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.

Circ_0026359 induces HOXA9 to regulate gastric cancer malignant progression through miR‑140‑3p

Lu Shuirong,Lu Jinlai,Liu Lang,Sun Yilong,Zhao Yixuan,Tan Xi,Li Jingze 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.4

Recent researches indicate the key role of circRNA in gastric cancer (GC) progression. However, the role of circ_0026359 in GC progression remains unclear. This study aims to analyze the role of circ_0026359 in GC development and the underlying mechanism. The results showed that compared with controls, GC tissues and cells displayed high circ_0026359 and HOXA9 expression, and low miR-140-3p expression. Depletion of circ_0026359 repressed cell proliferation, migration, invasion and glycolysis, and induced cell apoptosis. Circ_0026359 knockdown inhibited neoplasm growth in vivo. Under-expression of miR-140-3p, a target miRNA of circ_0026359, relieved the effects of circ_0026359 knockdown on GC progression. Additionally, HOXA9 was regulated by the circ_0026359/miR-140-3p axis. Thus, circ_0026359 absence inhibited GC progression by miR-140-3p/HOXA9 pathway, which provided an effective therapeutic target for GC.

Establishment of a novel myocarditis mouse model based on cyclosporine A

Zhao Tian Hao,Jiang Yi Xuan,Chen Kai Qin,Qiu Dan,Xu Yan Zhe,Ye Chun,Ren Ting,Zhang Bo,Dai Bin,Hu Jue,Lu Jun,Zhou Fang Liang,Xiao Rong,Lu Fang Guo,Wei Ke 한국유전학회 2022 Genes & Genomics Vol.44 No.12

Background: Myocarditis is a myocardial injury that can easily cause adolescent death. Traditional research models of animal invasion with viral components, lipopolysaccharide (LPS) or porcine myocardial myosin, among others, have the shortcomings of potential biological safety hazards and high animal mortality. Objective: To explore the construction of a novel myocarditis model with cyclosporine A and the potential genes and pathways associated with it. Methods: BALB/c mice were used in this study, and cyclosporin A and LPS were injected into the peritoneal cavity of mice. The successful establishment of the model was assessed by detecting serum myocardial injury markers and inflammatory factors levels, HE, IHC staining, and RT-qPCR methods. Key genes were obtained using the GSE35182 dataset from the GEO database and validated with the RT-qPCR method. Results: We found that a large number of inflammatory cells infiltrated the myocardium of mice in each group of Cyclosporin A constructed model, while the expression of inflammatory factor indicators was increased, and this model has the characteristics of high degree of local inflammation in myocardial tissue, low mortality, and safe and non-toxic treatment. Using GSE35182 data, we selected 18 Hub genes and validated Hub genes in myocardial tissue with RT-qPCR and found that multiple signaling pathways such as Toll-likereceptor signaling pathway(TLRs), Rap1 signal pathway(Rap1), and Chemokine signaling pathway may be involved in the development of myocarditis. Conclusion: Cyclosporin A can construct a new myocarditis model, and TLRs, Chemokines and Rap1 signaling pathways may be the core pathways of myocarditis.

RNAi suppression of nuclear receptor genes results in increased susceptibility to sulfoxaflor in brown planthopper, Nilaparvata lugens

Lu Xu,Chun-Qing Zhao,De-Jin Xu,Guang-Chun Xu,Xiao-Long Xu,Zhao-Jun Han,Ya-Nan Zhang,Zhong-Yan Gu 한국응용곤충학회 2017 Journal of Asia-Pacific Entomology Vol.20 No.2

Nuclear receptors (NRs), which belong to a superfamily of ligand-dependent transcription factors, play essential roles in gene regulation to affect numerous physiological pathways. Twenty NR genes were identified in Nilaparvata lugens by using genomic, transcriptomic and GenBank databases, and categorized into NR0-NR6 subfamilies according to standard nomenclature. Among them, three NR geneswere classed into NR0, four into NR1, eight into NR2, one into NR3, one into NR4, two into NR5, and one into NR6, respectively. A phylogenetic tree of NRs from N. lugens and other representative species was constructed, which provided evolutionary insight into genetic distance. In order to investigate the NRs,whichwere induced by sulfoxaflor, time- and tissue-specific expression profiles of NR genes in fourth-instar nymphs were determined following LD50 sulfoxaflor treatment (0.28 ng/insect) and compared with control samples. NlUSP, NlE78, NlTLL, NlHR51, NlHR83, NlPNR and NlFTZ-F1 were highly expressed following 12–48 h of sulfoxaflor treatment. NlHR39 and NlDSF transcripts were detected in the head and the thorax, respectively. High-level and constitutive expression of NlHR3, NlTLL, NlHR83, NlFTZF1 and NlHR4 were found in the abdomen. Feeding of dsRNAs reduced the expression of NlHR3, NlUSP, NlTLL, NlHR83, NlPNR, NlFTZ-F1 and NlHR4 (35.48–49.77%) and caused significant nymph mortality (69.21–81.45%). These NRs, considered as insecticide targets, may play important function in sulfoxaflor detoxification.

Failure characteristics of combined coal-rock with different interfacial angles

Zhao, Tong-Bin,Guo, Wei-Yao,Lu, Cai-Ping,Zhao, Guang-Ming Techno-Press 2016 Geomechanics & engineering Vol.11 No.3

In order to investigate the influence of the interfacial angel on failure characteristics and mechanism of combined coal-rock mass, 35 uniaxial/biaxial compressive simulation tests with 5 different interfacial angels of combined coal-rock samples were conducted by PFC2D software. The following conclusions are drawn: (1) The compressive strength and cohesion decrease with the increase of interfacial angle, which is defined as the angle between structure plane and the exterior normal of maximum principal plane, while the changes of elastic modulus and internal friction angle are not obvious; (2) The impact energy index $K_E$ decreases with the increase of interfacial angle, and the slip failure of the interface can be predicted based on whether the number of acoustic emission (AE) hits has multiple peaks or not; (3) There are four typical failure patterns for combined coal-rock samples including I (V-shaped shear failure of coal), II (single-fracture shear failure of coal), III (shear failure of rock and coal), and IV (slip rupture of interface); and (4) A positive correlation between interfacial angle and interface effect is shown obviously, and the interfacial angle can be divided into weak-influencing scope ($0-15^{\circ}$), moderate-influencing scope ($15-45^{\circ}$), and strong-influencing scope (> $45^{\circ}$), respectively. However, the confining pressure has a certain constraint effect on the interface effect.

Effects of Zn Addition on Dynamic Recrystallization of High Strain Rate Rolled Al–Mg Sheets

Lu Zhao,Weijun Xia,Hongge Yan,Jihua Chen,Bin Su 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.5

Effects of Zn addition (0, 0.5, 1.0 and 1.5 wt%) on dynamic recrystallization (DRX) behavior of Al-9.2Mg alloy during highstrain rate rolling (with rolling temperature of 400 °C and strain rate of 8.6 s−1) are carefully investigated. The Zn contentplays a significant role in the enhanced DRX of Al-9.2Mg alloy. The critical strain (εc) and the peak strain (εp) are reducedfrom 0.178 ± 0.002 to 0.102 ± 0.001 and 0.211 ± 0.003 to 0.139 ± 0.002 with the Zn content increasing from 0 to 1.5%,respectively. Almost complete DRX grains are obtained in the Al-9.2Mg-0.5Zn alloy. The DRX volume fraction (FDRX), theaverage DRX grain size (AGS), the volume fraction of high-angle grain boundaries (FHAGBs) and the average grain boundaryangle (θAV) are 91.5%, 5.6 μm, 91.1% and 37.6 º, respectively. The Zn addition can enhance the formation of deformationbands (DBs) and promote the DRX process by providing the nucleation sites for new grains, while the increased dynamicprecipitates inhibit DRX. Continuous dynamic recrystallization (CDRX) is the dominant DRX mechanism, while discontinuousdynamic recrystallization (DDRX) is also existent. Effects of Zn addition on DRX process of the Al–Mg alloys canbe ascribed to the more DBs, the reduced stacking fault energy (SFE) and the dynamic precipitates.

Metadynamic Recrystallizaton Behavior of a Vanadium-Nitrogen Microalloyed Steel

Zhao Baochun,Zhao Tan,Li Guiyan,Lu Qiang 대한금속·재료학회 2015 METALS AND MATERIALS International Vol.21 No.4

The metadynamic recrystallizaton behavior of a V-N microalloyed steel was studied by performing a two-pass isothermal compression test at 900 °C-1050 °C at a strain rate of 0.1 s-1 to 7 s-1 with the inter-pass time of 0.2-2 s on a Gleeble-3800 thermo-mechanical simulator. The effects of the processing parameters on the metadynamic recrystallizaton behavior of the tested steel were analyzed. The activation energy of the tested steel was determined by regression method and the kinetic models were constructed. Our results showed that the metadynamic recrystallizaton of the tested steel can easily occur due to low activation energy. The effects of the processing parameters are marked and higher deformation temperature, strain rate, or longer time interval contributes to an increase in the metadynamic recrystallized volume fraction. However, it is difficult to observe work hardening in the second pass at a time interval of 0.2 s and stress tends to be steady. Finally, the kinetic models were confirmed by comparing the experimental and the predicted results.

Esomeprazole-a New proton Pump Inhibitor for the Treatment of Gastro-Oesophageal Reflux Disease and Peptic Ulceration

Zhao, Hai-Lu,Thomas, G Neil,pLeung, Wilson YS,Chen, Qian,Tomlinson, Brian Medical Publications Korea 2002 Medical Progress Vol.24 No.8

Crystal Structure and Thermal Stability Study on Tetrabutylammonium Hexamolybdate [n-Bu₄N]₂[Mo₆O₁₉](TBAM)

Zhao, Pu Su,Zhao, Zhan Ru,Jian, Fang Fang,Lu, Lu De Korean Chemical Society 2003 대한화학회지 Vol.47 No.6

$[n-Bu_4N]_2[Mo_6O_{19}]$(TBAM)의 결정구조는 X-ray 분석기로 결정되었다. 그 결정은 monoclinic 계이며 ${\alpha}$=16.314(5), b=17.288(5), c=17.776(4) ${\AA}$, ${\beta}$=101.47(3) 그리고 z=4의 결정파라미터를 갖는 sapce group 이 C2/c인 결정이다 $[Mo_6O{19}]^{2-}$ 음이온에서, Mo 원자는 팔면체의 여섯 개 모서리를 차지하며 각 Mo 원자는 여석개의 산소원자에 배위되어 찌그러진 팔면체 배위 기하학을 지닌다. Mo-Ot(말단기), Mo-Ob(연결된), 그리고Mo-Oc(중앙)의 평균거리는 각각 1.680 ${\AA}$, 1.931 ${\AA}$ 및 2.325 ${\AA}$ 이다. $[n-Bu_4N]^+$ 양이온에서 N원자는 약간 찌그러진 사면체 모형을 갖는다. 격자안에서 폭 넓은 C-H ${\cdots}$ O 수소결합이 있으며, 그것에 의하여 분자들을 연결하고 결정구조를 안정화 한다. 열분석에 의하여 제목의 열적분핸ㄴ 두개의 전이가 일어나며 356.0와 803.5 $^{\circ}$에서 각각 무게를 잃는다. 그리고 분해된 생성물은 $Mo_2O_2$로 추정된다. 따라서, 제목의 화합물은 높은 열적 안정성을 갖는다. The crystal structure of $[n-Bu_4N]_2[Mo_6O_{19}]$(TBAM) (n-Bu4N=tetrabutylammonium) has been determined by X-ray crystallography. It crystallizes in the monoclinic system, space group C2/c, with lattice parameters ${\alpha}$=16.314(5), b=17.288(5), c=17.776(4)${\AA}$ ${\beta}$=101.47(3), and Z=4. In $[Mo_6O{19}]^{2-}$ anion, Mo atoms occupy six vertices of octahedron and each Mo atom is coordinated by six oxygen atoms to adopt distorted octahedral coordination geometry. The average bond distance of Mo-Ot (terminal), Mo-Ob (bridged) and Mo-Oc (central) are 1.680 ${\AA}$, 1.931 ${\AA}$ and 2.325 ${\AA}$ respectively. In $[n-Bu_4N]^+$ cation, the N atom possesses a slightly distorted tetrahedral geometry. There are some potential extensive C-H ${\cdots}$ O hydrogen bonds in the lattice, by which connecte molecules and stabilize the crystal structure. Thermogravimetric analysis suggests that thermal decomposition of the title compound includes two transitions and it loses weight at 356.0 and 803.5 $^{\circ}$, respectively, and the residue presumable be $Mo_2O_2$. Accordingly, the title compound has high thermal stability.

Correlation of Adventitial Vasa Vasorum with Intracranial Atherosclerosis: A Postmortem Study

Lu Zheng,Wen Jie Yang,Chun Bo Niu,Hai Lu Zhao,Ka Sing Wong,Thomas Wai Hong Leung,Xiang Yan Chen 대한뇌졸중학회 2018 Journal of stroke Vol.20 No.3

Background and Purpose Vasa vasorum (VV) have been believed to be rare or non-existent in small-caliber intracranial arteries. In a series of human cerebral artery specimens, we identified and examined the distribution of VV in association with co-existing intracranial atherosclerosis. Methods We obtained cerebral artery specimens from 32 consecutive autopsies of subjects aged 45 years or above. We scrutinized middle cerebral artery (MCA), vertebral artery (VA), and basilar artery (BA) for the presence of adventitial VV. We described the distribution of VV, and the characteristics of co-existing atherosclerotic lesions. Results Among 157 intracranial arteries, adventitial VV were present in 74 of the 157 specimens (47%), involving MCA (n=13, 18%), BA (n=14, 19%), and VA (n=47, 64%). Although qualitatively these 74 adventitial VV distributed similarly in arteries with or without atherosclerotic lesions (disease-free arteries n=4/8; arteries of pre-atherosclerosis n=17/42; and arteries of progressive atherosclerosis n=53/107), the presence of adventitial VV in intracranial VA was associated with a heavier plaque load (1.72±1.66 mm2 vs. 0.40±0.32 mm2, P<0.001), severer luminal stenosis (25%±21% vs. 12%±9%, P=0.002), higher rate of concentric lesions (79% vs. 36%, P=0.002), and denser intraplaque calcification (44% vs. 0%, P=0.003). Histologically, intracranial VA with VV had a larger diameter (3.40±0.79 mm vs. 2.34±0.58 mm, P<0.001), thicker arterial wall (0.31±0.13 mm vs. 0.23±0.06 mm, P=0.002), and a larger intima-media (0.19±0.09 mm vs. 0.13± 0.04 mm, P=0.003) than VA without VV. Conclusions Our study demonstrated the distribution of adventitial VV within brain vasculature and association between vertebral VV and progressive atherosclerotic lesions with a heavier plaque load and denser intraplaque calcification.