Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH₃-PPD in beagle dogs

Li, Wei,Zhang, Xiangrong,Ding, Meng,Xin, Yanfei,Xuan, Yaoxian,Zhao, Yuqing The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol ($25-OCH_3-PPD$), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with $25-OCH_3-PPD$ capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of $25-OCH_3-PPD$. Results: There was no $25-OCH_3-PPD$einduced systemic toxicity in beagle dogs at any doses. The level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of $25-OCH_3-PPD$ administrated groups compared to the vehicle control group. There were also no significant differences between $25-OCH_3-PPD$ administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. $25-OCH_3-PPD$ is an extremely safe candidate compound for antitumor treatment.

Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH₃-PPD in beagle dogs

Wei Li,Xiangrong Zhang,Meng Ding,Yanfei Xin,Yaoxian Xuan,Yuqing Zhao 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.4

Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol (25-OCH₃-PPD), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with 25-OCH₃-PPD capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicity of 25-OCH₃-PPD. Results: There was no 25-OCH₃-PPD-induced systemic toxicity in beagle dogs at any doses. The level of 25-OCH₃-PPD at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of 25-OCH₃- PPD administrated groups compared to the vehicle control group. There were also no significant differences between 25-OCH₃-PPD administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of 25-OCH₃-PPD at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. 25-OCH₃-PPD is an extremely safe candidate compound for antitumor treatment.

Dielectric properties and thermal conductivity of Si3N4–SiC composite ceramics

Zang Xiangrong,Li Haiqing,Lu Yanping,Tan Huihui,Ji Huanli,Yan Ming,Liu Zheng 한국세라믹학회 2022 한국세라믹학회지 Vol.59 No.6

In this work, Si 3N4–SiC composite ceramics were prepared by hot pressing sintering with Y 2O3–MgO–Al2O3 as sintering additives in a fl owing nitrogen atmosphere. The crystal structure and microstructure of Si 3N4–SiC specimens with diff erent SiC content were studied. The XRD results show that the peaks of β-Si 3N4 and SiC were displayed and matched well on XRD patterns. Si 3N4 particles were basically long rod-shaped. Besides, the eff ects of SiC content on thermal conductivity and dielectric properties in W band (75–110 GHz) of sintered Si 3N4–SiC ceramics were researched. The dielectric constant fi rst decreased then increased with the increase of SiC content, while the trend of dielectric loss (tg δ) was opposite. The dielectric constant of Si 3N4–SiC composites for 35 wt% SiC reached a minimum range of 13–20 and tg δ values reached a maximum range of 0.72–0.96 in the frequency of 75–110 GHz. Meanwhile, the thermal conductivity of Si 3N4–SiC composites for 35 wt% SiC was 63.008 W/(m K) at room temperature. The variation of thermal conductivity as test temperature was also studied. The thermal conductivity decreased with increasing test temperature. When the test temperature was 300 °C, the thermal conductivity of the Si 3N4–SiC ceramics for 35 wt% SiC content was 36.022 W/(m K). The Si 3N4–SiC composite ceramics were expected to be applied as microwave absorbing materials.

Practical Design Methods for Fire Resistance of Restrained Cellular Steel Beams

Xing Chen,Xiangrong Chen,Gang Li 한국강구조학회 2019 International Journal of Steel Structures Vol.19 No.6

Thermal responses of steel beams under fi re can be intricate, considering the coupling eff ects between material thermalexpansion, mechanical property degradation, and constraints by surrounding structural members. While research eff orts have focused on catenary action of structural members without initial imperfections, few accurate and effi cient methods are found to reveal the fi re resistance of restrained cellular steel beams (RCSBs). In this paper, parametric and regression analysis are applied to investigate the thermal behavior of RCSBs with initial imperfections. Eight groups of RCSBs are set up to demonstrate how various design parameters may aff ect structural responses at elevated temperatures. The results indicate that axial restraint stiff ness ratio, load ratio, and opening diameter-to-height ratio signifi cantly aff ect the structural responses of RCSBs in fi re, followed by the rotational restraint stiff ness ratio and span-to-depth ratio as secondary eff ects. Through the orthogonal and regression analysis, simplifi ed formulas for four characteristic temperatures and four characteristic internal forces are defi ned, which agree with fi nite element results to a certain extent. Meanwhile, reasonable range of each design parameter is put forward for a more effi cient and applicable calculation of thermo-mechanical responses of RCSBs. The proposed formulas are practical, convenient and accurate enough to be applied for engineering design.

Development and Validation of a Prognostic Nomogram Based on Clinical and CT Features for Adverse Outcome Prediction in Patients with COVID-19

Zheng Yingyan,Xiao Anling,Yu Xiangrong,Zhao Yajing,Lu Yiping,Li Xuanxuan,Mei Nan,She Dejun,Wang Dongdong,Geng Daoying,Yin Bo 대한영상의학회 2020 Korean Journal of Radiology Vol.21 No.8

Objective: The purpose of our study was to investigate the predictive abilities of clinical and computed tomography (CT) features for outcome prediction in patients with coronavirus disease (COVID-19). Materials and Methods: The clinical and CT data of 238 patients with laboratory-confirmed COVID-19 in our two hospitals were retrospectively analyzed. One hundred sixty-six patients (103 males; age 43.8 ± 12.3 years) were allocated in the training cohort and 72 patients (38 males; age 45.1 ± 15.8 years) from another independent hospital were assigned in the validation cohort. The primary composite endpoint was admission to an intensive care unit, use of mechanical ventilation, or death. Univariate and multivariate Cox proportional hazard analyses were performed to identify independent predictors. A nomogram was constructed based on the combination of clinical and CT features, and its prognostic performance was externally tested in the validation group. The predictive value of the combined model was compared with models built on the clinical and radiological attributes alone. Results: Overall, 35 infected patients (21.1%) in the training cohort and 10 patients (13.9%) in the validation cohort experienced adverse outcomes. Underlying comorbidity (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.67–6.71; p < 0.001), lymphocyte count (HR, 0.12; 95% CI, 0.04–0.38; p < 0.001) and crazy-paving sign (HR, 2.15; 95% CI, 1.03–4.48; p = 0.042) were the independent factors. The nomogram displayed a concordance index (C-index) of 0.82 (95% CI, 0.76–0.88), and its prognostic value was confirmed in the validation cohort with a C-index of 0.89 (95% CI, 0.82–0.96). The combined model provided the best performance over the clinical or radiological model (p < 0.050). Conclusion: Underlying comorbidity, lymphocyte count and crazy-paving sign were independent predictors of adverse outcomes. The prognostic nomogram based on the combination of clinical and CT features could be a useful tool for predicting adverse outcomes of patients with COVID-19.

In Vitro and In Vivo Anticancer Activity of Gimatecan against Hepatocellular Carcinoma

Zhao, Youna,Lau, Lit-Fui,Dai, Xiangrong,Li, Benjamin Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.11

Objective: Gimatecan is a new camptothecin (CPT) analogue that inhibits tumor growth by targeting DNA topoisomerase I (TOP I) and introducing strong and persistent DNA cleavage. Anti-tumor activity has been demonstrated with a wide range of solid tumors in previous preclinical and clinical studies. Here, we investigated for the first time the effects of gimatecan on the proliferation of hepatocellular carcinoma (HCC) cells both in vitro and in vivo. Methods: Anticancer efficacy of gimatecan were evaluated in a panel of HCC cell lines and corresponding mouse xenograft models. Inhibition of cell proliferation was measured by CellTiter-Glo cell viability assay. In vivo, gimatecan and control preparations were orally administered every four days, for a total of four times. Tumor volume and body weights of the mice were measured twice weekly. Results: In vitro cytotoxicity evaluation showed that gimatecan inhibited the proliferation of a large panel of HCC cell lines in a dose dependent manner, with IC50 values ranging between 12.1~1085.0 nM. In vivo evaluation in mouse xenograft models showed significant antitumor effects of gimatecan at 0.8mg/kg and 0.4mg/kg as compared to the control group. Conclusion: This study suggested that gimatecan may have the potential to be used as a chemotherapeutic agent for the treatment of HCC.

The Associations of Family Functioning, General Well-Being, and Exercise with Mental Health among End-Stage Renal Disease Patients

Qi Wang,Hongjian Liu,Zheng Ren,Wenjing Xiong,Minfu He,Nan Li,Xinwen Fan,Xia Guo,Xiangrong Li,Hong Shi,Shuang Zha,Xiumin Zhang 대한신경정신의학회 2020 PSYCHIATRY INVESTIGATION Vol.17 No.4

Objective This study aims to explore the relationships of family functioning, general well-being, and exercise with psychological distress. Furthermore, we investigated the special roles of general well-being and exercise on the association between family functioning and psychological distress. Methods Of 769 end-stage renal disease (ESRD) patients participated in the cross-sectional study which consisted of the 12-item General Health Questionnaire (GHQ-12), the Family APGAR Scales, and the General Well-Being Schedule. The collected data were analyzed using multiple linear regression analysis and path analysis. Results The prevalence of psychological distress was 72.3%. Family functioning, general well-being and exercise were associated factors of psychological distress (p<0.05). The indirect effect of family functioning on psychological distress was partially mediated by general well-being (Effect=-0.08, 95% CI=-0.11, -0.04). In addition, the effect of family functioning on general well-being was moderated by exercise (Index=-0.092, SE=0.033, 95% CI=-0.159, -0.029). Conclusion The prevalence of psychological distress among ESRD patients was high. Family functioning, general well-being and exercise were associated with psychological distress. Family functioning could affect psychological distress partially by affecting general wellbeing. Furthermore, exercise had a significant moderating effect on the relationship between family functioning and general well-being.