Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis

Ying Yang,Dong Wang,Lei Cui,Hong-Hao Ma,Li Zhang,Hong-Yun Lian,Qing Zhang,Xiao-Xi Zhao,Li-Ping Zhang,Yun-Ze Zhao,Na Li,Tian-You Wang,Zhi-Gang Li,Rui Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Characteristics of registered studies for Coronavirus disease 2019 (COVID-19): a systematic review

Ming Yang,Ya-xi Shang,Zi-yu Tian,Min Xiong,Chun-li Lu,Jiang Yue,Zhang Yao,Zhang Ying-ying,Jin Xin-yan,Jin Qiu-bai,Zhang Ying-ying,Willcox Merlin L.,Liu Jian-ping 한국한의학연구원 2020 Integrative Medicine Research Vol.9 No.3

Background: The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. Methods: Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. Results: Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. Conclusion: Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.

Magnesium isoglycyrrhizinate inhibits L-type Ca2+ channels, Ca2+ transients, and contractility but not hERG K+ channels

Yue Lin,Yuanyuan Zhang,Qiongtao Song,Tao Song,Xue Han,Ying Zhang,Xuan Zhang,Xi Chu,Fenghua Zhang,Li Chu,Jianping Zhang 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.10

To explore the cardiovascular protective effectsof Magnesium isoglycyrrhizinate (MI), especially theunderlying cellular mechanisms related to L-type calciumchannels and myocardial contractility, and to examine theeffects of MI on hERG K? current expressed in HEK293cells. We used the whole-cell patch clamp technique,video-based edge detection and dual excitation fluorescencephotomultiplier systems to explore the effect of MIon L-type Ca2? currents (ICa-L) and cell contraction in ratcardiomyocytes. We also examined the rapidly activatingdelayed rectifier potassium current (IKr) expressed inHEK293 cells using a perforated patch clamp. MI inhibitedICa-L in a dose-dependent manner, with a half-maximalinhibitory concentration (IC50) of 0.22 mg/ml, and themaximal inhibitory effect was 61.10 ± 0.59%. MI at aconcentration of 0.3 mg/ml reduced cell shortening by24.12 ± 3.97% and the peak value of the Ca2? transient by36.54 ± 4.96%. MI had no significant influence on hERGK? channels expressed in HEK293 cells at all testpotentials. MI exerts protective effects on the heart via theinhibition of ICa-L and cell shortening in rat cardiomyocytes. However, MI had no significant influence on IKr;thus, MI may exert cardioprotective effects without causingdrug-induced long QT syndrome.

HPLC Determination of Malondialdehyde in ECV304 Cell Culture Medium for Measuring the Antioxidant Effect of Vitexin-4"-O-glucoside

Xi-xiang Ying,Hai-bo Li,Zheng-yun Chu,Yan-jun Zhai,Ai-jing Leng,Xun Liu,Wen-jie Zhang,Ting-guo Kang,Chun Xin 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

To investigate the antioxidant effect of vitexin-4"-O-glucoside, a flavone glycoside, isolated from the leaves of Crataegus pinnatifida Bge. var. major, we developed a simple and sensitive high-performance liquid chromatography (HPLC) method to determine levels of malondialdehyde (MDA) in ECV304 cell culture medium after induction by tert-butyl-hydroperoxide (TBHP). The preparation of analyzed samples involved a one-step derivatization with thiobarbituric acid (TBA). HPLC analysis was performed on a SynergiTM Hydro-RP, a polar end-capped C18 column (250×4.6 mm, 4 μm), using an acetonitrile-ammonium acetate aqueous solution (10 mM, pH 6.8) as the mobile phase under linear gradient conditions with UV detection at 532 nm. The calibration curve was linear over 0.0125-1.25 μM MDA (r = 0.9951). Relative standard deviations (RSDs) of intra-day and inter-day precision were less than 6.1% and 5.0%, respectively. The mean recovery was 96.9 ± 1.6%. The lower limit of quantification (LLOQ) of MDA was 0.0125 μM. This chromatographic method was successfully applied to investigating the in vitro antioxidant effect of vitexin-4"-O-glucoside. Vitexin-4"-O-glucoside (120 M) protected ECV304 cells from peroxidation induced by TBHP.

G1/S-specific Cyclin-D1 Might be a Prognostic Biomarker for Patients with Laryngeal Squamous Cell Carcinoma

Zhang, Ying-Yao,Xu, Zhi-Na,Wang, Jun-Xi,Wei, Dong-Min,Pan, Xin-Liang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: To investigate the prognostic role of antigen KI-67 (Ki-67) and G1/S-specific cyclin-D1 (cyclin-D1) in patients with laryngeal squamous cell carcinoma (LSCC). Methods: Immunohistochemical staining (IHS) was used to determine the protein expression of Ki-67 and cyclin-D1 in LSCC tissues. Kaplan-Meier survival curves was calculated with reference to Ki-67 and cyclin-D1 levels. Results: Cyclin-D1 and Ki67 were expressed in the nuclei of cancer cells. Among the total of 92 cancer tissues examined by immunohistochemistry, 60 (65.22%) had cyclin-D1 overexpression and 56 (60.87%) had Ki67 overexpression. Cyclin-D1 overexpression is associated with the advanced stage of the cancer (P=0.029), but not with gender, age, stage of cancer, histological differentiation, anatomical site, smoking history and alcohol consumption history. Ki67 overexpression is not associated with the advanced stage, gender, age, histological differentiation, anatomical site, smoking history and alcohol consumption history. A statistically significant correlation was found between lymph node status and the expression of Ki67 (p = 0.025). Overexpression of cyclin-D1 was correlated to shorter relapse-free survival period (P<0.001). Conclusions: Overexpression of cyclin-D1 can be used as a marker to predict relapse in patients with LSCC after primary curative resection.

HPLC Determination of Malondialdehyde in ECV304 Cell Culture Medium for Measuring the Antioxidant Effect of Vitexin-4"-O-glucoside

Ying, Xi-Xiang,Li, Hai-Bo,Chu, Zheng-Yun,Zhai, Yan-Jun,Leng, Ai-Jing,Liu, Xun,Xin, Chun,Zhang, Wen-Jie,Kang, Ting-Guo 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.7

To investigate the antioxidant effect of vitexin-4"-O-glucoside, a flavone glycoside, isolated from the leaves of Crataegus pinnatifida Bge. var. major, we developed a simple and sensitive high-performance liquid chromatography (HPLC) method to determine levels of malondialdehyde (MDA) in ECV304 cell culture medium after induction by tert-butyl-hydroperoxide (TBHP). The preparation of analyzed samples involved a one-step derivatization with thiobarbituric acid (TBA). HPLC analysis was performed on a $Synergi^{TM}$ Hydro-RP, a polar end-capped $C_{18}$ column ($250{\times}4.6\;mm$, $4\;{\mu}m$), using an acetonitrile-ammonium acetate aqueous solution (10 mM, pH 6.8) as the mobile phase under linear gradient conditions with UV detection at 532 nm. The calibration curve was linear over $0.0125-1.25\;{\mu}M$ MDA (r=0.9951). Relative standard deviations (RSDs) of intra-day and inter-day precision were less than 6.1% and 5.0%, respectively. The mean recovery was $96.9\;{\pm}\;1.6%$. The lower limit of quantification (LLOQ) of MDA was $0.0125\;{\mu}M$. This chromatographic method was successfully applied to investigating the in vitro antioxidant effect of vitexin-4"-O-glucoside. Vitexin-4"-O-glucoside (120 M) protected ECV304 cells from peroxidation induced by TBHP.

Inhibitory effects of osteoprotegerin on osteoclast formation and function under serum-free conditions

Ying-Xiao Fu,Jian-Hong Gu,Yi-Ran Zhang,Xi-Shuai Tong,Hong-Yan Zhao,Yan Yuan,Xue-Zhong Liu,Jian-Chun Bian,Zong-Ping Liu 대한수의학회 2013 Journal of Veterinary Science Vol.14 No.4

The purpose of this study was to determine whether osteoprotegerin (OPG) could affect osteoclat differentiation and activation under serum-free conditions. Both duck embryo bone marrow cells and RAW264.7 cells were incubated with macrophage colony stimulatory factor (M-CSF) and receptor activator for nuclear factor κB ligand (RANKL) in serum-free medium to promote osteoclastogenesis. During cultivation, 0,10, 20, 50, and 100 ng/mL OPG were added to various groups of cells. Osteoclast differentiation and activation were monitored via tartrate-resistant acid phosphatase (TRAP) staining,filamentous-actin rings analysis, and a bone resorption assay. Furthermore, the expression osteoclast-related genes, such as TRAP and receptor activator for nuclear factor κB (RANK),that was influenced by OPG in RAW264.7 cells was examined using real-time polymerase chain reaction. In summary,findings from the present study suggested that M-CSF with RANKL can promote osteoclast differentiation and activation,and enhance the expression of TRAP and RANK mRNA in osteoclasts. In contrast, OPG inhibited these activities under serum-free conditions.

Invited Mini Review : Microorganism lipid droplets and biofuel development

Ying Mei Liu,Cong Yan Zhang,Xi Peng Shen,Xue Lin Zhang,Simon Cichello,Hong Bin Guan,Ping Sheng Liu 생화학분자생물학회(구 한국생화학분자생물학회) 2013 BMB Reports Vol.46 No.12

Biosynthesis of adipic acid in metabolically engineered Saccharomyces cerevisiae

Zhang Xi,Liu Yingli,Wang Jing,Zhao Yunying,Deng Yu 한국미생물학회 2020 The journal of microbiology Vol.58 No.12

Adipic Acid (AA) is a valued platform chemical compound, which can be used as a precursor of nylon-6,6. Due to the generation of an enormous amount of nitric oxide metabolites and the growing depletion of oil resources as a result of AA production from a mixture of cyclohexanol and cyclohexanone, the microbial methods for synthesizing AA have attracted significant attention. Of the several AA-producing pathways, the reverse adipate degradation pathway in Thermobifida fusca (Tfu RADP) is reported to be the most efficient, which has been confirmed in Escherichia coli. In this study, the heterologous Tfu RADP was constructed for producing AA in S. cerevisiae by co-expressing genes of Tfu_ 0875, Tfu_2399, Tfu_0067, Tfu_1647, Tfu_2576, and Tfu_ 2576. The AA titer combined with biomass, cofactors and other by-products was all determined after fermentation. During batch fermentation in a shake flask, the maximum AA titer was 3.83 mg/L, while the titer increased to 10.09 mg/L during fed-batch fermentation in a 5-L bioreactor after fermentation modification.

Microstructures and Fatigue Life of SnAgCu Solder Joints Bearing Nano-Al Particles in QFP Devices

Liang Zhang,Xi-ying Fan,Yong-huan Guo,Cheng-wen He 대한금속·재료학회 2014 ELECTRONIC MATERIALS LETTERS Vol.10 No.3

Microstructures and fatigue life of SnAgCu and SnAgCu bearing nano-Al particles in QFP (Quad flat package) devices were investigated, respectively. Results show that the addition of nano-Al particles into SnAgCu solder can refine the microstructures of matrix microstructure. Moreover, the nano-Al particles present in the solder matrix, act as obstacles which can create a back stress, resisting the motion of dislocations. In QFP device, it is found that the addition of nano-Al particles can increase the fatigue life by 32% compared with the SnAgCu solder joints during thermal cycling loading.