中医移动医疗App信息服务现状研究

以“七麦数据”网站收录的中医移动医疗App作为研究对象，采用网络调查法和文献分析法，根据“七麦数据”对移动医疗App的分类，结合中医移动医疗App的信息服务内容和特点，将筛选出的中医移动医疗App划分为医疗健康类、中医养生类、知识传播类、全面综合类，并根据“七麦数据”网站中对各类中医移动医疗App的打分及累计下载量筛选出最具代表性的12款中医移动医疗App，从全面性、人性化、安全性、实用性4个一级指标和40个二级指标对其信息服务现状进行评价，指出当前中医移动医疗App信息服务存在的问题并提出建议。     

High Order Finite Difference Hermite WENO Fixed-Point Fast Sweeping Method for Static Hamilton-Jacobi Equations

In this paper, we combine the nonlinear HWENO reconstruction in [43] and the fixed-point iteration with Gauss-Seidel fast sweeping strategy, to solve the static Hamilton-Jacobi equations in a novel HWENO framework recently developed in [22]. The proposed HWENO frameworks enjoys several advantages. First, compared with the traditional HWENO framework, the proposed methods do not need to introduce additional auxiliary equations to update the derivatives of the unknown function $\phi$. They are now computed from the current value of $\phi$ and the previous spatial derivatives of $\phi$. This approach saves the computational storage and CPU time, which greatly improves the computational efficiency of the traditional HWENO scheme. In addition, compared with the traditional WENO method, reconstruction stencil of the HWENO methods becomes more compact, their boundary treatment is simpler, and the numerical errors are smaller on the same mesh. Second, the fixed-point fast sweeping method is used to update the numerical approximation. It is an explicit method and does not involve the inverse operation of nonlinear Hamiltonian, therefore any Hamilton-Jacobi equations with complex Hamiltonian can be solved easily. It also resolves some known issues, including that the iterative number is very sensitive to the parameter $ε$ used in the nonlinear weights, as observed in previous studies. Finally, to further reduce the computational cost, a hybrid strategy is also presented. Extensive numerical experiments are performed on two-dimensional problems, which demonstrate the good performance of the proposed fixed-point fast sweeping HWENO methods.     

肝X受体激动剂在肿瘤治疗中的研究进展北大核心

肝X受体(liver X receptors,LXRs)是孤儿核受体转录因子超家族成员,当LXRs被激活后,可调节靶基因的转录表达,不但参与胆固醇、脂肪、糖的代谢以及炎症等过程,并且在许多恶性肿瘤组织中均有表达。为全面了解肝X受体激动剂在治疗癌症中的研究现状,本文将从肝X受体激动剂与胃癌、肝癌、卵巢癌、乳腺癌、子宫内膜癌、肺癌以及结直肠癌的相关性方面进行综述。     

Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

呼吸机自动测量气道阻断压与标准测量方法的一致性

目的 验证呼吸机自动测量的气道阻断压(airway occlusion pressure,P0.1)与标准测量方法的一致性,以及不同触发形式对自动测量结果的影响。方法 选择采用非阻断自动测量P0.1的呼吸机,分别进行模拟肺和临床试验。调节全自动自主呼吸模拟肺,模拟具有不同呼吸努力和呼吸力学特征的48种状态,应用待检测呼吸机,以压力支持通气模式为模拟肺进行通气。临床研究部分纳入15例接受压力支持通气的成年患者。两部分研究均随机交叉应用压力和流量触发,采集呼吸机自动监测的P0.1后,采用标准呼气末气道阻断法进行P0.1测量,作为标准参考值。采用Bland-Altman检验分析P0.1呼吸机监测值与标准参考值的一致性,计算残差(呼吸机监测值-标准参考值)和95%一致性区间,比较不同触发形式对残差的影响。结果 在模拟肺验证中,P0.1呼吸机监测值与标准参考值之间的残差(95%一致性区间)在压力和流量触发下分别为0.04(－0.63~0.70)和－0.54(－1.44~0.36)cmH₂O(1 cmH₂O=0.098 kPa),两者相比差异具有统计学意义(P<0.001)。临床观察获得了相似的结果,压力和流量触发时的残差(95%一致性区间)分别为－0.11(－0.73~0.52)和－0.54(－1.50~0.59)cmH₂O,差异无统计学意义(P>0.05),表明呼吸机监测值与标准参考值间存在一致性。结论 压力触发时,呼吸机非阻断法自动测量的P0.1与标准方法具有良好的一致性。而流量触发明显低估P0.1,建议自动监测时切换到压力触发。     

茯苓多糖对ApoE-/-AS小鼠肝脏脂质沉积及胆固醇逆向转运相关蛋白表达的影响＊

目的 探讨茯苓多糖对载脂蛋白E基因敲除（ApoE^-/-）动脉粥样硬化（Atherosclerosis，AS）小鼠肝脏脂质沉积及胆固醇逆向转运的影响。方法 采用随机数字表法将30只ApoE^-/-小鼠随机分为模型组、茯苓多糖组、辛伐他汀组，每组10只，10只C57BL/6J小鼠作为正常组。正常组给予基础饲料喂饲，其余小鼠给予高脂饲料喂饲12周。茯苓多糖组以0.2 g/kg/d灌胃，辛伐他汀组以2.275 mg/kg/天灌胃，正常组和模型组给予等体积生理盐水灌胃，共干预4周。全自动生化分析仪检测小鼠血清三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平，苏木素-伊红（HE）染色观察小鼠肝脏病理形态学变化，油红O染色观察小鼠肝脏脂质沉积情况，ELISA检测各组小鼠血清载脂蛋白A1 （ApoA1）、对氧磷酶-1（PON1）含量，Real-time RT-qPCR法及Western Blot法检测肝脏胆固醇酯转运蛋白（CETP）、磷脂转运蛋白（PLTP）、卵磷脂胆固醇酰基转移酶（LCAT）mRNA及蛋白表达。结果 与正常组比较，模型组小鼠血清TG、TC、LDL-C含量均明显上升，HDL-C含量明显下降（P<0.01），肝细胞脂肪变性明显，肝脏脂质沉积明显，小鼠血清ApoA1、PON1含量均明显下降（P<0.01），小鼠肝脏CETP、PLTP mRNA及蛋白表达明显上升，LCAT mRNA及蛋白表达明显下降（P<0.01）。与模型组相比，茯苓多糖组血清TG、TC、LDL-C含量均显著下降（P<0.01），HDL-C含量呈上升趋势（P>0.05），肝细胞脂肪变性、脂质沉积程度均有所减轻，茯苓多糖组ApoA1含量明显上升（P<0.01），PON1含量呈上升趋势（P>0.05），茯苓多糖组CETP、PLTP mRNA及蛋白表达有所下降，LCAT mRNA及蛋白表达有所上升（P<0.05，P<0.01）。结论 茯苓多糖可能通过调控血脂水平与胆固醇逆向转运过程，改善ApoE^-/- AS小鼠肝脏脂质沉积，进而发挥防治AS作用。     

基于PI3K/Akt/mTOR信号通路探讨炙甘草汤抗大鼠MIRI致室速和室颤的作用机制

目的:通过磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路,探讨炙甘草汤干预心肌缺血再灌注损伤(MIRI)致心律失常(室速和室颤)的作用及其机制。方法:将72只SD大鼠随机分为假手术组,模型组,炙甘草汤低、中、高剂量组(11.43,22.86,45.72 g·kg~(-1)),稳心颗粒组(2.43 g·kg~(-1)),连续给药干预10 d。末次给药2 h,采用结扎冠状动脉左前降支法制备大鼠MIRI模型,记录心电图的变化。造模成功后采集血液及心脏组织,检测血清中肌酸肌酶(CK),乳酸脱氢酶(LDH)及丙氨酸氨基转移酶(AST)的含量;酶联免疫吸附测定(ELISA)检测心肌肌钙蛋白(CtnI)的含量;免疫组化法检测心肌PI3K,Akt,mTOR的表达;采用蛋白免疫印迹法(Western blot)检测心肌自噬相关蛋白微管相关蛋白1轻链3(LC-3),自噬标志物Beclin1和PI3K/Akt/mTOR信号通路相关蛋白表达及磷酸化p-PI3K,p-Akt,p-mTOR的水平。结果:模型组大鼠100%发生室速,91.67%发生室颤;与假手术组比较,模型组大鼠血清CK,LDH,AST以及CtnI的含量显著升高(P0.01),心肌组织中PI3K,Akt,mTOR表达显著升高(P0.01),LC3-Ⅱ/LC3-Ⅰ与Beclin1的相对表达量显著升高(P0.01),p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR显著降低(P0.01);与模型组比较,炙甘草汤高剂量组室速、室颤发生率显著降低(P0.01),较其他给药组持续时间短(P0.01);炙甘草汤高剂量组CK,LDH,AST水平及CtnI含量显著降低(P0.01);炙甘草汤给药组的PI3K,Akt,mTOR的表达随剂量的增加而显著降低(P0.01);LC-3,Beclin1的表达随炙甘草汤各剂量组的增加有不同程度地下降(P0.01),而PI3K/Akt/mTOR相关蛋白表达比值明显升高(P0.05,P0.01)。结论:炙甘草汤预处理能使异常升高的心肌酶CK,LDH,AST,CtnI降低,抑制细胞的过度自噬,上调PI3K,Akt和mTOR的表达,说明炙甘草汤抗MIRI致心律失常的作用可能与PI3K/Akt/mTOR信号通路有关。     

Noncoding telomeric repeat‐containing RNA inhibits the progression of hepatocellular carcinoma by regulating telomerase‐mediated telomere length

Telomeric repeat‐containing RNA (TERRA) is closely involved in the regulation of telomere length, which plays critical roles in tumorigenesis. However, the biological significance of TERRA in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we found that HCC cells show a frequent downregulation of TERRA and its positive regulator TTAGGG repeat binding factor‐1 (TRF1), whereas the negative regulator TTAGGG repeat binding factor‐1 (TRF2) was upregulated. We found that TERRA, TRF1, and TRF2 contributed to poor prognosis of HCC patients. Importantly, we found that the downregulation of TERRA significantly promoted HCC cell growth and metastasis in vitro and in vivo, whereas the upregulation of TERRA showed an opposite effect. Mechanistically, downregulation of TERRA significantly increased telomerase activity and promoted telomere elongation. Moreover, the inhibitory effects of TERRA overexpression on the growth and metastasis of HCC cells were reversed by treatment with TA‐65 that activates telomerase activity. In contrast, the protumor effect of TERRA downregulation was reversed by treatment with TMPyP4 that inhibits telomerase activity. Our findings reveal that TERRA plays a critical role in HCC cell growth and metastasis, indicating that TERRA is a potential therapeutic target for HCC.