2019 Chinese Hypertension League guidelines on home blood pressure monitoring

In China, automated blood pressure monitors have been readily available for home use. Home blood pressure monitoring has been indispensable in the management of hypertension. There is therefore a need to establish guidelines for home blood pressure monitoring on the basis of the 2012 consensus document. In this guidelines document, the committee put forward recommendations on the selection and calibration of blood pressure measuring devices, the frequency (times) and duration (days) of blood pressure measurement, and the diagnostic threshold of home blood pressure.     

Polymorphism in exons CpG rich regions of the cyp17-II gene affecting its mRNA expression and reproductive endocrine levels in female Japanese flounder (Paralichthys olivaceus)

Cytochrome P450c17-II (cyp17-II) gene is an important factor affecting the growth, gonad differentiation and development, and other reproductive traits of fish. There are three CpG rich regions in the coding region of cyp17-II gene in Japanese flounder (Paralichthys olivaceus). The aim of this study was to understand whether mutations in exons of the cyp17-II gene occured at CpG sites, and mutations and methylation status of those CpG sites were involved in regulation of the expression level of cyp17-II gene and the reproductive endocrine of Japanese flounder. The results showed that three single nucleotide polymorphisms (SNPs) were identified. SNP1 [(c. G594A (p.Gly 188Arg)] located in exon 4 of L1 locus, and SNP2 (c.A939G) and SNP3 (c.C975T) of L2 locus located in CpG rich region of the exon 6 of cyp17-II gene. Furthermore, the A to G transition at 939 bp position added a new methylation site to the cyp17-II coding region. According to multiple-comparison analysis, two loci (L1 and L2) were significantly associated with serum testosterone (T) level (P < 0.05) and the expression of cyp17-II in ovary (P < 0.01). Intriguingly, individuals with GG genotype of L2 locus containing eight CpG methylation sites had significantly lower serum testosterone level and cyp17-II mRNA expression than those with AA genotype containing seven CpG methylation sites. Moreover, the CpG site was highly methylated (?77.8%) at 938 bp position of individuals with GG genotype of L2 locus. These implied that the mutation and methylation status of the coding region of cyp17-II could influence the gene expression and the reproductive endocrine levels in female Japanese flounder and L2 locus could be regarded as a candidate genetic or epigenetic marker for Japanese flounder breeding programs.     

LRP1-Dependent Endocytic Mechanism Governs the Signaling Output of the Bmp System in Endothelial Cells and in Angiogenesis

Rationale: Among the extracellular modulators of Bmp (bone morphogenetic protein) signaling, Bmper (Bmp endothelial cell precursor-derived regulator) both enhances and inhibits Bmp signaling. Recently we found that Bmper modulates Bmp4 activity via a concentration-dependent, endocytic trap-and-sink mechanism. Objective: To investigate the molecular mechanisms required for endocytosis of the Bmper/Bmp4 and signaling complex and determine the mechanism of Bmper's differential effects on Bmp4 signaling. Methods and Results: Using an array of biochemical and cell biology techniques, we report that LRP1 (LDL receptor-related protein 1), a member of the LDL receptor family, acts as an endocytic receptor for Bmper and a coreceptor of Bmp4 to mediate the endocytosis of the Bmper/Bmp4 signaling complex. Furthermore, we demonstrate that LRP1-dependent Bmper/Bmp4 endocytosis is essential for Bmp4 signaling, as evidenced by the phenotype of lrp1-deficient zebrafish, which have abnormal cardiovascular development and decreased Smad1/5/8 activity in key vasculogenic structures. Conclusions: Together, these data reveal a novel role for LRP1 in the regulation of Bmp4 signaling by regulating receptor complex endocytosis. In addition, these data introduce LRP1 as a critical regulator of vascular development. These observations demonstrate Bmper's ability to fine-tune Bmp4 signaling at the single-cell level, unlike the spatial regulatory mechanisms applied by other Bmp modulators.     

Perception of worsening health predicts mortality in older men: The Health in Men Study (HIMS)

The main purpose of this study was to determine the most robust predictor of mortality among global self-rated health (SRH), time-comparative SRH or a combination of both measures. We also sought to determine factors associated with global SRH and time-comparative SRH measures. A prospective cohort study of 5583 community-dwelling older men aged 70 years or over living in Perth, Western Australia, was used. Older age, depressive symptoms, low social support, sensory impairment, presence of pain, and high Charlson score index were associated with both SRH measures. Global and time-comparative SRH were independent predictors of all-cause mortality (adjusted hazard ratio, HR=1.24 vs. 1.41 respectively); and the risk of death was almost doubled in those with both negative global SRH and perception of worsening health over the preceding 12 months (adjusted HR 1.98, 95%CI 1.58-2.47). In this group, the rate of death was especially high during the initial four years of follow up. We concluded that the two measures of SRH are likely to reflect the same domains of health, and the simultaneous use of both measures is the best predictor of short to medium term mortality.     

Fragment length analysis screening for detection of CEBPA mutations in intermediate-risk karyotype acute myeloid leukemia

During last years, molecular markers have been increased as prognostic factors routinely screened in acute myeloid leukemia (AML). Recently, an increasing interest has been reported in introducing to clinical practice screening for mutations in the CCAAT/enhancer-binding protein ?? (CEBPA) gene in AML, as it seems to be a good prognostic factor. However, there is no reliable established method for assessing CEBPA mutations during the diagnostic work-up of AMLs. We describe here a straightforward and reliable fragment analysis method based in PCR capillary electrophoresis (PCR-CE) for screening of CEBPA mutations; moreover, we present the results obtained in 151 intermediate-risk karyotype AML patients (aged 16?C80?years). The method gave a specificity of 100% and sensitivity of 93% with a lower detection limit of 1?C5% for CEBPA mutations. The series found 19 mutations and four polymorphisms in 12 patients, seven of whom (58%) presented two mutations. The overall frequency of CEBPA mutations in AML was 8% (n?=?12). CEBPA mutations showed no coincidence with FLT3-ITD or NPM1 mutations. CEBPA mutation predicted better disease-free survival in the group of patients without FLT3-ITD, NPM, or both genes mutated (HR 3.6, IC 95%; 1.0?C13.2, p?=?0.05) and better overall survival in patients younger than 65 of this group without molecular markers (HR 4.0, IC 95%; 1.0?C17.4, p?=?0.05). In conclusion, the fragment analysis method based in PCR-CE is a rapid, specific, and sensitive method for CEBPA mutation screening and our results confirm that CEBPA mutations can identify a subgroup of patients with favorable prognosis in AML with intermediate-risk karyotype.     

A Macaca mulatta model of fulminant hepatic failure

AIM: To establish an appropriate primate model of fulminant hepatic failure (FHF).METHODS: We have, for the first time, established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin. Clinical features, biochemical indexes, histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model.RESULTS: Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration. Coagulation activity was significantly decreased. Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h. The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h, respectively. The autopsy showed typical yellow atrophy of the liver. Hepatic encephalopathy of the models was also confirmed by hepatic coma, MRI and pathological changes of cerebral edema. The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices, imaging and histopathology.CONCLUSION: We have established an appropriate large primate model of FHF, which is closely similar to clinic cases, and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.