热惊厥幼龄大鼠脑内Prolactin蛋白及Zinc transporter 1 mRNA表达

目的 探讨热应激(Heat stress,HS)和热惊厥(Febrile convulsions,FC)对脑内催乳素蛋白(Prolactin,PRL)和锌离子转运体1(Zinc transporter 1,ZnT1)表达的影响,探讨FC的神经免疫学机制.方法 实验在浙江大学附属邵逸夫医院中心实验室进行.采用热水浴诱导FC模型.21 d龄雄性sD大鼠随机分为正常对照组(8只)和热应激组(28只),28只热应激处理大鼠中15只达到5级(设为热性惊厥组,FC),10只未出现惊厥(设为单纯热应激组,HS),3只达到2级惊厥,弃用.应用免疫组织化学技术对HS和FC大鼠PRL免疫反应性在不同脑区的表达进行分析,原位杂交检测ZnT1表达.各组阳性细胞数采用方差分析进行统计.结果 ①对照组大脑皮层偶见零星表达,着色淡且无定位分布特征.HS组PRL-IR阳性细胞在大脑皮层PIR、Ent和Rs区免疫染色较深,PRH、PAR和Fr区染色较浅;另外PRL-IR阳性细胞还分布于丘脑中线一带;而FC组则于大脑皮层、海马、杏仁核、丘脑及下丘脑见大量PRL-IR阳性细胞,呈弥漫性分布,无明显核团分布特征.②HS和FC两组大脑皮层各区PRL-IR阳性细胞数均明显高于对照组(P<0.01).FC组大鼠大脑皮层PIR、Ent、RS区PRL-1R阳性细胞数与HS组大鼠差异无统计学意义(F值分别为688.9、744.3、0.56,P>0.05),PRH和PAR区FC组明显高于HS组(F值分别为2.68、1.48,P<0.01).③FC组海马区域可见明显ZnT1 mRNA表达,而HS组和对照组无明显表达.结论 ①PfuL在HS组和FC组大脑皮层各区明显表达,而FC组在海马和杏仁核等前脑结构内亦有明显表达,表明PRL不仅与热应激的中枢调控有关,也参与海马等前脑结构对惊厥活动的中枢调控机制.②FC组海马ZnT1 mRNA明显表达提示FC组海马区域存在异常增高的锌离子转运.     

巴布剂基质配比的研究

目的 优选巴布剂基质配比.方法 采用正交试验设计法选择基质配比.以初黏力,剥离强度和内聚力的综合黏性得分为基质考察指标,对结果进行直观分析和方差分析.结果 优选基质配比为聚乙二醇:阿拉伯胶:卡波姆:聚丙烯酸钠=2∶1∶3∶2.结论 按优选最佳条件制备的巴布剂具有良好的延展性,外观平整光滑,且能满足黏弹性要求.     

抗PD-1单抗生物学活性测定方法的联合验证

针对抗PD-1单抗的报告基因活性测定法开展实验室间的联合验证,以研究该方法多实验室间的可应用和可转移性。本文采用两种协作方案,分别对该方法的检测内、检测间和实验室间精密度以及线性和准确性进行了研究。结果显示:该方法的检测内精密度的95%可置信区间为(1.72～16.89)%,检测间精密度为(2.63～17.67)%,实验室间精密度为(9.00～14.26)%;线性的相关系数均大于0.99,对于不同效价水平准确性的95%可置信区间, 50%为(91.83～104.40)%, 75%为(90.40～101.40)%, 100%为(94.71～105.60)%, 125%为(94.00～102.00)%, 150%为(96.73～104.30)%。联合验证结果证明,该针对抗PD-1单抗的报告基因测活法,其精密度、线性和准确性均良好,可应用于不同实验室抗PD-1单抗的放行检测及稳定性分析。     

Dynamic changes of renal cortical blood perfusion before and after percutaneous transluminal renal artery stenting in patients with severe atherosclerotic renal artery stenosis

Background:This study aims to observe the dynamic changes of renal artery (RA) disease and cortical blood perfusion (CBP) evaluated by contrast-enhanced ultrasound (CEUS) after percutaneous transluminal renal artery stenting (PTRAS) in patients with severe atherosclerotic renal artery stenosis (ARAS) and to analyze the relationship between CBP and prognosis.Methods:This was a single-center retrospective cohort study. A total of 98 patients with unilateral severe ARAS after successful PTRAS in Beijing Hospital from September 2017 to September 2020 were included. According to renal glomerular filtration rate (GFR) detected by radionuclide imaging at 12 months after PTRAS, all patients were divided into the poor prognosis group (n = 21, GFR decreased by ≥20% compared with baseline) and the control group (n = 77, GFR decreased by < 20% or improved compared with baseline). Renal artery stenosis was diagnosed by digital subtraction angiography, and renal CBP was evaluated by CEUS using TomTec Imaging Systems (Germany) before PTRAS, at 6 months and 12 months after discharge. The receiver operating characteristic (ROC) curve with area under the curve (AUC) was used to analyze the predictive value of CBP parameters, including area under ascending curve (AUC1), area under the descending curve (AUC2), rising time (RT), time to peak intensity (TTP), maximum intensity (IMAX), and mean transit time (MTT) for poor prognosis.Results:Among the 98 patients, there were 52 males (53.1%), aged 55–74 years old, with an average age of 62.1 ± 8.7 years, and an average artery stenosis of 82.3 ± 12.9%. The poor prognosis group was associated with significantly increased incidence of diabetes (76.2% vs. 41.6%), and lower levels of GFR of the stenotic kidney (21.8 mL/min vs. 25.0 mL/min) and total GFR (57.6 mL/min vs. 63.7 mL/min) (all P < 0.05), compared with the control group (P < 0.05). In addition, the rate of RA restenosis was significantly higher in the poor prognosis group than in the control group (9.5% vs. 0, χ² = 9.462, P = 0.002). Compared with the control group, the poor prognosis group was associated with significantly decreased baseline AUC1 and AUC2, and extended duration of TTP and MTT (P < 0.05). At 6 months and 12 months of follow-up, patients in the control group were associated with markedly increased AUC1, AUC2, and IMAX, and shorter duration of RT and MTT (P < 0.05). The ROC curve showed that the predictive values of AUC1, AUC2, RT, TTP, IMAX, and MTT for poor prognosis were 0.812 (95% CI: 0.698–0.945), 0.752 (95% CI: 0.591–0.957), 0.724 (95% CI: 0.569–0.961), 0.720 (95% CI: 0.522–0.993), 0.693 (95% CI: 0.507–0.947), and 0.786 (95% CI: 0.631–0.979), respectively.Conclusions:Preoperative renal CBP in severe ARAS patients with poor prognosis is significantly reduced, and does not show significant improvement after stent treatment over the first year of follow-up. The parameter AUC1 may be a good predictor for renal dysfunction after PTRAS in severe ARAS patients.Trial Registration:ChiCTR.org.cn, ChiCTR1800016252.     

Do methylenetetrahydrofolate dehydrogenase,cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?

Background:Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children''s intelligence changes in endemic fluorosis areas has been rarely explored.Methods:A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF_Cr) level. Four loci of MTHFD1 were genotyped, and the Combined Raven''s Test was used to evaluate children''s intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children''s UF_Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence.Results:In the high fluoride group, children''s IQ scores decreased by 2.502 when the UF_Cr level increased by 1.0 mg/L (β = −2.502, 95% confidence interval [CI]:−4.411, −0.593), and the possibility for having “excellent” intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group (P < 0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05).Conclusion:Our findings suggest that excessive fluoride exposure may have adverse effects on children''s intelligence, and changes in children''s intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.     

A study of the therapeutic mechanism of Jakyakgamcho-Tang about functional dyspepsia through network pharmacology research

Herbal medicines have traditionally been used as an effective digestive medicine. However, compared to the effectiveness of Herbal medicines, the treatment mechanism has not been fully identified. To solve this problem, a system-level treatment mechanism of Jakyakgamcho-Tang (JGT), which is used for the treatment of functional dyspepsia (FD), was identified through a network pharmacology study. The two components, paeoniae radix alba and licorice constituting JGT were analyzed based on broad information on chemical and pharmacological properties, confirming 84 active chemical compounds and 84 FD-related targets. The JGT target confirmed the relationship with the regulation of various biological movements as follows: cellular behaviors of muscle and cytokine, calcium ion concentration and homeostasis, calcium- and cytokine-mediated signalings, drug, inflammatory response, neuronal cells, oxidative stress and response to chemical. And the target is enriched in variety FD-related signaling as follows: MAPK, Toll-like receptor, NOD-like receptor, PI3K-Akt, Apoptosis and TNF signaling pathway. These data give a new approach to identifying the molecular mechanisms underlying the digestive effect of JGT.     

济南市市中区成年居民二手烟暴露现状及其相关知识态度调查

目的了解山东省济南市市中区成年居民二手烟暴露现状及其对二手烟危害相关知识态度知晓情况, 为进一步做好控烟宣传及政策制定提供参考依据。方法采用随机整群抽样方法对在济南市市中区杆石桥办事处2个居委抽取的2 497名18~69周岁成年居民进行问卷调查。结果济南市市中区成年居民吸烟吸烟率为33.04%, 二手烟暴露率为60.35%;不同特征居民二手烟暴露率比较, 不同性别、年龄、文化程度、职业成年居民二手烟暴露率差异均有统计学意义(均P<0.001);1 507名二手烟暴露者中, 暴露频率为1~3天/周、4~6天/周和几乎每天者分别占18.18%、27.27%和54.55%, 差异有统计学意义(χ²=17.529, P<0.001), 主要暴露场所为家中、工作场所和交通工具者分别占12.08%、77.90%和10.02%, 差异有统计学意义(χ²=19.026, P<0.001);有63.12%的成年居民知晓二手烟会引发心脏病, 有65.24%的成年居民知晓二手烟会引发儿童肺部疾病, 有77.77%的成年居民知晓二手烟会引发肺癌;有67.08%的成年居民支持公共场所禁烟, 有69.84%的成年居民支持工作场所禁烟。结论济南市市中区成年居民二手烟暴露水平较高, 危害较大, 应进一步加强控烟, 提高无烟环境的创立。