目的 修订肺癌患者联合药物治疗间歇期症状评估问卷，并评价其信效度。方法 以中文版安德森症状评估量表及肺癌特异性模块为基础，经文献分析、专家会议和认知性访谈形成测试版问卷。于2023年10-12月便利选取福州、莆田2所三级甲等医院278例肺癌患者进行调查，评价其信效度及偏倚风险。结果 修订后问卷含7个症状系统、60个条目，跳转式作答后实际作答21个条目。总问卷Cronbach's α系数为0.856，各维度为0.639～0.747；内容效度指数为0.81。验证性因子分析显示模型拟合尚可（χ2/df=2.366，RMSEA=0.070，CFI=0.858），各维度因子载荷、组合信度及平均方差提取量均达到可接受标准，区分效度良好。COSMIN-RoB评价结果为良好。结论 该问卷信效度良好，可用于评估肺癌患者联合药物治疗间歇期症状严重程度。

Objective To revise the Symptom Assessment Questionnaire for Lung Cancer Patients During Combined Drug Therapy Intervals and evaluate its reliability and validity. Methods Based on the Chinese version of the M. D. Anderson Symptom Inventory and its lung cancer-specific module, a preliminary questionnaire was developed through literature review, expert panel discussions, and cognitive interviews. From October to December 2023, a convenience sample of 278 lung cancer patients was recruited from two tertiary hospitals in Fuzhou and Putian, China. Reliability, validity, and risk of bias were evaluated. Results The revised questionnaire comprised seven symptom-system domains and 60 items, with 21 items completed through a skip-logic design. The overall Cronbach's α coefficient was 0.856, and the coefficients for each domain ranged from 0.639 to 0.747. The content validity index of the questionnaire was 0.81. Confirmatory factor analysis demonstrated an acceptable model fit (χ2/df = 2.366, RMSEA = 0.070, CFI = 0.858). Factor loadings, composite reliability, and average variance extracted of all domains met acceptable standards, indicating good discriminant validity. The overall risk of bias was rated as good according to the COSMIN Risk of Bias checklist. Conclusion The revised questionnaire demonstrated satisfactory reliability and validity and can be used to assess symptom severity in lung cancer patients during combined drug therapy intervals.

药物流产是终止早期妊娠的常用方法，但流产后仍易出现阴道持续出血、不全流产、盆腔感染及月经紊乱等并发症，影响患者生殖健康。生化汤作为中医经典方剂，具有活血化瘀、温经止痛、祛瘀生新之功效，在药物流产后并发症的临床治疗中应用广泛。本文通过梳理近年相关文献，从生化汤概述、药物流产及其并发症、生化汤的临床应用、作用机制及使用禁忌等方面进行系统综述，重点分析现有研究的局限性及争议性问题，并对未来研究方向提出展望，以为临床应用生化汤治疗药物流产后并发症提供理论依据与实践参考。?

       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．

随着糖尿病发病率不断攀升,人们逐渐聚焦于糖尿病合并骨质疏松。围绕此疾病,国内外学者开展了广泛而深入的研究,临床实践聚焦于两点：糖尿病的精准治疗和骨质疏松的有效干预。在确保血糖稳定的基础上,致力于抑制骨吸收、促进骨形成。在此治疗理念指导下,临床医生应当更加全面了解血糖管理与抗骨质疏松药物的作用机制并合理应用,更大程度改善患者的临床症状及预后。然而,药物作用机制复杂,联合应用存在潜在药物相互作用问题。未来研究方向包括探索更安全有效的联合治疗方案,更加精确化地治疗以提高临床疗效。文章分析了降糖药物及抗骨质疏松药物对疾病的疗效,并展望未来的研究方向,旨在为临床实践提供更为深刻与全面的指导。

As the incidence of diabetes mellitus continues to rise,people are also gradually focusing on diabetes mellitus combined with osteoporosis,which puts patients at a higher risk of fragility fracture．Scholars at home and abroad have conducted extensive and in-depth research around this condition,and clinical practice has focused on two points：first,the precise treatment of diabetes,and second,the effective intervention of osteoporosis．On the basis of ensuring blood glucose stabilization,we are committed to inhibiting bone resorption and promoting bone formation．Under the guidance of this therapeutic concept,we should have a more comprehensive understanding of the mechanism of action of blood glucose management and anti-osteoporosis drugs and apply them rationally,aiming to improve the clinical symptoms and prognosis of patients to a greater extent through dual intervention． However,the mechanism of action of different drugs is complex,and there are potential drug-drug interactions and safety issues associated with their combined use．Future research directions should include exploring safer and more effective combination therapies,developing novel drugs,and more precise and individualized treatments to improve clinical efficacy．This article analyzes the efficacy of glucose-lowering drugs and anti-osteoporosis drugs on the disease and looks forward to future research directions,aiming to provide more profound and comprehensive guidance for clinical practice．

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.