Gene therapy refers to the introduction of normal genes into human target cells for correcting gene defects or exerting therapeutic action,and thus achieves the goal of treatment of disease.Bone marrow stromal cells (BMSCs) are stem cells that possess self-renewal and multi-directional differentiation potential and easy to amplify in vitro,and they also express many therapeutic exogenous genes in vitro or in vivo.So BMSCs have been regarded as an ideal target cell of cell and gene therapy.This article reviews the biological characteristic of BMSCs,some commonly used gene therapy vectors and their applications in gene therapy of central nervous system diseases.

Aim To investigate the effect of chronic intermittent hypobaric hypoxia ( CIHH) on the paeonol induced vasomotion of isolated rat ’ s thoracic aorta rings and its underlying mechanisms. Methods Spra-gue-Dawlay ( SD ) rats were randomly divided into 2 groups: control group ( CON ) and CIHH treatment group ( CIHH) . CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 5 000 m altitude, 6 hours daily for 28 days. CON rats lived in the same en-vironment as CIHH animals except hypoxia. Organ bath technique was used to observe the effect of pae-onol on isolated thoracic aorta rings of rats. Results There were no significant differences of noradrenaline ( NE )- and KCl-induced contraction in thoracic aorta rings among CIHH and CON rats;CIHH enhanced va-sodilative effects of paeonol on isolated thoracic aorta rings of rats; the vasodilative effects on CIHH rats could be partly decreased by β-receptor blocker prop-ranolol,ATP-sensitive potassium channel ( KATP ) bloc-ker glibenclamide and NO synthase inhibitor L-NAME. Paeonol significantly inhibited NE-induced intracellular and extracellular calcium-dependent contraction in CIHH rats. Paeonol didn ’ t inhibit NE-induced con-traction by intracellular calcium release and its inhibi-tory effect couldn ’ t be blocked by glibenclamide in CON. Vasodilative effects of paeonol couldn ’ t be re-versed by indomethacin, a cyclooxygenase inhibitor, in CIHH and CON rats. Conclusion CIHH significantly enhances vasodilative effects of paeonol on isolated tho-racic aorta rings of rats. Besides promoting the signa-ling pathway of paeonol in CON, CIHH significantly enhances vasodilative effects of paeonol via activating KATP and inhibiting Ca2+ release from sarcoplasmic re-ticulum.

Objective To investigate the relationship between serum inflammatory cytokines levels and Parkinson disease (PD) with pain. Methods A total of 90 PD patients and 88 healthy controls were selected. Serum inflammatory cytokines were detected by multiplex microsphere flow immunofluorescence luminescence assay. Motor symptoms (UPDRS-Ⅲ),stages of disease (H-Y stage) and pain symptoms (KPPS score) were assessed. The relationship between inflammatory cytokines and PD with pain and the diagnostic value of serum IL-1β for PD with pain were analyzed. Results Compared to the HC group,the levels of serum IL-1β,IL-6 and IL-17 were significantly higher in the PD group (P<0.01). Serum IL-1β levels were higher in the PD with pain group than in the PD without pain group (P<0.001). Serum IL-1β levels in PD patients were positively correlated with KPPS scores (r=0.371,P<0.001). Binary logistic regression analysis showed that higher serum IL-1β level was a risk factor for PD with pain (P=0.001). The ROC curve showed that the area under the curve for serum IL-1β diagnosis of PD with pain was 0.741.Conclusion Serum IL-1β level in PD patients is associated with pain symptoms and may be a biological marker for the diagnosis of PD with pain.

Objective:To investigate the clinical features of direct and indirect carotid cavernous fistulas (CCFs).Methods:Patients with CCF treated in the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020 were enrolled retrospectively. Relevant clinical data were collected, including the main clinical manifestations, neuroimaging features, and treatment methods. The clinical features of direct and indirect CCFs were compared.Results:A total of 31 patients were enrolled in the study, 29 (93.5%) had ocular symptoms, of which conjunctival hyperemia and edema ( n=24, 77.4%), exophthalmos ( n=19, 61.3%) and orbital murmur ( n=18, 58.1%) were most common. There were 23 patients (74.2%) in direct CCF group and 8 (25.8%) in indirect CCF group. The former had more history of head trauma (78.2% vs. 12.5%; P=0.002), more flow volume (high-flow CCFs: 100% vs. 37.5%; P<0.001) and more likely to cause orbital murmur (69.6% vs. 25.0%; P=0.043). Endovascular embolization was safe and effective. The common methods of endovascular embolization were EVAL glue combined with coil embolization ( n=18, 66.7%) and detachable balloon embolization alone ( n=6, 22.2%). Conclusion:Ocular manifestations are most prominent in patients with CCFs. Direct CCF is more common, usually with a history of head trauma, and the clinical and imaging features are more typical. Interventional embolization is the preferred treatment option for patients with CCF.

BACKGROUND:Large numbers of experimental data have confirmed that bone marrow mesenchymal stem cel s have a positive therapeutic effect on cerebral ischemia-reperfusion injury, but there are few reports about intravenous administration of bone marrow mesenchymal stem cel conditioned medium in the treatment of stroke.
OBJECTIVE:To investigate the effects of the conditioned medium of rat bone marrow mesenchymal stem cel s on the recovery of neurological function in rats after cerebral ischemia-reperfusion injury.
METHODS:The bone marrow mesenchymal stem cel s were isolated from rat bone marrow. When cel s at passage 2 or 3 reached 90%confluence, the original culture medium was removed. Then the cel s were cultured in serum-free DMEM for 18 hours. After that, the culture solution was col ected as the conditioned medium of rat bone marrow mesenchymal stem cel s. Adult rats were subjected to 2 hours of right middle cerebral artery occlusion. Ischemia-reperfusion injury rats were randomly assigned to three groups:control group, simple culture medium group and conditioned medium group, and respectively given injection of normal saline, DMEM, conditioned medium (10 mL/kg) via the tail vein at 2, 24, 48 hours after operation.
RESULTS AND CONCLUSION:There was no difference in the behavioral tests among the three groups at postoperative 2 hours (P>0.05). Compared with the control and simple culture medium group, neurological impairment was significantly improved in the conditioned medium group at postoperative 1, 3, 5 days (P<0.05), but there was no significant difference between the control and simple culture medium groups. At postoperative 5 days, brain edema was significantly eased in the conditioned medium group in comparison to the control and simple culture medium groups (P<0.05), and there was also no difference between the latter two groups (P>0.05). These results suggest that rat bone marrow mesenchymal stem cel s-conditioned medium via intravenous administration can significantly ease brain edema and improve the neurologic function after cerebral ischemia-reperfusion injury.

Objective To analyze the clinical manifestations and MRI characteristics of hypertrophic olivary degeneration (HOD) to improve our knowledge for this disease and reduce misdiagnosis.Methods Twelve patients with HOD,admitted to our hospital from 2009 to 2012,were chosen in our study; their clinical data,including onset age,protopathy and other clinical manifestations,and imaging data,including SE sequence axial T1WI,T2WI and FLAIR fast spin-echo imaging,were analyzed.Results The protopathy in these 12 patients included pontine hemorrhage in 5,cerebellar infarction in 3,cerebral hemorrhage in 2,midbrain infarction in 1 and surgery for cerebellar tumor in 1.The main clinical symptoms included palatal myoclonus in 7,ataxia in 6,ocular myoclonus in 5,glossolalia in 3,diplopia in 2 and extremity tremor in 2.The region of inferior olivary nucleus (ION)presented high intensity on T2WI and iso-or mild hypointensity on T1WI in all 12 patients.Bilateral ION showed high signals in 5 in FLAIR; enlargement of the ION in 11 patients were noted.Conclusions HOD is a pathological phenomenon that occurs after injury to the dentato-olivary pathway.Its hallmarks include hypertrophy of the olive with increased T2 signal intensity on magnetic resonance imaging,and it often manifests with oculopalatal myoclonus clinically.

BACKGROUNDParaquat (PQ), an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ mainly accumulates in the lung, and the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. The aim of this study was to evaluate whether lysine acetylsalicylate (LAS) could protect the lung from the damage of PQ poisoning and to study the mechanisms of protection.

METHODSA model of PQ poisoning was established in 75 Sprague-Dawley rats by intragastric administration of 50 mg/kg PQ, followed by treatment with 200 mg/kg of LAS. The rats were randomly divided into sham, PQ, and PQ + LAS groups, with 25 in each group. We assessed and compared the malonaldehyde (MDA) content, superoxide dismutase activity (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) in serum and lung and the hydroxyproline (HYP) content, pathological changes, apoptosis and expression of Bcl-2/Bax protein in lung of rats on days 1, 3, 7, 14 and 21 after PQ poisoning and LAS treatment.

RESULTSCompared to the PQ group rats, early treatment with LAS reduced the MDA and HYP contents, and increased the SOD, GSH-Px, and CAT activities in the serum and lung on days 1, 3, 7, 14, and 21 after PQ poisoning (all P < 0.05). After early LAS treatment, the apoptotic rate and Bax expression of lung decreased, the Bcl-2 expression increased, and the Bcl-2/Bax ratio increased, compared to the PQ group rats. Furthermore, the pathological results of lungs revealed that after LAS treatment, early manifestations of PQ poisoning, such as hemorrhage, edema and inflammatory-cell infiltration, were improved to some degree, and collagen fibers in the pulmonary interstitium were also obviously reduced.

CONCLUSIONIn this rat model of PQ poisoning, LAS effectively ameliorated the lung injury induced by PQ, possibly through antioxidation, anti-fibrosis, anti-apoptosis, and anticoagulation.

Animals ; Antioxidants ; metabolism ; Aspirin ; analogs & derivatives ; standards ; therapeutic use ; Catalase ; metabolism ; Glutathione Peroxidase ; metabolism ; Lung ; drug effects ; metabolism ; Lung Injury ; chemically induced ; drug therapy ; metabolism ; Lysine ; analogs & derivatives ; standards ; therapeutic use ; Male ; Malondialdehyde ; metabolism ; Paraquat ; toxicity ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo examine the temporal and spatial expression of vascular endothelial growth factor (VEGF) and angiopoietins (Ang) in rat brain after cerebral ischemia, and to elucidate the roles they played in angiogenesis and vascular permeability.

METHODSRats were subjected to either middle cerebral artery occlusion (MCAO) or sham operation. Reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry were used to detect the expression of VEGF, Ang-1 and Ang-2 at different time points after ischemia. CD31 was used to label endothelial cells after MCAO. Vascular permeability was determined by Evans blue.

RESULTSVEGF was markedly increased at 2 h, had an initial peak at 12 h (0.7249 ± 0.1933, P < 0.01), and a second peak at 7 days (0.5264 ± 0.1519, P < 0.01). Ang-2 mRNA and protein significantly increased after MCAO, both of them peaked at 12 h (0.6747 ± 0.2416, P < 0.01; 1.1197 ± 0.1780, P < 0.01). In contrast, Ang-1 mRNA and protein gradually decreased after MCAO, respectively reaching a minimum at 3 d (0.3220 ± 0.1427, P < 0.01) and 1 d (0.1298 ± 0.0293, P < 0.01). Changes in the expression of these factors correlated with the progress of angiogenesis and vascular permeability. Evans blue test revealed that the vascular permeability gradually increased, and peaked at day 1 after ischemia [(6.219 ± 0.887) µg/g, P < 0.01].

CONCLUSIONDynamic temporal changes in VEGF, Ang-1 and Ang-2 expression stimulate the cerebral angiogenesis after focal cerebral ischemia.

Angiopoietin-1 ; genetics ; metabolism ; Angiopoietin-2 ; genetics ; metabolism ; Animals ; Blotting, Western ; Capillary Permeability ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; physiopathology ; Male ; Neovascularization, Physiologic ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo explore the characteristic of hypoxia-induced immune injury, its mechanisms and the intervention measure.

METHODSThe change of immune organ index, T lymphocyte subsets of peripheral blood and immune organ in mice during hypoxia were detected. Lymphocyte apoptosis of immune organ, pathology of lung and kidney in mice were observed. Then by way of prophylaxis we studied the effect of Chinese Traditional Medicine on hypoxia-induced immune injury in mice.

RESULTS(1) Exposure to hypoxia at 8 000 m simulated altitude for 8 h resulted in marked decrease in CD4+ CD8+ thymocytes and marked increase in CD4+ CD8-, CD4- CD8+ thymocytes (P < 0.01). After 3 days of hypoxia, the mice had a much lower percentage of CD4+ T-cell (P < 0.05). The ratio of CD4+/CD8+ decreased significantly and aforesaid changes of thymocyte were further enlarged. Also mice had a pronounced increase in rates of late apoptosis or necrosis of spleen lymphocyte and thymocyte (P < 0.05). After 6 days of hypoxia, index of spleen was significantly increased (P < 0.05), index of thymus was significantly decreased (P < 0.05) and CD3+, CD4+, CD8+ lymphocyte percentage of spleen were significantly decreased (P < 0.01). Also late apoptosis or necrosis lymphocytes of spleen and thymus were further increased (P < 0.01), viable cell rates of spleen lymphocyte and thymocytes were markedly decreased (P < 0.01), early apoptosis rates of spleen lymphocyte were markedly increased (P < 0.01). There was no significant change in the percentage of CD8+ lymphocyte in peripheral blood during the whole hypoxia period. (2) New Compound Codonopsis Pilosula (NCCP), Xiang Qi Polysaccharide (XQP) and NCCP + XQP could significantly increase the number of peripheral blood CD3+, CD4+ and spleen CD4+, but had no significant influence on the number of spleen CD8+. XQP and XQP+ NCCP could significantly decrease the number of CD4+ CD8+ (P < 0.01), increase that of CD4+ CD8- (P < 0.01), and had no significant influence on CD4- CD8+ in thymus. However, NCCP didn't influence the component of thymocytes.

CONCLUSIONAfter hypoxia at 8 000 m simulated altitude decrease of lymphocyte of periphery in mice may be related with increase of apoptosis and necrosis of lymphocyte, and with increase of distribution of lymphocyte to lung in early period of exposure. NCCP and XQP have hopeful prospect in intervention study of hypoxia-induced immune injury.

Altitude ; Animals ; Apoptosis ; drug effects ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Drugs, Chinese Herbal ; pharmacology ; Flow Cytometry ; Hypoxia ; immunology ; pathology ; prevention & control ; Lung ; cytology ; Lymphocyte Count ; Male ; Medicine, Chinese Traditional ; Mice ; Mice, Inbred BALB C ; Spleen ; cytology ; T-Lymphocyte Subsets ; cytology ; drug effects ; Thymus Gland ; cytology

Objective To investigate the effect of matrine on Fas expression in C6 glima in a tumor-bearing rat model. Methods Cultured cerebral glioma C6 cells wgre injected stereotactically into the lef tcaudate nucleus of the rats.The ratswere randomized into untreated group,bomeol-treated group,low-dose matrine group,high-dose maaine group,low-dose matrine+bomeol group,and high-dose matrine+borneol group.The effect of matrine on the quality of life of the rats and the glioma volume was evaluated according to the survival state of the rats and by gross observation,magnetic resonance imaging(MRJ)and HE smining of the brain tissue.Immunohistochemistry was performed to detect Fas expression in the glioma cells. Results The survival state ofthe rats,gross observation of the brain specimen. and results of MRI and HE staining all showed that matrine significantly improved the quality oflife of the glioma-bearing rats and inhibited the glioma cell proliferation.Fas expression Was significantly higher in low-dose matrine+bomeol group(98.16±11.82) and high-dose matrine+bomeol group(112.80±12.12)than in untreated group(39.09±7.79),bomeol group(46.87±7.43),low-dose matrinc group(42.41±7.83),and high-dose matrine group(44.20±7.47)(P＜0.05).Fas expression Was obviously upregulated in the high-dose matrine+bomeol group aS compared with the low-dose matrine+bomeol group(P＜0.05).Conclusion Matrine Can significantly upregulate Fas expression in glioma and inhibit glioma cell proliferation in the glioma-bearing rat model.