与正常组织细胞微环境相比,肿瘤微环境具有一定的异质性,包括偏酸性、氧化还原状态失衡、存在高浓度活性氧以及酶过量表达等。根据以上肿瘤微环境特点,可设计出一系列通过各种特殊微环境响应型连接臂相连的小分子或聚合物前药纳米粒。其中,多柔比星阿霉素作为一类最常见的广谱抗肿瘤药物在治疗肿瘤的过程中发挥重要作用。文章探讨了在肿瘤微环境特异性的生理状态下针对不同微环境所设计的多柔比星前药及其释放特性等,归纳总结了肿瘤微环境响应型多柔比星前药的研究进展。

Compared with normal tissue cell microenvironment, there is some differences in tumor microenvironment, such as partial acidity, imbalance of redox state, high concentration of reactive oxygen species and cathepsin. According to the above characteristics of tumor microenvironment, a series of small molecule or polymer prodrug nanoparticles connected by various special microenvironment responsive structures can be designed. Doxorubicin, as one of the most common broad-spectrum antitumor drugs, plays an important role in the treatment of tumors. This review discusses the doxorubicin prodrug designed for different tumor microenvironments under the physiological state of tumor microenvironment specificity and their release characteristics, and summarizes the research progress of tumor microenvironment-responsive doxorubicin prodrug.

       肿瘤治疗仍然是生物医学研究的一个突出领域。围绕各种化学治疗（化疗）药物和其他治疗药物的不良反应和靶向疗效的研究推动了各种药物载体的发展。这些载体聚焦于提高肿瘤部位的药物浓度，最大限度地减少全身不良反应，并改善治疗效果。在已报道的递送系统中，可注射水凝胶由于其微创的药物递送特性，已成为化疗药物体内递送的重要载体形式。文章系统地总结了可注射水凝胶的类型和特征，并进一步概括了可注射水凝胶装载药物的方式，同时深入讨论可注射水凝胶在治疗肿瘤的各种药物的递送应用。文章对原位注射水凝胶在治疗肿瘤方面存在的潜在性挑战和可能的解决方案提供了动态前瞻性的参考。可注射的水凝胶作为药物传递系统用于肿瘤治疗具有良好的发展前景。

       Tumor treatment remains a prominent area of biomedical research．The  researches surrounding the adverse 

reactions and targeted efficacy of various chemotherapy drugs and other therapeutic drugs have driven the development of various drug carriers．These carriers focus on increasing drug concentration at tumor site，minimizing systemic adverse reactions，and improving treatment outcomes．In the reported delivery systems，injectable hydrogels have become an important carrier for the delivery of chemotherapeutic drugs in vivo due to their minimally invasive characteristics．This review systematically summarized the types and characteristics of injectable hydrogels，and further summarized their drug loading methods．At the same time，the application of injectable hydrogels in the delivery of various drugs for tumor treatment was discussed in depth．This  review provides dynamic and prospective reference for the potential challenges and possible solutions of the in situ injectable hydrogels for tumor therapy．Injectable hydrogels as drug delivery systems are with good prospects for tumor treatment．

       目的   通过分析广州某三甲医院临床试验用药品规范管理体系构建前后试验用药品超温次数及质控发现缺陷项数量变化情况，为药物临床试验规范开展提供参考。方法   结合某医院临床试验用药品管理实践，以试验用药品超温次数、质控发现缺陷项数量占项目比为评价指标，使用卡方检验进行比较。结果   某医院实施临床试验用药品规范管理体系后，发生试验用药品超温次数由实施前的9次下降至3次，呈明显下降趋势，2018—2020年试验用药品管理方面质控发现缺陷项数量占项目比为70.25%，2021—2023年占项目比为18.90%，实施前后组间比较差异有统计学意义（P＜0.001）。结论   构建临床试验用药品规范管理体系，可以减少试验用药品超温次数和试验用药品管理方面质控发现缺陷项数量，从而保证药物临床试验的质量。

       Objective   To analyze the changes in the number of excessive temperature incidents and the proportion of quality control issues in drug management before and after the establishment of construction and practice of standardized management system in a tertiary hospital in Guangzhou，to provide a reference for drug clinical trials standard development．Methods  Based on the management practice of investigational medicinal products from a hospital，the number of excessive temperature incidents and the proportion of quality control issues in drug management were taken as evaluation index and compared using chi-square tests．Results  After implementing the standardized management system for investigational drugs，the number of temperature exceeding incidents decreased from 9 times to 3 times，showing an obvious decreasing trend，and from 2018 to 2020，the  proportion of quality control issues in drug management accounted for 70.25%，while from 2021 to 2023，it accounted for 18.90%．There was a statistically significant difference between the groups before and after the implementation（P＜0.001）．Conclusions  The establishment of  standardized management  system for investigational medicinal  products can  reduce the  number of excessive temperature incidents and the proportion of quality control issues in drug management，and ensure the quality of drug clinical trials．

       目的   探讨免疫及靶向药物联合肝动脉灌注化学治疗（化疗）治疗晚期肝癌的临床疗效。方法   选取甘肃省武威市人民医院2021年1月—2024年1月收治的78例晚期肝癌患者进行回顾性分析，其中20例患者采取单纯肝动脉灌注化疗（HAIC）治疗为单化疗组，30例患者采取HAIC联合程序性细胞死亡受体-1（PD-1）抗体治疗为免疫组，28例患者采取HAIC联合PD-1抗体免疫治疗与甲磺酸仑伐替尼胶囊靶向治疗为联合组。对比三组临床疗效、治疗前后胚抗原（CEA）、糖类抗原125（CA125）、甲胎蛋白（AFP）表达水平，不良反应发生率，并采用Piper疲乏修正量表（PFS-R）、世界卫生组织生存质量量表简表（WHOQOL-BREF）对两组癌因性疲乏程度及生存质量进行评价。结果   单纯化疗组、免疫组、联合组客观缓解率分别为15.00%、40.00%、64.29%，疾病控制率为30.00%、66.67%、82.14%，联合组高于单纯化疗组与免疫组（χ ² =11.720，P=0.003；χ ² =13.890，P＜0.001）；治疗后三组患者CEA、CA125、AFP水平均降低，且联合组［CEA：（13.62±4.24）ng/mL、CA125：（31.62±13.66）U/mL、AFP：（35.21±5.93）ng/mL］低于免疫组［（17.85±3.32）ng/mL、（59.26±9.35）U/mL、（42.12±4.12）ng/mL］及单纯化疗组［（23.73±4.79）ng/mL、（64.57±5.23）U/mL、（47.46±5.32）ng/mL］，对比差异有统计学意义（F=7.698，P＜0.001；F=11.480，P＜0.001；F=14.952，P＜0.001；P＜0.05）；所有患者均无5级不良反应及严重肝功能损害出现，且三组血小板减少、白细胞减少、腹痛、呕吐、消化道出血、厌食等不良反应发生率对比差异无统计学意义（P＞0.05）；治疗后三组患者PFS-R评分均降低，联合组（3.85±1.13）分低于免疫组（5.39±1.25）分及单纯化疗组（6.33±1.26）分，WHOQOL-BREF评分均升高，联合组（348.58±66.12）分高于免疫组（297.24±72.21）分及单纯化疗组（256.35±41.67）分，对比差异有统计学意义（F=2.526，P=0.014；F=2.167，P=0.033）。结论   免疫及靶向药物联合肝动脉灌注化疗治疗晚期肝癌疗效显著，可有效控制疾病进展的同时，降低机体肿瘤标志物水平，安全性可控，同时可改善患者生存质量，减轻癌因性疲乏程度。

       Objective  To explore the clinical efficacy of immune and targeted drugs combined with hepatic artery infusion chemotherapy（HAIC）in the treatment of advanced liver cancer．Methods  A retrospective analysis was conducted on 78 patients with advanced liver cancer admitted to our hospital from January 2021 to January 2024．Among them，20 patients were treated with simple HAIC and divided into a single chemotherapy group．Thirty patients were treated with HAIC combined with PD-1 antibody，and divided into an immune group．Twenty-eight patients were treated with HAIC combined with PD-1 antibody immunotherapy and lenvatinib mesylate capsule targeted therapy，and divided into a combination group．The clinical efficacy of three groups，the expressionlevels of CEA，CA125，AFP，and incidence of adverse reactions before and after treatment were compared．Piper Fatigue Correction Scale（PFS-R）and the WHO QOL-BREF were used to assess cancer-related fatigue in both groups．The degree of fatigue and quality of life were assessed．Results  The objective response rates of the simple chemotherapy group，the immune group，and the combination group were 15.00%，40.00% and 64.29%，respectively．The disease control  rates were 30.00%，66.67% and 82.14%，respectively．The indicators above of the combination group was significantly higher than those in the simple chemotherapy group and the immune group（χ ² =11.720，P=0.003；χ ² =13.890，P＜0.001；P＜0.05）．After treatment，the levels of CEA，CA125 and AFP were all decreased in the three groups，and those in the combined group （CEA［13.62±4.24］ng/mL，CA125［31.62±13.66］U/mL，AFP：Ng/mL［35.21±5.93］）were lower than those in the immune group（17.85±3.32 ng/mL，59.26±9.35 U/mL，/ 42.12±4.12 ng/mL）and single chemotherapy group（23.73±4.79 ng/mL，64.57±5.23 U/mL47.46±5.32］ng/mL），the differences were statistically significant（F=7.698，P＜0.001；F=11.480，P＜0.001；F=14.952，P＜0.001；P＜0.05）．All patients had no grade 5 adverse reactions or severe liver function damage，and there was no statistically significant difference in the incidence adverse reactions such as thrombocytopenia，leukopenia，abdominal pain，vomiting，gastrointestinal bleeding，and anorexia among the three groups（P＞0.05）．After treatment，the PFS-R score of the three groups was decreased，and the combined group（3.85±1.13）score was lower than that of the immune group（5.39±1.25）and the chemotherapy group（6.33±1.26）．While the WHOQOL-BREF score was increased，the score of combination group（348.58±66.12）was higher than that of immune group（297.24±72.21）and chemotherapy group（256.35±41.67），and the difference was statistically significant（F=2.526，P=0.014；F=2.167，P=0.033；P＜0.05）．Conclusions  The combination of immune and targeted drugs with hepatic artery infusion chemotherapy has a significant therapeutic effect on advanced liver cancer．It can effectively control disease progression，reduce tumor marker levels in the body，improve patient quality of life，and alleviate cancer-related fatigue，with controllable safety