2006年 · 第119卷第16期

Though tens thousands of people are suffering from spinal cord injury (the majority are young people), effective treatments are rare. To patients doctors may say "we have done our best, let's wait and see if some miracle will happen." It is glad that decades' researches have shed some light on the mechanism of spinal cord damage and identified several targets for intervention.

With the development of modern neuroimaging and the improvement of surgical instruments or devices as well as operative skills, minimally invasive neurosurgery has been progressing rapidly with great changes in surgical concepts and methods.1 Based on these changes, anatomic research has been carried out to explore new surgical approaches dealing with anticipated microtrauma. These approaches have made or been making things possible. Keyhole microsurgery has evolved into an important subject of modern minimally invasive neurosurgery。

Abstract：Background Axonal regeneration in lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. This paper studied the action of neural stem cell (NSC) in promoting corticospinal axons regeneration and synapse reformation in rats with injured spinal cord.Methods NSCs were isolated from the cortical tissue of spontaneous aborted human fetuses in accordance with the ethical request. The cells were discarded from the NSC culture to acquire NSC-conditioned medium. Sixty adult Wistar rats were randomly divided into four groups (n=15 in each): NSC graft, NSC medium, graft control and medium control groups. Microsurgical transection of the spinal cord was performed in all the rats at the T11. The NSC graft group received stereotaxic injections of NSCs suspension into both the spinal cord stumps immediately after transection; graft control group received DMEM injection. In NSC medium group,NSC-conditioned medium was administered into the spinal cord every week; NSC culture medium was administered to the medium control group. Hindlimb motor function was assessed using the BBB Locomotor Rating Scale. Regeneration of biotin dextran amine (BDA) labeled corticospinal tract was assessed. Differentiation of NSCs and the expression of synaptophysin at the distal end of the injured spinal cord were observed under a confocal microscope. Group comparisons of behavioral data were analyzed with ANOVA.Results NSCs transplantation resulted in extensive growth of corticospinal axons and locomotor recovery in adult rats after complete spinal cord transection, the mean BBB scores reached 12.5 in NSC graft group and 2.5 in graft control group (P＜ 0.05). There was also significant difference in BBB score between the NSC medium (11.7) and medium control groups (3.7, P＜ 0.05). BDA traces regenerated fibers sprouted across the lesion site and entered the caudal part of the spinal cord. Synaptophysin expression colocalized with BDA positive axons and neurons distal to the injury site. Transplanted cells were found to migrate into the lesion, but not scatter along the route of axon grows. The cells differentiated into astrocytes or oligodendrocytes, but not into the neurons after transplantation. Furthermore, NSC medium administration did not limit the degree of axon sprouting and functional recovery of the injured rats compared to the NSC graft group.Conclusions Human embryonic neural stem cells can promote functional corticospinal axons regeneration and synapse reformation in the injured spinal cord of rats. The action is mainly through the nutritional effect of the stem cells on the spinal cord。

Abstract：Background In China, the feasibility of keyhole approach in surgical treatment of petroclival meningioma has not been well evaluated. This report summarized our experience in 25 patients with petroclival meningioma who had been treated with keyhole approach surgery.Methods From July 2000 to July 2005, 25 patients with petroclival meningioma were subjected to resection via subtemporal, retrosigmoid or combined keyhole approaches. The extent of tumor resection was evaluated by MRI 3 months after surgery, and postoperative complications were investigated.Results The maximum diameter of tumors ranged from 2 to 7 cm (mean, 4.5 cm). Gross total resection (GTR)was achieved in 14 patients, giving a GTR rate of 56%. Subtotal resection (STR) was carried out in 8 patients and partial resection in 3. Thirteen patients kept normal neurological status, whereas others suffered from cranial nerve deficits (Ⅶ, Ⅶ, Ⅲ and lower CN). One patient died in the postoperative period.Conclusions Keyhole approach surgery, especially the combined keyhole approach is suitable for the treatment of petroclival meningioma. It provides easy and quick access to the supra- and infratentorial juxta-clival region without drilling of the petrous bone. Complications related to the approach can be minimized。

Abstract：Background The surgical treatment of intramedullary spinal cord tumor aims at complete removal and minimal postoperative deficit. This study was undertaken to evaluate the microsurgical features of intramedullary spinal cord tumors and the time for surgery and prognosis.Methods Twenty-one patients with intramedullary spinal cord tumor who had been treated at Nanfang Hospital,Guangzhou, China since 2000 were studied retrospectively. Fifteen patients were men and 6 women, aged 2-60 years (mean 29.28 years). Thirteen patients had the tumor in the cervical segments, 4 in medulla-cervical segments, 1 in cervicothoracic segment, and 3 in thoracic spine. All the patients underwent microsurgery for the tumor through posterior approaches by laminectomy. The tumor was exposed through dorsal myelotomy, then tumor plane was removed carefully from the entire rostrocaudal area. The dura was sutured routinely. In case of tumors occupying too many spinal segments, titanium strip was applied to reconstruct the vertebral plate and keep the spinal column stable. All the patients were subjected to MR imaging early after operation. Results Complete removal of the tumor was made in 15 patients, subtotal removal in 5, and partial resection in 1. Neurological recovery was related primarily to preoperative neurological conditions of the patients. Patients with minor neurological deficit showed stable sensory and motor function or minor loss in the early postoperative period, and neurological function tended to improve with time. But those with significant or long-standing deficit could hardly demonstrate any recovery. The dissection interface between the tumor and normal cord tissue was the most important factor influencing the extent of surgical removal.Conclusions Intramedullary spinal cord tumor mostly take place in cervical segments, with glioma as the commonest type. Microsurgery is the major treatment of choice, by which tumor plane could be totally resected. Excellent microsurgical expertise and careful recognition of tumor plane are essential to removal of the tumor while retaining neurological functions. Titanium strip fixation is helpful to reconstruct vertebral stability. Preoperative neurological conditions of patients are directly related to their postoperative recovery. We underscore the importance of early diagnosis and radical microsurgical treatment of intramedullary spinal cord tumor。

Abstract：Background Water-electrolyte disturbance and endocrine alterations are common complications of adult patients with craniopharygioma in the postoperative period and may affect their recovery and prognosis. Some of these complications even lead to death. Appropriate remedy based upon the status of water-electrolyte balance and the endocrine system is essential to good therapeutic results of adult patients with craniopharyngioma.Methods The alterations in water-electrolyte balance (117 patients) and endocrine status (42) of adult patients with craniopharyngioma after surgery were analyzed retrospectively.Results Most patients with craniopharyngioma experienced postoperative water-electrolyte disturbances and hypotonic dehydration. Moreover, the incidences of hypothyroidism and hypoadrenocorticism were relatively high.Conclusion It is critical to deal with dehydration and endocrine disorders for a sound outcome of craniopharyngioma surgery。

Abstract：Background This study was undertaken to obtain differentially expressed genes related to human glioma by cDNA microarray and the characterization of a novel full-length gene. Methods Total RNA was extracted from human glioma and normal brain tissues, and mRNA was used as a probe. The results of hybridization procedure were scanned with the computer system. The gene named 507E08clone was subsequently analyzed by northern blot, bioinformatic approach, and protein expression.Results Fifteen differentially expressed genes were obtained from human glioma by hybridization and scanning for four times. Northern blot analysis confirmed that the 507E08 clone was low expressed in human brain tissue and over expressed in human glioma tissues. The analysis of BLASTn and BLASTx showed that the 507E08clone was a novel full-length gene, which codes 203 amino acid of protein and is called human ribosomal protein 14.22 gene. The nucleotide sequence had been submitted to the GenBankTM with the accession number of AF329277. After expression in E. Coli., protein yielded a major band of apparent molecular mass 22 kDa on an SDS-PAGE gel.Conclusions cDNA microarray technology can be successfully used to identify differentially expressed genes.The novel full-length gene of human ribosomal protein 14.22 may be correlated with the development of human glioma。

Abstract：Background Intracranial aneurysm (IAN) is a protruding bubble or a sac on a brain artery that balloons out over time, which may lead to spontaneous subarachnoid hemorrhage (SAH), ultimately disability and mortality.Current research indicates that the disease is due to multiple causes, including environmental factors and various congenital abnormalities of blood vessels. Apart from congenital predisposition, various high-risk factors such as sex, age, hypertension, and atherosclerosis are involved in the formation of intracranial aneurysms. The aim of this study was to investigate the risk factors associated with the formation of sporadic intracranial aneurysms in Chinese Han ethnic patients.Methods A total of 251 patients with intracranial aneurysm and 338 patients with other cerebral diseases (control group) were enrolled in this study. Single factor and logistic regression model were used to analyze the association of intracranial aneurysms with age; sex; cigarette smoking; alcohol or cocaine consumption; history of hypertension, coronary artery disease, diabetes mellitus and inherited connective tissue disease; and the levels of fasting blood glucose and blood fat. The data expressed as mean ± standard deviation were processed with the statistical software SPSS13. Quantitative and qualitative data were analyzed by the independent-sample t test,and the chi-square test respectively. Logistic regression method was used to analyze the multiple factors.Results In the 251 patients, 163 (64.94%) were at age of 40 to 60 years. Sex (OR, 1.41; 95% CI, 1.01-1.96), cigarette smoking (OR, 1.81; 95% CI, 1.06-3.10), hypertension (OR, 2.32; 95% CI, 1.30-4.16) and fasting blood glucose were significantly associated with intracranial aneurysm (P＜0.05). Intracranial aneurysm was correlated with alcohol consumption, coronary artery disease, and the level of blood lipids (P＞0.05). Using logistic regression analysis, we identified female sex and advanced age as significant risk factors for sporadic intracranial aneurysms.Conclusions Sporadic intracranial aneurysms mostly occur in people aged 40 to 60 years. Feminine, cigarette smoking, and hypertension are independent risk factors for the disease, and the gender is the most significant factor. Advanced age can increase the effect of these risk factors。

Abstract：Background Osteoarthritis (OA) is a chronic and incurable disease, lacking effective treatment. Gene therapy offers a radical different approach to the treatment of arthritis. Even though the etiology of OA remains unclear, there is now considerable evidence to suggest that interleukin-1 (IL-1) and tumor necrosis factor- α (TNF- α ) are the main mediators in the pathogenesis of OA. The goal of this study was to determine the efficacy of local expression of interleukin-1 receptor antagonist (IL-1Ra) and soluble tumor necrosis factor-α receptor type Ⅰ (sTNF-RI) by direct adenoviral-mediated intra-articular gene delivery in the rabbit model of osteoarthritis. Methods Adenoviral vectors containing IL-1Ra or sTNF-RI genes were constructed. OA was induced in both hind knees of 12 New Zealand white rabbits by the excision of the medial collateral ligment plus medial meniscectomy. Five days after surgery, approximately 1×108 plaque-forming units (pfu) of adenovirus were injected into the joint space of the knee through the patellar tendon. A total of 12 operated rabbits were divided into four groups. Three experimental rabbit groups received 1×108 pfu of adenovirus encoding either IL-1Ra (3 rabbits), sTNF-RI (3 rabbits) or IL-1Ra and sTNF-RI in combination (3 rabbits), into both knee joints respectively. An inflamed control group of 3 rabbits received approximately 1×108 pfu of Ad-GFP into both joints. Three days after injection of the adenovirus, both knees of each rabbit were lavaged with 1 ml of saline solution through the patellar tendon. At day 7, the rabbits were sacrificed, and the knees were lavaged, dissected and analyzed for effects of transgene expression. Levels of IL-1Ra and sTNF-RI expression in recovered lavage fluids were measured using a cytokine ELISA kit. Cartilage from the lesion areas of medial femoral condyle and synovium were fixed, embedded, sectioned and stained with hematoxylin and eosin (cartilage and synovium) and toluidine blue (cartilage). The samples were examined by light microscopy and quantitatively evaluated. Results Intra-articular delivery of IL-1Ra resulted in a significant inhibition of cartilage degradation, but did not affect synovial changes. In contrast, rabbit knee joints receiving sTNF-RI alone showed no detectable reduction in cartilage degradation. However, double gene transfer of IL-1Ra and sTNF-RI resulted in a higher suppression of the cartilage degradation and an observable reduction in synovitis. These data add to and confirm that IL-1Ra has good chondroprotective properties, but TNF-α blockade has little effect on joint destruction.Conclusion The enhanced therapeutic effects of both antagonists in combination suggest inhibition of multiple inflammatory cytokines may be more efficaciousthan blockade of either cytokine alone in treating OA。

Abstract：Background With the widespread use of ventilators in treating critically ill patients, the morbidity of ventilator-induced lung injury (VILI) is increasing accordingly. VILI is characterized by a considerable increase in microvascular leakiness and activation of inflammatory processes. In this study we investigated the effects of inflammatory mediators in VILI rat serum on endothelial cytoskeleton and monolayer cellular permeability, as well as the therapeutic effect of ulinastatin, to explore the pathogenesis and the relationship between biotrauma and lung oedema induced by VILI.Methods Thirty healthy male Sprague-Dawley rats were randomly divided into three groups: group A (normal tidal volume ventilation), group B (high tidal volume ventilation) and group C (high tidal volume ventilation plus ulinastatin). The serum of each rat after ventilation was added to endothelial cell line ECV-304 medium for two hours to observe the effects of serum and/or ulinastatin on endothelial fibrous actin and permeability. Results Compared to rats ventilated with normal tidal volume, serum of rats ventilated with high tidal volume caused a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity at the peripheral filament bands and formation of the long and thick stress fibres in the centre resulting in endothelial contraction and higher permeability. Prior treatment with ulinastatin lessened the above changes significantly. The changes of permeability coefficient of endothelial permeability after group A, B or C rats serum stimulation were (6.95 ±1.66)%, (27.50±7.77)% and (17.71±4.66)% respectively with statistically significant differences (P＜0.05)among the three groups.Conclusions The proinflammatory mediators in the serum of the rats given high tidal volume ventilation increases endothelial permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin lessens the permeability by inhibiting of proinflammatory mediators。

Abstract：Objective To review the recent research progress in dystrophin-related muscular dystrophy includes X-linked hereditary Duchenne and Becker muscular dystrophies (DMD and BMD).Data sources Information included in this article was identified by searches of PUBMED and other online resources using the key terms DMD, dystrophin, mutations, animal models, pathophysiology, gene expression, stem cells, gene therapy, cell therapy, and pharmacological.Study selection Mainly original milestone articles and timely reviews written by major pioneer investigators of the field were selected.Results The key issues related to the genetic basis and pathophysiological factors of the diseases were critically addressed. The availabilities and advantages of various animal models for the diseases were described. Major molecular and cellular therapeutic approaches were also discussed, many of which have indeed exhibited some success in pre-clinical studies but at the same time encountered a number of technical hurdles, including the efficient and systemic delivery of a functional gene and myogenic precursor/stem cells to repair genetic defects.Conclusions Further understanding of pathophysiological mechanisms at molecular levels and regenerative properites of myogenic precursor/stem cells will promote the development of multiple therapeutic strategies. The combined use of multiple strategies may represent the major challenge as well as the greatest hope for the therapy of these diseases in coming years。

Atrial fibrillation (AF) is fairly common in patients with chronic mitral valve disease and a markedly dilated left atrium. These patients rarely return to sinus rhythm spontaneously, even after a successful mitral valve operation. The Maze procedure,developed by Cox and associates,1-5 has been used in patients undergoing a mitral valve operation.Restoration of normal sinus rhythm and atrial contraction in such patients have been reported by some groups. This study will summarize retrospectively a group of patients who underwent the Cox Maze procedure for the treatment of AF associated with rheumatic mitral valve disease in China。

Naive helper T (Th) cells are divided into two subsets, Th1 and Th2. Th1 cells produce predominantly interferon-γ (IFN-γ), and Th2 cells produce interleukin-4 (IL-4), IL-5 and IL-13, but not IFN-γ.1 In asthma, an imbalance in the Th1/Th2 cytokine ratio characterized with a shift towards a predominantly Th2 cytokine profile in asthma occurs.2 The differentiation of naive helper T cells towards Th1 or Th2 cells is regulated by the ranscription factors T-box expressed in T-cells (T-bet) and GATA-binding protein-3 (GATA-3).3 We therefore hypothesized that the altered Th1/Th2cytokine expression in asthma is the result of a shift from T-bet to GATA-3 profile. In this study, we demonstrated that the ratio of T-bet/GATA-3 could predict the imbalance of Th1/Th2 cytokine in asthma patients。

Aniridia is a dominantly inherited eye anomaly characterized by the near or complete absence of the iris with an incidence of approximately 1:80 000.1 Other ocular complications include glaucoma, cataract, and optic nerve hypoplasia。

Splenic hamartoma is a benign malformation composed of an anomalous mixture of normal splenic elements.1 Approximately half of the patients with the tumor are asymptomatic and diagnosed accidentally by autopsy or splenectomy.2-5 The tumor-related renal hematological and dermatological abnormalities can be treated by removal of the tumor.1 Splenic hamartoma which is related to renal diseases including extramembranous glomerulonephritis, membranoproliferative glomerulonephritis and renal adenocarcinoma has been reported previously.1'6 In December 2002, we treated a patient with splenic hamartoma complicated by renal pelvic stone detected accidentally by ultrasonography。