Inherited antithrombin (AT) deficiency carries a 50% risk of venous thromboembolism (VTE) during pregnancy. Here, we investigated the molecular basis of type I AT deficiency in two women with recurrent VTE in the first trimester of pregnancy. Phenotype analysis showed both probands had almost 50% of normal AT levels. Two novel heterozygous AT mutations were identified: g.7920C>T resulting in a Trp225Cys mutation in case 1 and g.13863C>A causing an Ala404Asp mutation in case 2. Transient expression of either wild-type (WT) or mutant AT expression vectors in HEK293T and CHO cells showed impaired secretion of both AT mutant proteins. Immunofluorescence analysis revealed that the staining of AT-Trp225Cys in both endoplasmic reticulum (ER) and Golgi apparatus was similar to that of AT-WT, and the staining of AT-Ala404Asp was mainly present in ER but was weaker than that of AT-WT. These results revealed that the type I AT deficiency in two patients was caused by impaired secretion of the AT-Trp225Cys and AT-Ala404Asp mutant proteins, respectively. The two mutations are associated with a high risk of thrombotic onset and women with these AT mutations are prone to VTE in early pregnancy. 相似文献
Background and objective: Pneumonia Severity Index (PSI) predicts mortality better than C onfusion, U rea >7 mmol/L, R espiratory rate >30/min, low Bl ood pressure: diastolic blood pressure <60 mm Hg or systolic blood pressure <90 mm Hg, and age >65 years (CURB‐65) for community‐acquired pneumonia (CAP) but is more cumbersome. The objective was to determine whether CURB enhanced with a small number of additional variables can predict mortality with at least the same accuracy as PSI. Methods: Retrospective review of medical records and administrative data of adults aged 55 years or older hospitalized for CAP over 1 year from three hospitals. Results: For 1052 hospital admissions of unique patients, 30‐day mortality was 17.2%. PSI class and CURB‐65 predicted 30‐day mortality with area under curve (AUC) of 0.77 (95% confidence interval (CI): 0.73–0.80) and 0.70 (95% CI: 0.66–0.74) respectively. When age and three co‐morbid conditions (metastatic cancer, solid tumours without metastases and stroke) were added to CURB, the AUC improved to 0.80 (95% CI: 0.77–0.83). Bootstrap validation obtained an AUC estimate of 0.78, indicating negligible overfitting of the model. Based on this model, a clinical score (enhanced CURB score) was developed that had possible values from 5 to 25. Its AUC was 0.79 (95% CI: 0.76–0.83) and remained similar to that of PSI class. Conclusions: An enhanced CURB score predicted 30‐day mortality with at least the same accuracy as PSI class did among older adults hospitalized for CAP. External validation of this score in other populations is the next step to determine whether it can be used more widely. 相似文献
Haemophilia A (HA) is the most common hereditary bleeding disorder caused by F8 gene mutation. Linkage analysis is an auxiliary strategy to direct mutation analysis for genetic counselling of HA. Here we characterize and validate a novel panel of six short tandem repeat (STR) loci for genetic counselling in Chinese HA pedigrees. The panel was analysed in 116 unrelated healthy female patients and 108 male patients, and verified in 169 unrelated pedigrees with HA. The six STR loci in the panel spanned a distance of 0.3 Mb from each side of the F8 gene. Three of them, F8Up226, F8Up146 and F8Down48, were first described here. Markers F8Up226, F8Up146, F8Int13, F8Int25, F8Down48 and DXS1073 exhibited the number of alleles 16, 9, 8, 6, 9 and 10, and heterozygosity rates of 74.8%, 44.8%, 60.9%, 42.6%, 61.7% and 62.0% respectively. Haplotype frequencies analysis suggested that the genotypes of haplotype provided a highly informative content (56.5%). The panel was informative in 167 of 169 unrelated haemophilic pedigrees with the combined diagnostic rate of 98.8%. In eight pedigrees could not be diagnosed by mutation detection linkage studies using the panel were informative in all the pedigrees and a reliable diagnosis was made in seven pedigrees. The novel panel of the six STR loci represents a high degree of informativeness and a low fraction of recombination. Linkage analysis using this panel provides an alternative strategy when direct mutation detection is not feasible for genetic counselling in Chinese HA families. 相似文献
This study aimed to determine whether functional gastrointestinal disorders are more common among adolescents with self-reported poor sleep.
Methods
Junior middle school and senior high school students (n?=?1,362) were recruited from schools in Shanghai. Students completed two questionnaires: the questionnaire for irritable bowel syndrome (IBS) in adolescents and the Pittsburgh Sleep Quality Index.
Results
The prevalence of poor sleep was 34.29% [95% confidence interval (CI)?=?31.77?C36.81] and there was no significant difference between genders (P?=?0.991). The tendency towards poor sleep increased with age, with age group yielding a significant effect (P?=?0.001). In junior middle school and senior high school students, the propensity towards poor sleep was 30.10% (95% CI?=?27.08?C33.12%) and 42.11% (95% CI?=?37.67?C46.55%), respectively. Among students with poor sleep, the prevalence of IBS was 19.70% (95% CI?=?16.09?C23.31). After adjusting for age, sex, night pain, and psychological factors, IBS was significantly more common in students with poor sleep (odds ratio?=?1.92; 95% CI?=?1.07?C2.58).
Conclusion
We conclude that IBS is prevalent in students with poor sleep. Poor sleep was independently associated with IBS among adolescents in Shanghai China. 相似文献
Atherosclerosis is characterized by accumulation of lipids and inflammatory cells in the arterial wall. Oxidized low-density
lipoprotein (ox-LDL) plays important role in the genesis and progression of atheromatous plaque. Various scavenger receptors
have been recognized in the past two decades that mediate uptake of ox-LDL leading to formation of foam cells. Inhibition
of scavenger receptor A and CD36 has been shown to affect progression of atherosclerosis by decreasing foam cell formation.
Lectin-type oxidized LDL receptor 1 (LOX-1) participates at various steps involved in the pathogenesis of atherosclerosis,
and in experimental studies its blockade has been shown to affect the progression of atherosclerosis at multiple levels. In
this review, we summarize the role of ox-LDL and scavenger receptors in the formation of atheroma with emphasis on effects
of LOX-1 blockade. 相似文献