目的   开发一种多功能纳米颗粒输送系统来刺激骨再生和血管形成，用于逆转骨质疏松症。方法   通过制备基于外消旋聚乳酸 Poly（D，L-lactide）即PLA的纳米颗粒来封装淫羊藿苷。随后，通过红细胞膜包被这些纳米颗粒以增强生物相容性。为了提高靶向特异性，进一步合成了由阿仑膦酸盐修饰的聚乙二醇-磷脂酰乙醇胺（PEG-DSPE） 组成的骨靶向聚合物脂质，并将其掺入细胞膜涂层中。结果   多功能纳米颗粒输送系统可通过调节骨髓间充质干细胞 （BMSC）功能，从而增强成骨和血管生成能力。结论   本研究结果表明，多功能纳米颗粒输送系统可以在体外刺激骨形成和血管形成，表明其有成为骨质疏松症先进治疗策略的潜力。

       Objective  To developed a multifunctional nanoparticle system to stimulate bone regeneration and vascularization as a therapeutics strategy for osteopovost．Methods  Poly（D，L-lactide）（PLA）-based nanoparticles were fabricated to encapsulate the icariin，which is renowned for its osteogenic potential．These nanoparticles were then coated with  red blood cell membranes to enhance biocompatibility．To further improve targeting specificity，a bone-targeted polymer-lipid consisting of alendronate-modified PEG-DSPE was synthesized and incorporated into the cell membrane coating．Results  The delivery system was designed to modulate the function of bone marrow mesenchymal stem cells，thereby enhancing both osteogenesis and angiogenesis．Conclusions  Our findings demonstrated that the therapeutic system could enhance bone formation and vascularization in vitro，indicating its potential as an advanced treatment strategy for osteoporosis．

目的 评估调脂药物靶点所介导的脂质表型（HMGCR、PCSK9和NPC1L1）与高血压肾病风险之间潜在的因果相关性。方法 使用来自欧洲人群公开可获得的全基因组关联研究（GWAS）汇总数据进行孟德尔随机化（MR）分析。采用与低密度脂蛋白胆固醇（LDL-C）相关的遗传变异,根据选定的调脂药物靶基因筛选工具变量,使用逆方差加权法作为主要MR分析方法,并进行敏感性分析确保结果的稳健性。结果 基因预测的LDL-C水平与较高的高血压肾病风险相关（OR=1.19,95% CI：1.03~1.38,P=0.021）。较高的HMGCR介导的LDL-C水平与高血压肾病风险存在正向因果相关性（OR=4.08,95% CI：2.86~5.81;P<0.001）。然而,PCSK9和NPC1L1介导的LDL-C水平与高血压肾病风险无相关性。Cochran Q检验、MR-PRESSO检测和MR-Egger截距测试显示工具变量之间不存在异质性或水平多效性。结论 HMGCR介导的LDL-C与高血压肾病的发病风险存在因果相关性,针对HMGCR基因的他汀类药物在高血压肾病的防治中可能具有潜在益处。

Objective To assess the potential causal relationship between lipid phenotypes mediated by lipid-lowering drug targets（HMGCR,PCSK9 and NPC1L1）and the risk of hypertensive nephropathy．Methods Mendelian randomization（MR）analysis was conducted using summary data from publicly available European ancestry genome-wide association studies（GWAS）．Genetic variants associated with low-density lipoprotein cholesterol（LDL-C）were used as instrumental variables based on selected lipid-lowering drug target genes screening tools．Inverse variance weighting was selected as the main MR analysis method,with sensitivity analyses conducted to ensure the robustness of the results．Results Genetically predicted LDL-C levels were associated with a higher risk of hypertensive nephropathy（OR=1.19,95% CI：1.03~1.38,P=0.021）．Higher LDL-C levels mediated by HMGCR were positively causally related to increased risk of hypertensive nephropathy（OR=4.08,95% CI：2.86~5.81;P<0.001）．However,LDL-C levels mediated by PCSK9 and NPC1L1 showed no significant association with the risk of hypertensive nephropathy．Cochran’s Q test,MR-PRESSO,and MR-Egger intercept tests showed no heterogeneity or horizontal pleiotropy among instrumental variables．Conclusions The findings of this study support the causal relationship between LDL-C mediated by HMGCR and increased risk of hypertensive nephropathy,suggesting potential benefits of statin therapy for hypertensive nephropathy．

药物治疗抵抗在临床实践中成为肿瘤治疗失败的主因。最近的研究指出,肿瘤细胞的耐药性可能源于其内部高度的细胞异质性,而这种异质性的基础则是肿瘤可塑性。肿瘤细胞可塑性可能引发一系列反应,包括对治疗的耐药性发展、免疫系统逃逸以及对周围组织和血管系统的侵袭和转移等。本文简要介绍肿瘤细胞可塑性的表现形式以及其在药物治疗抵抗的非遗传适应性机制与靶向治疗新策略。

Drug therapy resistance has emerged as a primary cause of treatment failure in cancer management．Recent research indicates that the resistance of tumor cells may stem from their high degree of intracellular heterogeneity,with the underlying basis being tumor plasticity．Tumor cell plasticity can trigger a cascade of responses,including the development of resistance to treatment,evasion of the immune system,and invasion and metastasis into surrounding tissues and the vascular system．This article provides a brief overview of the manifestations of tumor cell plasticity and its non-genetic adaptive mechanisms in drug therapy resistance,along with novel strategies for targeted treatment．

药物递送系统对于各类疾病意义非凡,但传统药物载体面临细胞毒性强、组织相容性低、半衰期短和靶向性弱等诸多挑战。血小板及其相关衍生物作为新型药物载体具有更为显著的优势。由于血小板自身的生理特点,以及在肿瘤、心血管疾病、血栓性疾病、感染等多种疾病中发挥的病理生理作用,血小板能够弥补传统药物载体的缺陷,具有极大的临床转化意义。该文总结了血小板相关药物递送系统目前的研究进展,以期为新型药物载体研究提供参考。

Drug delivery systems are important for various diseases,but conventional therapeutic drug have many shortcomings,such as high cytotoxicity,low histocompatibility,short half-life and weak targeting．Platelets and their derivatives have more significant advantages as novel drug carriers．Platelets play an important role in the pathophysiology of a wide range of diseases including oncology,cardiovascular diseases,thrombosis and infection．In this paper,we summarized the current research progress of platelet-related drug delivery systems to provide a reference for the research of novel drug delivery systems．

目的 探讨对于重症肺部感染患者采用药物+纤维支气管镜肺泡灌洗吸痰术治疗的效果。方法 选取2021年9月—2023年5月在郑州市第一人民医院ICU中94例肺部感染患者,分为观察组、对照组,对照组进行常规治疗,观察组采用药物+纤维支气管镜肺泡灌洗吸痰术治疗,对比两组患者的疗效、症状的缓解时间、炎性因子、实验室相关指标以及不良反应。结果 治疗后,观察组患者的治疗有效率91.49%高于对照组76.60%（χ²=3.887,P<0.05）,观察组患者的发热、肺部湿啰音、咳嗽以及咳痰等症状的缓解时间分别为（3.09±1.25）（4.17±2.24）（3.95±1.53）（4.05±1.77）d,均低于对照组（5.14±2.43）（7.03±3.23）（6.40±2.62）（6.32±1.81）d（t=5.143、4.988、5.536、6.147,P<0.05）,观察组的 C 反应性蛋白（C-reactive protein,CRP）、白细胞介素-6（Interleukin-6,IL-6）以及Toll样受体4（Toll-like receptor 4,TLR-4）水平分别为（3.64±0.87）mg/L、（54.59±10.65）ng/mL、（7.94±1.57）%,均低于对照组（7.51±1.43）mg/L、（87.66±11.17）ng/mL、（12.11±2.48）%（t=15.850、14.690、9.740,P<0.05）,观察组的气道压力、动脉血二氧化碳分压（partial pressure of carbon dioxide in artery,PaCO₂）水平分别为（6.92±3.60）cmH₂O、（43.19±6.29）mmHg,低于对照组（8.68±2.98）cmH₂O、（55.43±5.95）mmHg,观察组动脉氧分压（Partial arterial oxygen pressure,PaO₂）（86.06±5.31）mmHg、血氧饱和度（oxyhemoglobin saturation,SpO₂）（98.03±6.63）%高于对照组（68.04±5.19）mmHg、（90.22±5.51）%要高（t=2.582、9.692、16.638、6.221,P<0.05）,观察组中的不良反应发生率为2.13%与对照组10.64%比较差异无统计学意义（χ²=2.849,P>0.05）。结论 对处于ICU中的肺部感染患者治疗时,使用药物+纤维支气管镜肺泡灌洗吸痰术能够改善患者症状,降低炎性因子水平。

Objective To investigate the efficacy of medication combined with bronchoscopic alveolar lavage and sputum aspiration in ICU patients with severe pulmonary infection. Methods Ninety-four patients with pulmonary infection in the ICU of Zhengzhou First People's Hospital from September 2021 to May 2023 were selected and divided into observation group and control group．The control group received routine treatment,and the observation group was treated with medication and bronchoscopic alveolar lavage and sputum aspiration．The efficacy,duration of symptom remission,inflammatory factors,laboratory-related indicators and adverse reactions were compared between the two groups. Results After treatment,the effective rate of 91.49% in observation group was significantly higher than 76.60% in control group（χ²=3．887,P<0.05）．The relief time of fever,pulmonary rale,cough and sputum in observation group was（3.09±1.25）d,（4.17±2.24）d,（3.95±1.53）d,and（4.05±1.77）d,respectively,which were significantly lower than the control group[（5.14±2.43）d,（7.03±3.23）d,（6.40±2.62）d and（6.32±1.81）d]（t=5.143,4.988,5.536,6.147,P<0.05）．The levels of CRP,IL-6 and TLR-4 in the observation group were（3.64±0.87）mg/L,（54.59±10.65）ng/mL and（7.94±1.57）%,respectively．They were significantly lower than（7.51±1.43）mg/L,（87.66±11.17）ng/mL and（12.11±2.48）% in the control group（t=15.850,14.690,9.740,P<0.05）．The airway pressure and PaCO₂ levels of the observation group were（6.92±3.60）cmH₂O and（43.19±6.29）mmHg,respectively,which were significantly lower than those of the control group[（8.68±2.98）cmH₂O and（55.43±5.95）mmHg]．The levels of PaO₂[（86.06±5.31）mmHg] and SpO₂[（98.03±6.63）%] in the observation group were higher than those in the control group[（68.04±5.19）mmHg and（90.22±5.51）%],and there were statistically significant differences（t=2.582,9.692,16.638,6.221,P<0.05）．The adverse reactions of 2.13% in the observation group were lower than 10.64% in the control group,and there was no statistically significant difference（χ²=2.849,P>0.05）. Conclusions In ICU patients with severe lung infection,the treatment of drugs combined with alveolar lavage and fiberoptic bronchoscopic aspiration is better,and can significantly improve the symptoms and inflammatory factor levels of patients．

目的 探讨常规超声心动图联合二维斑点追踪技术评估急性白血病患儿在接受蒽环类药物治疗后产生的心脏毒性,早期检测左心功能障碍。方法 采用前瞻性非随机观察研究,选取新诊断急性淋巴细胞白血病患儿20例,分别于确诊白血病后接受蒽环类药物治疗前、接受所有蒽环类药物剂量后以及确诊白血病1年后,进行常规超声心动图和二维斑点技术监测评估心脏毒性。结果 左室流出道速度积分TVI和E、E/E’在治疗期间下降,并在诊断后1年恢复至治疗前数值。在二维斑点追踪纵向应变中,GLPS-LAX、GLPS-A2C、LV-GLPS在完成所有蒽环类药物剂量后与诊断后比较差异有统计学意义,以及诊断后1年与蒽环类药物治疗后比较差异有统计学意义。但GLPS-A4C各时间点比较差异无统计学意义。结论 常规超声心动图联合二维斑点追踪技术的纵向整体应变可早期发现白血病患儿化疗所致的左室功能障碍。

Objective To evaluate cardiotoxicity in children with acute lymphoblastic leukemia treated with anthracyclines by echocardiography combined with 2D speckle tracking imaging,and to detect left heart dysfunction early．Methods In this prospective nonrandomized study,20 children with newly diagnosed acute lymphoblastic leukemia were assessed for cardiotoxicity by echocardiography and 2D speckle tracking imaging in three periods during the treatment．Results The left ventricular outflow tract velocity integral TVI and E,E/E’ decreased during treatment,and went back to the pre-treatment value one year after diagnosis．In the longitudinal strain of 2D speckle tracking imaging,in GLPS-LAX,GLPS-A2C,LV-GLPS,there were statistical differences between treatment completed and after diagnosis,and between 1 year after diagnosis and treatment completed．However,GLPS-A4C has no statistical significance．Conclusion sThe conventional echocardiography combined with longitudinal overall strain of 2D speckle tracking imaging can comprehensively evaluate the early changes of left ventricular dysfunction caused by chemotherapy in children with leukemia．

目的 为临床合理使用替考拉宁以及更好地管理接受替考拉宁治疗的患者。方法 从药学角度对2022年日本《2022 JSC/JSTDM临床实践指南:替考拉宁治疗药物监测》(简称《指南》)涉及替考拉宁治疗的9个临床问题进行解读。结果 《指南》指出药-时曲线下面积/最小抑菌浓度是替考拉宁的关键药动学/药效学参数。替考拉宁治疗药物监测(TDM)的目的是明确目标谷浓度(C_min),对于严重或复杂的耐甲氧西林金黄色葡萄球菌(MRSA)感染,指南建议替考拉宁C_min为20~40 mg/L。肾功能正常或轻度受损的非复杂性的MRSA感染,目标C_min为15~30 mg/L。严重和/或复杂性MRSA感染,如感染性心内膜炎和骨髓炎,替考拉宁C_min为20~40 mg/L。结论 《指南》针对不同病理状态下患者替考拉宁目标C_min的确定,为临床治疗中替考拉宁TDM、个体化给药提供参考。

Objective To make rational use of teicoplanin and better management of patients treated with teicoplanin. Methods Nine clinical issues related to the treatment of teicoplanin in Clinical practice guidelines for therapeutic drug monitoring of teicoplanin: a consensus review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring (Japan, 2022) were interpreted from the perspective of pharmacy. Results The guidelines indicated that the area under drug-time curve/minimum inhibitory concentration was the key pharmacokinetic/pharmacodynamic parameters of teicoplanin.The purpose of therapeutic drug monitoring (TDM) of teicoplanin is to specify the target trough concentration (C_min), which guidelines recommend for severe or complex methicillin-resistant Staphylococcus aureus (MRSA) infection is 20-40 mg/L.The target C_min for uncomplicated MRSA infection with normal or mildly impaired renal function is 15-30 mg/L.For severe and/or complex MRSA infections, such as infective endocarditis and osteomyelitis, the C_min of teicoplanin was 20-40 mg/L. Conclusions The guidelines are aimed at the determination of target C_min of teicoplanin in patients with different pathological conditions, and provide reference for individual drug administration and teicoplanin TDM in clinical treatment.

目的 本文主要分析乳腺癌患者应用蒽环类药物序贯曲妥珠单抗治疗对其心脏毒性的相关危险因素,并按照危险因素选择合适患者的治疗方案。方法 研究纳入了2019年6月—2022年6月在本院接受治疗的300例乳腺癌患者,患者接受蒽环类药物序贯曲妥珠单抗治疗,按照患者治疗期间是否发生心脏毒性进行分组,即为11例发生心脏毒性(观察组),289例患者未发生心脏毒性(对照组)。记录2组患者个人基础资料、肿瘤分期、病史、蒽环类药物以及联合化疗等因素,通过Logistic回归逐一对各项因素展开分析,了解相关危险因素。结果 在本次研究分析中,心脏毒性发生例数为11例,发生率为3.67%。其中289例患者未出现心脏毒性,患者用药后未出现相关反应。2组患者在联合放疗、高脂血症、蒽环类药物种类均有差异,差异有统计学意义(P<0.05)。结论 乳腺癌患者应用蒽环类药物序贯曲妥珠单抗后,发生心脏毒性的几率升高,其危险因素主要包括高脂血症史、应用表柔比星治疗以及左胸放疗史。

肿瘤相关巨噬细胞（TAMs）是肿瘤微环境中最丰富的免疫细胞之一,M2-TAMs在肿瘤发生、发展、转移和治疗过程中发挥重要作用,被认为是肿瘤治疗中的重要靶点。已有的研究表明,通过将促肿瘤的M2-TAMs重编程为促炎的M1-TAMs可实现抑制肿瘤生长和转移。本综述在介绍TAMs与肿瘤治疗相关背景的基础上,重点关注纳米药物重编程TAMs增强抗肿瘤的研究进展。本文将从TAMs靶向递送各种活性物质进行重编程TAMs和纳米药物介导的异常肿瘤微环境调节的间接重编程TAMs两种方式,综述近年来基于纳米药物递送系统的调控策略及典型例子。

Tumor associated macrophages（TAMs）is one of the most abundant immune cells in the tumor microenvironment．M2-TAMs play an important role in tumor genesis,progression,metastasis and treatment,and is additionally a very important target in tumor therapy．Previous studies have shown that inhibition of tumor growth and metastasis can be achieved by reprogramming M2-TAMs to M1-TAMs．On the basis,this review focuses on the analysis progress of nano-drug reprogramming TAMs to boost anti-tumor．In this paper,we reviewed two methods of reprogramming TAMs for targeted delivery of various active substances and indirect reprogramming TAMs for abnormal tumor microenvironment regulation mediated by nanomedicine．The regulatory strategies and typical samples of nanomedicine delivery systems in recent years were summarized.

目的 分析药物性牙龈增生（DGO）治疗中半导体激光及牙周基础治疗的应用效果,以期进一步提升DGO治疗有效性,促使患者快速康复。方法 分析于我院进行治疗的88例DGO患者基本资料,按照入院顺序使用奇偶号法将其等分为各44例的对照组和研究组,予对照组患者实施常规牙周基础治疗,予研究组患者实施牙周基础治疗联合半导体激光治疗,对比2组治疗相关数据。结果 治疗前2组患者牙龈增生指数（GHI）比较差异无统计学意义（P>0.05）,经过治疗,研究组患者各阶段GHI均低于对照组,差异存在统计学意义（P<0.05）;治疗前2组患者龈沟出血指数（SBI）、探诊深度（PD）以及菌斑指数（PLI）比较差异无统计学意义（P>0.05）,经过治疗研究组各项治疗评分均比对照组更为理想,差异存在统计学意义（P<0.05）;治疗后研究组总有效率为97.73%,对照组总有效率为81.82%,差异存在统计学意义（P<0.05）。结论 对DGO患者实施牙周基础治疗下的半导体激光干预能够在更大程度上改善患者病情,同时缩短治疗周期,提升治疗总有效率,应用效果理想,可在临床推广使用。