Network Meta-analysis of 3 kinds of Chinese medicine injections in treatment of acute exacerbations of chronic obstructive pulmonary disease / 中国中药杂志

To evaluate the efficacy and safety of traditional Chinese medicine injections( CMI) in the treatment of acute exacerbation of chronic obstructive pulmonary disease( AECOPD). PubMed,Cochrane Library,CNKI,CBM,Wan Fang and VIP database( since the date of database establishment to July 2018) were retrieved through computer for controlled randomized trials( CRTs) of 3 kinds of traditional Chinese medicine injections( Chuankezhi Injection,Tanreqing Injection,Xuebijing Injection) for AECOPD. After the methodological quality of included researches were evaluated,and the valid data were extracted,statistical analysis was performed with Stata 14,RevMan 5.3 is used for risk bias map. There were including 4 RCTs and 20 quasi-RCTs,which involving 579 patients.The results of network Meta-analysis showed that: ①there were significant differences in the forced expiratory volume in the first second between the 3 CMI and control groups,and there was no significant difference between CMI; ②3 kinds of CMI adjuvant therapy AECOPD,According to the forced expiratory volume in the first second of the probability ranking results,Tanreqing Injection is more effective,followed by Xuebijing Injection and Chuankezhi Injection. Based on the present evidence,3 kinds of CMI can improve the forced expiratory volume in the first second on the basis of Western medicine routine treatment of AECOPD,having better safty. In addition,the conclusion of this study still needs a large number of RCTs with reasonable design and proper method to confirm it.

Clinical and imaging features of Hallervorden-Spatz syndrome and its deep brain stimulation treatment / 中华神经医学杂志

Objective To explore the clinical and imaging features of Hallervorden-Spatz syndrome (HSS) and its deep brain stimulation (DBS) treatment.Methods A 12-year-old boy with HSS,admitted to our hospital from June 2010,was chosen in our study; the clinical and imaging features and the DBS therapy outcome were retrospectively analyzed.Results The patient (12 years old) was at an early onset,predominantly presented with dystonia,cognitive impairment,dysarthria and pyramidal signs; the symptoms were rapidly progressive.Brain MRI revealed a typical "eye-of-tiger" sign.Significant improvement of motor function after DBS of the internal globus pallidus (Gpi) and no significant improvement of cognitive dysfunction and dysarthria were noted; and the benefit of surgery was maintained during the 1 year follow-up.Conclusion The characteristic imaging manifestations and clinical features are very important for HSS diagnosis; DBS of the internal globus pallidus (Gpi) can improve the motor function; and DBS is one of the limited optional therapies for HSS.

Role of silence information regulator 1 in regulation of lipopolysaccharide-induced secretion of interleukin-6 and tumor necrosis factor-a in activated BV-2 cells / 中华神经医学杂志

Objective To observe the effect oflipopolysaccharide (LPS) on the cell form of BV-2 cells and the expressions of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) so as to detect the role of silence information regulator 1 (SIRT1) in regulation of LPS-induced proinflammatory cytokines production in activated BV-2 cells.Methods BV-2 cells were divided into control group (normal culture medium) and treatment groups; BV-2 cells in the treatment groups were subdivided into LPS treatment groups,Resveratrol+LPS treatment groups and Sirtinol+LPS treatment groups (cultured with different concentrations of LPS,SIRT1 activator Resveratrol or SIRT1 inhibitor Sirtinol,respectively).MTT assay was employed to identify the cell survival after the inducement.Based on the above MTT results,the cells were then grouped into the control group,LPS treatment group,Resveratrol+LPS treatment group and Sirtinol+LPS treatment group having suitable concentrations of LPS,Resveratrol and Sirtinol; then,the levels of IL-6 and TNF-a were measured with enzyme-linked immuno sorbent assay (ELISA) at 12 and 24 h after the inducement; and the expression of SIRT1 at 24 hafter the inducement was detected by Western blotting.Results As compared with those in the control group,the BV-2 cells in the LPS treatment group had increased cell number,hypertrophic cell body,and shorten cell processes.The cell survival rate increased with increased concentrations of LPS.As compared with those in the control group,the levels of IL-6 and TNF-a in LPS treatment group increased and level of SIRT 1 decreased with significant differences (P＜0.05).Significantly increased levels of IL-6and TNF-a and obviously decreased expression of SIRT1 in the Resveratrol+LPS treatment group were noted as compared with those in the LPS treatment group (P＜0.05); conversely,significantly decreased levels of IL-6 and TNF-a and obviously increased expression of SIRT1 in the Sirtinol+LPS treatment group were noted as compared with those in the LPS treatment group (P＜0.05).Conclusion LPS can change the morphology of BV-2 cells,and induce the levels ofproinflammatory cytokines; impairment of SIRT1 may contribute to such progress obviously.

Protection role of silent information regulator 1 in toxicity of activated BV-2 cells to PC12 cells / 中华神经医学杂志

Objective To observe the effects of silent information regulator 1 (SIRT1) on toxicity of activated BV-2 to PC12 cells and the possible mechanisms.Methods BV-2 microglial cells and PC12 cells were routinely cultured in vitro; ELISA was used to measure to the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) stimulated by lipopolysaccharide (LPS,1 μg/mL) in BV-2 cells.MTT assay was employed to identify the cell viability of PC12 cells injured by culture medium of activated BV-2 and determined the suitable concentrations of resveratrol (a potent SIRT1 activator,5,10,25,50 and 100 μmol/L) and nicotinamide (a known SIRT1 inhibitor,5,10,25 and 50 mmol/L).PC12 cells were divided into groups as follows:control group Ⅱ,LPS+BV-2 co-cultured group,resveratrol treatment group and nicotinamide treatment group (pretreated with resveratrol or nicotinamide for 2 h,and then subjected to culture medium of activated BV-2 cells,in the presence of resveratrol or sirtinol for 18 h); the cell viability was measured by OD value in MTT assay,and the expressions of SIRT1 and acetyl-p53 were detected by Western blotting.Results TNF-α and IL-6 secretions increased gradually at 6,12 and 24 h after LPS being induced BV-2,with significant difference between each two time points (P＜0.05).PC12 cell viability decreased in the LPS+BV-2 co-cultured group as compared with that in the control group Ⅰ,LPS treatment group and BV-2 supernate group (P＜0.05).The cell viability of cells in the 100 μmol/L resveratrol treatment group and 50 μmol/L niacinamide treatment group decreased as compared with that in the control group Ⅱ (P＜0.05),therefore,50 μmol/L resveratrol and 25 μmol/L nicotinamide were chosen in the next experiment.As compared with those in the control group Ⅲ,the cell viability and SIRT1 expression significantly decreased,and acetyl-p53expression significantly increased in the LPS+BV-2 co-cultured group (P＜0.05); as compared with those in the in the LPS+BV-2 co-cultured group,the cell viability and SIRT1 expression significantly increased,and acetyl-p53 expression significantly decreased in the 50 μmol/L resveratrol treatment group,and opposite results were noted in the 25 μmol/L nicotinamide treatment group (P＜0.05).Conclusion SIRT1 can inhibit toxicity of activated BV-2 to PC12 cells,the mechanism of which is partly via p53 activation.

Role of SIRT1 in apoptosis of lipopolysaccharide-induced PC12 cells / 中华神经医学杂志

Objective To study the role of SIRT 1 in apoptosis of PC 12 neuronal cells induced by lipopolysaccharide (LPS). Methods PC12 cells were cultured with different concentrations of LS (50 μg/mL,500 μg/mL,750 μg/mL,1000 μg/mL and 1250 μg/mL),and some other PC12 cells were routinely cultured as controls. MTT assay was employed to identify the cell survival 24 h after the inducement,and accordingly,the suitable LPS concentration for subsequent experiments was determined based on MTT results. And then, cell apoptosis in the experimental groups under the suitable LPS concentration at different times (1/2,2,18,24,and 48 h) and control group was noted by flow cytometry and Hoechst 33258 staining; Western blotting was used to detect the SIRT1 level in PC12 cells. Results Hoechst 33258 staining indicated that a few apoptotic bodies were noted 1/2 h after inducement,expressing as karyopyknosis and karyorrhexis; apoptotic bodies began to increase 18 h after inducement,reaching their peak level 24 h after inducement; and a decreased trend was observed 48 h after inducement. Flow cytometry indicated that significantly higher apoptosis rate at each time point was noted as compared with that in the control group (P＜0.05); and Hoechst 33258 staining showed the same result. Western blotting revealed that the SIRT1 expression was (1.84±0.04) in the control group,decreasing to (1.17±0.09) 1/2 h after the inducement,and reaching the lowest level (0.62±0.03) 24 h after the inducement; and then, the expression was increased to (0.77±0.02) 48 h after the inducement;significant difference on the expression at each time point was noted as compared with that in the control group (P＜0.05). Conclusion LPS can induce PC12 cell apoptosis and SIRT1 protein expression is inhibited,indicating that SIRT1 may take part in the apoptosis and play a protective role to PC12 cells.

Protective function of human urinary kallidinogenase in rats after focal cerebral ischemic reperfusion and its effect on caspase-3 expression / 中华神经医学杂志

Objective To study the effect of human urinary kallidinogenase (HUK) on neural cell apoptosis in rats after focal cerebral ischemia-reperfusion (FCIR) injury and on Caspase-3 expression.Methods Sixty-six SD rats were randomly divided into sham-operated group (n=6),ischemic-reperfusion group and HUK treatment group.The latter 2 groups were subdivided into 6,12,24,72 and 168 h reperfusion groups (n=6).Middle cerebral artery occlusion models of transient focal cerebral ischemia in the latter 2 groups were established by suture-occluded method. Rats of the HUK treatment group were given tail vein injection of HUK once daily at dosage of 17.5 ×10-3 PNAU/mL and at 1.0 mL/kg manner 3 h after reperfusion. The numbers of apoptotic cells and Caspase-3 positive cells in the cerebral cortex were evaluated with terminal dUTP nick end labeling (TUNEL) assay and immunohistochemistry. Results Cell apoptosis was noted 6 h after the focal cerebral ischemia-reperfusion,reaching its peak level at 24 h,and the apoptotic cells could still be seen at 168 h after the injury.And the expression of Caspase-3 positive cells peaked at 24 h after the injury,and high expression was still noted at 168 h after the injury. The levels of apoptotic cells and the expression of Caspase-3 positive cells in HUK treatment group at different time points (except for 168 h subgroup) decreased significantly as compared with those in ischemic-reperfusion group (P＜0.05). Conclusion HUK may decrease the number of apoptotic cells in the initial 72 h of FCIR injury by down-regulating the Caspase-3 expression.

Polymorphisms of catechol-O-methyl transferase gene and dopamine transporter gene in dopamine metabolism system of patients with post-stroke depression / 中华神经医学杂志

Objective To investigate the association of post-stroke depression (PSD) with gene polymorphisms of catechol-O-methyl transferase (COMT) Val1 08/158Met and dopamine transporter 40bp variable number of tandem repeats (VNTR) in dopamine metabolism system. Methods Sixty-eight patients with PSD and 91 patients only suffered from stroke, admitted to our hospital from January 2010to June 2010, were chosen; the gene polymorphisms ofCOMT Val108/158Met and DAT 40 bp VNTR were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The genotypes of COMT gene amplifications were wild type (G/G),homozygous mutant type (A/A) and heterozygous type (A/G); 7 repeated genotypes (7/7, 9/7, 10/7, 10/9,10/10, 11/10 and 11/11) were noted in the DA T gene amplifications; frequencies of COMT alleles and genotypes were significantly different between the 2 groups (x2=5.703, P=0.017;x2=6.489, P=0.039). The frequencies of COMT alleles and genotypes were significantly different between the 2 female groups (x2=4.610, P=0.032;x2=6.547, P=0.024), but no significant differences were found between the 2 male groups (P＞0.05). The frequencies and heterozygosity of DAT alleles and genotypes showed no obvious differences between the 2 groups (P＞0.05). Conclusion The gene polymorphism of COMT Val108/158Met may be associated with PSD, while that of DAT 40bp VNTR is not.

Insulin-like growth factor 1 protects dopaminergic neurons from L-dopa-induced toxicity via JAK/STAT pathway / 中华神经医学杂志

Objective To explore the protective effect of insulin-like growth factor 1 (IGF-1) on apoptosis of dopaminergic neurons induced by L-dopa via JAK/STAT signaling pathway. Methods PC12 cells were induced to differentiate into dopaminergic neurons with 100 μg/L β-NGF; MTT assay was employed to identify the changes in the viability of PC12 cells following L-dopa treatment at 0, 10,20, 50, 100, 150 and 200 μmol/L, and the different concentrations of IGF-1 at 0, 10, 25, 50 and 100 nmol/L with the same concentration of L-dopa (150 μmol/L); Western blotting was used to detect the levels of P-JAK2/P-STAT3 in PC12 cells treated with PBS (controls), L-dopa, L-dopa+IGF-1 and L-dopa+IGF-1+AG490 for 24 h, and then the apoptosis rate was assessed by flow cytometry and Hchest33258 staining. Results Western blotting showed that the expressions of P-JAK2 and P-STAT3 were detected in the L-dopa+IGF-1 and L-dopa+IGF-1+AG490 treatment groups but not in the control group or L-dopa treatment group; the expression of P-STAT3 in the L-dopa+IGF-1+AG490 treatment group was obviously lower than that in the L-dopa+IGF-1 treatment group (P<0.05). Hchest33258 staining indicated that L-dopa treatment group had the most obvious karyopyknosis and karyorrhexis,much more apoptotic bodies than the L-dopa+IGF-1 and L-dopa+IGF-1+AG490 treatment groups. Flow cytometry showed that the apoptosis rate was significantly different among the 4 groups (F=180.991,P=0.000): as compared with the control group, the other 3 groups had a higher apoptosis rate (P<0.05);L-dopa treatment group (38.13 ±2.54 %) enjoyed the highest level, followed by L-dopa+IGF-1 +AG490treatment group (25.60±1.30 %) and L-dopa+IGF-1 treatment group (20.17±1.54 %). Conclusion L-dopa has toxic effect on PC12 cells; IGF-1 could protect the PC12 cells from the neurotoxic effect of L-dopa and JAK2/STAT3 signaling pathway is activated in this procedure.

Cilostazol inhibits expression of P38 mitogen-activated protein kinase and proliferation of human vascular endothelial cells / 中华神经医学杂志

Objective To observe the effect ofcilostazol(CLZ)on proliferation of human vein endothelial cells(VECs)in vitro and activity ofphosphorylation P38 mitogen-activated protein kinase (MAPK).Methods Human umbilical vein endothelial cell(HUVEC)line EA.hy926 culturedin vitro was treated with CLZ at concentrations of 10,30,100 and 300 μmo/L for 24 h; blank controls were also employed.The ratio of cell proliferation was determined by MTT assay; the protein expression of phosphorylation P38MAPK was evaluated by Western blotting.Results The proliferation ratio(A value)of HUVECs was(0.909±0.013)in the control group,and(0.903 ±0.026),(0.851 ±0.023),(0.699±0.013),and(0.651±0.036)in the 10,30,100 and 300 μno/L CLZ-treatment groups,respectively; as compared with that in the blank control group,the A value in the 30,100 and 300 μmo/L CLZ-treatment groups was significantly lower(P＜0.05); and a decreased trend at dose-dependent manner was noted among the 30,100 and 300 μno/L CLZ-treatment groups.As compared with that in the control group,the protein expression of phosphorylation P38MAPK in the 30,100 and 300 μmo/L CLZ-treatment groups was significantly decreased(P＜0.05),and the protein expression of phosphorylation P38MAPK in 300 μmo/L CLZ-treatment group was significantly lower than that in 30 μno/L CLZ-treatment group (P＜0.05).Conclusion CLZ can obviously inhibit the protein expression of P38MAPK and in vitro proliferation of VECs.

Effect of human urinary kallikrein on expression of VEGF in focal cerebral ischemia-reperfusion rats / 中华神经医学杂志

Objective To explore the effect of human urinary kallikrein on the expression of VEGF in focal cerebral ischemia-reperfusion rats. Methods Fifty-six male SD rats were randomly divided into sham operated group (n=8), saline group (n=24) and human urinary kallikrein group (n=24).The latter 2 groups were made into middle cerebral artery occlusion (MCAO) models, and subdivided into 5 subgroups according to the five time points of 6, 12, 24, 72 h, and 7 d after ischemia-reperfusion.We used the methods of nerve function scales, TTC staining, infarct size estimation, detection with light microscope to evaluate the MCAO rat models at different time points, and analyzed the changes of the expression of VEGF in the center and the periphery of infarcts at different time points by immunohistochemical methods. Results The degrees of neurological impairment in the rats of human urinary kallikrein group were lighter than those of saline group (P＜0.05). The average infarct size of rats at 24 h was (53 261.96±7 326.75) μm3 in human urinary kallikrein group, (92 715.84±13 755.44) μm3 in saline group, and the difference between the 2 groups was significant (P＜0.05). The expression of VEGF in the rats of human urinary kallikrein group was higher than that of saline group at different time points (P＜0.05). Conclusions Human urinary kallikrein has neuroprotective effect after ischemia reperfusion injury, and can promote the levels of VEGF expression.

Effect of edaravone on the apoptosis and expression of Cuspase-3 protein following focal cerebral ischemia/reperfusion injury in rats / 中华神经医学杂志

Objective To explore the effect of edaravone (ED) on the neurological functionaldeficits, apoptosis and expression of caspase-3 protein following focal cerebral ischemia/reperfusion(I/R)injury in rats. Methods A total of 24 male Sprague-Dawley (SD) rats were randomly allocated intothe sham-operation group, cerebral I/R group, normal saline treatment group and ED treatment group, 6rats in each group. Rat models with focal cerebral I/R injury induced by middle cerebral artery occlusion(MCAO) were established using a modified suture method. ED (3mg/kg) or equal volume of normalsaline was injected intraperitoneally immediately after cerebral ischemia and 12 h after reperfusion in thetreatment groups;the rats in sham-operation group underwent the same modeling procedure withoutischemia by nylon suture. The neurological behavioral deficits were evaluated 24 h after I/R injury;,immunohistochemical staining and Western blot assay were applied to detect the change in the expressionof caspase-3 protein; in situ TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay was used tostudy the change in neuronal apoptosis. Results The scores of neurological behavioral deficit scale,the positive cells and expression of caspase-3 protein, and the apoptotic cells in the ED treatment groupwere significantly decreased, compared with that of the I/R group and normal saline treatment group(P<0.05 for each comparison). Conclusion ED may effectively reduce neuronal apuptosis andneurological functional deficits after cerebral I/R injury, which might be related with the inhibition of thecaspase-3 protein expression.

Effects of human urinary kallikrein on cell apoptosis of rats with acute focal cerebral ischemia-reperfusion injury / 中华神经医学杂志

Objective To study the effects of human uriilary kallikrein(HUK)on the number of apoptotic cells and the expressions of Bcl-2 and Bax proteins in rats after focal cerebral ischemia and reperfusion(FCIR) injury. Methods Eighty-four Spmque-Dawley(SD)male rats were randomly divided into sham-operated group(n=12),ischemia-reperfusion group(n=36),and HUK-treated group (n=36). Transient focal cerebml ischemia models were established by middle cerebml artery occlusion.Six rats were chosen from sham-operated group,ischemia-reperfusion group,and HUK-treated group for measuring infarct sizes.The rest were used to evaluate neurologic fhnction impaiment and measure the nunlber of apoptotic cells and Bcl-2 or BaX protein positive cells in cerebral cortex with TUNEL and immunohistochemistry.The latter 2 groups were subdivided into 6,12,24,72,168 h reperfusio groups (each n=6). Results The neurologic function impairmlent score,the infarct sizes,the apoptotic cells and the expression of Bax protein of HUK-treated group at different time points (except 168 h group)significantly decreased compared wilh those of ischemia-reperfsion group (p＜0.05).The expression of Bcl-2 protein of HUK-treated group at different time points(except 168 h group) remarkably increased compared with that of ischemia-reperfusion group(P＜0.05). Conclusions HUK can excrt a protection against FCIR injury, maybe through up-regulating Bcl-2 and down-regulating Bax protein in the initial 3 d of FCIR injury to decrease the number of apoptotic cells

P-JAK2 and P-STAT3 protein expression and cell apoptosis following focal cerebral ischemia-reperfusion injury in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in phosphorylated JAK2 and STAT3 protein expression of and cell apoptosis following focal cerebral ischemia-reperfusion injury in rats.</p><p><b>METHODS</b>A rat models of focal cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion using modified filament method. Immunohistochemistry and Western blot analysis were used to detect the expression of P-JAK2 and P-STAT3 proteins, and TUNEL assay was employed to examine the cell apoptosis.</p><p><b>RESULTS</b>P-JAK2 and P-STAT3 protein expression increased significantly after cerebral ischemia-reperfusion injury in rats. The immunoreactivity was prominent in the peripheral of the ischemic region and reached the peak level at 24 h of reperfusion, followed by slight decrement. The apoptotic cells increased obviously after cerebral ischemia-reperfusion injury, also reaching the peak level at 24 h of reperfusion.</p><p><b>CONCLUSION</b>The expression of phosphorylated JAK2 and STAT3 may be involved in the ischemic cellular events including apoptosis. JAK2/STAT3 signaling pathway plays a role in the pathophysiological process of cerebral ischemia/reperfusion cell injury and repair.</p>