平贝碱乙的分离和鉴定

本文报道了自东北平贝母(Fritillaria ussuriensis Maxim)中分得一种新的甾体生物碱,经光谱(IR,MS,¹HNMR及¹³CNMR)解析和衍生物制备,推定其结构为5α,17β,22α-cevanine-3 β,6α,12α,14α,16β,20β-hexol,定名为平贝碱乙。     

单克隆抗体博来霉素A6偶联物对白血病细胞特异性结合与内化

抗CCT2单克隆抗体博来霉素A6偶联物可吸附胶体金颗粒(McAb-A6-Au)。电镜观察表明,在4℃,1h,表面有McAb-A6-Au颗粒的CEM细胞最高达78%;在37℃,4h,内化McAb-A6-Au颗粒的CEM细胞高达72%。而抗原性无关的U937细胞仅为14%。并且McAb-A6-Au颗粒能直接穿过细胞膜、核膜进入细胞浆和细胞核。37℃,1h已有10～18%的CEM细胞核内有McAb-A 6-Au颗粒。实验结果提示了单抗与博来霉素A6的偶联物与选择性地结合靶细胞,而且进入细胞速度快、穿透力强,有可能成为治疗白血病药物。     

Incidence of respiratory disorders in neonates born between 34 and 36 weeks of gestation following exposure to antenatal corticosteroids between 24 and 34 weeks of gestation

We studied the effect of antenatal corticosteroids on the incidence of respiratory disorders in singleton neonates born between 34 and 36 weeks of gestation. Retrospective analysis was conducted of the incidence of respiratory distress syndrome (RDS) and other respiratory disorders (need for mechanical ventilation, continuous positive airway pressure, and prolonged oxygen therapy) among singleton neonates delivered between 34 and 36 weeks of gestation who were exposed to antenatal corticosteroids, compared with neonates who were not exposed. Statistical analyses included two-tailed T tests, two-way analysis of variance for continuous data, and chi-square analysis for ratios. A probability of 0.05 was considered significant. Between January 1, 2000, and December 31, 2004, 1078 neonates were born between 34 and 36 weeks of gestation. Information regarding antenatal corticosteroids was available in 1044: 574 neonates (53.2%) were exposed to antenatal corticosteroids and 470 (43.6%) were not. One thousand and eighteen neonates were admitted to the neonatal intensive care unit. Respiratory disorders were diagnosed in 140 of those exposed to antenatal steroids (24.4%) and in 382 of the nonexposed (81.3%) ( P < 0.0001). Two hundred and ten neonates (20.6%) developed RDS: Of those, 43 were exposed to antenatal corticosteroids and 167 were not (incidence of RDS was 7.5% and 35.5%, respectively; P = 0.0001). The beneficial effects of corticosteroids were similar in both genders. It appears that the exposure of singleton pregnancies to antenatal corticosteroids between 24 and 34 weeks of gestation is associated with a significantly lower incidence of respiratory disorders among neonates born at 34 to 36 weeks of gestation. Further studies are needed to determine whether administering antenatal steroids to women experiencing preterm labor after 34 weeks of gestation would be associated with a similar beneficial effect.     

Investigation of COVID-19 Outbreak among Wildland Firefighters during Wildfire Response,Colorado, USA, 2020

A COVID-19 outbreak occurred among Cameron Peak Fire responders in Colorado, USA, during August 2020–January 2021. The Cameron Peak Fire was the largest recorded wildfire in Colorado history, lasting August–December 2020. At least 6,123 responders were involved, including 1,260 firefighters in 63 crews who mobilized to the fire camps. A total of 79 COVID-19 cases were identified among responders, and 273 close contacts were quarantined. State and local public health investigated the outbreak and coordinated with wildfire management teams to prevent disease spread. We performed whole-genome sequencing and applied social network analysis to visualize clusters and transmission dynamics. Phylogenetic analysis identified 8 lineages among sequenced specimens, implying multiple introductions. Social network analysis identified spread between and within crews. Strategies such as implementing symptom screening and testing of arriving responders, educating responders about overlapping symptoms of smoke inhalation and COVID-19, improving physical distancing of crews, and encouraging vaccinations are recommended.     

Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.     

The association of differing measures of overweight and obesity with prevalent atherosclerosis: the Dallas Heart Study.

OBJECTIVES: This study sought to evaluate the associations between different measures of obesity and prevalent atherosclerosis in a large population-based cohort. BACKGROUND: Although obesity is associated with cardiovascular mortality, it is unclear whether this relationship is mediated by increased atherosclerotic burden. METHODS: Using data from the Dallas Heart Study, we assessed the association between gender-specific obesity measures (i.e., body mass index [BMI]; waist circumference [WC]; waist-to-hip ratio [WHR]) and prevalent atherosclerosis defined as coronary artery calcium (CAC) score >10 Agatston units measured by electron-beam computed tomography and detectable aortic plaque measured by magnetic resonance imaging. RESULTS: In univariable analyses (n = 2,744), CAC prevalence was significantly greater only in the fifth versus first quintile of BMI, whereas it increased stepwise across quintiles of WC and WHR (p trend <0.001 for each). After multivariable adjustment for standard risk factors, prevalent CAC was more frequent in the fifth versus first quintile of WHR (odds ratio 1.91, 95% confidence interval 1.30 to 2.80), whereas no independent positive association was observed for BMI or WC. Similar results were observed for aortic plaque in both univariable and multivariable-adjusted analyses. The c-statistic for discrimination of prevalent CAC was greater for WHR compared with BMI and WC in women and men (p < 0.001 vs. BMI; p < 0.01 vs. WC). CONCLUSIONS: We discovered that WHR was independently associated with prevalent atherosclerosis and provided better discrimination than either BMI or WC. The associations between obesity measurements and atherosclerosis mirror those observed between obesity and cardiovascular mortality, suggesting that obesity contributes to cardiovascular mortality via increased atherosclerotic burden.     

COVID-19 risk index (CRI): a simple and validated emergency department risk score that predicts mortality and the need for mechanical ventilation

Journal of Thrombosis and Thrombolysis - Although certain risk factors have been associated with morbidity and mortality, validated emergency department (ED) derived risk prediction models specific...