Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.     

复方丹参滴丸对老年冠心病患者血流变学、血脂及炎性反应递质的影响

目的：探究复方丹参滴丸对老年冠心病患者血流变学、血脂及炎性反应递质的影响。方法：选取2015年1月至2017年12月海南省人民医院收治的老年冠心病患者154例作为研究对象，按照随机数字表法随机分为对照组和观察组，每组77例。对照组采用常规西药治疗，观察组在此基础上加服复方丹参滴丸。比较治疗前后2组患者的血流变学、血脂、炎性反应递质和疗效。结果：观察组治疗有效率为92.21%，明显高于对照组治疗有效率79.22%，差异有统计学意义（P<0.05）。治疗后，2组总胆固醇（TC）、三酰甘油（TG）和低密度脂蛋白（LDL）水平均升高，差异有统计学意义（P<0.05），且观察组高于对照组，2组差异有统计学意义（P<0.05）。2组血流变学指标、高密度脂蛋白（HDL）、IL-6和TNF-α水平治疗后均降低（P<0.05），且观察组降低更明显，差异有统计学意义（P<0.05）。结论：复方丹参滴丸联合常规西药治疗冠心病患者，能够调节脂代谢，降低炎性反应，改善血流变学。     

Low-molecular-weight chitosan relieves enterotoxigenic Escherichia coli-induced growth retardation in weaned pigs

The objective of the present study was to evaluate the effects of low-molecular-weight chitosan (LMWC) on the growth performance, immune responses and intestinal health of weaned pigs challenged by enterotoxigenic Escherichia coli (ETEC). A total of 32 weaned pigs were randomly allocated to four treatments: non-challenged (fed with basal diet), ETEC-challenged (fed with basal diet) and ETEC-challenged plus 50 or 100 mg/kg LMWC supplementation, respectively. After 11 days feeding, the non-challenged pigs were infused with sterilised Luria–Bertani culture, while the remaining pigs were infused with 2.6 × 10¹¹ colony-forming units of ETEC. At 3 days post-challenge, all pigs were administered d-xylose at 0.1 g/kg body weight. One hour later, blood samples were obtained, and the pigs then euthanised to collect intestinal samples. Data showed that only 100 mg/kg LMWC supplementation attenuated (P < 0.05) the average daily gain reduction caused by ETEC. Furthermore, besides the decreased (P < 0.05) serum tumour necrosis factor-α and immunoglobulin (Ig) G concentrations detected in ETEC-challenged pigs supplemented with LMWC at 50 or 100 mg/kg, the higher dose (100 mg/kg) also decreased (P < 0.05) the serum IgM concentration and increased (P < 0.05) the villus height and villus height-to-crypt depth ratio in both the jejunum and ileum, and the sucrase activity in the ileal mucosa. Moreover, LMWC supplementation (50 or 100 mg/kg) in ETEC-challenged pigs elevated (P < 0.05) the mRNA levels of jejunal mucosal peptide transporter 1 and ileal mucosal peptide transporter 1, divalent metal transporter 1 and zinc transporter 1, and decreased (P < 0.05) the ileal and caecal E. coli abundances, while 100 mg/kg LMWC additionally elevated (P < 0.05) the ileal Bacillus abundance, and caecal and colonic Bifidobacterium abundances. These results suggest that LMWC helps alleviate ETEC-induced growth retardation in weaned pigs, which could be associated with the inhibition of the immune responses and improved intestinal health.     

ICU患者家属创伤后成长体验的质性研究

目的 深入了解神经外科ICU患者家属创伤后成长的真实体验。方法 采用质性研究中描述性现象学研究法,于2019年4月—8月对12名上海市某三级甲等综合医院神经外科ICU患者家属进行深入访谈,借助Nvivo 11软件管理访谈资料,采用Colaizzi 7步分析法进行归纳分析并提炼主题。 结果 共提炼出4个主题：人生哲学的改变,包括对生命的欣赏、关注自身健康、确立生活的优先次序、不确定的未来;个人力量增强,包括挖掘优势潜能、责任感增强、自我依靠感增强;与他人关系改善,包括“为己利他”行为、人际交往中获益;有效应对,包括设定希望、向下比较、学会自我调适。 结论 神经外科ICU患者家属在对抗逆境的过程中能体验到创伤后成长,呈现积极的自我变化现象,临床医护人员应关注患者家属的积极体验,将创伤后成长与临床心理护理整合,促成临床干预向以激发潜能、培养积极力量、促进成长为主题的范式转变。     

Intraoperative lateral rectus electromyographic recordings optimized by deep intraorbital needle electrodes

ObjectiveWe demonstrate the advantages and safety of long, intraorbitally-placed needle electrodes, compared to standard-length subdermal electrodes, when recording lateral rectus electromyography (EMG) during intracranial surgeries.MethodsInsulated 25 mm and uninsulated 13 mm needle electrodes, aimed at the lateral rectus muscle, were placed in parallel during 10 intracranial surgeries, examining spontaneous and stimulation-induced EMG activities. Postoperative complications in these patients were reviewed, alongside additional patients who underwent long electrode placement in the lateral rectus.ResultsIn 40 stimulation-induced recordings from 10 patients, the 25 mm electrodes recorded 6- to 26-fold greater amplitude EMG waveforms than the 13 mm electrodes. The 13 mm electrodes detected greater unwanted volume conduction upon facial nerve stimulation, typically exceeding the amplitude of abducens nerve stimulation. Except for one case with lateral canthus ecchymosis, no clinical or radiographic complications occurred in 36 patients (41 lateral rectus muscles) following needle placement.ConclusionsIntramuscular recordings from long electrode in the lateral rectus offers more reliable EMG monitoring than 13 mm needles, with excellent discrimination between abducens and facial nerve stimulations, and without significant complications from needle placement.SignificanceLong intramuscular electrode within the orbit for lateral rectus EMG recording is practical and reliable for abducens nerve monitoring.     

UHILIC-MS/MS法同时测定复方三维右旋泛酸钙糖浆中5种维生素的含量

目的 建立一种超高效亲水作用色谱串联三重四极杆质谱法（UHILIC-MS/MS）,同时测定复方三维右旋泛酸钙糖浆中维生素B₁、维生素B₂、维生素B₆、烟酰胺和泛酸钙的含量。方法 采用超高效液相色谱仪,Waters ACQUITY BEHHILIC Amide色谱柱（2.1 mm×100 mm,1.7 μm）,以90%乙腈（含0.5%甲酸）-10 mmol/L甲酸铵水（含0.5%甲酸）为流动相,进行梯度洗脱,流速0.30 ml/min;在电喷雾（ESI）正离子模式下,用多反应监测（MRM）模式进行含量测定。结果 在5 min内,样品中5种维生素分别在各自考察的浓度范围内呈良好的线性关系,相关系数（r）均大于0.998 4;整体加样回收率在93.27%~100.39%之间,RSD为1.41%~4.96%;10批样品中维生素B₁、维生素B₂、维生素B₆、烟酰胺、泛酸钙的含量测定结果分别为32.40~38.91、7.002~8.462、9.677~11.17、33.64~39.58、3.276~3.771 mg/250 g。结论 本研究建立的UHILIC-MS/MS方法可快速实现对复方三维右旋泛酸钙糖浆中5种维生素类成分定性鉴定或定量检测,为复方三维右旋泛酸钙糖浆的开发利用和质量评价提供了可靠的技术检测方法。     

一测多评法测定复方人参片中的8种苷类成分

目的 建立一测多评法（quantitative analysis single-marker,QAMS）测定复方人参片中8种苷类成分的含量。方法 采用Agilent XDB-C₁₈色谱柱（4.6 mm×250 mm,5 μm）,流动相水（A）-乙腈（B）,梯度洗脱;体积流量1.0 mL·min^-1;检测波长203 nm;柱温：25℃。以人参皂苷Rb₁为内标,计算人参皂苷Rg₁、人参皂苷Re、淫羊藿苷、人参皂苷Rc、人参皂苷Rb₂、人参皂苷Rb₃、人参皂苷Rd的相对校正因子,测定其含量。结果 8种成分在各自范围内线性关系良好（r ≥ 0.999 0）,加样回收率为95.6%~104.4%,RSD为1.22%~2.73%,QAMS测定结果与外标法测定结果无显著性差异。结论 该法准确度、灵敏度高、专属性好、操作简单、重复性好。     

复方鱼腥草合剂中3个有效成分及防腐剂的含量测定

目的 考察市售复方鱼腥草合剂的质量。方法 收集10批不同厂家生产的复方鱼腥草合剂,应用HPLC测定3个有效成分（绿原酸、连翘酯苷A、黄芩苷）及防腐剂（苯甲酸钠、羟苯乙酯）含量。结果 10批复方鱼腥草合剂中绿原酸的含量为29.74~84.13μg·mL^-1、连翘酯苷A的含量为22.69~113.44 μg·mL^-1、黄芩苷的含量为0.587~1.662 mg·mL^-1;苯甲酸钠和羟苯乙酯含量均符合标准规定。结论 复方鱼腥草合剂质量情况较乐观,但是不同批次内在质量有较大差异,现行标准的质量控制方法较简单,不能有效控制其质量,建议修订完善标准。