Botulinum toxin for lower limb spasticity in children with cerebral palsy: a single-blinded trial comparing dilution techniques

OBJECTIVE: To compare the effect of equivalent doses of botulinum toxin type A given in high-volume or low-volume injections on lower limb spasticity in children with cerebral palsy. DESIGN: A total of 17 subjects whose modified Ashworth scale scores in the calf flexors bilaterally ranged from 2 to 3 were enrolled. The right gastrocnemius was injected with botulinum toxin type A using a high-volume preparation (100 IU/4 ml), and the left gastrocnemius was injected with a low-volume preparation (100 IU/1 ml). The amplitude and area of the compound muscle action potential for both medial gastrocnemius muscles, the dynamic muscle range, static muscle range, modified Ashworth scale for both ankles, and the Gross Motor Functional Classification System were assessed before and after treatment. RESULTS: Spasticity was reduced in both legs. There was no significant difference in the changes in the amplitude and area of compound muscle action potential (P = 0.74 and 0.30, respectively), dynamic muscle range (P = 0.7), static muscle range (P = 0.65), and modified Ashworth scale (P = 1) in the right vs. left legs after botulinum toxin type A injection. The high-volume preparation did not cause more pain. CONCLUSIONS: A higher volume preparation with a 4-fold dilution of botulinum toxin type A does not yield better results than a low-volume preparation.     

痛风患者血红蛋白水平与非酒精性脂肪性肝病关系的研究

目的:探讨痛风合并非酒精性脂肪性肝病（NAFLD）患者血红蛋白的特征以及血红蛋白水平与NAFLD的关系。 方法:选取住院痛风患者537例,行腹部超声检查,根据NAFLD程度（无、轻、中重度）分为单纯痛风组、痛风合并轻度 脂肪肝、痛风合并中重度脂肪肝3组。以血红蛋白水平四分位分组,Q1组（血红蛋白<135 g/L）、Q2组（135 g/L≤血 红蛋白＜145 g/Ｌ）、Q3组（145 g/L≤血红蛋白＜154 g/L)、Q4组（血红蛋白≥154 g/L）。测量身高、体重、腰围 、臀围、血压。抽取肘静脉血测血常规、总胆固醇、甘油三酯、高密度脂蛋白-胆固醇、低密度脂蛋白-胆固醇、肝酶 、尿素氮、肌酐、尿酸、糖化血红蛋白、血糖、胰岛素,计算稳态模型评估-胰岛素抵抗指数（HOMA-IR）。结果:3组 间一般资料比较显示,脂肪肝程度越重组年龄越小,体重指数、腰臀比越大;红细胞计数、血红蛋白、红细胞压积、 红细胞分布宽度标准差（SD）、红细胞分布宽度变异系数（CV）、甘油三酯、谷丙转氨酶、谷草转氨酶、γ转肽酶、 空腹血糖、糖化血红蛋白、血尿酸、HOMA-IR均随着脂肪肝程度的加重而明显升高 （F=3.08～34.85,均P<0.05）。病 程、累及关节数、血小板、血尿素氮、血肌酐、碱性磷酸酶随着脂肪肝的加重而下降（F=3.46～14.54,均P<0.05）。 血红蛋白水平与年龄、血尿素氮、血肌酐呈负相关（r=-0.153、-0.222、-0.134,均P<0.01）;血红蛋白水平与谷丙 转氨酶、谷草转氨酶、血尿酸、有无脂肪肝呈正相关（r=0.238、0.132、0.107、0.239,均P<0.01）。随着血红蛋白 水平升高,NAFLD患病率呈明显升高趋势,而NAFLD的病变程度呈加重趋势（χ2=25.57,P<0.001）,Q1组~Q4组的 NAFLD总患病率分别为16.2%、18.43%、21.6%和20.48%;Logistic回归分析显示,随着血红蛋白水平的升高,发生 NAFLD的风险明显增大。以Q1组作对照,Q2组的OR值为1.410（95%CI:0.848～2.345）,Q3组的OR值为2.087（95%CI: 1.619～4.532）, Q4组的OR值为3.113（95%CI:1.748～5.542）,差异有统计学意义。调整年龄、性别因素后,Q4组 发生NAFLD的OR值为2.507（95%CI:1.382～4.548）,差异仍有统计学意义。结论:痛风合并NAFLD患者的血红蛋白水 平随着NAFLD的严重程度而呈明显升高趋势;随着血红蛋白水平的升高,NAFLD呈显著上升趋势,进一步分析显示血红 蛋白水平与NAFLD的发生有独立相关性。     

Safety and immunogenicity of a novel human Enterovirus 71 (EV71) vaccine: a randomized, placebo-controlled, double-blind, Phase I clinical trial

There is an urgent need for a novel vaccine that is effective against human Enterovirus 71 (EV71) outbreaks. A double-blind, randomized controlled study was to evaluate the safety and immunogenicity of a human EV71 vaccine in healthy adults, children and infants. The vaccine dosages were 200 U and 400 U for children and adults, and 100 U, 200 U and 400 U for infants. Subjects were randomized to receive different dosages of the vaccine or placebo. Adults received intramuscular injection on Days 0, 14 and 28. Children and Infants received on Days 0, 28 and 56. The novel human EV71 inactivated vaccine was well tolerated and highly immunogenic in healthy volunteers, especially in infant populations. For immune response, the seropositive rates (with titers ≥≥1:8) of neutralizing antibody [NTAb] increased to 100% for all dosage groups after the second vaccination. For NTAb seronegative infants before vaccination, after one dose, the NTAb GMTs were 29.7 (95% CI, 13.1-67.2), 10.1 (95% CI, 6.6-15.3), and 27.4 (95% CI, 14.3-52.2) in the 100 U, 200 U, and 400 U vaccine groups, respectively; after two doses, the GMTs were 114.1 (95% CI, 44.5-292.4), 159.5 (95% CI, 49.3-515.3), and 509.0 (95% CI, 181.3-1429.1), respectively. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT01273246 and NCT01273233.     

江门市围绝经期妇女亚健康状态流行病学调查及其影响因素分析

目的:调查江门市围绝经期妇女亚健康状态的发生情况和影响因素,提出合理的医学干预和保健措施。方法:采用统一调查问卷和亚健康积分量化表筛选的方法对江门市500例40～60岁妇女进行调查。结果:围绝经期妇女亚健康状态发生率为76.4%,其发生和年龄、工作状况、收入、文化程度、运动、生活作息方式和自我保健意识等方面的因素密切相关。结论:江门市妇女围绝经期亚健康状态发生率较高,医务人员和卫生部门应加强健康教育,提高其保健意识和保健行为。     

Regulation of microtubule-based microtubule nucleation by mammalian polo-like kinase 1

Bipolar spindle formation is pivotal for accurate segregation of mitotic chromosomes during cell division. A growing body of evidence suggests that, in addition to centrosome- and chromatin-based microtubule (MT) nucleation, MT-based MT nucleation plays an important role for proper bipolar spindle formation in various eukaryotic organisms. Although a recently discovered Augmin complex appears to play a central role in this event, how Augmin is regulated remains unknown. Here we provide evidence that a mammalian polo-like kinase 1 (Plk1) localizes to mitotic spindles and promotes MT-based MT nucleation by directly regulating Augmin. Mechanistically, we demonstrated that Cdc2-dependent phosphorylation on a γ-tubulin ring complex (γ-TuRC) recruitment protein, Nedd1/GCP-WD, at the previously uncharacterized S460 residue induces the Nedd1-Plk1 interaction. This step appeared to be critical to allow Plk1 to phosphorylate the Hice1 subunit of the Augmin complex to promote the Augmin-MT interaction and MT-based MT nucleation from within the spindle. Loss of either the Nedd1 S460 function or the Plk1-dependent Hice1 phosphorylation impaired both the Augmin-MT interaction and γ-tubulin recruitment to the spindles, thus resulting in improper bipolar spindle formation that ultimately leads to mitotic arrest and apoptotic cell death. Thus, via the formation of the Nedd1-Plk1 complex and subsequent Augmin phosphorylation, Plk1 regulates spindle MT-based MT nucleation to accomplish normal bipolar spindle formation and mitotic progression.     

Inhibition of human thrombin by the constituents of licorice: inhibition kinetics and mechanistic insights through in vitro and in silico studies

Thrombin inhibition therapy is a practical strategy to reduce thrombotic and cardiovascular risks via blocking the formation of blood clots. This study aimed to identify naturally occurring thrombin inhibitors from licorice (one of the most popular edible herbs), as well as to investigate their inhibitory mechanisms. Among all tested licorice constituents, licochalcone A was found as the most efficacious agent against human thrombin (IC₅₀ = 7.96 μM). Inhibition kinetic analyses demonstrated that licochalcone A was a mixed inhibitor against thrombin-mediated Z-Gly-Gly-Arg-AMC acetate hydrolysis, with a K_i value of 12.23 μM. Furthermore, mass spectrometry-based chemoproteomic assays and molecular docking simulations revealed that licochalcone A could bind to human thrombin at both exosite I and the catalytic site. In summary, our findings demonstrated that the chalcones isolated from licorice were a new class of direct thrombin inhibitors, also suggesting that licochalcone A was a promising lead compound for developing novel anti-thrombotic agents.

Licochalcone A, a bioactive compound from licorice, displayed strong inhibition of thrombin.     

学习倦怠对大学生积极与消极心理状况的预测作用

目的:考察大学生的学习倦怠对积极与消极心理状况的预测作用。方法:选取786名在校学生,使用大学生学习倦怠量表(LBUS,包括情绪低落、行为不当和成就感低3个因子)调查学习倦怠,简版心理健康连续体量表(MHC-SF)(成人版)调查积极心理健康状况(MHC-SF将心理健康分成颓废萎靡、中等程度、振作向上3种状态),28项一般健康问卷(GHQ-28)调查消极心理状况(GHQ-28将心理状况分成病理和非病理两种)。结果:大学生LBUS总分及3个因子分与MHC-SF得分呈负相关(r=-0.48~-0.14,均P0.01),LBUS总分及情绪低落、行为不当因子分与GHQ-28得分呈正相关(r=0.14~0.41,P0.01)。判别分析表明,学习倦怠能预测积极心理状况,对颓废萎靡、中等程度和振作向上的正确预测率分别为63.2%、51.2%和64.1%,总的预测率为56.4%;学习倦怠的3个因子对预测积极心理均有贡献。Logistic回归分析表明,大学生学习倦怠能够正向预测消极心理状况,对病理和非病理被试的筛选正确率分别为67.5%和55.9%,总正确预测率为62.0%。情绪低落因子对消极心理状况具有正向预测作用(OR=1.11)。结论:学习倦怠能够有效预测大学生的积极和消极心理状况。     

Salvage therapy with tigecycline for recurrent infection caused by ertapenem-resistant extended-spectrum β-lactamase-producing Klebsiella pneumoniae

Optimal antimicrobial therapy for infections due to ertapenem-resistant Enterobacteriaceae remains undetermined. In this study, a diabetic patient with recurrent pyomyositis and osteomyelitis caused by extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae developed ertapenem resistance after imipenem/cilastatin treatment, which was a currently recommended therapy. He was finally treated successfully using tigecycline. Ertapenem resistance was in part explained by the production of SHV-type ESBL and the absence of an outer membrane protein, OmpK36. Our observation suggests that tigecycline may be an alternative for invasive infections caused by ESBL-producing Enterobacteriaceae with decreased susceptibility to carbapenem.