Synthesis of spiro[indolenine]-methanofullerenes via Deoxofluor promoted deoxygenative cyclopropanation of 1,2-(3-indole)-fullerenols.

Deoxofluor-promoted intramolecular cyclopropanation of 1,2-(3-indole)fullerenols has been developed as a straightforward and efficient protocol for the synthesis of various spiro[indolenine]-methanofullerenes. This approach exhibits low cost, operational simplicity, and convenient conditions, and thus has potential application value.

Bromadiolone poisoning leading to subarachnoid haemorrhage: A case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Many cases of rodenticide poisoning have been reported. Bromadiolone, often called a super-warfarin, is a second-generation dicoumarin rodenticide with long half-life. The main clinical manifestations of bromadiolone poisoning are excessive or inappropriate bleeding of skin mucosa, digestive tract and urinary tract. However, the phenomenon of central nervous system (CNS) toxicity is an uncommon medical emergency. We present a case of SAH and intracerebral haematoma mediated by bromadiolone intoxication, revealing that bromadiolone poisoning might cause intracerebral haematoma. CASE DESCRIPTION: A 44-year-old woman presented with skin mucosa haemorrhage and haematuresis initially. The patient developed lethargy, headache, nausea and vomiting. The toxicology test result revealed that the presence of bromadiolone in her blood. Coagulation test results showed a longer prothrombin time (PT), activated partial thromboplastin time (APTT) and a high international normalized ratio (INR). SAH, frontal lobe haematoma, midline shift and brain oedema were discovered by skull CT examination. The coagulation disorders were addressed after the treatment of vitamin K and fresh frozen plasma. The intracranial symptoms were relieved after surgery and the treatment with mannitol. WHAT IS NEW AND CONCLUSION: This case suggests that bromadiolone poisoning should be diagnosed and treated as early as possible. Bromadiolone poisoning might cause SAH and intracerebral haematoma, which is rare but potentially lethal. It is important to strengthen the diagnosis and post-treatment monitoring.

Application of Preoperative CT/MRI Image Fusion in Target Positioning for Deep Brain Stimulation.

Objective To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.Methods 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.Results 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.Conclusion Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.

MiR-25 suppresses 3T3-L1 adipogenesis by directly targeting KLF4 and C/EBPα.

In the past decade, miRNA emerges as a vital player in orchestrating gene regulation and maintaining cellular homeostasis. It is well documented that miRNA influences a variety of biological events, including embryogenesis, cell fate decision, and cellular differentiation. Adipogenesis is an organized process of cellular differentiation by which pre-adipocytes differentiate towards mature adipocytes. It has been shown that adipogenesis is tightly modulated by a number of transcription factors such as PPARγ, KLF4, and C/EBPα. However, the molecular mechanisms underlying the missing link between miRNA and adipogenesis-related transcription factors remain elusive. In this study, we unveiled that miR-25, a member of miR-106b-25 cluster, was remarkably downregulated during 3T3-L1 adipogenesis. Restored expression of miR-25 significantly impaired 3T3-L1 adipogenesis and downregulated the expression of serial adipogenesis-related genes. Further experiments presented that ectopic expression of miR-25 did not affect cell proliferation and cell cycle progression. Finally, KLF4 and C/EBPα, two key regulators of adipocyte differentiation, were experimentally identified as bona fide targets for miR-25. These data indicate that miR-25 is a novel negative regulator of adipocyte differentiation and it suppressed 3T3-L1 adipogenesis by targeting KLF4 and C/EBPα, which provides novel insights into the molecular mechanism of miRNA-mediated cellular differentiation.

Research advances in the application of methylprednisolone in the treatment of acute spinal cord injury.

Acute spinal cord injury(ASCI),mainly caused by traffic accidents and fall injuries,is a catastrophic event that can profoundly affect the trajectory of a patient's life. Debate continues over the medical management of ASCI,in particular the usefulness,dosage,and potential risks of methylprednisolone(MP). Although the results of American National Acute Spinal Cord Injury Study 2 and 3 trials led to the wide adoption of a high-dose MP regimen for ASCI patients,the reliabilities of their study methods and data were still questionable. Based on the currently available literature,we conclude that high-dose MP is no longer a recommended therapy for ASCI;however,due to the lack of effective treatment,it remains a useful option for this condition.

[Application of positron-emission tomography-magnetic resonance imaging fusion in biopsy and resection of gliomas].

OBJECTIVE: To assess the value and feasibility of positron-emission tomography-magnetic resonance imaging (PET-MRI) fusion technology in delineating tumor boundaries and positioning biopsy targets of gliomas so as to facilitate the diagnosis and treatment of gliomas. METHODS: A total of 18 patients with a preoperative diagnosis of gliomas discharged from our hospital from January 2010 to April 2011 were recruited. All of them underwent the preoperative examinations of MRI, fluorodeoxyglucose (FDG) PET and fluoroethyl-choline (FECH) PET. The digital image data were transferred into Brain LAB planning software and three types of images automatically fused. The tumor contours were drawn on the basis of each image modality separately. The extent of tumor resection or biopsy target was determined on the integrated information including tumor contours on PET and MRI images and intraoperative observation of tumor texture. RESULTS: On PET scans, the average standard uptake value (SUV) of glioblastomas was higher than that of grade II-III gliomas. With regard to the patients with both biopsy and tumor resection, the pathological diagnosis of the specimen obtained from the PET-guided biopsy was consistent with that of subsequently resected tissue. All 11 patients undergoing tumor resection were classified according to relationship between the image-based tumor contour and actual extent of resection. Six of them benefited from contour delineated by FDG PET images and 3 of them benefited from FECH PET. The combined contribution ratio of both PET methods was 9/11. CONCLUSION: PET-MRI fusion technology may accurately delineate tumor boundary and sensitively target the region of high proliferation or metabolism. A more radical resection and more accurate histological diagnosis can be thus achieved and yield a probably better prognosis of gliomas.

[Significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery].

OBJECTIVE: To explore the significance of pseudocapsule in the excision of pituitary adenomas in transsphenoidal surgery. METHODS: For 22 patients with pituitary adenomas over a period of 2 years at Peking Union Medical College Hospital, resection of pseudocapsule was applied for complete tumor removal. Pituitary function test and radiological imaging were performed at pre-operation, 3 months post-operation and at subsequent 6-12 months intervals postoperatively. RESULTS: All pituitary adenomas were totally removed under microscope. The symptoms of headache, disorder of sight and visual field disappeared postoperatively in nonfunctional pituitary adenomas. The GH levels of 2/5 growth hormone secreting adenoma patients were 4.2 and 7.7 µg/L while it was under 1 µg/L for another 3. The postoperative level of prolactin was 4.3 µg/L in prolactin secreting adenoma. The level of adrenocorticotropic hormone decreased under 5 ng/L except one was 15.7 ng/L. Leakage of cerebrospinal fluid occurred intraoperatively in 3 patients and postoperatively in 1. No leakage was found after repair. Diabetes insipidus occurred in one patient and was controlled with Minirin. Pseudocapsule was confirmed by pathological examination. Special staining revealed reticulum fibers in pseudocapsule. CONCLUSION: Resection of pseudocapsule may achieve a higher remission rate without deteriorating pituitary function.

Nontraumatic convexal subarachnoid hemorrhage: A case report.

BACKGROUND: Nontraumatic convexal subarachnoid hemorrhage (cSAH) is a rare type of atypical subarachnoid hemorrhage. It mainly presents as a focal and transient neurological deficit with similar manifestations as transient ischemic attack. CASE SUMMARY: We report a case of a 64-year-old man who visited the hospital with paroxysmal left-sided numbness and weakness is presented in this study. Computed tomography examination indicated a high-density image of the right frontal-parietal sulcus. Digital subtraction angiography showed severe stenosis at the right anterior cerebral artery A2-A3 junction (stenosis rate approximately 70%). CONCLUSION: The findings of this case indicate that anterior cerebral artery stenosis may lead to the occurrence of cSAH.

[Effect of moxibustion on JAK2/STAT3 signal pathway in synovial tissues of rabbits with adjuvant arthritis under the overexpression of NLRP3 inflammatory bodies].

OBJECTIVE: To observe the effect of moxibustion on Janus protein tyrosine kinase 2/signal transducer and activator of transcription 3 (JAK2-STAT3) signal pathway and interleukin (IL)-1ß and IL-18 in synovial fluid of adjuvant arthritis (AA) rabbits, so as to explore the mechanism of moxibustion in the treatment of rheumatoid arthritis. METHODS: Twenty-eight rabbits were randomized into control, model, moxibustion, and NLRP3 overexpression groups, with 7 rabbits in each group. AA rabbit model was established by injection of Freund's complete adjuvant (FCA, 0.5 mL/kg) into the rabbits' bilateral hind-knee joint cavities. On the third day after modeling, the NLRP3 lentiviral vector (40 µL) were injected into the bilateral hind-knee joint cavities of rabbits in NLRP3 overexpression group. Moxibustion was used to bilateral "Shenshu" (BL23) and "Zusanli" (ST36), 5 cones every time, once daily, 6 days a week for 3 weeks in the moxibustion and NLRP3 overexpression groups. The perimeters of rabbits' hind legs were measured after modeling and after the intervention. The contents of IL-1ß, IL-18 in synovial fluid were detected by ELISA and the expression levels of NLRP3, JAK2 and STAT3 mRNAs in synovial tissue were detected by real-time PCR. RESULTS: In comparison with the control group, the perimeters of bilateral knee joints were significantly increased at each time point (P<0.05),and the contents of IL-1ß, IL-18 in synovial fluid and the expression levels of NLRP3, JAK2, STAT3 mRNA in synovial tissue were significantly increased (P<0.05) in the model group. Compared with the model group, the perimeters of bilateral knee joints were significantly decreased (P<0.05), and the contents of IL-1ß, IL-18 in synovial fluid and the expression levels of NLRP3, JAK2, STAT3 mRNAs in synovial tissue were significantly decreased (P<0.05) in the moxibusion group. Compared with the moxibustion group, the above indexes were higher in the NLRP3 overexpression group (P<0.05). CONCLUSION: Moxibustion may play an anti-inflammatory and detumescent role in AA rabbits by regulating JAK2-STAT3 signal pathway, and its therapeutic effect may be closely related to the expression of NLRP3.

[Thyroid-stimulating hormone pituitary adenomas: clinical characteristics, diagnosis and treatment].

OBJECTIVE: To study the clinical characteristics, diagnosis and surgical effects of thyroid-stimulating hormone pituitary adenomas (TSH-omas). METHODS: The clinical data of 19 patients (14 female and 5 male) with TSH-omas were analyzed retrospectively in this study from January 2001 to December 2008. The patients ranged from 20 to 70 years old (average 40.5 years old) and had disease histories from 1 to 228 months (average 55 months). Among these patients, 15 of them complained of thyrotoxicosis symptoms, while the other 4 patients' symptoms were associated with headache and/or visual disturbance caused by the tumor mass effect. Initially, 12 of the 15 patients with thyrotoxicosis symptoms were misdiagnosed with Grave's disease. As a result 2 of them received (131) Iodine, and one received subtotal thyroidectomy. All of these patients underwent transsphenoidal microsurgery. RESULTS: Average follow-up period was 3.6 years (6 months-7 years). Pathological analysis of the surgical specimen showed pituitary adenoma in all patients, immunohistochemistry were positive for TSH in 17 cases, negative for TSH in 2, positive for growth hormone in 2, positive for prolactin in 1, and positive for adrenocorticotrophic hormone in 1. Postoperative MRI revealed that the tumors in 15 patients were removed totally, though 4 patients still had residual tumors. The thyroid hormone level tests suggested that 13 patients could be considered normal 3 months after their tumors were removed, though 2 of patients with normal postoperative MRI and thyroid hormones showed increased levels of TSH. For these 2 patients, tumors did not recur and their thyroid hormone levels returned to normal after pituitary radiotherapy. The cure rate was 11/19 after surgery and 13/19 after surgery plus pituitary radiotherapy. CONCLUSIONS: The screening test for hyperthyroidism patients with high TSH levels is a key point to improve the accuracy rate in early diagnoses of TSH-omas. The transsphenoidal microsurgery is first choice to treat TSH-omas, while pituitary radiotherapy and somatostatin analogs are beneficially adjunctive therapies.

[Clinical application of neuronavigation in transsphenoidal microsurgery of pituitary adenomas].

OBJECTIVES: To summarize the experiences in clinical application of neuronavigation in transsphenoidal microsurgery of specific pituitary adenomas, and to discuss its indications. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Management of pulmonary thromboembolism in post-operative neurosurgical patients].

OBJECTIVE: To summarize the diagnosis and treatment of pulmonary thromboembolism (PTE) in post-operative neurosurgical patients. METHODS: We retrospectively analyzed the clinical data of 7 patients who experienced pulmonary thromboembolism after neurosurgical operations in our department from October 2009 to March 2010. RESULTS: Of these 7 patients, 6 were confirmed with computed tomographic pulmonary angiography (CTPA) and 1 was diagnosed according to the clinical manifestations and other diagnostic examinations. All the patients were treated initially with low-dose heparin or low-molecular-weight heparin and then with warfarin. Two patients were implanted with permanent inferior vena cava filters before anticoagulation. One received anticoagulant therapy and died of respiratory failure due to pulmonary embolism on the fourth post-operative day. Six patients were discharged after significant improvement. CONCLUSIONS: Many risk factors may cause PTE peri-operatively. Post-operative CTPA may be indicated. Anticoagulation and other management strategies may be applied to improve the outcome.

[Mechanism on moxibustion for rheumatoid arthritis based on PD-1/PD-L1 signaling pathway].

OBJECTIVE: To explore the mechanism of moxibustion on the treatment of rheumatoid arthritis (RA) in the perspective of programmed cell death-1 and its ligand 1 (PD-1/PD-L1). METHODS: A total of 30 Japanese big ear white rabbits were randomly divided into a control group, a model group and a moxibustion group, 10 rabbits in each one. In the model group and the moxibustion group, RA model was prepared by the injection of Freund's complete adjuvant (FCA) into the hind knee joint cavities of each rabbit. In the control group, 0.9% sodium chloride solution of the same dose was injected. On the 8th day of experiment, in the moxibustion group, moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36), 5 cones at each acupoint, on the bilateral sides alternatively, once a day, 6 treatments as one course, with an interval of 1 days between the treatment courses. Totally, 3 courses of treatment were required. On the 1st, 7th, 14th, 21st and 28th days of experiment, successively, the circumference of the bilateral knee joints was measured with the tape. On the 28th day of experiment, H.E. staining was adopted to observe the histopathological morphology and to evaluate the score of knee synovial tissue. ELISA was used to determined the concentrations of soluble PD-1 (sPD-1) and its ligand 1 (sPD-L1), the interleukin 2 (IL-2) and IL-17 in knee synovial fluid and the concentrations of sPD-1 and sPD-L1 in serum. The histochemistry method was used to determine the expressions of membrane PD-1 (mPD-1) and its ligand 1 (mPD-L1) in spleen tissue. RESULTS: On the 14th, 21st and 28th days of experiment, the circumference of both knee joints was increased in each of the rabbits in the model group as compared with the control group (P<0.01), and it was reduced significantly in the moxibustion group as compared with the model group (P<0.01). Compared with the control group, the hyperplasia of synovial tissue and fibrous tissue, as well as inflammatory cell infiltration were increased obviously in the model group (P<0.01), and they were reduced significantly in the moxibustion group as compared with the model group (P<0.01, P<0.05). Compared with the control group, the concentrations of IL-2 and IL-17 in knee synovial fluid were increased in the rabbits of the model group (P<0.01). Compared with the model group, after the intervention with moxibustion, the concentrations of IL-2 and IL-17 in knee synovial fluid were reduced in the rabbits of the moxibustion group (P<0.05). Compared with the control group, the concentrations of sPD-1 and sPD-L1 in knee synovial fluid and serum in the rabbits of the model group were all increased (P<0.05). Compared with the model group, the concentration of sPD-1 in the knee synovial fluid and serum were reduced in the rabbits of moxibustion group (P<0.05). Compared with the control group, the expressions of mPD-1 and mPD-L1 in spleen tissue were increased obviously in the rabbits of the model group (P<0.05). Compared with the model group, the expression of mPD-L1 in spleen tissue was up-regulated in the rabbits of the moxibustion group (P<0.05). CONCLUSION: Moxibustion could inhibit the over-activation of T cells by enhancing the negative regulation of PD-1/PD-L1 signaling pathway so as to play its effect in treatment of RA.

Novel Subgroups in Subarachnoid Hemorrhage and Their Association With Outcomes-A Systematic Review and Meta-Regression.

Background and Purpose: Subarachnoid hemorrhage (SAH) has long been classified into two main forms, aneurysmal SAH (aSAH) and non-aneurysmal SAH (naSAH), but the related risk factors for aSAH and naSAH are heterogeneous. Our objective was to determine the risk factors for SAH of known or unknown origin with respect to diagnostic evaluation in a large patient cohort. We sought to determine whether our classification system can further predict middle long-term stroke and death. Methods: We performed a systematic review and meta-analysis to identify risk factors for each SAH subtype. The discovery phase analyzed 11 risk factors from case studies in the literature. Kruskal-Wallis, Cox regression, logistic regression, and Kaplan-Meier analyses were used to compare the two groups. Results: A total of 14,904 (34.53%) male and 22,801 (52.84%) female patients were eligible for this study. At a median follow-up of 45.6 months, the 5-years overall survival was 97.768% (95% CI: 0.259-0.292) for aSAH patients and 87.904% (95% CI: 1.459-1.643) for naSAH patients. The 10-years survival rate was 93.870% (95% CI: 2.075-3.086) and 78.115% (95% CI: 2.810-3.156), respectively. Multi-risk factor subgroups showed significant intergroup differences. We identified eight risk factors (drugs, trauma, neoplastic, vessels lesion, inflammatory lesion, blood disease, aneurysm, peri-mesencephalic hemorrhage) using logistic regression, which were optimally differentiated among the aSAH [aSAH-S (AUC: 1), a-d-SAH (AUC: 0.9998), aSAH-T (AUC: 0.9199), aSAH-N (AUC: 0.9433), aSAH-V (AUC: 1), aSAH-I (AUC: 0.9954), a-bd-SAH (AUC: 0.9955)] and naSAH [na-pmSAH (AUC: 0.9979), na-ni-ivl-SAH (AUC: 1), na-t-SAH (AUC: 0.9997), na-ne-SAH (AUC: 0.9475), na-d-SAH (AUC: 0.7676)] subgroups. These models were applied in a parallel cohort, showing eight risk factors plus survival rates to predict the prognosis of SAH. Conclusions: The classification of risk factors related to aSAH and naSAH is helpful in the diagnosis and prediction of the prognosis of aSAH and naSAH patients. Further validation is needed in future clinical applications.

Identifying Modifiable Risk Factors for Relapse in Patients With Schizophrenia in China.

BACKGROUND: Preventing relapse of schizophrenic patients is really a challenge. The present study sought to provide more explicit evidence and factors of different grades and weights by a series of step-by-step analysis through χ2 test, logistic regression analysis and decision-tree model. The results of this study may contribute to controlling relapse of schizophrenic patients. METHODS: A total of 1,487 schizophrenia patients were included who were 18-65 years of age and discharged from 10 hospitals in China from January 2009 to August 2009 and from September 2011 to February 2012 with improvements or recovery of treatment effect. We used a questionnaire to collect information about relapse and correlative factors during one year after discharge by medical record collection and telephone interview. The χ2 test and logistic regression analysis were used to identify risk factors and high-risk factors firstly, and then a decision-tree model was used to find predictive factors. RESULTS: The χ2 test found nine risk factors which were associated with relapse. Logistic regression analysis also showed four high-risk factors further (medication adherence, occupational status, ability of daily living, payment method of medical costs). At last, a decision-tree model revealed four predictors of relapse; it showed that medication adherence was the first grade and the most powerful predictor of relapse (relapse rate for adherence vs. nonadherence: 22.9 vs. 55.7%, χ2 = 116.36, p < 0.001). The second grade factor was occupational status (employment vs. unemployment: 19.7 vs. 42.7%, χ2 = 17.72, p < 0.001); the third grade factors were ability of daily living (normal vs. difficult: 28.4 vs. 54.3%, χ2 = 8.61, p = 0.010) and household income (household income ≥ 3000 RMB vs. <3000 RMB: 28.6 vs. 42.4%, χ2 = 6.30, p = 0.036). The overall positive predictive value (PPV) of the logistic regression was 0.740, and the decision-tree model was 0.726. Both models were reliable. CONCLUSIONS: For schizophrenic patients discharged from hospital, who had good medication adherence, more higher household income, be employed and normal ability of daily living, would be less likely to relapse. Decision tree provides a new path for doctors to find the schizophrenic inpatient's relapse risk and give them reasonable treatment suggestions after discharge.

[Specific expression in brain of exogenous gene by transpassing blood-brain barrier after intravenous injection].

OBJECTIVE: To study the expression of exogenous LacZ gene in brain via a delivery of OX26-pGFAP-IL. METHODS: pCMV-Liposome, OX26-pCMV-IL, OX26-pGFAP-IL and blank liposome were injected into rats via femoral vein. At 24 h post-injection, the method of Q-PCR was adopted to calculate the relative quantities of LacZ gene mRNA in brain and peripheral organs. At 48 h post-injection, the protein expression of LacZ gene was detected by the activity of beta-galactosidase and the method of histochemical stain. RESULTS: The result of Q-PCR showed that, at 24 h post-injection, the relative quantities of LacZ mRNA in OX26-pCMV-IL group (49.2 x 10(-6)) and OX26-pGFAP-IL group (44.9 x 10(-6)) were significantly higher than pCMV-liposome and blank liposome groups (P < 0.05). In peripheral organs, the relative quantity of LacZ mRNA in OX26-pCMV-IL group were significantly higher than that in OX26-pGFAP-IL group (P < 0.05). At 48 h post-injection, the activity of beta-galactosidase in OX26-pCMV-IL (0.67 pg/mg) and OX26-pGFAP-IL groups (0.92 pg/mg) were significantly higher than pCMV-liposome and blank liposome groups (P < 0.05). There was no significant difference between OX26-pCMV-IL group and OX26-pGFAP-IL group in terms of the expression of beta-galactosidase. The result of histochemical stain showed that OX26-pGFAP-IL achieved a specifically positive expression in brain and had a decreased expression in peripheral organs. CONCLUSION: OX26-pGFAP-IL injected via femoral vein can cross the brain-blood barrier and achieve a specific expression in brain under the control of GFAP promoter. OX26-pGFAP-IL decreases the non-specific expression in peripheral organs and it may be used as an non-viral gene therapy for intra-cranial diseases.

Transplantation of neural stem cells modified by human neurotrophin-3 promotes functional recovery after transient focal cerebral ischemia in rats.

The study tested the hypothesis that transplantation of human neurotrophin-3 (hNT-3) over-expressing neural stem cells (NSCs) into rat striatum after a severe focal ischemia would promote functional recovery. Rat NSCs, transduced by Flag-tagged hNT-3 gene mediated by lentiviral vector (LV), were transplanted into the striatum ipsilateral to the injury of adult rats 7 days after 2-h occlusion of the middle cerebral artery (MCAO). From 3 days to 2 weeks after transplantation, the modified cells (NSCs-hNT3, as defined by Flag immunofluorencence staining) that survived the transplantation procedures could secrete significantly higher levels of neurotrophin-3 protein in the graft sites than controls (P<0.001). Furthermore, the rats that accepted NSCs-hNT3 exhibited enhanced functional recovery on neurological and behavioral tests, compared with controlled animals transplanted with saline or untransduced NSCs. This study suggests: (1) LV is an ideal vector to transduce foreign gene into the NSCs; (2) modified NSCs could carry therapeutic genes to disease tissues and express effectively; (3) modified cells could survive in the ischemic brains and continue to secrete neurotrophin-3 abundantly for over 2 weeks, which might have values for enhancing functional recovery after stroke.

Magnetic resonance imaging characteristics and surgical results of adrenocorticotropin-secreting pituitary adenomas.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI) characteristics and surgical results of adrenocorticotropin (ACTH)-secreting pituitary adenomas. METHODS: MRI characteristics and relationship between MRI positive rate and surgical results of 266 patients with pathologically confirmed Cushing's disease were analyzed retrospectively. All patients underwent thin-section sagittal and coronal scans of the pituitary gland before and after administration of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) on a 1.5 Tesla MRI scanner, and dynamic enhanced MRI was performed in 39 patients. All patients underwent transsphenoidal adenomectomy. Endocrinological examinations and assessments were performed. RESULTS: Preoperative MRI revealed normal results in 41 (15.4%) cases, microadenoma in 179 (67.3%), macroadenoma in 42 (15.8%), and huge adenoma in 4 (1.5%). Pituitary apoplexy was found in 13 (4.9%) cases. Positive rate of ACTH-secreting adenomas was 84.6% (225/266) on MRI scans, and that of small microadenomas was 87.2% (34/39) on dynamic enhanced MRI scans. Preoperative endocrinological tests of 199 cases supported the diagnosis of typical Cushing's disease, while the other 67 cases had atypical endocrinological results. The endocrinological cure rate, remission rate, and inefficacy rate were 85.7%, 7.9%, and 6.4%, respectively. There was no difference in the initial endocrinological cure rate between the patients with positive and normal MRI results (90% vs. 87.8%, P = 0.904). CONCLUSIONS: Enhanced coronal pituitary MRI is helpful for preoperative localization of ACTH-secreting pituitary microadenoma. Dynamic enhanced MRI may improve detection rate of microadenoma. There is no marked difference in the surgical results for patients with preoperative MRI results indicating presence or absence of microadenoma.

[Cost-effectiveness analysis of two therapeutic methods for prolactinoma].

OBJECTIVE: To evaluate the therapeutic responses to transsphenoidal surgery and medical therapy in terms of normalization of prolactin (PRL), mortality, morbidity and the cost-effectiveness of PRL normalization in order to establish an individualized therapeutic protocol for the patients with prolactinoma. METHODS: A retrospective study was undertaken of a consecutive series of patients with prolactinoma who were followed for at least 1 year after transsphenoidal surgery or medical treatment. The clinical characteristics and the long-term outcomes (normalization of PRL, morbidity or mortality) were assessed. Utilizing the principle of medical economics and data from the two types of treatment, we worked out a Markov chain and calculated the lowest cost of two kinds of therapeutic protocols. RESULTS: (1) The success rate of normalizing serum PRL through surgical treatment in microadenoma was 85% (22/26), and that of medical treatment was 95% (19/20). There was no statistical difference between the two therapies (P > 0.05). The success rate of normalizing serum PRL through surgical treatment in macroadenoma was 45% (19/42), and that of medical treatment was 5/5. There was a statistical difference between the two therapies (P < 0.05). (2) According to the Markov model, it would cost a microprolactinoma patient 25,129.25 yuan to normalize serum PRL by surgical treatment. This is comparable to the cost of medical treatment which would be 24,943.99 yuan. Whereas for a macroprolactinoma patient surgery would cost 35,208.20 yuan and medical treatment would cost 25,344.38 yuan. CONCLUSIONS: Medical therapy is superior to surgical treatment in regard to complication rate and cost-effectiveness for macro- and extra big prolactinomas. Transsphenoidal surgery remains an option for patients with microadenomas. Markov model is an effective way to predict the treatment cost for patients with hyperprolactinoma at different ages and with different causes.