Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study

Wang Lu,Dai Ying-Jie,Cui Yu,Zhang Hong,Jiang Chang-Hao,Duan Ying-Jie,Zhao Yong,Feng Ye-Fang,Geng Shi-Mei,Zhang Zai-Hui,Lu Jiang,Zhang Ping,Zhao Li-Wei,Zhao Hang,Ma Yu-Tong,Song Cheng-Guang,Zhang Yi,Ch 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3

Background and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; <i>P</i>=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, <i>P</i>=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Prognostic Value of PLCE1 Expression in Upper Gastrointestinal Cancer: a Systematic Review and Meta-analysis

Cui, Xiao-Bin,Peng, Hao,Li, Su,Li, Ting-Ting,Liu, Chun-Xia,Zhang, Shu-Mao,Jin, Ting-Ting,Hu, Jian-Ming,Jiang, Jin-Fang,Liang, Wei-Hua,Li, Na,Li, Li,Chen, Yun-Zhao,Li, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: A number of studies have identified a shared susceptibility locus in phospholipase C epsilon 1 (PLCE1) for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). However, the results of PLCE1 expression in esophageal and gastric cancer remain inconsistent and controversial. Moreover, the effects on clinicopathological features remain undetermined. This study aimed to provide a precise quantification of the association between PLCE1 expression and the risk of ESCC and GCA through meta-analysis. Materials and Methods: Eligible studies were identified from PubMed, Wanfang Data, ISI Web of Science, and the Chinese National Knowledge Infrastructure databases. Using RevMan5.2 software, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were employed to assess the association of PLCE1 expression with clinicopathological features relative to ESCC or GCA. Results: Seven articles were identified, including 761 esophageal and gastric cancer cases and 457 controls. Overall, we determined that PLCE1 expression was associated with tumor progression in both esophageal cancers (pooled OR=5.93; 95%CI=3.86 to 9.11) and gastric cancers (pooled OR=9.73; 95%CI=6.46 to 14.7). Moreover, invasion depth (pooled OR=3.62; 95%CI=2.30 to 5.70) and lymph node metastasis (pooled OR=4.21; 95%CI=2.69 to 6.59) were linked with PLCE1 expression in gastric cancer. However, no significant associations were determined between PLCE1 overexpression and the histologic grade, invasion depth, and lymph node metastasis in esophageal cancer. Conclusions: Our metaanalysis results indicated that upregulated PLCE1 is significantly associated with an increased risk of tumor progression in ESCC and GCA. Therefore, PLCE1 expression can be appropriately regarded as a promising biomarker for ESCC and GCA patients.

Adoptive Immunotherapy for Small Cell Lung Cancer by Expanded Activated Autologous Lymphocytes: a Retrospective Clinical Analysis

Zhang, Guo-Qing,Li, Fang,Sun, Sheng-Jie,Hu, Yi,Wang, Gang,Wang, Yu,Cui, Xiao-Xia,Jiao, Shun-Chang Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.4

Background: To investigate the clinical efficacy of expanded activated autologous lymphocytes (EAAL) in patients with small cell lung cancer (SCLC). Materials and Methods: A total of 32 SCLC patients were selected and randomly divided into EAAL treatment and control groups, 16 cases in each. EAAL were obtained by proliferation of peripheral blood mononuclear cells (PBMCs) of patients followed by phenotype determination. Clinical data of all patients were recorded. Patients of both groups were followed up and the overall survival (OS) were compared retrospectively. Results: After culture and proliferation in vitro, the percentages of $CD3^+$, $CD3^+CD8^+$, $CD45RO^+$, $CD28^+$, $CD29^+$, $CD8^+CD28^+$ and $CD3^+CD16^+/CD56^+$ cells increased markedly (p<0.05). The OS of the EAAL treatment group was longer than that of control group, but the difference was not statistically significant (p=0.060, HR=0.487, 95%CI 0.228~1.037). 1- to 3-year survival rates in EAAL treatment group were longer than those in control group, but there was still no significant difference (p>0.05). COX multivariate regression analysis showed that the number of chemotherapy cycles and the application of EAAL immunotherapy were independent prognostic factors for SCLC patients. The OS in females and chemotherapy${\leq}6$ cycles were obviously prolonged after EAAL immunotherapy. Conclusions: In vitro induction and proliferation of EAAL is easy and biologically safe. Generally, EAAL adoptive immunotherapy can evidently prolong the OS of SCLC patients.

On/off Switch Mediated by Exo+ Polymerases: Experimental Analysis for Its Physiological and Technological Implications

Zhang, Jia,Chen, Lin-Ling,Guo, Zi-Fen,Peng, Cui-Ying,Liao, Duan-Fang,Li, Kai Korean Society for Biochemistry and Molecular Biol 2003 Journal of biochemistry and molecular biology Vol.36 No.6

The potential physiological role and technological application of the premature termination of DNA polymerization through the off-switch of exo+ polymerases were studied using 3' phosphorothioate-modified or unmodified primers with single base mismatch distal to the 3' terminus. With exonuclease-digestible unmodified primers, a gradient premature termination of DNA polymerization was observed when amplified with exo+ polymerases. With 3' allele specific phosphorothioate-modified primers, an efficient off-switch effect occurred in the discrimination of a single nucleotide polymorphism when directly using genomic DNA. Clearly, the off-switch of exo+ polymerases is useful in biomedical research.

Human Recombinant Endostatin Combined with Cisplatin Based Doublets in Treating Patients with Advanced NSCLC and Evaluation by CT Perfusion Imaging

Zhang, Feng-Lin,Gao, Er-Yun,Shu, Rong-Bao,Wang, Hui,Zhang, Yan,Sun, Peng,Li, Min,Tang, Wei,Jiang, Bang-Qin,Chen, Shuang-Qi,Cui, Fang-Bo Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Aims: To study the effectiveness of human recombinant endostatin injection (Endostar(R)) combined with cisplatin doublets in treating advanced non-small cell lung cancer (NSCLC), and to evaluate outcome by CT perfusion imaging. Methods: From April 2011 to September 2014, 76 patients with advanced NSCLC who were treated with platinum-based doublets were divided into group A (36 patients) and group B (40 patients). Endostar(R) 15mg/day was administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A, and combined with chemotherapy from the first day in Group B. Endostar(R) in the two groups was injected intravenously for 14 days. Results: Treatment effectiveness in the two groups differed with statistical significance (p<0.05). Effectiveness evaluated by CT perfusion imaging, BF, BV, MTT and PS also demonstrated significant differences (all p<0.05). Adverse reactions in the two groups did not significantly vary (p> 0.05). Conclusions: The response rate with Endostar(R) administered 4 days before chemotherapy and combined with chemotherapy from day 5 in group A was better than Endostar(R) combined with chemotherapy from the first day, and CT perfusion imaging could be a reasonable method for evaluation of patient outcomes.

Mycobacterium vaccae induces a strong Th1 response that subsequently declines in C57BL/6 mice

Lijiao Zhang,Yanlong Jiang,Ziyin Cui,Wentao Yang,Limin Yue,Yingcong Ma,Shaohua Shi,Chun-fang Wang,Chun-feng Wang,Aidong Qian 대한수의학회 2016 Journal of Veterinary Science Vol.17 No.4

Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immuneresponses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. bovisBacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organpathology between M. vaccae and M. bovis BCG revealed that M. vaccae was more malignant than M. bovis in mice. We also demonstratedthat serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-), tumor necrosis factor alpha,monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especiallyafter week 4. Furthermore, when the numbers of CD3+CD4+IFN-+ and CD3+CD4+IL4+ cells in the infected mice were observed by flowcytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergenceof CD3+CD4+IFN-+ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4+CD25+FoxP3+and CD4+CD25+CD152+Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increasedthe production of type I IFNs, which was associated with a reduced Th1 response.

On/off Switch Mediated by Exo+ Polymerases: Experimental Analysis for Its Physiological and Technological Implications

( Jia Zhang ),( Lin Ling Chen ),( Zi Fen Guo ),( Cui Ying Peng ),( Duan Fang Liao ),( Kai Li ) 생화학분자생물학회 2003 BMB Reports Vol.36 No.6

The potential physiological role and technological application of the premature termination of DNA polymerization through the off-switch of exo+ polymerases were studied using 3` phosphorothioate-modified or unmodified primers with single base mismatch distal to the 3` terminus. With exonuclease-digestible unmodified primers, a gradient premature termination of DNA polymerization was observed when amplified with exo+ polymerases. With 3` allele specific phosphorothioate-modified primers, an efficient off-switch effect occurred in the discrimination of a single nucleotide polymorphism when directly using genomic DNA. Clearly, the off-switch of exo+polymerases is useful in biomedical research.

Thermal Stability and Crystallization Kinetics of Cu-Zr-Al-Ag BMGs Investigated with Isothermal Electrical Resistance Measurement

Li-Fang Wang,Xiao Cui,Qi-Dong Zhang,Fang-Qiu Zu 대한금속·재료학회 2014 METALS AND MATERIALS International Vol.20 No.4

The thermal stability and crystallization kinetics of the CuxZr84-xAl8Ag8 (x = 42, 40, 38, and 36) bulk metallicglasses (BMGs) were studied by measurement of isothermal electrical-resistance. As the composition becomesricher in Zr, the longer incubation time at the same relative annealing temperature, and the larger local activationenergy needed to achieve the same crystallized volume-fraction, indicate improved thermal stability,which resists crystallization. The improved thermal stability is attributed to a denser atomic random-stackingstructure and larger negative heat-of-mixing. During isothermal annealing processes, the four BMGs exhibitedthe same nucleation mechanism, which is a decreasing rate of nucleation over time. However, the crystal growthmechanisms of the four BMGs are different. The crystallization of the Cu36Zr48Al8Ag8 and Cu38Zr46Al8Ag8BMGs is interface-controlled growth, contrasting with diffusion-controlled growth for the Cu40Zr44Al8Ag8 andCu42Zr42Al8Ag8 alloys. The different growth modes may be caused by fluctuations in composition due tochanges in the quantity and distribution of Cu-rich and Ag-rich regions.

Distinctive Slow β Relaxation and Its Impact on Mechanical Property of LaCe Based Bulk Metallic Glasses

Xiao Cui,Jing Guo,Qi‑dong Zhang,Xiao‑jun Meng,Bing‑chuan Bian,Ren‑gao Zhao,Yu‑bai Ma,Fang‑qiu Zu 대한금속·재료학회 2020 METALS AND MATERIALS International Vol.26 No.10

The slow β relaxation which occurring at temperatures far below glass transition temperature, typically playing importantroles in the plastic deformation behavior of metallic glasses. Compared with polymer glasses, most of the metallic glasses donot exhibit obvious β relaxation based on dynamic mechanical analysis. In the current work, prominent β relaxation behaviorsof a series (LaxCe100−x) Al10Co25(x = 50, 60, 70, 80) bulk metallic glasses (BMGs) at low temperature are observed usingdynamic mechanical analysis. Compared with other BMGs, the LaCe based BMGs show a pronounced β relaxation peak andrelative low peak temperature, the activation energy of the β relaxation based on Arrhenius equation are calculated around79.3 kJ/mol to 86.4 kJ/mol, which obey an empirical rule that Eβ ≈ (26 ± 4) RTg, with the coefficient of 23. Experimentalresults from room temperature compression tests for the LaCe based BMGs indicate that low temperature activated β relaxationbehaviors facilitate the good plasticity of the LaCe based BMGs.

OsMSR15 encoding a rice C2H2-type zinc finger protein confers enhanced drought tolerance in transgenic Arabidopsis

Xin Zhang,Bin Zhang,Ming Juan Li,Xu Ming Yin,Li Fang Huang,Yan Chun Cui,Man Ling Wang,Xin Jie Xia 한국식물학회 2016 Journal of Plant Biology Vol.59 No.3

Zinc nger proteins (ZFPs) play important roles in plant responses to biotic and abiotic stresses. Through microarray analysis, an Oryza sativa L. multi-stress-responsive gene, OsMSR15, was identied and subsequently cloned from rice Pei’ai 64S (Oryza sativa L.). Expression of OsMSR15 was strongly up-regulated by cold, drought and heat stresses in different tissues at different developmental stages of rice. OsMSR15 contains two C2H2-type zinc nger motifs, a nuclear localization signal (B box), a Leu-rich domain (L-box) and a conserved EAR-motif close to its C-terminus. The OsMSR15-GFP fusion protein was localized to the nucleus. Yeast-one hybrid assay showed that OsMSR15 possesses transcriptional activation ability. Expression of OsMSR15 in Arabidopsis conferred drought tolerance, and transgenic plants showed hypersensitivity to exogenous ABA during the seed germination and post-germination stages. Transgenic plants also showed higher levels of free proline, less electrolyte leakage and increased expressions of a number of stress-responsive genes, including LEA3, RD29A, DREB1A and P5CS1 under drought stress. The obtained results indicate that OsMSR15 is an important regulator involved in plant response to drought stress.