基于生物活性与效应基准的中药质量 评价技术发展现状与展望

中药质量的评控问题是制约中药现代化发展的瓶颈,因此有必要在现有检测方法的基础上结合生物评价,继而更为全面地保证中药质量。生物评价是完善中药质量标准、保证临床功效和安全性评价的重要方法,已成为中药质量标准化发展趋势之一。在此处主要论述了近年来基于生物活性与效应基准的中药质量评价技术和已取得的部分研究进展,同时对目前中药质量生物评价研究与应用中存在的主要问题进行探讨,进一步对其未来应用做出展望,从而更好的对中药质量进行控制。     

基于熵权法评价干燥方法对经典名方华盖散基准样品质量属性的影响

目的 优选经典名方华盖散基准样品的干燥方法。方法 采用真空干燥、真空带式干燥、喷雾干燥、冷冻干燥方法制备华盖散基准样品,应用扫描电子显微镜、差式扫描量热分析、HPLC等方法测定基准样品的质量属性,以得粉率、玻璃化转变温度及成分含量转移率等为评价指标,运用熵权法对各指标赋予权重进行综合评价。结果 喷雾干燥基准样品粒子呈类球形、粒径最小,冷冻干燥基准样品不规则、蓬松、溶化性好。指标成分盐酸麻黄总碱、苦杏仁苷、橙皮苷、甘草苷、甘草酸转移率分别为85.66%～104.78%、90.81%～104.16%、91.42%～94.86%、83.98%～94.69%、87.85%～94.45%,指纹图谱相似度均大于0.9。结论 经综合评价得出冷冻干燥方法最佳,3批验证工艺重复性、可行性较好,为经典名方基准样品质量属性研究提供了理论依据和实践价值。     

经典名方甘草泻心汤基准样品的量值传递研究

目的 建立经典名方甘草泻心汤（Gancao Xiexin Decoction,GXD）基准样品的HPLC图谱及指标性成分含量测定方法,研究GXD基准样品量值传递规律。方法 制备15批GXD基准样品,建立特征图谱并选用《中药色谱指纹图谱相似度评价》软件进行相似度评价,明确特征峰并对其进行归属。测定指标性成分甘草苷、甘草酸、黄芩苷、盐酸小檗碱、表小檗碱、黄连碱、巴马汀的含量,计算指标成分转移率,分析指标成分在饮片-基准样品中量值传递的规律。结果 15批GXD基准样品指纹图谱相似度均大于0.90,共指认22个共有峰,甘草5个、黄芩5个、甘草和黄芩共有3个、黄连6个、黄芩和黄连共有2个、干姜1个;各指标成分从药材-饮片平均转移率分别为98.69%、98.13%、96.94%、94.59%、91.76%、88.08%、94.16%;饮片-基准样品平均转移率为49.08%、42.24%、28.34%、26.72%、29.32%、33.62%、47.93%。结论 特征图谱与多指标成分含量测定方法相结合,对GXD药材-饮片-基准样品的量值传递过程进行分析研究,为经典名方GXD制剂开发提供参考。     

Clinical Benchmark for Gastric Stapling Procedures

To help answer the call to cut costs of surgical care, hospitals and physicians have joined to compare methods of care for the more common Diagnosis Related Group (DRG) diagnoses to form a Benchmark. Since many bariatric surgeons are the only ones performing this surgery in their primary hospitals, they do not have two or more surgical routines for comparison. This presentation compares data for the preoperative work-up, operating-room, and methods of postoperative care used by 29 members of the American Society for Bariatric Surgery (ASBS). There was representation of both academic and private surgeons and hospitals. To target areas for possible savings, the hospital bills of 16 patients without complication were compared. The synthesis of this information revealed significant differences in the extent and cost of preoperative work-up, antibiotic coverage, other postoperative care, and length of stay. These differences are examined under the assumption that patient outcome was the same.     

Preliminary Risk assessment for Acrylamide and Peripheral Neuropathy

Acrylamide (ACM) is a high-volume industrial chemical with diverse uses in manufacturing, construction and laboratory research. ACM is a well-established neurotoxic agent causing peripheral neuropathy with impairment in the arms and legs of exposed workers, most thoroughly studied in Swedish tunnel workers exposed to ACM grouting. A quantitative risk assessment was performed to assess ACM risk to workers. Using data from a published paper investigating peripheral neuropathies in Chinese chemical workers, estimates of exposure response for vibration perception threshold and nerve conduction velocities were calculated, based on hemoglobin adducts and air concentrations as exposure metrics. The benchmark dose procedure was applied in order to calculate excess risks of impairment, defined as adverse performance exceeding the 95^th percentile in unexposed populations, at various concentrations of airborne ACM exposure. Under the assumptions in this risk assessment, after three years of inhalation exposure at 0.3 mg/m³, the excess attributable impairment manifest in vibration perception and nerve conduction velocity is estimated to occur in 1-2% of workers. For 10 years at 0.3 mg/m³ ACM inhalation (equivalent to 3 years at 1.0 mg/m³) the excess prevalence of impairment would be 2-14% of workers, assuming the effect continues to accrue linearly in time. Using published data, the risks of impairment from peripheral neuropathy attributable to exclusively airborne ACM exposure can be predicted for exposure periods less than 10 years. The risks associated with dermal and airborne ACM exposures can be estimated by characterizing working process environments using ACM Hb-adduct levels and possibly monitored with urinary biomarkers.     

Comparative hazard identification of nano- and micro-sized cerium oxide particles based on 28-day inhalation studies in rats

There are many uncertainties regarding the hazard of nanosized particles compared to the bulk material of the parent chemical. Here, the authors assess the comparative hazard of two nanoscale (NM-211 and NM-212) and one microscale (NM-213) cerium oxide materials in 28-day inhalation toxicity studies in rats (according to Organisation for Economic Co-operation and Development technical guidelines). All three materials gave rise to a dose-dependent pulmonary inflammation and lung cell damage but without gross pathological changes immediately after exposure. Following NM-211 and NM-212 exposure, epithelial cell injury was observed in the recovery groups. There was no evidence of systemic inflammation or other haematological changes following exposure of any of the three particle types. The comparative hazard was quantified by application of the benchmark concentration approach. The relative toxicity was explored in terms of three exposure metrics. When exposure levels were expressed as mass concentration, nanosized NM-211 was the most potent material, whereas when expression levels were based on surface area concentration, micro-sized NM-213 material induced the greatest extent of pulmonary inflammation/damage. Particles were equipotent based on particle number concentrations. In conclusion, similar pulmonary toxicity profiles including inflammation are observed for all three materials with little quantitative differences. Systemic effects were virtually absent. There is little evidence for a dominant predicting exposure metric for the observed effects.     

基于信息化血糖监测系统建立血糖基准报告研究

背景　随着糖尿病患病率的增高，住院患者血糖管理已成为医院关注的焦点，但目前尚缺乏公认的绩效指标定义、指标测算和标准化血糖基准报告，影响了医院血糖管理持续质量改进。目的　基于信息化血糖监测系统（IGMS）构建血糖基准报告，一为同行建立标准化血糖报告提供方法学指导，二为同行提供血糖基准参考。方法　纳入2019年10月至2020年3月遂宁市中心医院安装了IGMS（该系统能自动上传血糖数据和按需求查阅血糖数据）的非重症监护病区（10个内科和7个外科）的糖尿病患者或高血糖患者（无糖尿病病史但随机末梢血糖超过11.1 mmol/L），排除住院第1天的血糖数据。采用群体（population）、患者（patient）和患者日（patient-day）三种模型报告理想血糖、高血糖和低血糖发生率，低血糖报告增加患者低血糖发生天数比、发生频次比和管理及时性比，采用四分位数分析不同病区的血糖数据，并与美国、澳大利亚、重庆和广东医疗机构的血糖数据进行比较。结果　三种模型平均血糖、理想血糖、平均高血糖和任意高血糖（>10.0 mmol/L、≥15.0 mmol/L、≥16.7 mmol/L）、任意低血糖（≤3.9 mmol/L、<3.0 mmol/L、<2.8 mmol/L、<2.2 mmol/L）比较，差异均有统计学意义（P<0.001）。17个病区任意低血糖≤3.9 mmol/L发生>3次者312例（3.9%），发生>3 d者202例（2.5%），复测血糖时间≤15 min者446例（5.6%），>30 min者2 187例（27.5%）。患者日任意高血糖≥15.0 mmol/L、任意低血糖≤3.9 mmol/L、理想血糖下四分位数分别为38.6%、5.5%和38.0%，上四分位数分别为21.5%、2.1%和58.1%。17个病区与美国、澳大利亚、重庆医疗机构的平均高血糖和任意高血糖（>10.0 mmol/L、≥15.0 mmol/L、≥16.7 mmol/L）、任意低血糖（≤3.9 mmol/L、<3.0 mmol/L、<2.8 mmol/L、<2.2 mmol/L）比较，差异均有统计学意义（P<0.05）。本研究内分泌病区和广东省某内分泌病区血糖、理想血糖、任意高血糖≥16.7 mmol/L、任意低血糖≤3.9 mmol/L比较，差异均有统计学意义（P<0.05）。结论　IGMS允许医疗机构建立全方位、标准化血糖报告。因目的不同，其选择模型也不同。群体模型更适用药物管理和风险管理人员，患者模型更适用个体化护理评估，患者日模型适用于某单元或单位进行质量改进方向和目标的制定。     

SLS人体单次斑贴试验阳性对照物基准模型的建立

目的:建立十二烷基磺酸钠(SLS)人体单次斑贴试验阳性基准模型。方法:60名健康受试者使用0.01%、0.05%、0.10%、0.50%和1.00%SLS进行第一阶段皮肤单次斑贴试验,确定阳性对照物的初步合适浓度区间。然后再选取60名健康受试者根据第一阶段合适浓度范围设计浓度进行第二阶段试验,进一步确定合适浓度。结果:第一阶段的试验提示,阳性基准物的浓度在0.01%~0.05%之间,第二阶段确定0.02%SLS的1级皮肤反应人数≤5例,2级皮肤反应人数2例,该反应率与标准中的阳性结果最为接近。结论:建议以0.02%SLS作为人体单次斑贴试验的阳性对照物基准模型。