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   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