The Maximum Tolerance Dose of Shenqi Wuweizi Tablet in Mice

Shenqi Wuweizi tablet is a Chinese medicine preparation mainly composed of Codonopsis pilosula, Astragalus membranaceus, Kadsura longipedunculata and Ziziphus jujube with many curative effects. The maximum tolerance dose of Shenqi Wuweizi tablet in mice was studied, and its acute toxicity in mice was ex- plored. The results showed that Shenqi Wuweizi tablet did not cause the death of mice at the maximum dosage and mice did not show toxic reaction, so it could be used in livestock production and clinical veterinary treatment. The study provided a theoretical basis for application of Shenqi Wuweizi tablet in livestock production and clinical veterinary medication safety.

Stepwise Method Based on Confidence Bound and Information Incorporation for Identifying the Maximum Tolerable Dose

The primary goal of a phase I clinical trial is to find the maximum tolerable dose of a treatment. In this paper, we propose a new stepwise method based on confidence bound and information incorporation to determine the maximum tolerable dose among given dose levels. On the one hand, in order to avoid severe even fatal toxicity to occur and reduce the experimental subjects, the new method is executed from the lowest dose level, and then goes on in a stepwise fashion. On the other hand, in order to improve the accuracy of the recommendation, the final recommendation of the maximum tolerable dose is accomplished through the information incorporation of an additional experimental cohort at the same dose level. Furthermore, empirical simulation results show that the new method has some real advantages in comparison with the modified continual reassessment method.

Review on Hydroxyurea Usage in Young Children with Sickle Cell Disease: Examining Hemoglobin Induction, Potential Benefits, Responses, Safety, and Effectiveness

Sickle cell disease (SCD) is a prevalent condition, particularly in the countries of sub-Saharan Africa, where the presence of specific genes associated with Malaria contributes to its high prevalence. Patients with sickle cell disease frequently experience painful episodes necessitating hospitalization, and their hemoglobin levels are typically lower than those of the general population. There are different treatment options available to manage complications, such as transfusing blood, hydroxyurea, and strong anti-pains. However, with all these treatments, patients still commonly experience pain crises and suffer from organ damage. Hydroxyurea, the sole approved medication for sickle cell anemia in developed and developing countries, is widely used in children despite being primarily indicated for adults. Multiple studies have demonstrated the efficacy of hydroxyurea in inducing HbF production in young children with SCD. Elevated HbF levels have been associated with improved clinical outcomes, including a reduction in vaso-occlusive crises, acute chest syndrome, and the need for blood transfusions. Furthermore, increased HbF levels have been shown to ameliorate disease-related organ damage, such as pulmonary hypertension and sickle cell retinopathy. The response to hydroxyurea treatment in young children with SCD is variable. Some patients achieve substantial increases in HbF levels and experience significant clinical benefits, while others may have a more modest response. Factors influencing the response include baseline HbF levels, genetic modifiers, treatment adherence, and dose optimization. Safety is a crucial consideration when using hydroxyurea in young children. Studies have shown that hydroxyurea is generally well-tolerated, with the most common adverse effects being myelosuppression, gastrointestinal symptoms, and dermatological manifestations. However,long-term effects and potential risks, such as renal dysfunction and reproductive impacts, require further investigation. The effectiveness of hydroxyurea in young children with SCD has been demonstrated in various clinical trials and observational studies. These studies have shown a significant reduction in disease-related complications and improved quality of life. However, optimal dosing, treatment duration, and long-term outcomes are still areas of ongoing research. This review focuses on recent studies investigating the benefits, effectiveness, responses, and safety of hydroxyurea in pediatric individuals diagnosed with sickle cell disease.

蜂蜜中苦参碱和氧化苦参碱的膳食摄入风险评估

目的明确我国各地蜂蜜中苦参碱和氧化苦参碱含量情况,对其膳食摄入风险进行评估,并对其最大残留限量(maximum residue limit,MRL)进行推算。方法对苦参碱和氧化苦参碱作为中药成分的现有毒理学数据和临床试验数据进行统计分析,结合现有蜂蜜中苦参碱和氧化苦参碱含量水平、分布特征等数据,根据每日允许摄入量(acceptable daily intake,ADI)、急性参考剂量(acute reference dose,ARfD)、人均体重和蜂蜜消费量进行苦参碱和氧化苦参碱短期、长期膳食摄入风险评估。根据评估方法,推算蜂蜜中苦参碱和氧化苦参碱的MRL。结果苦参碱和氧化苦参碱的短期风险熵数(short-term risk quotient,RQa)分别为0.03200%和0.18115%,长期风险熵数(long-termriskquotient,RQc)分别为0.00019%和0.00133%,均远小于100%;当RQc=100%时,推算苦参碱和氧化苦参碱的MRL均为157.5 mg/kg。结论中国蜂蜜中苦参碱和氧化苦参碱的膳食暴露人体健康风险非常低,完全可接受。推算出蜂蜜中苦参碱和氧化苦参碱的MRL要远高于欧盟的限量要求,为打破我国蜂蜜出口贸易壁垒提供了数据支持。

耳机和个人音乐播放器声安全标准解析

阐述了耳机和个人音乐播放器声安全给听力健康带来的风险问题,并介绍了新版安全标准新增的耳机和个人音乐播放器声安全部分的主要内容和技术背景。通过对声安全和声剂量测试的方法与限值要求等内容进行详细说明,分析新标准经过半年实际使用后的实施情况,旨在使行业内尽快了解并掌握新标准,从而推动新标准顺利实施。

A Phase Ⅰ trial of dose escalation of topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer

Objective The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer.

Pesticide food safety standards as companions to tolerances and maximum residue limits

Allowable levels for pesticide residues in foods, known as tolerances in the US and as maximum residue limits （MRLs） in much of the world, are widely yet inappropriately perceived as levels of safety concern. A novel approach to develop scientifically defensible levels of safety concern is presented and an example to determine acute and chronic pesticide food safety standard （PFSS） levels for the fungicide captan on strawberries is provided. Using this approach, the chronic PFSS level for captan on strawberries was determined to be 2 000 mg kg-1 and the acute PFSS level was determined to be 250 mg kg-1. Both levels are far above the existing tolerance and MRLs that commonly range from 3 to 20 mg kg-~, and provide evidence that captan residues detected at levels greater than the tolerance or MRLs are not of acute or chronic health concern even though they represent violative residues. The benefits of developing the PFSS approach to serve as a companion to existing tolerances/MRLs include a greater understanding concerning the health significance, if any, from exposure to violative pesticide residues. In addition, the PFSS approach can be universally applied to all potential pesticide residues on all food commodities, can be modified by specific jurisdictions to take into account differences in food consumption practices, and can help prioritize food residue monitoring by identifying the pesticide/commodity combinations of the greatest potential food safety concern and guiding development of field level analytical methods to detect pesticide residues on prioritized pesticide/commodity combinations.

Clinical Outcome of Low Dose Contrast during Percutaneous Coronary Intervention in Patients with Moderate to Severe Kidney Impairment

Background: Chronic kidney disease patients are at a greater risk for nephropathy requiring dialysis after percutaneous coronary intervention. Such patients are usually deferred due to fear of “Renalism”.?Objectives This study assesses the outcome of Low dose contrast protocol during PCI in CKD patients whose e-GFR 60 ml/min/1.72 m and investigates a safety margin for contrast use in these high-risk categories.?Methods: Patients were into three groups according to CV/e-GFR ratio: Group (A) low-dose: CV/e-GFR ratio 2.0 Group (B) medium-dose: CV/e-GFR ratio > 2.0 and × bodyweight\s.creatinine). Group (C) high-dose: CV/e-GFR ratio > MACD. Results: A total of 73 patients were enrolled. Average age was 54 ± 8 years,81.4% were male and 18.6% were females and 52% were diabetic. Mean baseline e-GFR was 40 ± 8.0 ml/min/1.73m2. Contrast Volume used in group A was (58.26 ± 15.05) (n = 24), in group B (109.42 ± 17.11) (n = 26) and in group C (304.5 ± 60.30) (n = 23), respectively. The incidences of CI-AKI in the 3 groups were 0%, 11.5% and 35%, respectively (p = 0.02). All-cause death 0%, 17% and introduction of maintenance hemo dialysis was 0%, 11.5% and 26%, respectively (p Conclusion: Low dose contrast protocol is safe, effective and easily applicable technique without CI-AKI or death.

Processing of Landsat 8 Imagery and Ground Gamma-Ray Spectrometry for Geologic Mapping and Dose-Rate Assessment, Wadi Diit along the Red Sea Coast, Egypt

Maximum Likelihood (MLH) supervised classification of atmospherically corrected Landsat 8 imagery was applied successfully for delineating main geologic units with a good accuracy (about 90%) according to reliable ground truth areas, which reflected the ability of remote sensing data in mapping poorly-accessed and remote regions such as playa (Sabkha) environs, subdued topography and sand dunes. Ground gamma-ray spectrometric survey was to delineate radioactive anomalies within Quaternary sediments at Wadi Diit. The mean absorbed dose rate (D), annual effective dose equivalent (AEDE) and external hazard index (Hex) were found to be within the average worldwide ranges. Therefore, Wadi Diit environment is said to be radiological hazard safe except at the black-sand lens whose absorbed dose rate of 100.77 nGy/h exceeds the world average. So, the inhabitants will receive a relatively high radioactive dose generated mainly by monazite and zircon minerals from black-sand lens.

电子束辐照处理葡萄干的最高耐受剂量的确定

为评估辐照对葡萄干食用品质的影响,本试验选用有辐照杀虫和杀菌市场应用需求的红、绿葡萄干作为材料,利用0、2、3、4、5和6 kGy吸收剂量的电子束进行辐照处理,采用国家标准方法或常规方法测定处理样品的理化指标和感官指标。结果表明,6 kGy以下吸收剂量的电子束辐照对红、绿葡萄干的总糖、总酸和Vc含量等理化指标,以及外观、口感和风味等感官指标的影响不显著;对红、绿葡萄干的色泽均有显著影响,因此色泽是决定最高耐受剂量的重要指标。电子眼的感官分析结果表明,随着吸收剂量的增加,红葡萄干的L^(*)、a^(*)和b^(*)值均明显增加,绿葡萄干的L^(*)、a^(*)值也明显增加,但对其b^(*)值影响不大,这与感官分析结果一致,即辐照后葡萄干颜色变浅,绿葡萄干变黄、红葡萄干变红。室温贮藏30和60 d后,各辐照组葡萄干色泽与对照组色泽逐渐趋于一致,表明辐照仅加速了葡萄干的颜色变化。在色泽指标变化的基础上,综合理化指标、外观、口感和风味的变化情况,得出两种葡萄干的最高耐受吸收剂量均为4 kGy。本研究结果为建立科学的辐照工艺确定葡萄干最高耐受吸收剂量提供了方法和依据。

电子束辐照对新疆干果品质的影响及其最高耐受剂量的确定

目的 探究电子束辐照对4种新疆干果品质的影响,确定干果辐照工艺的最高耐受剂量。方法 采用0、2、4、6、8和10 kGy不同剂量电子束处理枸杞干、红枣干、无花果干、小白杏干,研究不同辐照剂量对水分、维生素C、总酸、总糖4种理化指标及色度、外观、风味、色泽和口感等5种感官品质的影响。结果 仅8 kGy辐照处理对枸杞干口感指标有不良影响,其他3种干果的感官指标几乎不受辐照处理的影响;10 kGy以内的辐照处理对红枣干的品质无不良影响;无花果干的总酸含量在辐照剂量>6kGy时有所上升,维生素C含量在10 kGy处理时显著低于对照;辐照剂量≥6 kGy时,小白杏干维生素C含量显著降低。结论 通过对电子束辐照新疆干果的品质影响及最高耐受辐照剂量的研究,确定枸杞干、红枣干、无花果干和小白杏干的最高耐受剂量分别是8、10、6和6 kGy。为电子束辐照在新疆干果灭菌工艺中的应用提供了理论基础。

红白蓝参活力饮活性成分的提取工艺及急性毒性研究

旨在确定红白蓝参活力饮中多糖和黄酮的最佳提取工艺以及评价活力饮提取物的安全性。本试验采用正交法对红白蓝参活力饮有效成分提取工艺进行优化,通过观察和测定小鼠灌胃水提液7 d时其精神状态、死亡情况、小鼠体重和脏器系数的变化判断其安全性。结果显示,影响红白蓝参活力饮提取效果的因素依次是提取次数、提取时间、液药质量比,其最佳提取工艺为提取2次,每次60 min,液药质量比20∶1;安全性试验表明小鼠给药后7 d时精神状态良好,对小鼠的死亡率、体重、脏器系数均无显著影响(P>0.05)。研究表明,红白蓝参活力饮的提取工艺可行且提取物安全性高,为红白蓝参活力饮的开发奠定了基础。

脯氨酸丹参素冰片酯对小鼠急性毒性研究

目的探究抗高血压1类新药脯氨酸丹参素冰片酯的急性毒性,评价其安全性。方法24只小鼠,雌雄各半,随机分为溶剂对照组和给药组,根据脯氨酸丹参素冰片酯溶液的最大浓度(150 mg·mL^(-1)),单次灌胃,连续观察7 d,记录小鼠毒性反应、体重及饮食饮水量,7 d后小鼠处死,观察主要脏器变化,测定心、肝、肾、肺脏等主要脏器指数,HE染色观察脏器病理性改变。结果实验过程中,脯氨酸丹参素冰片酯给药后小鼠均未出现死亡。与溶剂对照组相比,脯氨酸丹参素冰片酯给药后7 d内,小鼠活动、体重、饮食饮水量均无显著性差异。给药组肝、肾、肺脏指数与对照组相比无显著差异(P>0.05)。与溶剂对照组小鼠相比,雄性小鼠给药组心脏指数无显著差异(P>0.05),而雌性小鼠给药组的心脏指数具有显著降低(P<0.05),且心肌细胞排列紊乱。结论测得脯氨酸丹参素冰片酯对小鼠灌胃的最大耐受量为3000 mg·kg^(-1)。脯氨酸丹参素冰片酯毒性小,安全性较好。

南鹤虱水提物急性毒性实验初探

目的:通过南鹤虱水提液对小鼠的急性毒性实验,初步评价其安全性,以期为临床合理、安全使用南鹤虱提供依据。方法:取20只SPF级ICR小鼠,随机分为两组(空白对照组和给药组),给药组以最大给药量灌胃南鹤虱水提物浓缩液,连续灌胃两次(隔8 h灌胃1次),空白对照组灌胃等量纯水,观察并记录14 d内小鼠毒性反应症状、体重、摄食量及死亡情况。观察期结束后,观察解剖后小鼠的主要脏器病变情况,并计算脏器指数。结果:预实验中小鼠全部存活,因此无法测出LD_(50)。最大给药量实验中,小鼠均未产生明显的毒性症状,其体质量与对照组小鼠体重比较差异无统计学意义(P>0.05)。小鼠单次灌胃南鹤虱水提物最大给药量120 g生药/kg,相当于60 kg成人临床推荐剂量的1600倍。结论:南鹤虱水提物无明显毒性,在规定剂量下用药是安全可靠的。

露天矿山爆破振动危害与防治措施探讨

露天矿山爆破作业中炸药爆炸产生的地震波会给开采环境和周边人员、事物造成不同程度的影响。鉴于此,从爆破技术与安全管理的角度出发,针对爆破作业有害效应中的爆破振动,阐述爆破振动产生的基本原理,分析其产生的原因和规律,并结合矿山爆破实践经验,提出相应的技术措施。

鸭嘴花碱经口单次给药安全性评价研究

目的:通过研究鸭嘴花碱急性毒性,评价鸭嘴花碱的安全性。方法:将120只昆明种小鼠,雌雄各半,随机均等分为6组,每组20只。按40 mL·kg^(-1)小鼠灌胃体积给予相应剂量的药物,密切观察4 h,记录小鼠毒性反应与死亡率。连续观察14天,记录小鼠一般状态,解剖观察脏器并计算脏器指数,对存活小鼠肝脏、肾脏进行HE染色和生化指标检测。结果:小鼠对鸭嘴花碱最大耐受量(MTD)为153.6mg·kg^(-1)。观察14天后,与空白组比较,小鼠一般状态、脏器指数无明显变化;病理结果显示无肝肾毒性;血浆中ALT、Cre无显著变化,AST、BUN含量有下降趋势。结论:小鼠对鸭嘴花碱的MTD为153.6mg·kg^(-1),该剂量下对小鼠安全性高。

复方参及合剂对小鼠急性毒性实验研究

目的:研究复方参及合剂对小鼠急性毒性作用,评价其安全性。方法:根据“君臣佐使”原则,将复方参及合剂按不同比例配制成低剂量(1.0 g/kg)、中剂量(2.0 g/kg)、高剂量(3.0 g/kg),采用经典急性毒性实验方法,灌胃给药对小鼠进行急性毒性研究。结果:小鼠均未表现出任何毒性反应,且均无实验动物死亡,解剖后观察各脏器组织均无明显变化。未测出半数致死量(LD50),小鼠最大给药量(MLD)为9.0 g/kg,相当于临床成人拟推荐日剂量0.3 g/70 kg的2100倍。与正常对照组相比,复方参及合剂不同剂量组小鼠体质量无统计学意义(P>0.05),血常规指标、血液生化指标和脏器组织HE染色病理学检查均无显著性差异(P>0.05)。结论:复方参及合剂无急性毒性作用,该组方安全可靠。

煤矿井下探伤装置人员误入剂量估算模型研究

在评审核技术利用项目环评文件中发现,Ⅱ类射线装置的辐射风险预测及风险管理存在诸多内容缺失或错误,无法定量描述在人员误入情况下的受照剂量,难以采取正确的应对措施。以Ⅱ类射线装置在煤矿井下作业环境中的应用为例,基于辐射防护基本理论,构建了一种快速剂量估算的物理和数学模型,目的是准确评估潜在的人员误入辐射风险。通过案例分析,量化了人员受辐射剂量与其移动速度和距离之间的数理关系,同时证明散射线是该环境中主要的辐射源。该研究提出的模型不仅适用于煤矿井下或地面类似的工作环境,也可用于评估其他密封源作为辐射源项的Ⅱ类射线装置。

常见污水消毒工艺设计探讨

常见的污水消毒工艺包括紫外线消毒和接触消毒两类,一般根据用地多少和是否再生利用进行选择。污水性质、排放标准和再生利用的要求决定消毒处理的程度,进而决定紫外线消毒的有效剂量和消毒剂残留浓度、接触时间。紫外线消毒灯管老化系数默认为0.5,套管结垢系数默认为0.6;采用固定堰控制渠道水位时,应防止最大时流量对应的堰上水头超出最上层灯管的有效杀菌范围。出水SS低可适当降低消毒药剂量;对于采用稳定性较差的次氯酸钠,北方或进水偏碱性的污水厂应严格执行30 min有效接触时间,消毒设施设计水量对应最大时流量。

Fe_3O_4及Fe_3O_4-Glu纳米颗粒的毒性和致突变性研究

[目的]研究直径约15nm的四氧化三铁纳米颗粒(nano_Fe3O4)、谷氨酸包覆的四氧化三铁纳米颗粒(nano_Fe3O4_Glu)的毒性及致突变性。[方法]①单次给药实验 :在以往急性毒性实验的基础上 ,对昆明种小鼠口服一次给药 ,分别得到nano_Fe3O4、nano_Fe3O4_Glu的最大耐受量。②小鼠骨髓细胞微核试验 :nano_Fe3O4 及nano_Fe3O4_Glu分别设150mg/kg、300mg/kg和600mg/kg 各三个剂量组 ,另设阴性对照组和环磷酰胺组 ,分别计算其微核率。③小鼠精子畸形试验 :两种受试物分别设150mg/kg、300mg/kg、600mg/kg三个剂量组及阴性对照组和环磷酰胺组 ,连续5d染毒 ,染毒后第35d处死 ,分别计算其精子畸形率。④体外CHL细胞染色体畸变试验 :nano_Fe3O4 设1.05μg/ml、2.10μg/ml、4.20μg/ml三个剂量组 ,nano_Fe3O4_Glu设30μg/ml、60μg/ml、120μg/ml三个剂量组 ,另设阴性、阳性对照组和空白对照组。在加S9mix和不加S9mix时 ,分别计算细胞染色体畸变率。[结果]两种受试物的小鼠经口染毒最大耐受量均大于600mg/kg ;小鼠骨髓细胞微核试验中两种受试物的微核率均低于2‰ ;小鼠精子畸形试验中 ,nano_Fe3O4 各剂量组小鼠精子畸形率均高于3.8% ,与阴性对照组比较有统计学差异 (P<0.01) ;体外CHL细胞染色体畸变试验中 ,在加与不加体外?