Predictive score of the outcomes after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Stroke has become the leading cause of disability and death in China. At present, intravenous thrombolysis is one of the most effective treatment for acute ischemic stroke, but not all patients can benefit from intravenous thrombolysis. In recent years, the exploration of predictive models for the outcomes after intravenous thrombolysis in patients with acute ischemic stroke has attracted increasing attention. This article systematically reviews the scoring models for predicting the functional outcome, death and symptomatic intracranial hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke, with the aim of screening the scoring system suitable for clinical application and providing reference for the clinical diagnosis, evaluation and treatment of acute ischemic stroke.

Early neurological deterioration after intravenous thrombolysis in patients with acute ischemic stroke: predictors and impact on short-term outcomes / 国际脑血管病杂志

Objective To investigate the predictors of early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke and its impact on short-term outcomes. Methods From January 2017 to April 2019, patients with acute ischemic stroke treated with intravenous thrombolysis in the Second Affiliated Hospital of Xuzhou Medical University were enrolled retrospectively. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 days after admission increased by ≥2 compared with the baseline. The short-term outcomes were evaluated by the modified Rankin Scale at discharge. 0-2 was defined as good outcomes and 3-6 was defined as poor outcomes. Multivariate logistic regression analysis was used to determine the independent predictors of END and their correlation with short-term outcomes. Results A total of 199 patients with acute ischemic stroke received intravenous thrombolysis were enrolled. The median age was 68 years (interquartile range: 62- 76 years), 69 were women (34. 7％), and the baseline median NIHSS score was 6 (interquartile range: 3- 12). END occurred in 35 patients (17. 6％). Symptom progression occurred mainly 2 days after admission (31 patients, 88. 6％). Most of the causes of END were ischemic progression or recurrence (28 patients, 80. 0％). The univariate analysis showed that fasting blood glucose and symptomatic intracranial hemorrhage were associated with END (all P < 0. 05). However, multivariate logistic regression analysis did not find independent predictors of END. Excluding 12 patients with missing short-term outcome data, a total of 187 patients were included in the short-term outcome analysis. Among them, 110 patients had good outcomes and 77 had poor outcomes. Univariate analysis showed that ischemic heart disease, atrial fibrillation, mild stroke, etiological classification, baseline NIHSS score, absolute lymphocyte count, fasting blood sugar, neutrophil/lymphocyte ratio, whether to receive interventional therapy, and END were correlated with short-term outcomes (all P < 0. 05 ). Multivariate logistic regression analysis indicated that high baseline NIHSS score (odds ratio 1. 350, 95％ confidence interval 1. 182-1. 541; P < 0. 001) and END (odds ratio 32. 540, 95％ confidence interval 6. 149- 172. 21; P < 0. 001 ) were the independent risk factors for short-term poor outcomes. Conclusions END still occurs in some patients after intravenous thrombolysis for acute ischemic stroke, and END is an independent risk factor for short-term poor outcomes.

Distribution and antimicrobial resistance profile of the clinical bacterial strains isolated from Beijing Children's Hospital from 2009 to 2015 / 中国感染与化疗杂志

Objective To investigate the distribution and antimicrobial resistance profile of the common pathogens isolated during the period from 2009 to 2015.Methods All the bacterial strains isolated from pediatric inpatients in Beijing Children's Hospital during the period from 2009 to 2015 were analyzed. Antimicrobial susceptibility was determined by disk diffusion method and Phoenix 100 Automated Microbiology System. Results were analyzed according to the guidelines of CLSI (2014) using WHONET 5.6 software.Results The total strains were 26630. The most common gram-positive isolates were Streptococcus pneumoniae,Staphylococcusaureusand coagulase-negative Staphylococcus (CNS), while the most frequently isolated gram-negative microorganisms were Klebsiella spp.,Pseudomonas aeruginosa and Escherichia coli. The prevalence of S. pneumoniae was up to 25.7 % (4101/15973) in all respiratory tract specimens. About 50.2 % of the S. pneumoniae isolates were not susceptible to penicillin. The prevalence of methicillin-resistant strains was 20.6 % in S. aureus (MRSA) and 87.8 % in coagulase negative Staphylococcus (MRCNS) on average. The prevalence of MRSA increased from 11.1 % in 2009 to 29.8 % in 2015. No S. pneumoniae or staphylococcal strains were found resistant to vancomycin or linezolid. The Enterococcus strains were still highly susceptible to vancomycin and linezolid. Overall 0.3 % of the Enterococcus faecium isolates were resistant to vancomycin. The extended-spectrum beta-lactamases (ESBLs) producing strains accounted for 71.4 % -78.1 % of E. coli and 65.1 % - 76.9 % of K. pneumoniae isolates. The carbapenem-resistant E. coli and K. pneumoniae were reported for the first time in 2010, but in 2014, the strains resistant to carbapenems had increased to more than 7 % in E. coli, and higher than 20 % in K. pneumoniae. In 2015, up to 27.7 % and 25.7 % of P. aeruginosa isolates were resistant to imipenem and meropenem, respectively, and 59.9 % of the A. baumannii isolates were resistant to imipenem and meropenem. Beta-lactamase was positive in 46.3 % of the H. influenzae isolates. Conclusions MRSA and the carbapenem-resistant strains of E. coli,K. pneumoniae and A. baumannii are still on the rise in pediatric inpatients, which poses a serious threat to clinical practice and implies the importance of strengthening infection control.

Effects of FKBP51 acting on Caspase-3 and rat hippocampal CA1 area neuronal necrosis in cerebral ischemia reperfusion injury / 中国基层医药

Objective To explore the effect of FKBP51 acting on Caspase-3 and hippocampal CA1 area neu-ronal necrosis in cerebral ischemia reperfusion injury of rat.Methods SD rats were randomly divided into Sham group,ischemia reperfusion group ( I/R group ) , TE buffer group ( TE group ) , FKBP51 antisense oligonucleotide group (FKBP51 ASODN group) and FKBP51 missense oligonucleotide group (FKBP51 MSODN group).Transient global cerebral ischemia rats models were made by four-vessel method.We used Western blot to detect the expression of FKBP51,the effect of FKBP51 ASODN to FKBP51 expression and Caspase-3 activity;while we used HE staining technique to detect FKBP51 ASODN effect to rat hippocampal CA1 area neuronal necrosis.Results (1) In Sham group and I/R group (0min,15min,30min,1h,3h,6h,1d,3d),FKBP51 expressed,and the difference among the groups was no statistical significance (F=0.64,P>0.05).(2)The expression of FKBP51 in FKBP51 ASODN group was obviously reduced, and the difference was statistically significant compared with Sham group ( t =8.21, P <0.05).(3)The expression of Cleaved-Caspase-3 in Sham group obviously declined than the other groups,the differ-ence between them was statistically significant (F=12.31,P<0.05);The expression of FKBP51 in FKBP51 ASODN group was decreasing compared with FKBP51 MSODN group,and the difference was statistical significance(t=9.71, P<0.05).(4)HE staining showed:the number of Sham group (186.3 ±2.5) hippocampal CA1 pyramidal cells was most.The cells arranged densely,and nucleoli were large and round,the difference was statistically significant com-pared with the other groups (χ2 =81.91,P<0.05);The hippocampal CA1 pyramidal cells of I/R group (15.4 ± 2.6),TE group (18.5 ±2.2) and FKBP51 MSODN group (17.5 ±1.8) were almost completely disappeared,only left a few residual cells,a great quantity of denaturated cells which presented karyopykosis,tinctorialed endochylema, ruptured of membrane and released cell content;the hippocampal CA1 pyramidal cells FKBP51 ASODN group (92.8 ±2.6) survival increased significantly compared with other group,the difference was statistically significant (χ2 =52.36,P<0.05).Conclusion In cerebral ischemia reperfusion injury,FKBP51 can enhance the activation of Caspase-3 (Cleaved-Caspase-3) expression and inhibit the survival of the neurons.

Meta analysis of T-SPOT.TB test for diagnosing tuberculous meningitis / 重庆医学

Objective To investigate the diagnostic value of the T-SPOT.TB test for diagnosing tuberculous meningitis(TBM) by meta-analysis.Methods A systematic retrieval from the databases of PubMed,EMBASE,etc.was performed.The literature on the T-SPOT.TB test for diagnosing TBM was collected.Two reviewers independently screened the literature,extracted the data and judged the quality.The meta analysis was conducted by the Meta-Disc 1.4 software.Results 8 articles were included,involving 425 patients including 232 cases of TBM.In the peripheral blood group,the combined sensitivity was 80%(95%CI:0.74-0.85),the combined specificity was 74%(95%CI:0.67-0.80),the area under the curve(AUC)of summary receiver operating characteristic (SROC)was 0.858 7;the diagnostic odds ratio(DOR)was 15.50.In the CSF group,the combined sensitivity was 76%(95%CI:0.70-0.82),the combined specificity was 83%(95%CI:0.77-0.88),AUC was 0.892 7;DOR was 22.62.Conclusion Adopting the T-SPOT.TB test conduces to increase the diagnostic rate of TBM.The diagnostic accuracy of the T-SPOT.TB test for CSF may be higher than that for peripheral blood.

Effect of FKBP51 on JNK pathway in cerebral ischemia-reperfusion injury / 中国医师杂志

Objective To investigate effect of FK506 binding protein 51 (FKBP51) on the c-JunN-terminal kinase (JNK) pathway in cerebral ischemia-reperfusion injury.Methods Transient global cerebral ischemia rat models were made by four-vessel method.Healthy male SD (Sprague Dawley) rats were randomly divided into:sham group,ischemia/reperfusion group (I/R group),FKBP51 antisense oligonucleotide group (FKBP51 ASODN group),FKBP51 missense oligonucleotide group (FKBP51 MSODN group),and solvent control group (TE group).The effect of FKBP51 ASODN on expression of FKBP51 protein and JNK was detected,and c-Jun phosphorylation was detected by Western blot.Results (1) FKBP51 protein expression in the FKBP51 ASODN group was reduced.The change of FKBP51 protein expression between the FKBP51 ASODN and sham groups was statistically significant (P ＜ 0.05).(2) The expression differences of total JNK protein between all the groups were not statistically significant (P ＞ 0.05).The expression of p-JNK in sham group was significantly less than the other groups (P ＜ 0.05).The expressions of p-JNK in I/R 3d,TE,and FKBP51 MSODN groups were higher relative to Sham group; however,the differences among those three groups were not statistically significant (P ＞ 0.05).The expression of p-JNK in FKBP51 ASODN group was significantly less than FKBP51 MSODN group (P ＜ 0.05).(3) The expression differences of total c-Jun protein among all groups were not statistically significant (P ＞ 0.05).The expression of p-c-Jun in sham group was significantly less than the other groups (P ＜ O.05).The expressions of p-c-Jun in I/R 6 h,TE,and FKBP51 MSODN groups were higher relative to the sham group; however,the differences among those three groups were not statistically significant (P ＞ 0.05).The expressions of p-c-Jun in FKBP51 ASODN group was significantly less than FKBP51 MSODN group (P ＜ 0.05).Conclusions FKBP51 might activate JNK signaling pathway in cerebral ischemia-reperfusion injury.

Effect of the FKBP51 · PHLPP · Akt signal module on the phosphorylation of Akt and hippocampal neuronal injury after the cerebral ischemia/reperfusion / 中华行为医学与脑科学杂志

Objective To investigate the effects of the FKBP51 · PHLPP · AKT signal module on the phosphorylation of Akt and hippocampal neuronal injury after the cerebral ischemia / reperfusion induced neuronal death in rat hippocampus.Methods Transient(15 min)brain ischemia was induced by the four-vessel occlusion in Sprague-Dawley rats.6 rats were used in each group.The antisense oligodeoxynucletides(AS ODN)of PHLPP2 (PH domain and leucine rich repeat protein phosphatases) was used to suppress the assembly of FKBP51 · PHLPP · Akt signal module by intracerebroventricular infusion once per day for 3 days before ischemia.After 6 hours reperfusion,interactions of PHLPP2 and FKBP51 (FK506 binding protein 5) with Akt were detected by immunoprecipitation (IP) and the phosphorylation of Akt was detected by western blot (IB).After 5 days reperfusion,rats were perfusion-fixed with paraformaldehyde and Hematoxylin-Eosin staining was used to examine the survival number of CA1 pyramidal cells of hippocampus.Results Compared to PHLPP2 MS ODN group(1.24±0.24,1.68±0.11,0.58±0.01),PHLPP2 AS ODN suppressed the assembly of the FKBP51 · PHLPP · Akt signaling module(1.06±0.01,1.04±0.13),and increased the phosphorylation of Akt(0.76±0.02) (P＜0.05).Furthermore,compared to PHLPP2 MS ODN group (20.1±2.5),the number of surviving neurons significantly increased in PHLPP2 AS ODN group(88.3±2.7)(P＜0.05).Conclusion The increasing assembly of FKBP51 · PHLPP · Akt signal module can damage CA1 pyramidal cells of hippocampus by inhibiting the phosphorylation level of Akt.

Effects of a Rho kinase inhibitor fasudil hydrochloride on GluR6 and neuronal apoptosis in cerebral ischemia/reperfusion injury / 中华行为医学与脑科学杂志

Objective To investigate the neuralprotective effect of Rho kinase inhibitor fasudil hydrochloride in cerebral ischemia/reperfusion injury in rats.Methods The SD rats were randomly divided into four groups:the sham group,the ischemia/reperfusion group,the fasudil hydrochloride group and the physiological saline group.Fasudil hydrochloride were injected intraperitoneally 30 minutes before ischemia.And the physiological saline group were treated with the intraperitoneal injection of the same volume of saline.The phosphorylation and protein expression of GluR6 at 6 hours during reperfusion were detected using immunoprecipitation and immunoblotting analysis to examine the effect of Fasudil hydrochloride.Furthermore,TUNEL staining was used to examine the apoptosis of neurons in rat hippocampal CA1 regions after 3 days reperfusion.Results 1.Immunoprecipitation and immunoblotting analysis were used to analyze the phosphorylation of GluR6 in serine site.The results showed that the GluR6 serine phosphorylation level increased significantly at 6h of reperfusion compared with the sham group (P＜0.05).Fasudil hydrochloride group could inhibit the increased phosphorylation of GluR6 at 6h of reperfusion compared with the ischemia/reperfusion group and saline group,respectively (P ＜ 0.05).2.TUNEL staining was used to examine the apoptosis of neurons in 3 days after reperfusion in CA1 regions of hippocampus.The results indicated that significant numbers of TUNEL positive cells (40.20 ± 2.77) were observed 3 days after ischemia/reperfusion.The numbers of viable neurons per 1 mm length of CA1 pyramidal cells were quantitatively analyzed.Fasudil hydrochloride markedly decreased the neuronal loss compared with the ischemia/reperfusion group (19.80 ± 2.86) (P＜0.05).Conclusion Fasudil hydrochloride can inhibit induced phosphorylation of GluR6 by the ischemia/reperfusion.Fasudil hydrochloride can reduce the neurons apoptosis in hippocampal CA1 regions,and perform a neuralprotective effect on ischemia/reperfusion injury in rats.

Rho kinase inhibitor fasudil protect neurons in hippocampal CA1 region following cerebral ischemia reperfusion through inhibiting MLK3-JNK signal transduction pathway in rats / 国际脑血管病杂志

Objective To investigate the effect of Rho kinase inhibitor fasudil on taxed lineage kinase 3 (MLK3), c-Jun NH2-terminal kinase (JNK) phosphorylation, caspase-3expression, and neuronal injury in hippocampal CA1 region follwong cerebral ischemic rep erfusion in rats. Methods A total of 72 Sprague-Dawley rats were randomly divided into sham operation, ischemia-reperfusion, normal saline, and fasudil groups. A global cerebral ischemic model was prepared by four-vessel ligation. The levels of MLK3 and JNK phosphorylation, and caspase-3 expression were detected by Western blot analysis. Cresy1 violet staining was used to detect the numbers of survival neurons in hippocampal CA1 region. Results When 6 hours after ischemia-reperfusion, the level of MLK3 phosphorylation in the fasudil group (1.13 ± 0. 03)was significantly lower than that in the normal saline group (2. 08 ± 0. 01 ,P = 0. 000 3), while the levels of MLK3 was no significant difference. When 3 hours after ischemia-reperfusion, the level of JNK phosphorylation in the fasudil group (1.27 ±0. 02)was significantly lower than that in the normal saline group (2.09 ±0. 01, P=0. 000 2), while the levels of JNK was no significant difference. When 6 hours after ischemia-reperfusion, the expression level of caspase-3in the fasudil group (1.28 ± 0. 02) was significantly lower than that in the normal saline group (2. 10 ± 0. 01, P = 0. 000 6). When 5 days after ischemia-reperfusion, the pyramidal cells in hippocampal CA1 region almost completely disappeared in the ischemia-reperfusion group, and only a few cells left (9. 8 ±2. 1). The numbers of survival pyramidal cell (8. 28 ± 3.2) in hippocampal CA1 region in the fasudil group was significantly more than that in the normal saline group (11.8 ± 1.6, P ＜0. 05). Conclusions Fasudil may significantly inhibit the ischemia-reperfusion-induced phosphorylation of MLK3 and JNK, as well as the expression of caspase-3, and thus reduce neuronal injury in hippocampal CA1 region.

Deletion of the LMP-1 gene integrated in the nasopharyngeal carcinoma cell line SUNE-1 / 中国病理生理杂志

AIM: To study the EBV LMP-1 gene integrated in the chromosome of poorly differentiated nasopharyngeal carcinoma cell line SUNE-1. METHODS: The LMP-1 gene of SUNE-1 was detected with PCR; Deletion of LMP-1 was examined by restriction endonuclease analysis and PCR. The deletion was precisely localized by DNA sequencing. RESULTS: The LMP-1 gene integrated in the chromosome of SUNE-1 could be deleted or non-deleted. The two introns of LMP-1 gene were shown being lost in SUNE-1 cell line. CONCLUSION: Deletion of intron 1 and intron 2 happen in some of the LMP-1 gene integrated in the chromosome of SUNE-1.

THE STUDY OF NEUROPROTECTION OF bcl-2 GENE BY TRANSFECTING IT INTO PC12 CELL LINE / 解剖学报

Objective To investigate the biological effects of bcl-2 gene on neurons. Methods The recombinant expression plasmid pc DNA3-bcl-2 was constructed from pSFFV-bcl-2,then it was introduced into PC12 cell line by liposome method.Western blotting and immunohistochemistry in situ were applied to exam the exogenous gene expression.The two groups of cells(Group A,PC12 transfected by pcDNA3-bcl-2 and Group B,PC12 transfected by pcDNA3) were exposed to cisplatin with the concentration of 10*!?mol/L,50*!?mol/L, and 100*!?mol/L 72 hours later,the survival cells were estimated.Cell cycle indexes between these two groups were also studied by FCM. Results The recombinant expression plasmid pcDNA 3-bcl-2 was constructed successfully and PC12 cell line transfected by the plasmid could express Bcl-2 protein effectively.Compared with the control(25 79%),there was a significant decrease of cells from the S phase in PC12 with bcl-2 gene(8.81%).After exposed with 10*!?mol/L,50*!?mol/L,and 100*!?mol/L cisplatin,the surviving cells in group A were 276?13,185?11 and 108?10 respectively,which increased much more than in group B while they were 100?9,12?3 and 2?2 accordingly.Conclusions bcl-2 can protect PC12 cells against cytotoxic insults of cisplatin,and it suggested that it might act via cell cycle controlling.