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.     

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。     

新疆急慢性布鲁菌病患者炎性细胞因子免疫水平研究

目的 探讨新疆急、慢性布鲁菌病患者细胞因子（IL-4、IL-6、IL-10、IL-17、TNF-α、INF-γ）、炎性因子（PCT、hs-CRP）及RF、ESR、ASO、血培养的临床诊断意义。方法 对布鲁菌病住院患者（病例组）和正常对照人群（对照组）采用多重微球流式免疫荧光发光法和生化等技术检测多种细胞因子及炎性因子,并进行统计学分析。结果 病例组和对照组IL-4、IL-6、IL-10、IL-17、TNF-α和IFN-γ分别为2.74(0.97~6.25)和0.56(0.53~0.64)、34.10(13.05~60.8)和0.78(0.41~2.52)、1.83(1.15~2.75)和0.89(0.77~1.13)、6.77(2.48~13.74)和1.03(0.68~1.20)、35.23(5.79~74.98)和1.33(0.80~2.17)、212.96(42.3~436.72) pg/mL和1.69(1.36~1.89) pg/mL,病例组明显高于对照组,差异均有统计学意义（P<0.05）。急性组和慢性组IL-6、IL-10、IL-17、TNF-α、IFN-γ分别为65.32(36.27~68.60)和29.38(11.30~53.09)、2.38(1.51~3.34)和0.89(0.77~1.13)、11.98(3.92~16.49)和5.27(2.24~12.49)、50.88(16.59~96.69)和28.24（5.30~64.40）、319.00（145.14~588.52）pg/mL和160.52（36.5~418.54） pg/mL,PCT和hs-CRP分别为0.08(0.06~0.12) pg/mL和0.04(0.03~0.06) pg/mL、12.60（5.0~30.8）mg/L和3.30（1.2~16.2） mg/L,差异均有统计学意义（P<0.05）;低抗体滴度组和高抗体滴度组IL-6、PCT 、hs-CRP 、RF、ESR、血培养阳性率分别为30.46(11.30~50.02) pg/mL和46.20(17.72~79.69) pg/mL、0.04(0.03~0.06) pg/mL和0.07(0.04~0.11) pg/mL、3.03(0.85~9.70) mg/L和13.65(2.97~31.43) mg/L、3.0（0.8~9.7）IU/mL和13.6（3.0~31.4）IU/mL、15（7~31）mm/h和27（15~46）mm/h、15.3%和33.3%,差异均有统计学意义（P<0.05）。单因素分析显示6种细胞因子均为布鲁菌病患病程度的危险因素,多因素Logistic回归分析显示IL-6和INF-γ水平是布鲁菌病患病程度的独立危险因素。结论 IL-4、IL-6、IL-10、IL-17、TNF-α、IFN-γ及PCT、hs-CRP等指标不仅能及时准确反映布鲁杆菌感染发病程度和临床分期的免疫状况,而且IL-6和INF-γ表达水平具有独立的临床诊断评估作用,血培养在急性期或高滴度组具有重要的临床诊断价值。     

索拉非尼治疗转移性肾癌疗效与不良反应的关系

目的:探索索拉非尼在治疗转移性肾细胞癌（mRCC）患者中的不良反应与疗效之间的关系。方法:回顾性研究西京医院接受索拉非尼治疗的mRCC患者63例，利用卡方检验分析肿瘤控制率与不良反应的发生频率和严重程度的相关性，利用Kaplan-Meier方法分析16种不良反应，筛选出与患者PFS，OS相关的不良反应，将P＜0.05变量纳入多变量Cox比例风险回归模型进行进一步的多因素分析，确定独立预后因素。结果:63例接受索拉非尼治疗的患者中，完全缓解2例（3.2％），部分缓解16例（25.4％），疾病稳定37例（58.7％），疾病进展8例（12.7％）。中位PFS为12.0个月，中位OS为24.0个月。卡方检验结果示肿瘤控制率与不良反应的发生频率和严重程度相关（均P＜0.05）。多变量分析显示，更好的PFS的独立预后因素包括腹泻（OR 0.255,95％CI 0.130~0.500,P=0.000）和皮疹（OR 0.235,95％CI 0.114~0.482,P=0.000）。OS的独立预后因素包括腹泻（OR 0.454,95％CI 0.246~0.839,P=0.012），皮疹（OR 0.405,95％CI 0.211~0.776，P=0.006）和高血压（OR 0.373,95％CI 0.177~0.784,P=0.009）。结论:索拉非尼治疗mRCC患者的疗效与不良反应的发生频率和严重程度呈正相关。皮疹和腹泻是影响PFS的独立保护因素，皮疹，腹泻和高血压是影响OS的独立保护因素。这一结论仍需大量前瞻性研究证实。