Establishment of a Risk Prediction Model for Metabolic Syndrome in High Altitude Areas in Qinghai Province, China: A Cross-Sectional Study.

Purpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China. Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation. Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies. Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.

Efficacy of Sildenafil on healthy humans in high­altitude hypoxia at rest and during exercise: A meta­analysis.

The current meta-analysis aimed to fully evaluate the efficacy of Sildenafil in healthy humans at different altitudes, focusing on echocardiographic and hemodynamic parameters. Relevant studies were retrieved from the Cochrane, Embase and PubMed databases. Odds ratios (OR) were determined for dichotomous data and weighted mean differences with 95% confidence intervals (CIs) for continuous data. A total of 16 RCTs were included in the current meta-analysis. Short-term treatment with Sildenafil significantly elevated resting heart rate (P<0.01) at altitudes <4,000 meters. No significant differences in heart rate were observed between the Sildenafil and placebo groups at rest and during exercise at an altitude of >4,000 meters (P>0.05). Sildenafil improved resting cardiac output at an altitude of >5,000 meters (P<0.01) and exercising arterial oxygen saturation at <4,000 meters (P<0.01). Sildenafil reduced resting pulmonary artery systolic pressure (PASP) at altitudes >4,000 meters (P<0.01) and exercising PASP at altitudes >5,000 meters (P<0.01). Therefore, Sildenafil efficacy in healthy humans with high-altitude hypoxia is related to altitude and rest or exercise.

Functional characterization of a heterologously expressed Brassica napus WRKY41-1 transcription factor in regulating anthocyanin biosynthesis in Arabidopsis thaliana.

Previous studies have shown that a plant WRKY transcription factor, WRKY41, has multiple functions, and regulates seed dormancy, hormone signaling pathways, and both biotic and abiotic stress responses. However, it is not known about the roles of AtWRKY41 from the model plant, Arabidopsis thaliana, and its ortholog, BnWRKY41, from the closely related and important oil-producing crop, Brassica napus, in the regulation of anthocyanin biosynthesis. Here, we found that the wrky41 mutation in A. thaliana resulted in a significant increase in anthocyanin levels in rosette leaves, indicating that AtWRKY41 acts as repressor of anthocyanin biosynthesis. RNA sequencing and quantitative real-time PCR analysis revealed increased expression of three regulatory genes AtMYB75, AtMYB111, and AtMYBD, and two structural genes, AT1G68440 and AtGSTF12, all of which contribute to anthocyanin biosynthesis, in the sixth rosette leaves of wrky41-2 plants at 20 days after germination. We cloned the full length complementary DNA of BnWRKY41-1 from the C2 subgenome of the B. napus genotype Westar and observed that, when overexpressed in tobacco leaves as a fusion protein with green fluorescent protein, BnWRKY41-1 is localized to the nucleus. We further showed that overexpression of BnWRKY41-1 in the A. thaliana wrky41-2 mutant rescued the higher anthocyanin content phenotype in rosette leaves of the mutant. Moreover, the elevated expression levels in wrky41-2 rosette leaves of several important regulatory and structural genes regulating anthocyanin biosynthesis were not observed in the BnWRKY41-1 overexpressing lines. These results reveal that BnWRKY41-1 has a similar role with AtWRKY41 in regulating anthocyanin biosynthesis when overexpressed in A. thaliana. This gene represents a promising target for genetically manipulating B. napus to increase the amounts of anthocyanins in rosette leaves.