A Study on the Multi-Compartment Linear Circulation Pharmacokinetic Model for the Targeting Drug Delivery System

By analyzing the observed phenomena and the data collected in the study, a multi-compartment linear circulation model for targeting drug delivery system was developed and the function formulas of the drug concentration-time in blood and target organ by computing were figured out. The drug concentration-time curve for target organ can be plotted with reference to the data of drug concentration in blood according to the model. The pharmacokinetic parameters of the drug in target organ could also be obtained. The practicability of the model was further checked by the curves of drug concentration-time in blood and target organ(liver) of liver-targeting nanoparticles in animal tests. Based on the liver drug concentration-time curves calculated by the function formula of the drug in target organ, the pharmacokinetic behavior of the drug in target organ(liver) was analyzed by statistical moment, and its pharmacokinetic parameters in liver were obtained. It is suggested that the (relative targeting index( can be used for quantitative evaluation of the targeting drug delivery systems.

Non-human primate models in drug addiction deserve more attention

Dear Editor, The process of relapse involves firm or aberrant memories of environmental cues associated with drug craving or addiction. To date, it is not known where these memories are stored in the brain, what kinds of regulatory biological factors or molecules are involved, nor why it is so difficult to stop addiction psychologically. Currently, rodent animal models, such as the self-administration and conditioning place preference / aversion paradigm are still widely used in the studies of drug withdrawal syndromes or drug-associate memories. However, the differences between humans and rodents--particularly in terms of genetics, and pathology and pharmacology--have significantly limited the application of further studies on this topic. Essentially, rodents lack the longterm or life-time memories humans possess and lose their drug-associated memory only after a few weeks of withdrawal.

Application of Modeling Drugs in Animal Models of Chemical Phlebitis: Review

Objective: This review aims to determine the impact of different drugs and methods on the successful establishment of an animal model for chemical phlebitis (CP). Design: Search the Cochrane Library, ProQuest Academic Journal Library, PubMed, Web of Science, Ovid, Embase, CINAHL complete (EESCO) and other related databases to determine the literature. Screen out articles consistent with this review and summarize them. Results: Since the establishment of the database, a total of 1463 articles have been retrieved. After reading the title, abstract and full text, and excluding non-related and duplicate articles, 22 reports were finally included. Among them, there are 8 articles using different medication methods to compare the effects of establishing a CP model. The included articles explored the effects of different animal models, drug types, and their dose, concentration, speed, and time on the CP model. Conclusion: The factors of dose, concentration and time were positively correlated with the incidence of CP. The effect of speed factors on CP and the results of different animal models are inconsistent. It requires further research in the future.

Modelling two different therapy strategies for drug T-20 on HIV-1 patients

A mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide （formerly called T-20） by impulsive differential equations is modeled by two different drug elimination kinetics, the first-order elimination kinetics and the Michaelis-Menten elimination kinetics. The model is a non-autonomous system of differential equations. For a time-dependent system, the disease-free equilibrium is mainly studied. Its stability, when the therapy is taken with perfect adherence, is obtained. To ensure the disease-free equilibrium remains stable, the analytical thresholds for dosage and dosing intervals are determined. The effects of super- vised treatment interruption are also explored. It is shown that the supervised treatment interruption can be worse than no therapy at all.

The potential role of the three-dimensional-bioprinting model in screening and developing drugs

Recently,we have read with great interest the original article used different spatial configuration models of colorectal cancer(CRC)for validating the antitumor efficacy with Diiminoquinone.We feel obliged to provide new insight into the drug screening models by integrating and analyzing the original method and result.These comments may provide comprehensive insights into threedimensional drug screening models and the difference between pathologic subtypes in CRC.

Evaluation of the Effect of Chemotherapeutic Drug Training on Mobile Terminal for Neuro-Oncology Nurses Based on Kirkpatrick’s Model

Background: Since there has been training, there has been discussion about the effect of training. But training evaluation is not systematic until Kirkpatrick came up with the training evaluation model in 1959. At present, the prevailing model in the systematic summary of training evaluation is still The Kirkpatrick’s model. This model was further improved in 1994, more responsive to contemporary needs, and thus widely used all over the world. At the beginning, it was widely used in human resource management of enterprises. In recent years, this model has been gradually used in the medical field to evaluate the effect of medical training. The Kirkpatrick’s model has a systematic, integrated and persuasive evaluation system for trainees. It has good effects in the pre-service nurse training, the professional image and code of conduct nurses training, and the geriatric nurse training. At present, there are few studies on the chemotherapeutic drug training of neurologist nurses in China. In clinical work, nurses’ cognitive and practical behaviors of chemotherapeutic drug protection and drug extravasation prevention and treatment are insufficient. It directly harms the health of nursing staff and increases the complications of chemotherapy, increases pain of tumor patients, delays or interrupts chemotherapy, and aggravates the economic burden of patients. Especially, Chemotherapeutic drugs for neuro-oncology have particularity and necessity of urgent training. Objective: To investigate the effect of chemotherapeutic drug training through mobile terminal for neuro-oncology nurses based on the Kirkpatrick’s model. Methods: The training content and evaluation questionnaire for chemotherapeutic drugs were designed by nursing management personnel and senior nurses in our department according to the guidelines and common diseases requiring chemotherapy in the department. The content includes the basic knowledge of neuro-oncology chemotherapy, pharmacological knowledge, toxic and side effect of chemotherapy, etc., which are regularly pushed through the mobile terminal-WeChat. Forty nurses participated in the training and the effect is evaluated by Kirkpatrick’s model. Result: After the training, 100% of nurses were satisfied with the training content and 97.5% with the training form. The scores of nurses in learning level such as basic pharmacological knowledge, drug configuration and exposure, drug treatment and infusion, observation of toxic and side effects, and treatment of drug extravasation were significantly higher than those before the training (P < 0.01). The scores of nurses in the behavior level such as drug allocation, health education, toxic and side effect observation and prediction, treatment of exosmosis, occupational protection were significantly higher than those before the training. After the training, the satisfaction of managers, chemotherapy physicians and chemotherapy patients on the behavior of nurses was significantly higher than that before the training (P < 0.01). Conclusion: The chemotherapeutic drug training through mobile terminal based on Kirkpatrick’s model can improve the ability of neuro-oncology nurses, so as to improve the satisfaction of physicians and patients.

AN ANALYTICAL SOLUTION FOR THE MODEL OF DRUG DISTRIBUTION AND ABSORPTION IN SMALL INTESTINE

According to the physiological and anatomical characteristics of small intestine,neglecting the effect of its motility on the distribution and absorption of drug and nutrient,Y.Miyamoto et al.proposed a model of two-dimensional laminar flow in a circular porous tube with permeable wall and calculated the concentration profile of drugby numerical analysis.In this paper,we give a steady-state analytical solution of the above model including deactivationterm.The obtained results are in agreement with the results of their numerical analysis. Moreover the analytical solution presented in this paper reveals the relation among the physiological parameters of the model and describes the basic absorption rule of drug and nutrient through the intestinal wall and hence pro- vides a theoretical basis for determining the permeability and reflection coefficient through in situ experiments.

高级别浆液性卵巢癌类器官模型的建立及鉴定

目的 建立并鉴定高级别浆液性卵巢癌类器官模型。方法 选取行卵巢癌细胞减灭术的10例高级别浆液性卵巢癌患者的卵巢癌组织,将卵巢癌组织消化成单细胞,在基质胶中培养7天,构建高级别浆液性卵巢癌类器官模型。比较类器官与原发肿瘤的形态学特征、免疫组化特征和苏木精-伊红(HE)染色结果。结果 10例患者的高级别浆液性卵巢癌类器官模型均成功构建。光学显微镜显示类器官数量可观,形态呈类圆形3D立体结构。HE染色显示,在高倍镜下,类器官细胞核异型性明显,局部区域形成微乳头状结构。免疫组化显示黏蛋白16(MUC16)强阳性,p53弥漫性强阳性,类器官与原发肿瘤的免疫组化染色情况一致。结论 体外成功构建的高级别浆液性卵巢癌类器官模型具有明显的上皮性特征,与原发肿瘤高度相似,可用于卵巢癌的药物筛选和基础研究建模。

The Presence of Phases and the Inability of the Classical Compartment Models to Provide Pharmacokinetic Parameters of Physiological Significance for Lipophilic Drugs

The first biphasic open one-compartment pharmacokinetic model is described. Its analytical solutions to drug concentration were developed from parameters of an open two-compartment pharmacokinetic model. The model is used to explain the unusually large compartment volumes and apparent volumes of distribution of lipophilic drugs, as well as to identify which of the pharmacokinetic parameters of the classical compartment models are biologically relevant.

Mixture Models for Estimating the Number of Drug Users in Thailand 2005-2007

It is difficult to measure the sizes of illegal drug user populations directly by using the survey method because of many “hidden drug addicts” and the difficulty of receiving a true response. Systematic and routine information on treatment episodes of drug users is adopted to estimate the population size in this study. Mixture models of zero-truncated Poisson distributions using the nonparametric maximum likelihood estimators (NPMLE) by means of capture-recapture repeated count data were used to project the number of drug users. The method was applied to surveillance data of drug users identified by treatment episodes in over 1140 health treatment centers in Thailand from the Bureau of Health Service System Development, Ministry of Public Health. We presented how this mixture model could be utilized to construct the unobserved frequency of drug users with no treatment episode and further estimated the total population size of drug users in the country from 2005 to 2007. The result of simulation was confirmed that mixture model is suitable when population is large. By means of mixture models, the estimations for the number of drug users were fitted with excellent goodness-of-fit values and we were also compared to the conventional Chao estimates. The NPMLE for the total number of drug users in Thailand 2005, 2006, and 2007 were 184,045 (95% CI: 181,297-86,793), 230,665 (95% CI: 226,611-234,719), 299,670 (95% CI: 294,217-305,123), respectively, also 125,265 (95% CI: 123,092-127,142), 166,287 (95% CI: 163,222-169,352), 228,898 (95% CI: 224,766 - 233,030) for the number of methamphetamine (Yaba) users, and 11,559 (95% CI: 10,234-12,884), 11,333 (95% CI: 9276-13,390), 8953 (95% CI: 7878-10,028) for the number of heroin users, respectively. The numbers of marijuana, kratom-plant, opium, and inhalant users were underestimated because their symptoms were mild and not severe enough to remedy in health treatment centers which led to the smaller size of the total number of drug users. The well-estimated sizes of heroin and methamphetamine addicts are high reliable because they are based on clearly evident count with a severe addiction problem to health treatment centers. The estimation by means of mixture models can be recommended to monitor drug demand trend and drug health service routinely;it is easy to calculate via the available programs MIXTP based on request.

Hydrodynamic modeling of ferrofluid flow in magnetic targeting drug delivery

Among the proposed techniques for delivering drugs to specific locations within human body, magnetic drug targeting prevails due to its non-invasive character and its high targeting efficiency. Magnetic targeting drug delivery is a method of carrying drug-loaded magnetic nanoparticles to a target tissue target under the applied magnetic field. This method increases the drug concentration in the target while reducing the adverse side-effects. Although there have been some theoretical analyses for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel. A mathematical model is presented to describe the hydrodynamics of ferrofiuids as drug carriers flowing in a blood vessel under the applied magnetic field. In this model, magnetic force and asymmetrical force are added, and an angular momentum equation of magnetic nanoparticles in the applied magnetic field is modeled. Engineering approximations are achieved by retaining the physically most significant items in the model due to the mathematical complexity of the motion equations. Numerical simulations are performed to obtain better insight into the theoretical model with computational fluid dynamics. Simulation results demonstrate the important parameters leading to adequate drug delivery to the target site depending on the magnetic field intensity, which coincident with those of animal experiments. Results of the analysis provide important information and suggest strategies for improving delivery in clinical application.

利用计算模拟技术建立头孢呋辛酯片体内、外相关性溶出度评价方法

目的利用计算模拟技术,探索建立前体药物头孢呋辛酯片的体内外相关性预测模型,用于仿制药生物等效性评估。方法参考文献中头孢呋辛酯片口服给药后的PK数据,结合参比制剂的血药浓度数据,利用GastroPlus TM软件搭建头孢呋辛酯片药代动力学模型;结合原研制剂在不同溶出条件、4种溶出介质(pH1.2盐酸溶液、pH4.0醋酸盐缓冲溶液、pH6.8磷酸盐缓冲溶液和水)中的体外溶出行为,筛选适宜的溶出条件;将在不同溶出介质中得到的溶出曲线作为体内释放曲线,预测头孢呋辛酯片在体内PK参数并与参比制剂的临床实测数据进行比较,探讨头孢呋辛酯片体内外相关的溶出度方法。结果成功建立了头孢呋辛酯片体内外相关的溶出度方法:桨法,转速为55 r/min,以pH4.0醋酸盐缓冲液900 mL为溶出介质。结论所建立的头孢呋辛酯片药代动力学预测模型,可用于仿制药的生物等效性虚拟评估,为该药物的质量与疗效一致性评价提供了新思路。

长爪沙鼠不同感音神经性耳聋模型的建立及比较

目的利用不同的耳毒性药物建立长爪沙鼠感音神经性耳聋模型,并对3种模型进行比较分析,为感音神经性耳聋的研究提供精准的动物模型。方法选择长爪沙鼠,建立硫酸卡那霉素和呋塞米联用(KM+Fur)、新霉素(Neo)及哇巴因(Oua)3种耳毒性药物的感音神经性耳聋模型,通过听性脑干反应(ABR)和耳蜗组织形态学检测,比较分析不同耳毒性药物的损伤特点。结果KM+Fur造模后,与对照组(14.00±1.80)相比,该组(71.00±5.26)长爪沙鼠的听力阈值显著上升,耳蜗HCs大量损伤,而SGNs无明显损伤;Neo造模后,与对照组相比,40 mmol·L^(-1) Neo仅影响沙鼠高频32 kHz时听力阈值(60.00±8.66),无明显的组织学改变;而100 mmol·L^(-1) Neo组的沙鼠各频率听力阈值均显著上升,且耳蜗HCs及SGNs均严重受损;Oua造模后,1 mmol·L^(-1) Oua和10 mmol·L^(-1) Oua均可引起沙鼠各频率听力阈值显著上升,但损伤范围不同,10 mmol·L^(-1) Oua使HCs和SGNs均严重受损,而1 mmol·L^(-1) Oua仅造成耳蜗SGNs损伤。结论利用KM+Fur可建立长爪沙鼠HCs特异性受损的感音神经性耳聋模型;40 mmol·L^(-1) Neo可建立高频区听功能损伤的感音神经性耳聋模型;利用100 mmol·L^(-1) Neo和10 mmol·L^(-1) Oua可以建立长爪沙鼠HCs和SGNs均受损的感音神经性耳聋模型;利用1 mmol·L^(-1) Oua可以建立长爪沙鼠耳蜗SGNs特异性受损的耳聋模型。

云南省毒品犯罪的空间特征与影响因素

研究省域中观尺度的毒品犯罪空间特征和影响因素对打击毒品犯罪、维护社会稳定具有重要意义。文章以云南省129个县区单元的毒品犯罪案件为数据,采用GIS统计分析、空间自相关分析、空间引力模型分析云南省毒品犯罪的空间差异格局和空间关联网络特征。构建由经济水平、收入水平、城镇化程度、受教育水平、流动人口、毒源地影响、地形复杂度组成的毒品犯罪影响因素指标体系,并以空间杜宾模型开展回归分析。结果表明:1)云南省毒品犯罪率呈显著的空间差异格局,高犯罪率集聚区主要分布在中缅边境;2)云南省各区县毒品犯罪在全局层面具有显著的空间关联与空间集聚特征,昆明市主城区—周边各区县以及云南边境各区县间的毒品空间关联网络强度较高;3)毒源地影响因素最为显著,呈显著负相关,距中缅边境(毒源地)距离与毒品犯罪率关系呈拉长的“倒S”型走向分布曲线,表现为大幅度下降、小幅度上升再下降的趋势。此外,经济水平对云南省毒品犯罪差异呈著负向影响,收入水平、城镇化程度为正向影响。

基于不同群体药动学分析工具建立真实世界丙戊酸群体药代动力学模型

目的:基于NONMEM和MONOLIX 2种不同群体药动学分析工具建立真实世界丙戊酸群体药动学模型(PPK),探索可能影响丙戊酸血药浓度的潜在协变量,为癫痫患者使用丙戊酸提供科学依据。方法:回顾性收集2021年1月—2022年12月南京医科大学第二附属医院收治的167例癫痫患者239个丙戊酸稳态血药浓度数据资料,按随机数字表法将其分为模型组(n=111)与验证组(n=56)。2种群体药动学分析工具同时建立适合真实世界的群体药动学模型,采用拟合度优度诊断、可视化预测检验对所得的模型进行内部验证和外部验证,评估模型的预测能力。结果:该群体药动学为一室模型,在使用NONMEM软件建立的最终模型中纳入了联合用药(DDI)-美罗培南和给药方式(ROUTE)作为协变量;而在使用MONOLIX软件建立的最终模型中纳入了联合用药(DDI)-美罗培南和体质量(BW)作为协变量。与此同时,与NONMEM相比较,MONOLIX软件所得到的最终模型具有更好的精密度和准确度。结论:本研究初步构建了适用于癫痫患者给予丙戊酸剂量指导的群体药动学模型。

头孢哌酮/舒巴坦致血小板减少列线图预测模型的建立与验证

目的探讨头孢哌酮/舒巴坦致成人住院患者血小板减少的预测因子,建立列线图预测模型并进行验证。方法回顾性收集西安市中心医院2021年6月30日至2023年6月30日使用头孢哌酮/舒巴坦治疗的成人住院患者资料,按7∶3随机分为训练集和内部验证集。采用单因素/多因素Logistic回归分析筛选头孢哌酮/舒巴坦致血小板减少的独立预测因子,通过R4.0.3软件“RMS”包绘制列线图;采用受试者工作特征曲线及C-index值评估模型的预测效能;采用Hosmer-Lemeshow拟合优度检验评价模型的校正度。以相同标准,收集西安市第一医院同期使用头孢哌酮/舒巴坦治疗的成人住院患者的临床资料,对列线图预测模型进行外部验证。结果共纳入西安市中心医院患者1045例,其中头孢哌酮/舒巴坦致血小板减少患者67例,发生率为6.41%。排除假阳性患者后,最终纳入患者473例,其中训练集331例、内部验证集142例。多因素Logistic回归分析结果显示,患者年龄[OR=1.043,95%CI(1.017,1.070)]、估算的肾小球滤过率(eGFR)[OR=0.988,95%CI(0.977,0.998)]、基线血小板[OR=0.989,95%CI(0.982,0.996)]、营养风险[OR=3.863,95%CI(1.884,7.921)]和累计限定日剂量数(DDDs)[OR=1.082,95%CI(1.020,1.147)]是头孢哌酮/舒巴坦致血小板减少的独立预测因子(P<0.05)。训练集和内部验证集的C-index值分别为0.824[95%CI(0.759,0.890)]和0.828[95%CI(0.749,0.933)],Hosmer-Lemeshow检验的χ^(2)值分别为0.441、1.804(P值分别为0.802、0.406)。外部验证集中,C-index值为0.808[95%CI(0.672,0.945)],Hosmer-Lemeshow检验的χ^(2)值为0.899(P值为0.638)。结论患者年龄、基线血小板、eGFR、营养风险和累计DDDs是头孢哌酮/舒巴坦致血小板减少的独立预测因子;所建列线图预测模型具有良好的预测效能和外推性,有助于临床快速、准确地识别头孢哌酮/舒巴坦致血小板减少的潜在风险。

骨骼肌芯片及其在生物医学领域的研究进展

骨骼肌作为人体最丰富的组织之一,是人体运动功能的主要承担者,并且在能量代谢、免疫调节和衰老过程中发挥重要作用。骨骼肌所处的微环境结构复杂,包括多种细胞类型、独特的三维结构以及力学特征。因此,建立高仿生的骨骼肌模型具有一定的挑战性。器官芯片可以精确地模拟人体组织的关键结构和功能特性,从而为骨骼肌模型的建立提供了一种新的途径。本文综述了目前骨骼肌芯片的构建及其在疾病建模、药物评价与再生医学等生物医学研究中的应用。依据人体骨骼肌组织微环境的特点,重点介绍了构建骨骼肌芯片的关键要素,包括动态培养环境、机械刺激、电刺激、血管化与神经化,以及其他工程策略包括各向异性支架的制备与两端锚定的策略等。目前的骨骼肌芯片在细胞来源及功能等方面仍存在一定的局限性。未来通过与基因编辑、生物传感等技术相结合,骨骼肌芯片有望在生物医学研究领域发挥更重要的作用。

基于糖代谢相关基因的卵巢癌预后模型的构建及验证

目的:建立糖代谢相关卵巢癌预后和药物反应的预测模型,探讨其临床意义。方法:由ICGC数据库和GSE26712数据集获取卵巢癌患者的基因表达谱和临床特征数据,从MSigDB中提取并收集糖代谢相关基因与之取交集得到糖代谢相关基因,使用多种算法,筛选出预后相关基因构建模型。对风险模型进行生存分析、基因功能富集分析和药物反应预测,使用cBioPortal在线工具呈现预后相关基因的遗传信息,运用Cytoscape软件显示预后相关基因和糖代谢共表达基因的网络。在正常卵巢组织细胞与上皮性卵巢癌组织细胞中对预后相关基因表达进行差异验证。结果:得到21个糖代谢相关基因进行LASSO回归分析,进一步进行多变量Cox回归分析,建立了包括LHPP(HR=1.51,95%CI为1.24~1.83,P<0.001)、PCK2(HR=0.72,95%CI为0.57~0.92,P=0.009)、PPP3CA(HR=1.35,95%CI为1.08~1.69,P=0.008)和NADK(HR=0.68,95%CI为0.52~1.89,P=0.005)的最优风险模型。使用cBioPortal在398份卵巢癌样本中探索这4个基因的遗传信息,提示基因结构域的改变可能影响蛋白的功能,Kaplan-Meier生存分析显示高风险组的总生存率较低风险组差(P<0.0001),ROC曲线提示模型区分度良好(2年AUC=0.773、3年AUC=0.839、4年AUC=0.852)。通过GSE26712和GSE9891进一步验证风险评分是卵巢癌患者预后独立危险因素,同时基于GSE9891数据集的临床信息,对风险评分、病理分级、FIGO分期、年龄等因素进行多因素Cox回归分析,发现该风险评分为独立预后因素(P<0.001)。KEGG富集分析提示,高风险评分组介导的生物学功能包括细胞周期、TNF、Hedgehog、DNA修复等通路,其中细胞周期通路显著富集(P<0.001),糖代谢相关基因主要通过细胞周期途径在卵巢癌的发生和进展中发挥关键作用;高风险组中,多数化疗药物敏感性更低,并基于细胞周期检查点抑制剂的研究发现4种药物(CGP-60474、BI-2536、CGP-082996和GW843682X)对高危人群具有较高的反应敏感性。RT-qPCR结果显示,LHPP、PPP3CA和NADK在卵巢癌细胞系(SKOV-3)中较正常卵巢细胞系(OSE)显著上调,PCK2在SKOV3细胞系中显著下调。HPA数据库证实在卵巢癌组织中这4个基因的免疫组化也与RT-qPCR结果呈相同的趋势。结论:本研究建立了基于4个糖代谢相关基因的卵巢癌风险模型,有助于预测卵巢癌患者的预后、生物学特征和潜在治疗药物,且该模型具有良好的稳定性和预测能力,为卵巢癌的预后提供分子标记物和治疗靶点。

构建胃癌中CD8^(+)T细胞相关预后模型并筛选治疗药物

目的:胃癌是高度异质性的恶性肿瘤,其病死率高,患者就诊时多已处于晚期且预后差。CD8^(+)T细胞可识别和消灭肿瘤细胞,对癌症的进展有重要影响。本研究旨在构建CD8^(+)T细胞浸润相关预后模型,为胃癌患者预后评估提供新的生物标志物及其药物治疗提供客观依据。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中下载371例胃癌样本的数据为训练集。从基因表达综合(Gene Expression Omnibus,GEO)数据库中下载433例胃癌样本的数据为测试集。计算训练集胃癌样本中CD8^(+)T细胞相对含量,将样本分为CD8^(+)T细胞高含量组和CD8^(+)T细胞低含量组,采用Kaplan-Meier法分析和比较2组之间的生存关系;采用加权基因共表达网络(weighted gene co-expression network analysis,WGCNA)分析训练集数据,筛选出与CD8^(+)T细胞最具相关性的基因模块;对该模块基因进行单因素Cox回归分析、最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)回归分析及多因素Cox回归分析筛选出与预后相关的基因,构建预后风险评分模型。应用模型计算训练集和测试集患者的风险评分并分别将患者分为高风险组和低风险组,并对模型进行内部及外部测试。应用肿瘤免疫单细胞枢纽2(tumor immune single-cell hub 2,TISCH2)数据库及人类蛋白质图谱(The Human Protein Atlas,HPA)数据库对模型基因进行验证。结合模型进行临床病理特征分析、功能富集分析、免疫相关性分析及化学治疗药物敏感性分析。结果:生存分析显示CD8^(+)T细胞低含量组的预后更差。WGCNA分析筛选出与CD8^(+)T细胞最具相关性的基因模块为Ebisque4。单因素Cox回归分析、LASSO逻辑回归分析及多因素Cox回归分析最终筛选出9个独立预后基因并构建预后风险评分模型。模型内部及外部测试结果均表明该模型具有较强的预测能力。TISCH2数据库验证表明模型基因在肿瘤微环境中具有不同的表达模式;HPA数据库验证表明模型基因的表达情况与预后模型较一致。临床病理特征分析表明风险评分与组织浸润深度相关;功能富集分析表明高风险组富集于分子间相互作用的通路,而低风险组则富集于代谢相关通路;免疫相关性分析表明高、低风险组之间的多个免疫细胞、免疫功能和免疫检查点均有差异;化学治疗药物敏感性分析表明高风险组对帕唑帕尼的敏感性更高,低风险组对西妥昔单抗的敏感性更高。结论:肿瘤微环境中的CD8^(+)T细胞浸润对胃癌患者的预后有显著的影响。基于CD8^(+)T细胞相关基因构建的预后模型具有普适性和临床适用性,对胃癌患者的药物治疗有重要的提示作用。

依达拉奉右莰醇合理性评价标准的建立及应用

目的通过属性层次模型分析评价安徽医科大学附属亳州医院依达拉奉右莰醇的临床应用情况,为医院的合理用药提供参考。方法参照依达拉奉右莰醇说明书、相关指南及专家共识,制定依达拉奉右莰醇药物利用评价标准。采用属性层次模型法对2022年6~12月我院190例应用依达拉奉右莰醇的患者病历进行药物分析评价,针对评价发现的问题进行药学干预,对2023年1~6月使用依达拉奉右莰醇的190份归档病历进行再评价。结果2022年6~12月依达拉奉右莰醇的主要不合理用药问题依次是用药监护(190份,100%)、用法用量(98份,51.58%)、疗程(62份,32.63%),19例(10%)患者病历评分≥90分(优秀),32例(16.84%)患者病历评分80~89分(良好),97例(51.05%)患者病历评分60~79分(合格),42例(22.11%)患者病历评分(MRS)<60分(不合格)。病历合格率为51.05%。经药学干预,2023年1~6月依达拉奉右莰醇的主要不合理用药问题显著降低,病历合格率由51.05%提高到73.16%(P<0.05)。结论我院依达拉奉右莰醇临床应用不合理情况较多,经临床药师干预沟通,病历合格率得到提高。属性层次模型法药物利用评价操作简单,评价结果直观,在临床用药中可以发挥一定作用。