学报

Nitrogen is one of the most important nutrient elements for plants and a major limiting factor in plant growth and crop productivity. Glutamine synthase (GS) is a key enzyme involved in the nitrogen assimilation and recycling in plants. So far, members of the glutamine synthase gene family have been characterized in many plants such as Arabidopsis, rice, wheat, and maize. Reports show that GS are involved in the growth and development of plants, in particular its role in seed production. However, the outcome has generally been inconsistent, which are probably derived from the transcriptional and post-translational regulation of GS genes. In this review, we outlined studies on GS gene classification, QTL mapping, the relationship between GS genes and plant growth with nitrogen and the distribution characters, the biological functions of GS genes, as well as expression control at different regulation levels. In addition, we summarized the application prospects of glutamine synthetase genes in enhancing plant growth and yield by improving the nitrogen use efficiency. The prospects were presented on the improvement of nitrogen utility efficiency in crops and plant nitrogen status diagnosis on the basis of glutamine synthase gene regulation.

Clinical application of neuronavigation in transsphenoidal microsurgery of pituitary adenomas / 中华外科杂志

<p><b>OBJECTIVES</b>To summarize the experiences in clinical application of neuronavigation in transsphenoidal microsurgery of specific pituitary adenomas, and to discuss its indications.</p><p><b>METHODS</b>From January 2006 to December 2010, 138 cases of transsphenoidal microsurgery for specific pituitary adenomas under neuronavigation were reviewed. The indications for neuronavigation in transsphenoidal microsurgery includes: recurrent or regrowth of residual pituitary adenomas after former transsphenoidal surgery in 36 cases, invasive pituitary adenomas in 45 cases, extremely laterally or deeply situated microadenomas in 45 cases, poor pneumatization of the sphenoid in 4 cases, skull base anomalies due to osteodysplasia fibrosa in 3 cases, narrow space between bilateral internal carotid arteries in 4 cases, distortion of nasal septum in 1 case.</p><p><b>RESULTS</b>In the recurrence group, 12 were totally removed, 9 subtotally removed; postoperative complications included hematoma within the tumor cavity in 2 cases, cerebrospinal fluid (CSF) leakage in 4 cases among which 3 developed intracranial infection and 2 communicating hydrocephalus, oculomotor paralysis in 1 case and hypopituitarism in 3 cases; 9 were cured and 8 remission. In the invasive group, 5 were totally removed, 27 subtotally removed; postoperative complications included hematoma within the tumor cavity in 1 case, CSF leakage and intracranial infection in 1 case; 2 were cured and 22 remission. None of the 30 invasive hormone-secreting adenomas were cured or remission. The 45 cases of hormone-secreting microadenomas were all totally removed, among which 38 were cured. Among the poor sphenoid pneumatization group, total and subtotal tumor removal were achieved in 2 cases respectively with only one cured. In the skull base anomaly group, 2 were totally removed and 1 subtotally removed, with only one cured. For the cases with narrow space between bilateral internal carotid arteries and distortion of nasal septum, all were totally removed and cured.</p><p><b>CONCLUSIONS</b>Transsphenoidal microsurgery under neuronavigation can be applied for pituitary adenomas in above specific indications. It is an accurate, safe and effective approach for specific pituitary adenomas, which can not only expand the indication of transsphenoidal microsurgery for pituitary adenomas, but also reduce the harmful exposure of X-rays for the operating staff.</p>

In vivo tracking of bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide after cerebral ischemia in rats by magnetic resonance imaging / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the feasibility of in vivo tracking of bone marrow mesenchymal stem cells (BMSCs) labeled with superparamagnetic iron oxide (SPIO) by magnetic resonance imaging (MRI) in rats after cerebral ischemia, and to analyze the influence of stem cell therapy on the volume of cerebral infarction.</p><p><b>METHODS</b>The samples of rat bone marrow were collected. BMSCs separated by density gradient centrifugation were cultivated and harvested until the third passage. BMSCs were labeled with SPIO, which was mixed with poly-L-lysine. The labeling efficiency was evaluated by Prussian blue staining. Transient middle cerebral arterial occlusion (MCAO) was performed successfully in 18 adult Sprague-Dawley rats that scored from 6 to 12 by the modified neurological severity test. The 18 rats were then randomly divided into group A, B, and C, with 6 rats in each group and Group C was regarded as control group. BMSCs were injected into the contralateral cortex of ischemia in group A, ipsilateral corpora striata in group B, while D-Hank's solution was injected into ipsilateral corpora striata (group C) 24 hours after MCAO. MRI was performed 1 day after MCAO, 1 day and 14 days after transplantation. The volume of infarcted brain tissue was measured and analyzed. Prussian blue staining of brain tissues was performed to identify the migration of BMSCs.</p><p><b>RESULTS</b>The labeling efficiency of BMSCs with SPIO was 96%. The transplanted BMSCs migrated to the ischemic hemisphere along the corpus callosum and to the border of the infarction, which was confirmed by MRI and Prussian blue staining. The changes of infarction volume were not significantly different among these three groups.</p><p><b>CONCLUSIONS</b>MRI is feasible for in vivo tracking of BMSCs labeled with SPIO in rats. The stem cell therapy may not be able to affect the volume of cerebral infarction.</p>

Neuronavigation guidance for motor cortex stimulation in resection of gliomas involving the precentral gyrus / 中华显微外科杂志

Objective To explore surgical treatment of gliomas involving the motor eloquent area. Methods Twelve cases of gliomas involving precentral gyrus were underwent awake surgery procedures assis- ted with neuronavigation and brain functional mapping by cortical electrical stimulation.Results Eleven ca- ses acquired accurate location of both lesions and eloquent areas by neuronavigation and direct cortical stimula- tion.7 cases of motor cortices and 2 cases of motor speech centers were confirmed during the operation.Re- section,verified by postoperative MRI,was total in 8 cases (66.7%) and subtotal in 4 patients.Histological examination revealed an infiltrative glioma in all cases (8 low grade astrocytomas,2 high grade astrocytomas and 2 glioblastoma).Four patients had no postoperative deficit,while the other 8 patients were impaired, with,in all cases except one,complete recovery in 7 days to one month.Conclusion Direct cortical elec- trical stimulations and awake surgery offer a reliable,precise and safe method,allowing functional mapping es- pecially useful in case of infiltrative cerebral tumors in eloquent areas.This technique allows improvement in the quality of tumoral resection and concurrently a minimization of the risk of definitive postoperative neurologi- cal deficit.

Effect of mailuoning injection on calcitonin gene-related peptide expression in facial nerve of rabbits with facial spasm / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of Mailuoning injection (MLN) in protecting facial nerve from injury.</p><p><b>METHODS</b>The New Zealand white rabbit model with facial spasm was established by compressing superficial temporal artery to make artificial demyelinated lesion of the main peripheral facial nerve trunk. The successful establishment was confirmed by using electrophysiological technique to determine abnormal muscle response (AMR) which is a characteristic for facial spasm. MLN was injected continuously through ear marginal vein for 2 weeks. The change of CGRP expression in facial nerve was detected by immunohistochemical technique.</p><p><b>RESULTS</b>As compared with the model group, CGRP expression in facial nerve was significantly increased in the MLN group (P <0.01), and CGRP immunoreactive positive fibers were not seen in the shamoperation group. In the model group, the facial nerve fibers degenerated obviously, myelin sheath loosened and dissociated, the turgent axons with vacuole or even completely disappeared. But the facial nerve lesion was lessened in the MLN group.</p><p><b>CONCLUSION</b>MLN has a significant protective effect on facial nerve demyelination in rabbits with facial spasm, which is closely related with its effect in improving CGRP expression in the facial nerve.</p>

The experimental study of rAAV2 transfecting neural stem cells-derived neurospheres / 中国应用生理学杂志

<p><b>AIM</b>To investigate the abilities of recombinant adeno-associated virus type 2 (rAAV2) transfecting neurospheres.</p><p><b>METHODS</b>The rAAV2 conjugated with FITC (rAAV2-FITC) was added into the culture medium of neurospheres and 30 minutes later the neurospheres were detected with a fluorescence microscopy to determine if the AAV can combine with neurospheres. The rAAV2 containing GFP reporter gene (rAAV2-GFP) was incubated with the neurospheres for a month and then detected the ability of transfecting neurospheres. The neurospheres transfected with rAAV2-containing GFP were transplanted to the brain of rats. A month later the rats were sacrificed and the brains were removed to detect if there are expressions of the reporter gene. The neurospheres were transfected with rAAV2 containing hypoxia responds elements (HRE) and vascular endothelium growth factor(VEGF) gene and reporter gene GFP (rAAV2-HRE-VEGF-GFP) and then cultured in low oxygen density environments. Seventy-two hours later the neurospheres were detected through a fluorescence microscopy.</p><p><b>RESULTS</b>The neurospheres incubated with rAAV2-FITC present bright green fluorescence. GFP, the reporter gene, can be seen clearly 1 month after being transfected with rAAV2-GFP. The same green fluorescence protein can be observed ex vivo as well. The fluorescence can be seen in neurospheres transfected by rAAV2-HREVEGF-GFP only in low oxygen density.</p><p><b>CONCLUSION</b>The rAAV2 can transfect neurospheres specifically and efficiently. Reporter gene can be expressed in the neurospheres in vivo and ex vivo. Expression of reporter gene can be adjusted by HRE.</p>

Experimental study on the proliferation and plasticity of neural stem cells in situ in adult rats after cerebral infarction / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the proliferation and plasticity of neural stem cells in situ in adult rats after cerebral infarction.</p><p><b>METHODS</b>Cerebral infarction models of rats were made and the dynamic expression of bromodeoxyuridine (BrdU) and BrdU/polysialylated neural cell adhesion molecule (PSA-NCAM) were determined by immunohistochemistry and immunofluorescence staining.</p><p><b>RESULTS</b>Compared with the controls, the number of BrdU-positive cells in the subventricular zone (SVZ) and hippocampus increased strikingly at day 1 (P < 0.05), reached maximum at day 7, and decreased markedly at day 14, but it was still elevated compared with that of the controls (P < 0.05); The number of BrdU-labeled with PSA-NCAM-positive cells increased strikingly at day 7 (P < 0.05), reached maximum at day 14, and markedly decreased at day 28, but it was still elevated compared with that of the controls (P < 0.05), and was equal to 60% of the number of BrdU-positive cells in the same period.</p><p><b>CONCLUSIONS</b>Our results indicate that cerebral infarction stimulate the proliferation of inherent neural stem cells in situ and most proliferated neural stem cells represent neural plasticity.</p>

Measurement of soluble CD44v6 in peripheral blood as assistant diagnosis of invasive pituitary adenomas / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the value of measuring the concentration of soluble CD44 splice variant 6 (sCD44v6) in peripheral blood in patients with invasive and non-invasive pituitary adenomas.</p><p><b>METHODS</b>The concentrations of sCD44v6 in peripheral blood were measured with ELISA in 68 patients with invasive pituitary adenomas and 100 patients with non-invasive pituitary adenomas.</p><p><b>RESULTS</b>The serum concentration of sCD44v6 in patients with invasive pituitary adenomas was lower than that in patients with non-invasive pituitary adenomas, while the latter was lower than that in healthy controls. The serum concentrations of sCD44v6 were (44.63 +/- 7.21), (34.53 +/- 6.41), and (26.34 +/- 4.95) ng/ml in patients with invasive microadenoma, macroadenoma, and giant adenoma, and (60.78 +/- 9.61), (57.78 +/- 10.00), and (37.22 +/- 5.17) ng/ml in patients with non-invasive microadenoma, macroadenoma, and giant adenoma, lower than that in the healthy control group (68.73 +/- 6.00) ng/ml. Significant differences were observed among groups (P < 0.005). The concentration of sCD44v6 in peripheral blood decreased as the tumor size increased (P < 0.01), which was particularly significant in invasive pituitary adenomas. The positive rate in the patients with invasive pituitary adenomas reached 89.71%.</p><p><b>CONCLUSION</b>Serum concentration of sCD44v6 in the peripheral blood is inversely correlated with tumor size and its invasive growth, which may provide certain value in the early diagnosis, treatment and prognosis of invasive pituitary macroadenoma and giant adenoma.</p>