Intestinal mucositis is a common and debilitating complication of the chemotherapeutic agent irinotecan (CPT-11), characterized by intestinal barrier disruption, oxidative stress, inflammation, and gut microbiota dysbiosis. Radix Hedysari polysaccharides (HPS) possess anti-inflammatory, antioxidant, and microbiota-regulating properties, but their protective effects against CPT-11-induced intestinal injury remain unclear. In this study, we investigated the protective effect and mechanism of HPS in CPT-11-induced intestinal mucositis using Drosophila melanogaster and BALB/c mouse models. HPS supplementation significantly improved survival and locomotor activity in CPT-11-induced flies, and ameliorated intestinal phenotypes including excessive feeding, increased excretion, crop enlargement, shortened gut length, impaired acid-base balance, and elevated intestinal cell death. HPS also suppressed reactive oxygen species (ROS) levels and modulated antioxidant-related genes (gstD1, cat, sod1, sod2) and the JAK pathway (STAT92E, UPD3, UPD3-1) in fly guts. In mice, administration of HPS reversed the CPT-11-induced gut microbial dysbiosis, restored microbial diversity, and suppressed serum pro-inflammatory cytokines (TNF-α and IL-6). Mechanistic studies revealed that HPS alleviated colonic injury by up-regulating the Keap1/Nrf2 antioxidant response and down-regulating the JAK1/STAT6 inflammatory signaling. These findings suggest that HPS has a protective role in CPT-11-induced intestinal mucositis via antioxidant, anti-inflammatory, and microbiota-modulatory activities, supporting its potential as a therapeutic agent for chemotherapy-induced intestinal injury.

Astragalus polysaccharide (APS) is the crucial active ingredient of Astragalus membranaceus, which has antioxidant, immunomodulatory and anti-inflammatory properties. However, the therapeutic effects and biological mechanisms of APS on chemotherapeutic intestinal mucositis (CIM) have not been clarified yet. Here, the protective mechanism and functional components of APS against CIM was investigated in both Drosophila melanogaster (fruit fly) and mice models. Administration of APS could remarkably attenuate the overall physiological impairments caused by CPT-11 in flies, including increased the survival rate, improved motility, restored the size of ovary and reproduction. APS supplementation could significantly alleviate CPT-11-induced intestinal damage, which involved in restoration of intestinal length, reduction of crop size and excretion, improvement of intestinal homeostatic imbalance, and restoration of intestinal shortened villi. Furthermore, the integration of transcriptomics and microbiomics demonstrated that APS exerted its protective effect mainly by mitigating oxidative stress associated with FoxO signaling, over-activated innate immunity and dysbiosis of intestinal flora. Subsequently, three molecular weight components (APS-I, APS-II and APS-III) were extracted from APS. Among the studied substances, APS-III as the lowest molecular weight demonstrated the highest efficacy in reducing intestinal mucositis compared to both APS-I and APS-II. Collectively, these results support that APS is intended to be constructed as an effective medication for addressing intestinal diseases.

Cytarabine (Ara-C) is a widely used drug in acute myeloid leukemia (AML). However, it faces serious challenges in clinical application due to serious side effects such as gastrointestinal disorders and neurologic toxicities. Until now, the mechanism of Ara-C-induced damage is not clear. Here, we used Drosophila melanogaster (fruit fly) as the in vivo model to explore the side effects and mechanism of Ara-C. Our results showed that Ara-C supplementation delayed larval development, reduced lifespan, impaired locomotor capacity, and increased susceptibility to stress response in adult flies. In addition, Ara-C led to the intestinal morphological damage and ROS accumulation in the guts. Moreover, administration of Ara-C promoted gene expressions of Toll pathway, IMD pathway, and apoptotic pathway in the guts. These findings raise the prospects of using Drosophila as in vivo model to rapidly assess chemotherapy-mediated toxicity and efficiently screen the protective drugs.

目的 探讨红芪多糖对急性放射性肺炎小鼠的保护作用及其机制.方法 小鼠随机分为空白组、模型组、吡非尼酮组(200 mg/kg)、红芪水煎液组(5 000 mg/kg)和红芪多糖低、中、高剂量组(15、30、60 mg/kg),每组 24只.预防给药 7d后,除空白组外,其余各组小鼠照射 16 Gy全胸X线进行造模,继续给药 7d.各组于造模前进行CT影像学检测,造模后第 6 天进行肺功能及CT影像学检测.最后一次给药 30 min后,采用ELISA法检测血清TNF-α、IL-6、MDA水平及 SOD、GSH-Px活性,HE染色观察肺组织病理形态变化,Western blot法检测肺组织 TNF-α、mTOR、HIF-1α、VEGF蛋白表达,RT-qPCR法检测肺组织mTOR、VEGF、HIF-1α mRNA表达.结果 红芪多糖可在一定程度上改善急性放射性肺炎小鼠的精神状态、活动量、皮毛光泽.与模型组比较,红芪多糖高剂量组小鼠每分钟通气量增加(P<0.01),小鼠肺脏CT值和肺系数降低(P<0.05,P<0.01);红芪多糖中、高剂量组小鼠血清TNF-α、IL-6、MDA水平降低(P<0.05,P<0.01),SOD、GSH-Px活性升高(P<0.05,P<0.01),肺组织病理炎性反应减轻,肺泡炎病理评分降低(P<0.05,P<0.01),肺组织 mTOR、VEGF、HIF-1α mRNA 表达和 TNF-α、mTOR、HIF-1α、VEGF蛋白表达降低(P<0.05,P<0.01).结论 红芪多糖可能通过调控HIF-1 信号通路来防治小鼠急性放射性肺炎的发生发展.

目的 基于网络药理学探究敦煌芮草膏减轻荨麻疹小鼠皮肤瘙痒的机制.方法 将小鼠随机分为空白组、模型组、丁酸氢化可的松乳膏组和敦煌芮草膏低、中、高剂量组,每组12只,采用卵白蛋白和氢氧化铝混悬液建立小鼠荨麻疹模型,记录24 h搔抓情况.空白组和模型组涂抹PBS,敦煌芮草膏低、中、高剂量组和丁酸氢化可的松乳膏组按照指尖单位法给药,持续18 d.给药结束后,每只小鼠自股动脉采血检测BASO、EOS水平,取背部皮肤组织检测IL-4、IgE、TNF-γ水平,HE染色观察皮肤组织病理变化.基于TCMSP、UniProt、OMIM等公共数据库和KEGG通路分析等网络药理学基本方法预测潜在通路.采用蛋白印迹法检测皮肤组织PI3K、Akt、p-PI3K、p-Akt蛋白表达以验证网络药理学预测结果.结果 与空白组比较,模型组小鼠血液中嗜碱性粒细胞计数及百分比、嗜酸性粒细胞计数及百分比,患处皮肤组织IL-4、IgE水平升高(P<0.01),TNF-γ水平降低(P<0.01);与模型组比较,敦煌芮草膏各剂量组均能降低小鼠血液中嗜碱性粒细胞计数及百分比、嗜酸性粒细胞及百分比和皮肤组织IL-4、IgE水平(P<0.01),并升高TNF-γ水平(P<0.01).网络药理预测该方可能通过PI3K/Akt信号通路发挥止痒作用.药理研究显示,敦煌芮草膏能下调PI3K、Akt、p-PI3K、p-Akt蛋白表达(P<0.01).结论 敦煌芮草膏能有效改善荨麻疹小鼠瘙痒症状,其作用机制可能与PI3K/Akt信号通路有关.

肠损伤是临床应用化疗药物的常见不良反应,限制了化疗药的进一步应用,并给病人造成严重的身心负担.目前化疗肠损伤的发生机制比较复杂,中医药具有极好的防治作用.本文综述化疗引起肠道菌群失调、氧化应激、炎症反应、细胞凋亡、免疫损伤等造成肠损伤的相关机制,总结中医药防治的作用,将为防治化疗肠损伤的中药研发提供理论基础.

目的 探讨归芪益元膏对气血两虚证模型大鼠的药效学作用.方法 以"限制饮食+负重游泳"和注射乙酰苯肼建立气血两虚大鼠模型,采用边造模边给药的方法,给予归芪益元膏进行灌胃干预.观察大鼠耳缘、鼻唇颜色,精神状态等证候学指标,并测定力竭游泳时间;腹主动脉取血,检测血常规;取胸腺和脾脏并称重,计算脏器指数,HE染色观察胸腺和脾脏形态;取肝脏、肌肉,测定肝糖原、肌糖原含量;取股骨,流式细胞术检测骨髓有核细胞凋亡.结果 与空白对照组相比,模型对照组大鼠出现活动减少,皮毛无光泽,呼吸短促等症状;且力竭游泳时间缩短,肝糖原、肌糖原含量降低,血中红细胞、白细胞、血红蛋白、血小板及红细胞压积均下降,骨髓有核细胞减少,骨髓有核细胞凋亡率上升,脾指数和胸腺指数降低(P＜0.01);同时,脾脏结节和淋巴细胞数减少,红、白髓线不明,大量红细胞渗出,胸腺萎缩,分叶不清晰,皮质变薄,皮质细胞排列不紧密.与模型对照组相比,归芪益元膏高、中、低剂量组大鼠力竭游泳时间增加,肝糖原、肌糖原含量增加,血中红细胞、白细胞、血红蛋白、血小板及红细胞压积增加,骨髓有核细胞增加,骨髓有核细胞凋亡率下降,脾指数和胸腺指数增加(P＜0.01);同时,脾脏结节和淋巴细胞数明显增多,红、白髓较清晰,胸腺分叶较清晰,可见皮质及髓质,皮质内细胞较模型组明显增多.结论 归芪益元膏能有效改善气血两虚证候,这可能与其提高机体能量供应,改善骨髓造血功能和增强免疫功能等有关.

Frostbite is a tissue injury that occurs when the body is exposed to extreme cold. Its pathological mechanism is complex and has not been fully elucidated. In high cold and high altitude areas,outdoor sports people have a high risk of injury, and severe frostbite has high disability and mortality. Exploring the pathological mechanism of frostbite is helpful to determine the treatment methods and timing. At present, the clinical treatment of frostbite is mainly symptomatic treatment, such as drug treatment and surgical treatment, but the curative effect can not meet the clinical needs. Therefore, it is of great significance to seek more efficient drugs or treatment methods. This article reviews the relevant research progress in pathophysiological mechanism, clinical treatment, cellular and molecular pathways of frostbite in recent years, in order to provide new ideas for future research and clinical treatment.

The article summarizes the characteristic horn medicine extracted from Dunhuang’s “Fu Xing Jue” to identify and treat urticaria, which has the effects of relieving the cold, dispelling wind and heat, activating blood and relieving itching, etc, and the efficacy of clinical flexible tailoring in the treatment of urticaria is very good, and can also provide valuable reference for the clinical treatment of itchy skin diseases.

角药依据中医基础理论知识,是3味药物有机结合,有助于扩展单味中药治疗范围,拓宽临床用方思路.而敦煌遗书中可提取柴胡、白芍、茯苓—疏肝止痛;乳香、没药、夏枯草—活血散结;香附、莪术、王不留行—通气散结;瓜蒌、牡蛎、山慈菇—化痰散结;枳实、陈皮、半夏—理气化痰;白芥子、贝母、甘草—化痰和中;柴胡、黄芩、桂枝—清热止痛;当归、仙茅、知母—调补冲任8组特色角药,通过灵活化裁可治疗临床常见乳癖疾病.疗效甚佳,常获痊愈,以便为临床治疗乳癖用药提供借鉴价值.

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicines. Astragalus membranaceus (AM), also named Huangqi, is one of the most commonly used fundamental herbs in China. Here, we aimed to investigate mechanism and bioactive compounds of AM on treating sodium dodecyl sulfate (SDS)- induced colitis in Drosophila flies. Our data showed that AM extract (AME) supplementation had no toxic effect in flies, and protected flies against SDS-induced lifespan shortening, intestinal morphological damage, and colon length shortening. Moreover, AME supplementation remarkably rescued SDS-induced intestinal stem cell (ISC) overproliferation and increased reactive oxygen species (ROS) level in the intestine. Mechanistically, AME remarkably rescued the altered expression levels of genes and proteins in c-Jun N-terminal kinase (JNK) and JAK-STAT signaling pathways induced by SDS in gut. Additionally, formononetin, isoliquiritigenin, isorhamnetin, astragaloside I, astragaloside III, vanillic acid, and caffeic acid in AM had protection against SDS-induced inflammatory damage in flies. Taken together, AME could ameliorate the intestinal inflammation partially by suppressing oxidative stress-associated JNK signaling and JAK-STAT signaling pathways. AME may provide a theoretical basis for natural medicine toward treating intestinal inflammatory disease in human.

目的 研究红芪不同提取分离部位抗肺间质纤维化的作用.方法 提取分离红芪各有效部位,采用喉镜引导下气管插管注入博来霉素法复制肺间质纤维化大鼠模型并随机分组,各组大鼠给予相应药物进行干预,检测大鼠一般状况、体质量、肺系数、脾脏及胸腺指数,肺组织中HA、LN、HYP水平,T细胞亚群及肺组织病理形态学.结果 红芪有效部位均可一定程度改善模型大鼠的精神状态、食量、活动量、皮毛光泽等;与模型组比较,红芪黄酮低、中剂量组和红芪皂苷高剂量组大鼠肺系数均降低(P<0.01),红芪多糖高剂量组大鼠在7 d和14 d的体质量均增加(P<0.01),红芪黄酮低剂量组可同时降低肺组织中HA、LN的水平(P<0.01),红芪黄酮各剂量组可降低HYP水平(P<0.01),红芪黄酮低剂量组大鼠CD3+CD4+CD8-细胞占比升高(P<0.01),红芪黄酮各剂量组大鼠CD4+/CD8+细胞比值升高(P<0.05).与模型组比较,HE染色发现各治疗组中肺泡炎及肺纤维化程度均减轻,其中红芪黄酮低剂量效果最好;Masson染色发现各治疗组肺纤维化程度均减轻,肺间隔略增宽,间质内可见小灶状胶原纤维沉积,病变范围较小,其中红芪黄酮中剂量组大鼠肺组织胶原纤维沉积减少.结论 红芪提取物多糖、黄酮及皂苷均可不同程度改善大鼠肺间质纤维化,其中红芪黄酮效果最佳.

目的 观察归芪益元膏联合化疗治疗小细胞肺癌局限期气阴两虚证的临床疗效.方法 将60例小细胞肺癌局限期气阴两虚证患者采用随机数字表法分为对照组和治疗组,各30例.对照组予化疗治疗,治疗组予归芪益元膏联合化疗治疗,21 d为1个疗程,共治疗4个疗程.2组治疗结束后随访12个月,比较2组的临床疗效、中位无进展生存期(mPFS)以及治疗前后的中医症状积分.结果 对照组总有效率为40.00％ (12/30)、总控制率为66.67％(20/30),治疗组总有效率为53.34％ (16/30)、总控制率为76.67％(23/30),2组总有效率、总控制率比较差异均无统计学意义(P＞0.05);治疗组mPFS为10个月,对照组为6个月,2组比较差异有统计学意义(P＜0.05);治疗后2组中医症状积分均明显降低,与同组治疗前比较差异有统计学意义(P＜0.05),且治疗组降低更明显,与对照组治疗后比较差异有统计学意义(P＜0.05).结论 归芪益元膏联合化疗治疗小细胞肺癌局限期气阴两虚证可明显改善患者的临床症状,延长患者生存期,疗效显著,值得临床推广应用.

Inflammatory bowel disease (IBD) is a chronic and life-treating inflammatory disease that can occur in multiple parts of the human intestine and has become a worldwide problem with a continually increasing incidence. Because of its mild early symptoms, most of them will not attract people's attention and may cause more serious consequences. There is an urgent need for new therapeutics to prevent disease progression. Natural products have a variety of active ingredients, diverse biological activities, and low toxicity or side effects, which are the new options for preventing and treating the intestinal inflammatory diseases. Because of multiple genetic models, less ethical concerns, conserved signaling pathways with mammals, and low maintenance costs, the fruit fly Drosophila melanogaster has become a suitable model for studying mechanism and treatment strategy of IBD. Here, we review the advantages of fly model as screening platform in drug discovery, describe the conserved molecular pathways as therapetic targets for IBD between mammals and flies, dissect the feasibility of Drosophila model in IBD research, and summarize the natural products for IBD treatment using flies. This review comprehensively elaborates that the benefit of flies as a perfact model to evaluate the therapeutic potential of phytochemicals against IBD.

目的 建立敦煌古医方大补肾汤(Dabushen Decoction,DD)标准煎液的HPLC指纹图谱及指标成分含量测定方法,并探寻其量值传递规律.方法 制备15批DD标准煎液,建立其HPLC指纹图谱,明确相似度及峰归属,测定指标成分5-羟甲基糠醛、甘草苷、肉桂酸、甘草酸、五味子醇甲的含量、全方出膏率及其转移率,分析饮片-标准煎液间的量值传递关系.结果 15批DD标准煎液指纹图谱的相似度均大于0.9,标定了 28个共有峰,并指认5个色谱峰(5-羟甲基糠醛、甘草苷、肉桂酸、甘草酸、五味子醇甲).指标成分5-羟甲基糠醛为1.173～1.404 mg/g,转移率为36.09％～40.79％;甘草苷为2.159～3.413 mg/g,转移率为31.91％～37.41％;肉桂酸为0.317～0.614mg/g,转移率为32.74％～40.64％;甘草酸为4.175～6.559 mg/g,转移率为20.95％～28.48％;五味子醇甲为0.225～0.275 mg/g,转移率为3.52％～4.29％;出膏率为22.24％～26.75％,转移率为93.14％～111.01％.结论 采用指纹图谱、多指标含量及出膏率相结合的评价模式对DD标准煎液进行量值传递分析,科学合理,系统全面,可为后续DD的制剂开发和质量控制提供参考.

文章通过敦煌医学窥见古代敦煌先民的养生之道,从养生理论、食疗养生以及形象医学中修身养生三方面进行分析总结,力求挖掘先民养生的本质,为中国传统养生体系的构建提供参考,为养生思想的发展提供思路.

哮喘是一种常见且易反复发作的气道免疫炎症疾病,多种细胞及其组分可共同参与并促进其病理过程.气道炎症是哮喘的基本特征,可引起气道高反应,常表现为炎症细胞的增加及炎性细胞的浸润.磷脂酰肌醇3激酶(phosphati-dylinositol 3-kinase,PI3K)的活化可导致丝氨酸/苏氨酸蛋白激酶(serine/threo-nine protein kinase,Akt)的募集、磷酸化,活化的Akt可磷酸化一系列细胞内蛋白从而介导下游反应.近年来,越来越多的研究表明PI3 K/Akt信号通路与哮喘气道炎症紧密相关,可通过多机制影响哮喘及其气道炎症的进展.本文就近年来PI3 K/Akt信号通路参与哮喘气道炎症反应的发生发展进行综述,为研究哮喘的临床治疗及平喘药物的开发提供理论基础.

目的 基于OPLS模型分析生态因子对当归质量的影响.方法 采用HPLC法测定10个产地当归药材中9种主要活性成分的含量,利用主成分分析法对其进行综合质量评价.运用OPLS法建立当归药材质量和生态因子回归模型,分析两者之间相关性和变量投影重要性.结果 不同地区生态因子对当归活性成分积累影响很大,在10种生态因子中平均气温、平均最低气温、平均日降水量和日照时数对当归质量影响最显著.结论 明确当归活性成分与生态因子之间的关系,可为当归药材规范化种植,提高当归的产量和质量以及指导临床合理用药提供参考.

目的 观察归芪益元膏联合吉非替尼及放疗治疗晚期肺腺癌气阴两虚证患者的临床疗效.方法 回顾性分析2015年7月至2020年7月于甘肃中医药大学附属医院肿瘤科收治的晚期肺腺癌气阴两虚证患者120例,采用随机数字表法分为治疗组和对照组,各60例.对照组给予吉非替尼及三维适形放疗治疗,治疗组在对照组治疗方法的基础上联合归芪益元膏口服.连续治疗7周后比较2组的临床疗效、治疗期间毒副反应发生情况及中位无进展生存期(mPFS).结果 对照组总有效率为51.67％(31/60),治疗组为70.00％(42/60);对照组总控制率为80.00％(48/60),治疗组为86.67％(52/60),2组比较差异均有统计学意义(P＜0.05).治疗组放射性食管炎、放射性肺炎、胃肠道反应(恶心、呕吐、腹泻)、皮疹和骨髓抑制(中性粒细胞减少、血小板减少)发生率明显低于对照组,2组比较差异均有统计学意义(P＜0.05或P＜0.01).治疗组mPFS为24个月,对照组为20个月,2组比较差异有统计学意义(P＜0.05).结论 归芪益元膏联合吉非替尼及放疗治疗晚期肺腺癌气阴两虚证临床疗效显著,可明显改善患者的预后,延长患者生存期,值得临床推广应用.