Research Progress in Toxicity and Toxicity-reducing and Efficacy-enhancing Compatibility of Radix Aconiti Lateralis Praeparata

Radix Aconiti Lateralis Praeparata contains alkaloids,flavonoids,polysaccharides,organic acids and organic alkalis,among which diester alkaloids are important effective ingredients,which can be used for treating heart failure,rheumatic heart disease,coronary heart disease,hypotension,shock and other diseases.However,it also contains the main ingredients that produce toxic effects and are highly toxic to the cardiovascular system,nervous system,digestive system,reproductive system,embryos,and livers and kidneys.In this study,we analyzed the toxicity-reducing and efficacy-enhancing effects of the compatibility of Radix Aconiti Lateralis Praeparata with with single herbs Glycyrrhiza uralensis Fisch.,Panax ginseng C.A.Meyer,Zingiber ojjicinale Rosc.and Rheum palmatum L.,aiming to provide references for further exploring the appropriate compatibility conditions of traditional Chinese medicine in the future and improving the safety of the clinical application of Radix Aconiti Lateralis Praeparata.

Toxicity of Multi-Walled Carbon Nanotubes,Graphene Oxide,and Reduced Graphene Oxide to Zebrafish Embryos

Objective This study was aimed to investigate the toxic effects of 3 nanomaterials, i.e. multi-walled carbon nanotubes （MWCNTs）, graphene oxide （GO）, and reduced graphene oxide （RGO）, on zebrafish embryos. Methods The 2-h post-fertilization （hpf） zebrafish embryos were exposed to MWCNTs, GO, and RGO at different concentrations （1, 5, 10, 50, 100 mg/L） for 96 h. Afterwards, the effects of the 3 nanomateria on spontaneous movement, heart rate, hatching rate, length of larvae, mortality, and malformations Is were evaluated. Results Statistical analysis indicated that RGO significantly inhibited the hatching of zebrafish embryos. Furthermore, RGO and MWCNTs decreased the length of the hatched larvae at 96 hpf. No obvious morphological malformation or mortality was observed in the zebrafish embryos after exposure to the three nanomaterials. Conclusion MWCNTs, GO, and RGO were all toxic to zebrafish embryos to influence embryos hatching and larvae length. Although no obvious morphological malformation and mortality were observed in exposed zebrafish embryos, further studies on the toxicity of the three nanomaterials are still needed.

Safety assessment of Chlorophytum alismifolium tuber extract (Liliaceae):Acute and sub-acute toxicity studies in Wistar rats

To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organization for Economic Co-operation and Development (OECD 425 and 407 guidelines respectively). In the acute toxicity experiment, a limit test (5000 mg/kg) was administered to five rats and monitored for 2 weeks. The sub-acute studies were conducted on 4 groups of rats. The first group served as control, while the 2nd, 3rd and 4th groups received MECA (150, 300 and 600 mg/kg respectively). The treatments were given orally and daily for 4 weeks. At the end of the experiment (29th day), the animals were euthanized to obtain blood samples and organs for haematological, biochemical and histological evaluations. Results: Acute toxicity study showed that the oral median lethal dose was >5000 mg/kg. In the sub-acute studies, the results showed no significant (P>0.05) changes in the haematological, hepatic and renal indices compared to control animals. In the fourth week, a significant (P<0.01) increase in body weight of the rats was observed at 150 mg/kg and 600 mg/kg compared to week one. However, there were no major changes in the organ/body weights of the rats. Histological examination of the kidney showed slight glomerular adhesion and tubular distortion. Moderate hepatic necrosis was observed at 150 mg/kg and 300 mg/kg. Conclusions: The results of this research revealed that the MECA tubers is virtually non-toxic after acute administration and it has low sub-acute toxicity potential in rats.

A Subchronic Toxicity Study on Lactobacillus Fermentum GM 090 in Rat

Lactobacillus fermentum （L. fermentum） is one of seven species in the genus Lactobacillus[1]. With a long history of safe use in fermented food production, Lactobacillus is considered as one of the most beneficial probiotics[23]. The most well-known potential health benefit is improving digestion and immune function[4.s]. Other beneficial functions of Lactobacillus strains include managing lactose intoleranceIs], lowering cholesterol and blood pressureIs], reducing inflammation[~], and prevention of cancerIs＇7]. L. fermentum is usually found during malt whisky fermentation]8]. L. fermentum CP34 was found to have the significant effect of decreasing the serum antigen-specific IgE levels compared to a control group[9].

Dynamics and Activity of Iron-Reducing Bacterial Populations in a West African Rice Paddy Soil under Subsurface Drainage: Case Study of Kamboinse in Burkina Faso

Iron toxicity is one of the main edaphic constraints that hamper rice production in West African savanna and forest lowlands. Although chemical reduction processes of various types of pedogenic iron oxides could not be underestimated, the bulk of these processes can be ascribed to the specific activity of Iron-Reducing Bacteria (IRB). The reducing conditions of waterlogged lowland soils boost iron toxicity through the reduction of almost all iron into ferrous form (Fe2+), which can cause disorder in rice plant and crop yield losses. Aiming to contribute at the improvement of rice yield in Africa, an experiment was developed to evaluate the impact of subsurface drainage on IRB dynamics and activity during rice cultivation. Twelve concrete microplots with a clay-loam soil and a rice variety susceptible to iron toxicity (FKR 19) were used for the experiment. Soil in microplots was drained for 7 days (P1), 14 days (P2), and 21 days (P3), respectively. Control (T) microplots without drainage were prepared similarly. The evolution of IRB populations and the content of ferrous iron in the paddy soil and in soil near rice root were monitored throughout the cultural cycle using MPN and colorimetric methods, respectively. Data obtained were analyzed in relation to drainage frequency, rice growth stage, and rice yield using the Student t test and XLSTAT 7.5.2 statistical software. From the results obtained, the subsurface drainage reduced significantly IRB populations (p = 0.024). However, the drainage did not affect significantly ferrous iron concentration in the soil near rice roots (p = 0.708). The concentration of ferrous iron (p < 0.0001) in soil near rice roots and the number of IRB (p < 0.0001) were significantly higher during the rice tillering and maturity stages. Although no significant difference was observed for rice yield among treatments (p = 0.209), the P2 subsurface drainage showed the highest yield and the lowest concentration of ferrous iron in soil near rice roots.

Dynamics and Activity of Sulfate-Reducing Bacterial Populations in Paddy Soil under Subsurface Drainage: Case Study of Kamboinse in Burkina Faso

Sulfide toxicity is a common disease generally associated with iron toxicity which occurs in rice fields when the Sulfate-Reducing Bacteria (SRB) produce sulfides ions in anaerobic conditions. The high quantity of sulfides ions in the soil solution upsets the mineral element balance in the rice, affects its growth and causes crop yield losses. In Burkina Faso, many rice field soils are abandoned due to sulfides toxicity. The present study was developed to evaluate the impact of subsurface drainage on SRB dynamics and activity during rice cultivation and the incidence on rice production. Twelve concrete microplots with a clay-loam soil and a rice variety susceptible to sulfides toxicity (FKR 19) were used for the experiment. Soil in microplots was drained for 7 days (P1), 14 days (P2), and 21 days (P3), respectively. Control (T) microplots without drainage were prepared similarly. The evolution of SRB populations and the content of sulfides ions in the paddy soil and in soil near rice roots were monitored throughout the cultural cycle using MPN and colorimetric methods, respectively. Data obtained were analyzed in relation to drainage frequency, rice growth stage, and rice yield using the Student’s t-test and XLSTAT 7.5.2 statistical software. From the results obtained, the subsurface drainage did not affect significantly SRB populations (P = 0.187). However, the drainage affected significantly sulfides concentration in the soil near rice roots (P = 0.032). The concentration of sulfides (P < 0.0001) in soil near rice roots and the number of SRB (P < 0.0001) were significantly higher during the rice tillering and maturity stages. Although no significant difference was observed for rice yield among treatments (P = 0.209), the P2 subsurface drainage showed the highest yield and a low concentration of sulfides in soil near rice roots.

Effect of Fertilization on the Dynamics and Activity of Iron-Reducing Bacterial Populations in a West African Rice Paddy Soil Planted with Two Rice Varieties: Case Study of Kou Valley in Burkina Faso

Iron toxicity is a major stress to rice caused by a high concentration of reduced iron, in the soil in many lowlands worldwide. To reduce iron toxicity in the West African lowlands, an investigation was performed at the site of the University of Ouagadougou, in pots containing an iron toxic soil from the Kou Valley (West of Burkina Faso). The experiment objective was to study the effect of mineral fertilizer on Iron Reducing Bacteria (IRB) dynamics and activity during rice cultivation, iron accumulation in rice plant and rice biomass yield under iron toxicity conditions. BOUAKE-189 and ROK-5 rice varieties, sensitive and tolerant to iron toxicity, respectively, were used for the experiment. The pots were amended with chemical fertilizers (NPK + Urea and NPK + Urea + Ca + Mg + Zn complex). Control pots without fertilization were prepared similarly. The kinetics of IRB and ferrous iron content in soil near rice roots were monitored throughout the cultural cycle using MPN and colorimetric methods, respectively. The total iron content was evaluated in rice plant using spectrometric method. Data obtained were analyzed in relation to fertilization mode, rice growth stage and rice yield using the student’s t-test and XLSTAT 2014 statistical software. The experiment revealed that NPK + Urea and NPK + Urea + Ca + Mg + Zn fertilization, decreased significantly (p < 0.0001) the number of IRB in the soil for BOUAKE-189 rice varieties. In most pots, highest IRB densities and ferrous iron content in soil were recorded from rice tillering and flowering to maturity stages, indicating that rice plants promoted microbial processes and iron reduction in soil. From the study, the NPK + Urea amendment decreased significantly ferrous iron content (p < 0.0001) in soil near BOUAKE-189 and ROK-5 rice varieties roots relatively to control pots. However, NPK + Urea + Ca + Zn + Mg amendment increased significantly ferrous iron content (p < 0.0001) in the soil near roots, Fe accumulation in plant biomass and rice yield for the two rice varieties.

Efficacy and toxicity of anlotinib plus camrelizumab versus anlotinib plus S-1 as second-line therapy for advanced esophageal squamous cell carcinoma:A real-world retrospective study

Background:No data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma(ESCC).Although anlotinib and the programmed death-1(PD1)inhibitor camrelizumab are used as treatments for ESCC,the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported.Therefore,this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC.Methods:Fifty-eight patients with advanced ESCC undergoing second-line therapy,either with anlotinib plus camrelizumab or anlotinib plus S-1,were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021.The primary endpoint was progression-free survival(PFS),with secondary endpoints including the objective response rate(ORR),disease control rate(DCR),and assessment of toxicity.Results:In patients with advanced ESCC,the anlotinib plus camrelizumab group(N=32)exhibited longer PFS(8.00 vs.4.53 months,P<0.001),higher ORR(28.1 vs.19.2%,P=0.431),and higher DCR(87.5 vs.65.4%,P=0.045)than those in the anlotinib plus S-1 group(N=26).Treatment-related adverse events(TRAEs)were predominantly grade 1/2 in both groups,with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab(P=0.033).Two patients(6.3%)developed grade 1/2 immune-related pneumonia.The incidence of grade 3/4 TRAEs did not differ significantly between the two groups.Multivariable Cox regression analysis identified that the drug regimen(P<0.001),Eastern Cooperative Oncology Group performance status(P=0.008),and differentiation grade(P=0.008)were independent prognostic factors for PFS.Conclusions:Anlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.

Cell Toxicity Effect of Cadmium on Yeast Cells by Detecting NADH Autofluorescence

The cytotoxic effect of cadmium is studied by detecting intracellular nicotinamide adenine dinucleotidea（NADH） autofluorescence in this work. NADH autofluorescence in processes of cadmium-induced apoptosis, necrosis and reversible injury are recorded timely. The relativity between time course of NADH autofluorescence and cadmium toxicity is established. The cell toxicity effect of Cadmium on yeast cells is studied by detecting the time courses of intracellular reduced NADH autofluorescence in this work. The relativity between time courses of NADH autofluorescence and Cadmium toxicity is established.

A stability-indicating LC–MS/MS method for zidovudine: Identification,characterization and toxicity prediction of two major acid degradation products

Zidvovudine(AZT) is a nucleoside analogue reverse transcriptase inhibitor(NRTI), a class of anti-retroviral drug. A stability-indicating assay method for AZT was developed in line with ICH guideline. Successful separation of AZT and its degradation products was achieved by gradient elution mode on reverse phase C_(18) column using 10 mM ammonium acetate: acetonitrile as the mobile phase at 0.8 mL/min flow rate, 25 μL injection volume, 30 °C column temperature and 285 nm detection wavelength. Two major acid degradation products were identified and characterized by liquid chromatography–electrospray ionization mass spectrometry(LC–ESI/MS/MS) and accurate mass measurements. The probable mechanisms for the formation of degradation products were identified based on a comparison of the fragmentation pattern of the [M + H]^+ions of AZT and its degradation products. One of the degradation products, DP-1, was isolated by semi-preparative high performance liquid chromatography(HPLC) using Waters XBridge Prep C_(18)(250 mm×10 mm, 5 μm).Degradation products showed higher toxicity compared to the drug in some models assessed by TOPKAT software. The method validation was performed with respect to robustness, specificity, linearity, precision and accuracy as per ICH guideline Q2(R1).

Reduced glutathione alleviates the toxic effect of 6-hydroxydopamine on bone marrow stromal cells

We studied the effect of reduced glutathione on bone marrow stromal cells （BMSCs） treated with 6-hydroxydopamine （6-OHDA）, which shows a toxic effect on dopaminergic neurons. The proliferation of BMSCs treated with 6-OHDA decreased, while that of BMSCs treated with reduced glutathione increased. The proliferation of BMSCs treated with both 6-OHDA and reduced glutathione was significantly higher compared with that treated with 6-OHDA alone. These findings indicate that reduced glutathione alleviates the toxic effect of 6-OHDA on BMSCs.

Mesh Force Modelling and Parametric Studies for Compound Oscillatory Roller Reducer

A compound oscillatory roller reducer(CORR)with a first-stage gear transmission and a second-stage oscillatory roller transmission is presented.The transmission principle of oscillatory roller transmission is introduced,and the tooth profile equation of the inner gear is derived.The analytical model of mesh force considering the installation errors and manufacturing errors is proposed.Then,parametric studies considering different errors on the mesh force are conducted.Results show that the design parameters are significant factors for mesh force.The mesh force is reduced by 17%as the eccentricity of disk cam increases from 2.5 mm to 4 mm.When the radius of the movable roller increases from 7 mm to 20 mm,the mesh force decreases by 8%.As the radius of disk cam increases from 125 mm to 170 mm,the mesh force is decreased by 26.5%.For the impacts of errors,the mesh force has a noticeable fluctuation when these errors exist including the manufacturing error of disk cam,the installation error of disk cam and the manufacturing error of movable roller change.The prototype of the reducer is manufactured and preliminary run-in test proved the feasibility of the transmission principle.

MOSSBAUER STUDY ON REDUCIBILITY OF SUPPORTED Eu_2O_3

The reduction process of Eu2O3 on TiO2 and other supports is investigated in detail by Mossbauer spectroscopy. The reducibility of Eu2O3 is greatly enhanced when it is supported on a surface of support. This is due to the solid-solid interaction between the oxide and the support.

Drag-reducing characteristics of cationic surfactant solution flow in copper pipe

The drag-reducing characteristics of a cationic surfactant solution flow in copper pipe have been investigated experimentally.The tested drag-reducing fluid was an aqueous solution of the cationic surfactant cetyltrimethyl ammonium chloride(CTAC).The experimental results show that the maximum drag reduction percentage reduces with the increase of fluid temperature at low concentration of CTAC,such as 100×10-6 or 150×10-6.Furthermore,the concentration and temperature changes of CTAC solution have significant influences on the drag-reducing ability.The drag-reducing effect of CTAC additives shows great potentials in the application in a district heating/cooling(DHC)system,especially for the radiant floor heating(RFH)system.

基于FAERS数据库的周期蛋白依赖性激酶4/6抑制剂血液毒性真实世界研究

目的 基于美国美国食品药品管理局(FDA)的不良事件报告系统(FAERS)分析3种周期蛋白依赖性激酶4/6(CDK4/6)抑制剂上市后的不良事件(AEs)信号,为临床用药安全提供参考。方法 提取FAERS数据库2015年第一季度至2022年第一季度共29个季度AEs,利用报告比值比法(ROR)和比例报告比值法(PRR)对CDK4/6抑制剂AEs进行数据挖掘。结果 CDK4/6抑制剂相关性血液毒性报告共有7 872份,各抑制剂血液毒性AEs占总AEs比例依次为哌柏西利(80.31%)>瑞博西利(15.36%)>阿贝西利(4.33%)。血液毒性常见中性粒细胞减少和贫血。哌柏西利(2 982/6 322,47.17%)和瑞博西利(613/1 209,50.70%)致中性粒细胞减少的报告占比较阿贝西利(117/341,34.31%)更高,血液毒性主要发生在药物开始使用后60 d内(1 630,61.86%),哌柏西利中位时间最长,且用药90 d后仍有32.9%的患者存在血液毒性,不同CDK4/6抑制剂血液毒性临床表现及发生强度存在差异。结论 哌柏西利、阿贝西利、瑞博西利均会导致明显的血液毒性,其中阿贝西利致血液毒性报告最少,但要警惕阿贝西利致贫血后导致死亡的风险。用药后的2个月内密切监测全血细胞计数,关注中性粒细胞、血红蛋白等水平,警惕CDK4/6抑制剂相关血液AEs的发生。

心脏收缩力调节器用于心力衰竭的机制和临床研究

心脏收缩力调节器(CCM)作为救治慢性射血分数降低的心力衰竭(HFrEF)的新型植入性电子治疗装置,因可增强心室肌收缩力、改善患者症状体征和心功能指标甚至远期预后,已迅速成为心血管领域倍受关注的热点。本文综述了CCM治疗HFrEF的机制和临床研究,并根据其机制和信号传递算法对其在射血分数保留的心力衰竭(HFpEF)、心脏再同步化治疗(CRT)反应不佳、合并心房颤动的HFrEF患者中的疗效进一步分析和展望,以期推动CCM可以满足更多、不同临床情况的心力衰竭患者的需求。

MOSSBAUER STUDY ON REDUCIBILITY OF SUPPORTED Eu2O3

The reduction process of Eu2O3 on TiO2 and other supports is investigated in detail by Mossbauer spectroscopy. The reducibility of Eu2O3 is greatly enhanced when it is supported on a surface of support. This is due to the solid-solid interaction between the oxide and the support.

马钱子减毒增效途径及机制研究进展

本文综述马钱子减毒增效的主要途径及其减毒增效的机制研究进展。马钱子减毒增效的主要途径包括炮制、配伍、新剂型与制剂新技术等;减毒增效的机制主要包括生物碱成分含量发生变化、生物碱药代动力学行为改变、影响CYP450酶的mRNA表达和酶活性、诱导血脑屏障上P-糖蛋白外向转运加速生物碱外排、缓释及靶向控制药物浓度梯度等。关于马钱子减毒增效的途径研究较多,但对其减毒增效的机制和原理研究较少且不甚深入,建议后续研究从毒性物质基础、体内暴露和体内过程、分子机制、量-时-毒-效关联性及转化规律等方面对马钱子减毒增效的机制进行深入研究。

青年脑肿瘤病人配偶照顾者经济毒性与照顾负担动态变化的纵向研究

目的:探讨青年脑肿瘤病人配偶照顾者在病人术后半年内经济毒性及照顾负担的动态变化,并分析二者间的相互预测关系。方法:基于便利抽样法,在病人术后14 d、3个月、6个月时采用一般情况调查表、患者报告结局的经济毒性综合评分量表修订版、照顾者负担量表对216名青年脑肿瘤配偶照顾者开展随访调查。结果:术后6个月内,配偶照顾者照顾负担呈下降趋势(P<0.01),经济毒性呈先上升后平稳趋势(P<0.05)。交叉滞后模型显示,术后14 d的经济毒性对术后3个月照顾负担有影响(P<0.01),术后3个月的经济毒性对术后6个月的照顾负担有影响(P<0.01)。结论:青年脑肿瘤病人配偶照顾者经济毒性及照顾负担在病人术后半年内呈动态变化,经济毒性能够影响随后的照顾负担。医护人员应重视青年脑肿瘤配偶照顾者的经济毒性水平,及时实施心理疏导,降低经济毒性对配偶照顾者的心理困扰,以减轻其照顾负担。