达立通颗粒主要活性成分在正常及功能性消化不良模型大鼠胃肠道组织中差异分布研究

目的 研究达立通颗粒主要活性成分在正常和功能性消化不良(FD)模型大鼠胃肠道组织中的分布差异。方法 采用夹尾刺激结合不规律饮食双因素干预方法建立FD模型。12只大鼠(对照、模型各6只)用于FD模型验证,进行胃、小肠排空实验,HE染色后进行胃肠组织病理学观察;36只大鼠(对照、模型各18只)用于胃肠道组织差异分布研究,禁食不禁水18 h,按22.4 g·kg^-1剂量(8倍临床等效剂量) ig给予达立通颗粒1次,于给药后1、3、6 h收集各组大鼠的胃、十二指肠、空肠、回肠和结肠。应用超高效液相色谱-串联四级杆/线性离子阱质谱(UPLC-QTRAP-MS/MS)法检测各组织牡荆素-4''-O-葡糖苷、原阿片碱、黄连碱、小檗碱、甜橙黄酮、川陈皮素、桔皮素、去甲基川陈皮素、木香烃内酯、去氢木香内酯、原儿茶酸、伞形花内酯、木犀草苷、橙皮苷、木犀草素、柚皮素、橙皮素、白杨素含量,采用ACQUITY HPLC^TMHSS T₃(50 mm×2.1 mm,1.8 μm)色谱柱,柱温为40℃,0.1 %甲酸水-乙腈为流动相,梯度洗脱,体积流量为0.3 mL·min^-1,进样量为2 μL。结果 与对照组比较,模型组大鼠体质量显著降低(P<0.001),胃、小肠排空率显著降低(P<0.001),十二指肠肠黏膜的紧密连接被破坏,但未出现胃肠组织的器质性病变,符合FD的病理特征。建立的UPLC-QTRAP-MS/MS方法中,各化合物线性关系良好,R² ≥ 0.990 0。对建立的检测方法进行专属性、精密度与准确度、提取回收率、稳定性和基质效应等方面的考察,均符合要求。各成分在对照和模型组大鼠胃肠道组织中浓度差异明显,且在各组织中达到最高浓度的时间点差异较大,模型组出现达峰时间延后的现象;与对照组比较,模型组大鼠胃组织中化合物的暴露水平降低,可能与FD引起胃肠道蠕动减慢有关。橙皮苷、橙皮素、柚皮素、原儿茶酸、去氢木香内酯、川陈皮素、去甲基川陈皮素、小檗碱和桔皮素在胃、十二指肠、空肠、回肠和结肠中暴露水平较高,且在对照组和模型组中各时间点下的浓度差异较显著。结论 经方法学验证,所建立的UPLC-QTRAP-MS/MS法灵敏、专属性强、准确性高,适用于大鼠胃肠道组织中达立通颗粒主要活性成分的胃肠组织分布研究。达立通颗粒主要活性成分在正常和FD模型大鼠胃肠组织分布具有显著性差异。     

A single centre evaluation of risk prediction models and imaging modalities in acute appendicitis

IntroductionPatients with suspected appendicitis remain a diagnostic challenge. The aim of this study was to validate risk prediction models, and to investigate diagnostic accuracy of ultrasonography and computed tomography (CT) in adults undergoing appendicectomy.MethodsA retrospective case review was performed of patients aged 16–45 years having an appendicectomy between January 2019 and January 2020 at a tertiary referral centre. Primary outcomes were the accuracy of a high risk appendicitis risk score and ultrasonography and CT imaging modalities compared with histological reports following appendicectomy.ResultsA total of 206 patients (52% female) were included in the study. Removal of a histologically normal appendix was equally likely in men and women (13.1% vs 11.2% respectively, relative risk: 1.17, 95% confidence interval: 0.56–2.44, p=0.674). A high risk appendicitis score correctly identified 84.0% (79/94) of cases in men and 85.9% (67/78) of cases in women. Ultrasonography was reported as equivocal in 85.7% (18/21) of low risk women and 59.0% (23/39) of high risk women. CT correctly detected or excluded appendicitis in 75.0% (6/8) of low risk women and 88.5% (23/26) of high risk women.ConclusionsThis study suggests that risk prediction models may be useful in both women and men to identify appendicitis. Ultrasonography gave high rates of equivocal results and should not be relied on for the diagnosis of appendicitis. CT is a highly accurate diagnostic tool and could be considered in those at low risk where clinical suspicion remains to reduce negative appendicectomy rates.