药物饲料添加剂吉他霉素耐药性风险评估

目的 为给兽药减量政策的制定、动物源性食品安全的维护提供理论依据。方法 利用每日允许摄入量（ADI）、估算每日摄入量（EDI）及慢性风险熵（CRQ），对中国居民通过摄入肉蛋乳等动物性食品暴露于吉他霉素的耐药性风险进行点评估。结果 随着年龄增长，中国居民的吉他霉素膳食暴露量逐渐降低。2～7岁人群吉他霉素的膳食暴露量最高，男女分别为2.17和2.29 μg/ ( kg·bw·d)；＞65岁人群膳食暴露量最低，男女分别为0.45和0.46 μg/ ( kg·bw·d)。2～7岁人群通过摄入乳制品的吉他霉素的膳食暴露量最大，男女分别为1.15和1.22 μg/ ( kg·bw·d)，8岁以上人群通过摄入肉类食品的吉他霉素的膳食暴露量最大。中国居民通过摄入肉蛋乳等动物性食品暴露于吉他霉素，各年龄段CRQ均小于1。其中2～7岁人群CRQ值最高，风险最大；65岁以上人群CRQ值最低，风险最小。结论 中国居民通过摄入动物性食品的吉他霉素耐药性风险较低，危害程度较小，但儿童通过摄入乳制品的吉他霉素耐药性风险较高，有必要制定乳制品中吉他霉素残留的限量标准。     

Coinheritance of generalized pustular psoriasis and familial Behçet‐like autoinflammatory syndrome with variants in IL36RN and TNFAIP3 in the heterozygous state

Generalized pustular psoriasis (GPP) is now known to be caused by biallelic variants in IL36RN and monoallelic variants in CARD14 and AP1S3. The presence of a modifier locus or oligogenic inheritance have been hypothesized. We report on a patient with a unique coinheritance of pathogenic variants in IL36RN (c.115+6T>C) and TNFAIP3 (c.547C>T, p.R183 * ) causing the genetic entities GPP and familial Behçet‐like autoinflammatory syndrome (AISBL). The heterozygous variant in IL36RN identified by Sanger sequencing was inherited from his unaffected father, while the heterozygous variant in TNFAIP3 was detected by whole‐exome sequencing and was also identified in the patient's AISBL‐affected maternal relatives. Further functional studies are required to research whether the variant of TNFAIP3 plays a part in the development of GPP or simply causes the Behçet's disease phenotype. However, our data suggest that whole‐exome sequencing for the heterozygous carrier of the IL36RN gene in GPP be used to find the potential second genetic locus.     

二至丸对绝经后骨质疏松鼠的作用观察及可能机制研究

目的:观察二至丸对绝经后骨质疏松模型鼠的治疗作用,并探讨其可能的作用机制。方法:将100只雌性SD鼠随机分为空白组(n＝20)和造模组(n＝80),造模组大鼠均接受双侧卵巢切除术致骨质疏松模型,将成模大鼠随机分为模型组、低剂量组、中剂量组及高剂量组，每组20只,造模12 h低剂量组、中剂量组及高剂量组分别予3、6、12 g/kg二至丸灌胃,1次/d。模型组与空白组均予1 mL生理盐水灌胃,连续干预8周,比较各组骨组织病理学、组织形态计量学、骨密度生物力、血脂代谢、组织Wnt/β-catenin通路标志性因子的改变。结果:与空白组比较,模型组脂肪细胞明显增大,脂肪细胞密度、面积、FLAW、PPARγ显著增加,外周血TC、TG和LDL-C含量上调(P<0.01)。与模型组比较,二至丸中剂量组和高剂量大鼠上述指标表达下调(P<0.05);与空白组比较,模型组大鼠BV/TV、Tb.Th,Joint、骨密度、弹性模量、最大载荷、Wnt3a、β-catenin、LRP5表达均减少(P<0.05);与模型组比较,二至丸中剂量组和高剂量组上述指标表达均显著增加(P<0.05)。结论:二至丸可明显改善骨质疏松症,其作用机制可能与激活Wnt/LRP5/β-catenin通路有关。     

Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia‐mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti‐neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)‐activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro‐inflammatory M1 phenotype to the anti‐inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.     

风池穴不同刺法对椎动脉型颈椎病的临床疗效评价

目的:探究风池穴不同刺法对椎动脉型颈椎病的临床疗效。方法:选择2018年4月—2019年1月北京中医药大学东直门医院针灸科门诊就诊的84例椎动脉型颈椎病患者作为研究对象,分为观察组43例、对照组41例。观察组采用短刺法针刺风池穴治疗,对照组采用平补平泻法针刺风池穴治疗,1个疗程后比较两组患者的ESCV、颈椎病症状分级量化表评分以及TCD相关指标,TCD指标观察基底动脉和双侧椎动脉的平均血流速度(Vm)、收缩期血流速度峰值(Vs)、血管搏动指数(PI)和血管阻力指数(RI)的变化。结果:治疗前后两组ESCV、颈椎病症状分级量化表评分比较,差异有统计学意义(P<0.05),且椎动脉、基底动脉的Vs、Vm较治疗前明显减慢,且观察组治疗效果优于对照组(P<0.05)。结论:针刺风池穴治疗椎动脉型颈椎病临床效果显著,且短刺法优于平补平泻法。     

大体积肺癌IMRT初次及二次计划剂量学变化研究

目的 采用刚性配准和形变配准方法获得大体积非小细胞肺癌(NSCLC) IMRT中靶区和危及器官(OAR)的累加剂量,并与初次计划的剂量进行比较。方法 选择 30例采用IMRT的大体积NSCLC患者,每位患者分别在放疗前和放疗20分次时进行4DCT模拟定位,基于初次4DCT的平均密度投影CT1-avg制定放疗计划为Plan1,基于二次4DCT的平均密度投影CT2-avg修改放疗计划为Plan2,分别采用刚性配准和形变配准方法将两次计划进行剂量累加得到Plan刚性和Plan形变。比较初次定位和二次定位之间大体肿瘤体积(GTV,以吸气末时相图像CT50%上的勾画为准)和OAR (OAR,以平均密度投影图像CTavg上的勾画为准)的体积变化,以及Plan2、Plan刚性、Plan形变的剂量体积指标相比Plan1的差异。结果 二次定位和初次定位相比,GTV、心脏体积分别缩小44.2%、5.5%,患侧肺、健侧肺、全肺体积分别增大5.2%、6.2%、5.8%(P<0.05);对于内GTV (IGTV,10个4DCT时相的GTV融合而来)和计划靶体积(PTV)的D95%、D98%、V100%,Plan2与Plan1相近(P>0.05),Plan刚性、Plan形变较Plan1均略有下降(P<0.05);对于脊髓、心脏、患侧肺、双肺剂量,Plan2、Plan刚性、Plan形变较Plan1均降低(P<0.05),其中心 脏V30Gy和 Dmean分别降低27.3%、16.5%、15.3%和15.2%、6.6%、5.6%,双 肺V20Gy和 Dmean分别降低15.6%、4.5%、3.7%和15.7%、6.2%、5.1%;Plan形变的IGTV和PTV的D95%、D98%,心 脏V40Gy,患侧肺和全肺 的V20Gy、Dmean高于Plan刚性(P<0.05)。形变配准后OAR相似指数明显高于刚性配准(P<0.05)。结论 Plan2中OAR剂量体积指标相比Plan1差别很大,因此它们在预测OAR放射性损伤方面均有较大偏差,而形变配准得到的剂量体积指标可以提高预测精度。