药学知识库发展与建设

介绍药学知识库内涵，分析建立药学知识库的必要性、意义、发展情况，从数据来源、模型构建、设计要点及应用几方面阐述其构建方法，提出未来发展方向。     

基于柱前衍生UPLC-MS/MS的宁陕地区猪苓单糖组成差异研究

目的:研究宁陕地区猪苓多糖中单糖组成的差异。方法:采用柱前衍生-超高效液相色谱-串联三重四极杆质谱法检测不同生长条件下猪苓多糖中单糖组成及含量。结果:不同生长年限、不同种植地点及地势、种植过程中是否翻窝、不同发育时期的猪苓多糖的单糖组成均存在差异。3年生猪苓相对2年生猪苓,半乳糖、核糖和木糖等9种单糖的含量降低,而葡萄糖醛酸含量增加;黑苓与灰苓中葡萄糖含量差异明显,黑苓葡萄糖含量均值最高可达灰苓的1.9倍;种植过程中不翻窝、选择坡地种植可能有利于猪苓中单糖成分的积累。结论:对宁陕地区不同猪苓样品单糖组成差异进行初步研究,为宁陕地区猪苓的规范化种植提供依据。     

定坤丹对雷公藤多苷诱导卵巢储备功能低下小鼠性激素和卵泡计数的影响

目的:建立雷公藤多苷诱导卵巢储备功能低下(DOR)小鼠模型,探讨定坤丹对DOR的治疗作用,为其临床应用提供科学依据。方法:将60只动情周期规律的雌性小鼠随机分为空白组、模型组、定坤丹低、中、高剂量组和戊酸雌二醇组,每组10只。除空白组外,其余各组予40 mg·kg~(-1)雷公藤多苷混悬液灌胃;同时定坤丹低、中、高剂量组分别予1. 64,3. 28,6. 56 g·kg~(-1)定坤丹混悬液灌胃,戊酸雌二醇组予0. 15 mg·kg~(-1)戊酸雌二醇混悬液灌胃,1次/d,连续30 d。观察小鼠的一般状况、体质量、性腺指数和动情周期变化,采用放射免疫法检测血清促卵泡生成素(FSH),促黄体生成素(LH)和雌激素(E_2)水平,苏木素-伊红(HE)染色观察卵巢形态和卵泡计数。结果:与空白组比较,模型组小鼠动情周期处于紊乱状态,子宫和卵巢指数明显下降(P0. 05),血清FSH水平明显上升(P0. 05),LH呈上升趋势,E_2呈下降趋势,各级生长卵泡和黄体数减少、闭锁卵泡明显增加(P0. 05)。与模型组比较,定坤丹组半数小鼠恢复规律动情周期,戊酸雌二醇组小鼠动情周期停滞在动情期;定坤丹中、高剂量组和戊酸雌二醇组小鼠子宫和卵巢指数增加,血清FSH值明显下降(P0. 05),LH呈下降趋势;定坤丹高剂量组和戊酸雌二醇组血清E_2值明显上升(P0. 05);定坤丹能增加各级生长卵泡和黄体数、减少闭锁卵泡数,其中以中剂量效果更佳(P0. 05),戊酸雌二醇组能明显增加原始卵泡、窦状卵泡和黄体数(P0. 05),但不能减少闭锁卵泡数。结论:定坤丹能够通过改善血清性激素,促进卵泡发育、减少卵泡闭锁从而对DOR起到治疗作用。     

下调REV7基因对于人结肠癌HCT116细胞放射敏感性影响及机制研究

目的 研究下调REV7基因表达对人结肠癌HCT116细胞放射敏感性影响及其机制。方法 对HCT116细胞进行培养并运用RNA干扰技术实现REV7基因下调,将细胞分为空白组、转染阴性RNA oligo片段阴性对照组、转染REV7 RNA oligo的REV7基因下调组。克隆形成实验反映细胞增殖水平,蛋白印迹法检测相关基因表达水平、细胞凋亡发生水平和非同源末端连接途径发生水平。结果 6Gy照后REV7 siRNA组细胞克隆形成率降低(P<0.05)。REV7 siRNA组REV7基因下调效率>60%。REV7 siRNA组γH2AX、Caspase9表达升高(P<0.05),Ku80、XRCC4表达降低(P<0.05)。结论 下调REV7基因能提高HCT116细胞放射敏感性,其机制可能与下调REV7后非同源末端连接的发生被削弱有关。     

A Network Pharmacology Study of Reduning Injection for the Treatment of Coronavirus Disease-19

Objective: The 2019 novel coronavirus (2019?nCoV) outbreak has escalated into a global pandemic. According to Chinese guidance for coronavirus disease?19 (COVID?19): Prevention, control, diagnosis, and management, Reduning injection can effectively treat, the disease caused by the virus. To identify the active ingredients of Reduning injection and COVID?19 disease?related pathways, we conducted a network pharmacology study. Methods: The Traditional Chinese Medicine Systems Pharmacology database was used to screen the chemical constituents and potential targets of Reduning injection. The gene names were converted to the corresponding protein names using UniProt. GeneCards and OMIM databases were used to select targets related to 2019?nCoV. Using Cytoscape 3.7.2 software platform and STRING database, we constructed drug?common target and target protein protein?protein interaction network diagrams. Rx64 3.6.2 software and Bioconductor biological information software package were used for? Gene Ontology (GO) functional enrichment and KEGG pathway analyses. Results: In Reduning injection, a total of 33 effective chemical components were obtained that were involved in 151 signaling pathways, of which 44 targets were considered therapeutically relevant. Conclusion: Reduning injection can be potentially applied for the treatment of COVID-19 based on the results of our network pharmacology study.     

综合护理干预对肺癌胸腔镜术后患者的影响

目的探讨对肺癌胸腔镜术后患者行综合护理干预对于并发症以及生存质量的临床影响。方法抽取到本院接受治疗的132例肺癌胸腔镜术后患者,研究时间为2017年1月—2018年12月,将其按照双盲法分成综合组和对照组,分别为66例患者。综合组行综合护理措施,对照组行常规护理措施,观察两组患者的临床资料,并且比较两组患者的并发症以及生存质量。结果综合组患者接受护理后并发症发生率3例(4.55%),明显低于对照组11例(16.67%),综合组生存质量评分均高于对照组,P<0.05。结论对肺癌胸腔镜术后患者行综合护理干预,降低并发症的发几率,提高了生存质量。     

Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies

We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD-L1)-positive tumors were required for eligibility in KEYNOTE-028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE-158) or 10 mg/kg every two weeks (KEYNOTE-028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE-158 enrolled 104 patients and KEYNOTE-028 enrolled 24 patients. Median (range) follow-up was 7.5 months (0.6-34.3) in KEYNOTE-158 and 5.7 months (0.6-55.4) in KEYNOTE-028. In KEYNOTE-158, ORR was 5.8% (6/104; 95% CI, 2.1%-12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2-26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5-9.6) and 2.0 (1.9-2.1) months. Among PD-L1-expressers (n = 61) and PD-L1-nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE-028, ORR was 13.0% (3/23; 95% CI, 2.8%-33.6%); median DOR was NR (range, 21.5-53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1-9.8) and 1.8 (1.4-3.1) months. Grade 3 to 5 treatment-related adverse events occurred in 13.5% of patients in KEYNOTE-158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE-028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD-L1 expression, and has manageable toxicity.     

活血清胰汤灌肠辅助手术治疗对急性重症胰腺炎患者的疗效观察

目的：探讨活血清胰汤灌肠辅助手术治疗急性重症胰腺炎对患者AMS、UAMY、LPS水平及免疫功能的影响。方法：选取2019年3月至2020年3月陕西省宝鸡市中医医院收治的急性重症胰腺炎患者70例作为研究对象，按随机数字表法将其分为对照组和观察组，每组35例。2组均采用经内镜逆行性胰胆管造影术进行治疗，对照组术后给予常规治疗，观察组术后在对照组的基础上加用活血清胰汤灌肠治疗，2组均治疗1周。比较2组治疗1周后的临床疗效；比较2组治疗前、治疗1周后的胰腺炎标志物水平、细胞免疫指标及体液免疫指标水平。结果：治疗1周后，观察组总有效率为94.29%，高于对照组（77.14%，P<0.05）。与治疗前比较，治疗1周后，2组血清AMS、LPS、UAMY及CD8+水平均降低，且观察组低于对照组（P<0.05）；2组血清CD3+、CD4+、IgG、IgM、IgA水平及CD4+/CD8+比值均升高，且观察组高于对照组（P<0.05）。结论：活血清胰汤灌肠辅助手术治疗急性重症胰腺炎，可通过降低患者血清AMS、LPS及UAMY水平，缓解炎性反应，同时可改善免疫功能，进而有助于提高疗效。