利用反向遗传学设计人偏肺病毒活疫苗

人偏肺病毒(HMPV)是引起全世界呼吸道疾病的重要原因·特别是在儿童中.需要HMPV疫苗来预防与婴儿感染相关的严重疾病.首要的策略是研制特别适用于防御呼吸道病毒的鼻腔免疫减毒活疫苗.反向遗传学提供一种高度鉴定的候选减毒疫苗研制方法.本文就利用反向遗传学设计HMPV疫苗的研究进展进行综述.     

Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine

BackgroundThe pathogenesis of chronic migraine remains unresolved. Recent studies have affirmed the contribution of GLUA1-containing AMPA receptors to chronic migraine. The dopamine D2 receptor, a member of G protein-coupled receptor superfamily, has been proven to have an analgesic effect on pathological headaches. The present work investigated the exact role of the dopamine D2 receptor in chronic migraine and its effect on GLUA1-containing AMPA receptor trafficking.MethodsA chronic migraine model was established by repeated inflammatory soup stimulation. Mechanical, periorbital, and thermal pain thresholds were assessed by the application of von Frey filaments and radiant heat. The mRNA and protein expression levels of the dopamine D2 receptor were analyzed by qRT‒PCR and western blotting. Colocalization of the dopamine D2 receptor and the GLUA1-containing AMPAR was observed by immunofluorescence. A dopamine D2 receptor agonist (quinpirole) and antagonist (sulpiride), a PI3K inhibitor (LY294002), a PI3K pathway agonist (740YP), and a GLUA1-containing AMPAR antagonist (NASPM) were administered to confirm the effects of the dopamine D2 receptor, the PI3K pathway and GULA1 on central sensitization and the GLUA1-containing AMPAR trafficking. Transmission electron microscopy and Golgi-Cox staining were applied to assess the impact of the dopamine D2 receptor and PI3K pathway on synaptic morphology. Fluo-4-AM was used to clarify the role of the dopamine D2 receptor and PI3K signaling on neuronal calcium influx. The Src family kinase (SFK) inhibitor PP2 was used to explore the effect of Src kinase on GLUA1-containing AMPAR trafficking and the PI3K signaling pathway.ResultsInflammatory soup stimulation significantly reduced pain thresholds in rats, accompanied by an increase in PI3K-P110β subunit expression, loss of dopamine receptor D2 expression, and enhanced GLUA1-containing AMPA receptor trafficking in the trigeminal nucleus caudalis (TNC). The dopamine D2 receptor colocalized with the GLUA1-containing AMPA receptor in the TNC; quinpirole, LY294002, and NASPM alleviated pain hypersensitivity and reduced GLUA1-containing AMPA receptor trafficking in chronic migraine rats. Sulpiride aggravated pain hypersensitivity and enhanced GLUA1 trafficking in CM rats. Importantly, the anti-injury and central sensitization-mitigating effects of quinpirole were reversed by 740YP. Both quinpirole and LY294002 inhibited calcium influx to neurons and modulated the synaptic morphology in the TNC. Additional results suggested that DRD2 may regulate PI3K signaling through Src family kinases.ConclusionModulation of GLUA1-containing AMPA receptor trafficking and central sensitization by the dopamine D2 receptor via the PI3K signaling pathway may contribute to the pathogenesis of chronic migraine in rats, and the dopamine D2 receptor could be a valuable candidate for chronic migraine treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01469-x.     

脑动脉硬化症中医临床分型研究

目的经过临床观察并通过相关统计学分析探讨血液流变学、血脂、经颅多普勒动脉指数(PI值)、脑电图、眼底镜检查与脑动脉硬化症(CAS)中医临床分型各型的相关性。方法对120例入院或门诊脑动脉硬化症患者根据脑动脉硬化症诊断标准、排除标准及中医辨证量表法分型标准进行诊断、中医分型及评分。空腹分别做血液流变学、血脂,经颅多普勒超声检查(PI值)、脑电图、眼底镜检查。结果各型相关辅助检查结果较正常值或对照组对比有显著差异性(P<0.05)。结论各型与相关临床辅助检查存在相关性。     

Ocular surface in patients with different degrees of myopia

AIM: To investigate the clinical features of the ocular surface in patients with different degrees of myopia. METHODS: A cross-sectional study was conducted involving 122 participants with myopia in Beijing Tongren Hospital from February to June, 2023. After completing the Ocular Surface Disease Index (OSDI) score scale, measurements were taken for refraction, biometric parameters and ocular surface parameters. The prevalence, severity and related parameters of the dry eye among different groups based on axial length (AL) were compared. Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters. RESULTS: Statistically significant differences were observed in refractive error, corneal thickness, anterior chamber depth, and subfoveal choroidal thickness among the groups (all P<0.05). With the increase in AL, the incidence and severity of dry eye increased significantly (P<0.05). Moreover, the tear film break-up time (BUT) shortened (P<0.05), and the corneal fluorescein staining (CFS) points increased significantly (P<0.05). OSDI scores were positively correlated with AL and spherical equivalent (SE; both P<0.05); BUT was negatively correlated with AL, SE, and corneal astigmatism (AST; all P<0.05); Schirmer I test (SIT) results were negatively correlated with AL and SE (both P<0.05). CONCLUSION: AL elongation is a risk factor for dry eye onset in myopic participants. The longer the AL, the more severe the dry eye is, with the increased CFS spots and tear film instability. Additionally, SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.     

人载脂蛋白A5基因c.553 G＞T多态性与血脂水平的相关性

目的 分析中国江苏地区汉族人群载脂蛋白A5 c．553G〉T基因多态性与血清脂质水平的关系。方法 用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）技术分别检测199例高三酰甘油血症患者和225例健康对照者载脂蛋白A5C．553G〉T多态性基因型,计算等位基因频率;用生物化学方法检测研究对象的血脂水平。结果 高三酰甘油血症组apoA5 c．553位点T等位基因频率显著高于健康对照组（12．56％ vs 4．67％,P〈0．001）,TT突变型纯合子血清三酰甘油水平较TG杂合子及GG野生型纯合子人群显著升高（P〈0．001）,而血清HDL—C水平则呈下降趋势（P=0．011）。结论 载脂蛋白A5 c．553G〉T基因多态性影响血清三酰甘油水平,与高三酰甘油血症存在一定的关联性。     

克氏针横形固定小儿胫骨开放性斜形骨折20例

1996～2005年,笔者采用克氏针横形固定治疗小儿胫骨开放性斜形骨折20例,效果良好. 1 材料与方法 1.1 病例资料本组20例,男12例,女8例,年龄4～13岁.均为新鲜开放性胫腓骨骨折,但胫骨折端为斜形,内外移位骨折16例,前后移位骨折4例.     

紫茎泽兰羟基泽兰酮在大鼠体内毒代动力学与组织分布

目的 探讨紫茎泽兰羟基泽兰酮(Euptox A)在大鼠体内的毒代动力学和组织分布.方法 将15只Wistar大鼠随机分为3组,每组5只;分别静脉给予Euptox A 25、50和100mg·kg-1后,于不同时间点采集血样;另18只大鼠随机分为3组,每组6只;静脉给予Euptox A 50mg·kg-1后,分别于10、...     

Socioeconomic status,individual behaviors and risk for mental disorders: A Mendelian randomization study

BackgroundThere is increasing attention on the association of socioeconomic status and individual behaviors (SES/IB) with mental health. However, the impacts of SES/IB on mental disorders are still unclear. To provide evidence for establishing feasible strategies on disease screening and prevention, we implemented Mendelian randomization (MR) design to appraise causality between SES/IB and mental disorders.MethodsWe conducted a two-sample MR study to assess the causal effects of SES and IB (dietary habits, habitual physical activity, smoking behaviors, drinking behaviors, sleeping behaviors, leisure sedentary behaviors, risky behaviors, and reproductive behaviors) on three mental disorders, including bipolar disorder, major depressive disorder and schizophrenia. A series of filtering steps were taken to select eligible genetic instruments robustly associated with each of the traits. Inverse variance weighted was used for primary analysis, with alternative MR methods including MR-Egger, weighted median, and weighted mode estimate. Complementary methods were further used to detect pleiotropic bias.ResultsAfter Bonferroni correction and rigorous quality control, we identified that SES (educational attainment), smoking behaviors (smoking initiation, number of cigarettes per day), risky behaviors (adventurousness, number of sexual partners, automobile speeding propensity) and reproductive behavior (age at first birth) were causally associated with at least one of the mental disorders.ConclusionsMR study provides robust evidence that SES/IB play broad impacts on mental disorders.     

Moderate Hypofractionated Helical Tomotherapy for Older Patients with Localized Prostate Cancer: Long-term Outcomes of a Phase I–II Trial

BackgroundOur previous study showed that two different regimens of moderate hypofractionated radiotherapy (HFRT) delivered with helical tomotherapy (HT) are well tolerated in older prostate cancer patients. We provide a longterm efficacy and toxicity after > 7 years of follow-up.Patients and methodsThe study recruited 33 patients from February 2009 to July 2011 (76 Gy/34F; Group-1); and 34 from July 2011 to February 2014 (71.6 Gy/28F; 50.4 Gy/25F for the risk of pelvic lymph nodes involvement (LNI) >15%; Group-2). The primary outcomes were biochemical failure (BF), biochemical failure and clinical disease failure (BCDF), progression-free survival (PFS), overall survival (OS), late genitourinary (GU) and gastrointestinal (GI) toxicity.ResultsThe average ages of two groups were 80 and 77 years and the proportions of patients with LNI > 15% were 69.7% and 73.5%, respectively. At the final follow-up in February 2020, 27.3% and 20.6% cases experienced BF, with a median time until BF of 3.3 years. A total of 38.8% patients reached primary endpoints, in which 18 deaths were reported BCDF events (45.5% vs. 32.4%, p = 0.271). There was no significant difference in 7-year PFS (68.6% vs. 74.8%, p = 0.591), BCDF (45.5% vs. 32.4%, p = 0.271) and OS (71.9% vs. 87.5%, p = 0.376) for full set analysis and for subgroup analysis (all p > 0.05). The incidence of grade ≥ 2 late GU (6.2% vs. 6.3%, p = 0.127) and GI toxicities (9.4% vs. 15.6%, p = 0.554) was comparable.ConclusionsIn older patients with localized prostate cancer, two moderate hypofractionated regimens were all well tolerated with similar, mild late toxicities and satisfactory survival, without necessity of prophylactic pelvic node irradiation.Key words: helical tomotherapy, radiation dose hypofractionation, progression-free survival, follow-up studies, prostatic neoplasms, adenocarcinoma     

覆盖义齿基牙的短期临床观察

目的：对覆盖义齿的基牙进行短期临床观察。方法：对30例覆盖义齿修复患者半年及1年后回访观察。结果：下颌基牙及非银汞充填覆盖基牙更易存积菌斑及结石,并出现牙龈问题。结论：对于能保持良好口腔卫生的患者,覆盖义齿是一种较好的选择。