Background Huddling is a behavioral strategy for small rodents to save energy and improve the survival rate under cold environments and in winter. Brown adipose tissue (BAT) is the main site of non-shivering thermogenesis (NST) in small mammals, playing an important role in maintaining body temperature and energy balance. However, the behavioral regulation in BAT thermogenesis in small mammals is rarely illustrated. We used male Brandt’s voles (Lasiopodomys brandtii) to explore the possible regulation mechanisms in BAT thermogenesis by the way of cold acclimation and huddling behavior. Results Results showed that there is a strong relationship between huddling behavior and NST in BAT. The hypothalamus, which is impacted by huddling behavior, influences PPAR signaling pathway in the BAT, and induces thermogenesis through Calcium signaling pathway. PPAR pathway causes crosstalk among NF-κB signaling pathway, Thermogenesis and Fatty acid metabolism to perform thermogenesis functions. Conclusions The results suggest that huddling behavior can modulate adaptive thermogenesis in BAT. Cold acclimation and huddling had a synergistic effect on the regulation of thermogenic function. In BAT, the specific pathway of thermogenesis is as follows: TRAF6-PPARγ-UCP1-SUCLG1.

目的:总结该院新型抗肿瘤药物处方专项点评情况,以促进临床合理用药.方法:回顾性分析 2018-2021 年该院新型抗肿瘤药物处方专项点评情况,对点评结果进行分析和汇总.结果:2018-2021 年该院新型抗肿瘤药物处方点评共 48 次,共抽取处方 4 800 张,其中合理处方 4 578 张,处方合格率为 95.38%.222 张不合理处方中,不规范处方 197 张(占 88.74%),不合理类型均为"开具处方未写临床诊断或临床诊断书写不全";用药不适宜处方 25 张(占 11.26%).超说明书用药共涉及 276 张处方,均为超说明书适应证用药;涉及的药品中,阿帕替尼的超说明书用药处方数最多,为 166 张(占 60.14%),其次为安罗替尼(49 张,占17.75%).结论:根据现行法规制度、临床指南等证据不断完善新型抗肿瘤药物点评规则和流程将使得处方更加规范,临床用药更加合理.

Skeletal muscle-based nonshivering thermogenesis (NST) plays an important role in the regulation and maintenance of body temperature in birds and large mammals, which do not contain brown adipose tissue (BAT). However, the relative contribution of muscle-based NST to thermoregulation is not clearly elucidated in wild small mammals, which have evolved an obligate thermogenic organ of BAT. In this study, we investigated whether muscle would become an important site of NST when BAT function is conditionally minimized in Brandt's voles (Lasiopodomys brandtii). We surgically removed interscapular BAT (iBAT, which constitutes 52%~56% of total BAT) and exposed the voles to prolonged cold (4 °C) for 28 days. The iBAT-ablated voles were able to maintain the same levels of NST and body temperature (~37.9 °C) during the entire period of cold acclimation as sham voles. The expression of uncoupling protein 1 (UCP1) and its transcriptional regulators at both protein and mRNA levels in the iBAT of cold-acclimated voles was higher than that in the warm group. However, no difference was observed in the protein or mRNA levels of these thermogenesis-related markers except for PGC-1α in other sites of BAT (including infrascapular region, neck, and axilla) between warm and cold groups either in sham or iBAT-ablated voles. The iBAT-ablated voles showed higher UCP1 expression in white adipose tissue (WAT) than sham voles during cold acclimation. The expression of sarcolipin (SLN) and sarcoplasmic endoplasmic reticulum Ca2+-dependent adenosine triphosphatase (SERCA) in skeletal muscles was higher in cold than in warm, but no alteration in phospholamban (PLB) and phosphorylated-PLB (P-PLB) was observed. Additionally, there was increased in iBAT-ablated voles compared to that in the sham group in cold. Moreover, these iBAT-ablated voles underwent extensive remodeling of mitochondria and genes of key components related with mitochondrial metabolism. These data collectively indicate that recruitment of skeletal muscle-based thermogenesis may compensate for BAT impairment and suggest a functional interaction between the two forms of thermogenic processes of iBAT and skeletal muscle in wild small mammals for coping cold stress.

目的:探讨醋酸阿比特龙仿制药与原研药治疗转移性去势抵抗前列腺癌(mCRPC)的疗效与安全性,为临床提供参考依据.方法:以 2017 年 4 月至 2022 年 6 月在中国医学科学院肿瘤医院使用醋酸阿比特龙仿制药与原研药治疗的mCRPC患者为研究对象,分为仿制药组和原研药组,各 114 例.收集并比较两组患者的人口学特征(年龄、既往史等)、治疗相关信息(转移部位、基线检验值、治疗方案和合并疾病等)、不良事件发生情况及疗效评价等信息.对两组患者的年龄、体重指数(BMI)、美国东部肿瘤协作组(ECOG)评分、Gleason评分、血红蛋白和基线前列腺特异性抗原(PSA)等 7 个指标进行倾向性评分匹配后,比较两组患者的PSA50 缓解率、PSA50 缓解中位时间以及安全性.结果:两组患者在BMI、ECOG评分、转移部位、基线血红蛋白、肝肾指标及合并慢性疾病方面的差异均无统计学意义(P＞0.05).仿制药组与原研药组患者的PSA50 缓解率[55.26%(63/114)vs.59.64%(68/114),P=0.592]、PSA50缓解中位时间[1.90(1.10,3.00)个月 vs.2.50(1.00,4.00)个月,P=0.120]比较,差异均无统计学意义.仿制药组与原研药组患者的常见不良反应如肝功能损伤、三酰甘油升高、低钾、乏力、肌酐升高、高血压和体液潴留的发生率比较,差异均无统计学意义(P分别为0.086、0.682、0.568、0.437、1.000、1.000 和 0.119).进行倾向性评分匹配后,仿制药组和原研药组患者均为37例,PSA50缓解率[45.95%(17/37)vs.64.86%(24/37),P=0.161]、PSA50 缓解中位时间[2.01(1.24,3.11)个月 vs.2.00(1.00,4.00)个月,P=0.894]和常见不良事件发生率(P分别为1.00、1.00、0.24、1.00、1.00、1.00和1.00)比较,差异均无统计学意义.结论:采用倾向性评分匹配后,醋酸阿比特龙仿制药与原研药治疗mCRPC患者的疗效和安全性无显著性差异.

目的:比较第三批国家药品集中带量采购中标的卡培他滨仿制药与卡培他滨原研药在真实世界中的安全性与有效性.方法:以 2020 年 11 月至 2021 年 11 月中国医学科学院肿瘤医院使用仿制与原研卡培他滨治疗的患者为研究对象,收集患者人口学特征、治疗相关信息、不良事件发生情况及疗效评价等信息.将患者分为仿制药组和原研药组,进行安全性和有效性评价.结果:纳入研究的患者共 254 例,经倾向性评分匹配后,仿制药组和原研药组各 118 例,两组患者在基本特征及不良反应方面的差异均无统计学意义(P≥0.05).利用一线治疗的病例进行有效性评价,两组患者客观缓解率、疾病控制率的差异均无统计学意义(P=0.05;P=0.196).结论:仿制与原研卡培他滨在有效性和安全性方面的差异无统计学意义.

目的 评估真实世界乳腺癌患者使用阿帕替尼的安全性,分析使用阿帕替尼的患者发生药品不良反应的危险因素,为阿帕替尼在乳腺癌患者中的安全使用提供参考.方法 回顾性分析某院2016年3月～2020年3月接受阿帕替尼治疗的乳腺癌患者193例,收集患者的基本病例资料及不良反应,采用Logistic回归分析患者的临床特征与药品不良反应的相关性.结果 193例患者中,有132例(68.39％)患者发生不良反应,多为1级或2级,最常见的不良反应为高血压(27.46％)、手足综合征(21.76％).多因素Logistic回归分析显示,初始服药剂量为425 mg/500mg的患者相比250 mg的患者发生不良反应(ADR)的风险增加(OR =4.719,95％ CI:2.315～9.621);联合化疗患者相对单药治疗患者发生ADR的风险增加(OR=4.569,95％CI:2.082～ 10.030).既往有高血压病史的患者相比无高血压病史的患者发生高血压的风险增加(OR=2.528,95％CI:1.084 ～5.891);初始服药剂量为425 mg/500 mg的患者相比250 mg的患者发生高血压的风险增加(OR=3.622,95％CI:1.762～7.448);联合化疗患者相对单药治疗患者发生高血压不良反应的风险增加(OR=3.386,95％CI:1.106～10.369).结论 阿帕替尼治疗乳腺癌不良反应可耐受,初始服药剂量和联合化疗是发生ADR的危险因素;既往高血压病史,初始服药剂量和联合化疗是发生高血压不良反应的危险因素.

目的:了解某市肿瘤药事质控管理现状及存在的问题,为下一步规范化肿瘤药事质控管理奠定基础.方法:通过"问卷星"软件制作问卷对该市药学质量控制和改进中心工作微信群的各质控医疗机构进行线上问卷调查.结果:共收到有效问卷62份,其中43家医院(69.35％)配备有肿瘤专科临床药师,多数医院肿瘤临床药师未细化专业(32家,94.12％),肿瘤相关专业较多的有癌痛(40家,64.52％)、营养(26家,41.94％).肿瘤临床药师开展工作方面,能进行化疗药物处方智能软件审核的医院较少(32.81％),但多数医院都能够从药物咨询、患者用药教育等方面开展工作,分别占被调查医院的83.87％、64.52％及51.61％.药学服务延伸下沉的范围主要是社区医院(48.39％)和医联体(48.39％),服务形式以用药宣教(69.35％)和处方点评(61.29％)为主.36家医院(58.06％)配备有新型抗肿瘤药物.仅有21家医院(33.87％)进行抗肿瘤药物分级管理,配备有静脉用药调配中心(PIVAS)的医院有限.结论:专业性较强的肿瘤专科临床药师的配备仍面临较大缺口,肿瘤专科临床药师对于临床的参与度有限,工作时长不能保证.为此,应加强药师队伍建设,加大肿瘤临床药师的配备,提高肿瘤药事质量控制水平,促进临床合理用药.

Precocious puberty mostly stems from endocrine disorders. However, more and more studies show that a high-fat diet (HFD) is closely related to precocious puberty, but its mechanism is unknown. Since gut microbiota is associated with hormone secretion and obesity, it inspires us to detect the mechanism of gut microbiota in triggering precocious puberty. The model of precocious puberty was established by feeding female mice with an HFD from 21 days old. After puberty, the serum hormone levels, gut microbiome sequencing, and metabolomics were collected. DNA was extracted from feces, and the V3-V4 region of the bacterial 16S rRNA gene was amplified, followed by microbial composition analysis. Subsequently, associations between precocious puberty and the microbiota were determined. We found that (1) HFD after weaning caused precocious puberty, increased serum estradiol, leptin, deoxycholic acid (DCA), and gonadotropin-releasing hormone (GnRH) in the hypothalamus; (2) Through correlation analysis, we found that GnRH was positively correlated with Desulfovibrio, Lachnoclostridium, GCA-900066575, Streptococcus, Anaerotruncus, and Bifidobacterium, suggesting that these bacteria may have a role in promoting sexual development. (3) "HFD-microbiota" transplantation promoted the precocious puberty of mice. (4) Estrogen changes the composition and proportion of gut microbiota and promotes precocious puberty. Therefore, the effect of HFD on precocious puberty is regulated by the interaction of gut microbiota and hormones.

间质性肺疾病涉及肺泡和间质炎症以及纤维化,是不同疾病类型的统称,多达200余种,在肺部疾病中具有较高的发病率和死亡率.因此,早期诊断及定量化评估是诊治间质性肺疾病的关键.人工智能技术因其强大的学习和分析能力,在医学影像中得到越来越多的应用.基于深度学习的人工智能技术可以通过自我学习,不断提高间质性肺疾病的诊断准确率,是实现计算机辅助诊断的重要方法.本文就以深度学习算法为中心的计算机辅助诊断技术在间质性肺疾病领域的应用研究现状进行总结.

目的 使用血型血清学和分子生物学方法对肿瘤患者ABO亚型标本进行分析.方法 2014年7月～2019年12月在中国医学科学院肿瘤医院进行治疗的实体肿瘤患者,经输血科常规血型血清学鉴定为ABO亚型标本32例,标本分别采用序列特异性引物-聚合酶链式反应(PCR-SSP)法及基因测序(PCR-SBT)技术进行血型分子生物学鉴定;PCR-SSP检测5例,PCR-SBT检测28例,其中1例同时进行PCR-SSP和PCR-SBT检测;对比分析血清学和基因分型结果.结果 本研究中66％(21/32)标本经基因分型检测确认为ABO亚型或存在突变,包含:7例B(A).04,2例 B(A).02,1 例 cisAB.01,3例为 BW.12,4例为 BEL.03,1 例A4EL.02,1 例 B 型974G＞C,1 例 A 型797insT,1例A型617C＞G;21例亚型或存在突变标本中,15例血型血清学与基因分型结果一致,6例为血清学吸附放散试验未检出A或B抗原.另34％(11/32)分子生物学分析未检出导致ABO亚型基因变异.结论 分子生物学技术能够很好的解决实体肿瘤患者抗原或抗体减弱以及亚型所致的ABO疑难血型鉴定,是准确鉴定疑难ABO血型的重要辅助方法.

目的 采用血清学和分子生物学方法对存在Lewis同种抗体的肿瘤患者进行Lewis抗原检测分析.方法 选取2014年8月至2018年6月经中国医学科学院肿瘤医院输血科鉴定存在Lewis血型同种抗体的肿瘤患者112例,分别进行Lewis血型血清学及FUT2、FUT3基因检测.结果 112例患者中,结直肠癌32例(28.6％),肺癌26例(23.2％),食管癌 12例(10.7％),宫颈癌 11 例(9.8％),其他肿瘤31 例(27.7％);抗 Lea67例(59.8％),抗 Leb12例(10.7％),抗 Lea合并抗 Leb 27例(24.1％),抗Lea合并其他抗体6例(5.4％).血清学分型结果均为Le(a-b-);FUT2基因测序发现5种等位基因,分别为分泌型(SeSe、SeSew、Sese)与弱分泌型(SewSew、Sewse),未发现非分泌型(sese);FUT3基因测序均为Lewis糖基转移酶失活型即lele,共23种等位基因组合.结论 存在Lewis同种抗体的肿瘤患者Lewis血型血清学检测结果与基因测序结果一致,血清学检测可用于存在Lewis血型抗体的肿瘤患者Lewis分型的准确检测.

目的 评估中国医学科学院肿瘤医院使用阿帕替尼治疗卵巢癌患者的安全性,并分析患者的临床特征与不良反应的相关性,为临床合理用药提供参考.方法 回顾性分析2016年1月至2019年12月在该院接受阿帕替尼治疗的54例卵巢癌患者临床资料,利用医院HIS系统检索并记录患者病历资料,采用美国国家癌症研究所常见不良反应事件评价标准(NCI-CTCAE)5.0版评价安全性;患者的临床特征与阿帕替尼的不良反应相关性采用logistic回归分析.结果 54例患者中,共有31例(57.41％)患者发生不良反应,常见的不良反应为高血压(38.89％)、蛋白尿(22.22％)和手足综合征(22.22％).多因素logistic回归分析显示,联合化疗和多线化疗是阿帕替尼致不良反应的影响因素(P<0.05);超重(体质指数>25 kg/m2)和存在过敏史是阿帕替尼致高血压的影响因素(P<0.05).结论 阿帕替尼治疗卵巢癌的不良反应较轻,多为1～2级,联合化疗和多线化疗是阿帕替尼致不良反应的影响因素,过敏史和超重是阿帕替尼致高血压的影响因素.

目的 通过分析阿帕替尼治疗胃癌患者的剂量选择情况,探索影响临床使用阿帕替尼初始剂量的影响因素.方法 回顾性分析124例接受阿帕替尼治疗的胃癌患者,用医院病历系统检索并记录患者病例资料,用卡方检验对患者的临床特征和药物不良反应与剂量进行相关性分析.结果 年龄、体重指数(BMI)、美国东部肿瘤协作组(ECOG)评分、转移部位数量、是否联合化疗是阿帕替尼剂量选择的影响因素(均P<0.05).发生血压升高和蛋白尿患者的平均剂量均显著高于未发生患者的剂量,差异均有统计学意义(均P<0.05).结论 为了确保患者的安全性和提高依从性,建议对于高龄(≥60岁)、偏瘦(BMI<18.5 kg·m-2)、体力状态差(ECOG评分=2)、转移部位数量较多(>2)、联合化疗的患者以低剂量作为起始剂量,做到个体化给药.

目的 比较2018版《国家基本药物目录》(NEML-2018)与2019版《WHO基本药物示范目录》(WHO-EML-2019)中抗肿瘤药物目录的差别,为NEML的持续完善提供参考.方法 采用描述性分析方法,从药品种类、数目、剂型、规格、适应证及儿童用药等方面对我国NEML-2018和WHO-EML-2019中收录的肿瘤药物进行比较,并对存在的问题进行分析.结果 NEML-2018中抗肿瘤药物的遴选基本符合我国国情和肿瘤流行病学特点,其与WHO-EML-2019收录的抗肿瘤药物品种数分别为35和59种,注射剂型分别为26和40种,口服剂型分别为15和30种.此外,NEML-2018没有专门的适应证描述和儿童用药标识.结论 与WHO-EML-2019相比,NEML-2018收录的抗肿瘤药物在药品种类、数量、剂型、规格、适应证和儿童用药标识方面均存在差距,今后NEML的修订要以WHO-EML为参考,加强循证评价和药物经济学分析,不断优化抗肿瘤药物目录的遴选.

Kidney cancer usually requires multidisciplinary individualized treatments. No matter what kind of treatment, drugs are essential. According to the "six-step process" (prescription legitimacy review, patient basic information evaluation review, treatment protocol review, organ function and laboratory index review, pretreatment review, and unconventional prescription review) in prescription review proposed by the anti-tumor drug prescription review expert group and referring to domestic and foreign kidney cancer guidelines and drug instructions in recent years, this consensus selects 9 targeted drugs and 4 immunotherapeutic drugs that are currently commonly used in China and elaborates the key review points in patient basic information evaluation review, treatment protocol review, and organ function and laboratory index review of kidney cancer drug treatment, in order to provide reference for clinical front-line pharmacists to review prescriptions of kidney cancer patients and promote rational drug use in clinic.

目的:了解我院药品不良事件及解决情况,探讨其对药品精细化质控管理环节改进及合理用药的影响.方法:回顾性分析2016年1月至2019年5月中国医学科学院北京协和医学院肿瘤医院(以下简称"我院")上报的105例药品不良事件报告,总结药品不良事件的特点、发生原因、解决方案以及对药事质控环节所带来的改进,并将结果运用到药品质量控制中,进一步规范药品管理.结果:我院上报的105例药品不良事件报告中,涉及的药品种类主要为调节水、电解质和酸碱平衡药,抗肿瘤药及辅助治疗药物,营养药.通过对药品不良事件发生原因的分析发现,由药品质量问题引起的有74例(占70.48％);由运输及储存过程不当引起的有6例(占5.71％);由药品使用不当引起的有25例(占23.81％).通过对药品不良事件发生原因的调查,药剂科质控小组针对部分药品不良事件提出了合理化解释及建议.结论:我院药品不良事件的上报促进了药品生产企业改进工艺,提高了药品质量;更加规范了医务人员对药品的存储及使用;改进了临床工作流程,确保了患者用药安全.

目的:探讨肿瘤药事质控在教学中的应用.方法:通过对抗肿瘤药临床应用管理体系的构建及药学服务质控路径的梳理,明确人才培养专业化和抗肿瘤药管理规范化的重要性和手段,阐明药事质控工作的质控点,形成肿瘤药事质控教学方案,并应用于肿瘤药学教育中.结果 与结论:抗肿瘤药临床应用管理体系的构建是肿瘤药事质控实施的基础,肿瘤药事质控路径教学方案的实施有利于培养知识结构合理、职责明确的现代化肿瘤药事质控人才.肿瘤药事质控教学方案可为肿瘤药事质控工作的顺利开展和实施及肿瘤规范化治疗提供参考.

过敏性肺炎(HP)是由于吸入各种抗原性有机物粒子而引起的弥漫性肉芽肿性间质性肺疾病(ILD).HP传统上分为急性期、亚急性期和慢性期.长期暴露于抗原可导致疾病发展为不可逆纤维化.对于HP,高分辨率CT(HRCT)是最敏感的检查,作为慢性HP与ILD鉴别诊断的关键手段,特别是在临床上不能进行肺活检的情况下HRCT可以提供重要线索.文章总结HP的HRCT典型表现,希望可以为临床提供早期诊断线索.

药食同源植物是指既可食用又能作为药材防病治病的植物,此类植物不良反应小、药用作用强且价格低廉,因此在临床上应用广泛.对于该类药物含有的活性成分进行深入研究能够更好地明确与发挥其药用价值和营养价值.20世纪以来,气相色谱质谱联用技术的飞速发展推动了药食同源植物的活性成分的发现与研究,在药食同源植物的质量分析与成分开发中得到广泛应用并成为其主流分析技术之一.本文从近年来气质联用技术发展以及其在药食同源植物中的应用两个方面,对该技术在药食同源类植物的活性成分分析中的应用进行了综述.

Objective: To investigate the differences in small airway lesions in patients with different types of idiopathic interstitial pneumonia (IIPs). Methods: A total of 46 patients with IIPs confirmed by video assisted thoracoscopic or open lung biopsy, hospitalized in the Respiratory and Critical Care Medicine of Beijing Chao-Yang Hospital, from Dec. 1998 through Nov. 2007 were studied, including 19 patients with idiopathic pulmonary fibrosis (IPF group), 14 with nonspecific interstitial pneumonia (NSIP group), and 13 cryptogenic organizing pneumonia (COP group). Pulmonary function and high resolution CT (HRCT) of the patients were examined before lung biopsy, and lung biopsy tissue were stained with hematoxylin-eosin. The abnormality of small airways in pathology, pulmonary function and HRCT were compared among these patients with IIPs. Results: Small airway inflammatory cell infiltration score (53.8±17.7) was significantly higher in the COP group than in the IPF group (38.8±9.7) (P<0.01). The fibrous tissue proliferation score in small airways (42.9±12.1) in the IPF group was significantly higher than that in the NSIP group (31.4±10.5) and the COP group (26.7±16.3) (both P<0.05). In the IPF group, NSIP group and COP group, the small airway function index was significantly reduced, and the maximum expiratory flow rate (V(25%), V(50%)) at 25% and 50% of the lung capacity was<80% predicted, the incidences of small airway dysfunction in the three groups were 63.2%, 69.2%, and 63.6%, respectively. There was no significant difference among the groups (P>0.05). Small airway inflammatory cell infiltration was negatively correlated with V(50%) of small airway function (r=-0.305, P=0.049). The bronchodilation rate in the HRCT of the IPF group (100%) was significantly higher than that of the NSIP group (50.0%) and the COP group (53.8%) (both P<0.01). Conclusion: The patients with IPF, NSIP and COP have abnormal pathologic, physiological and imaging changes of small airways, moreover have different characteristics.