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BackgroundLittle is known about the association of the single nucleotide polymorphism (SNP) of rs364585 near serine palmitoyl-transferase long-chain base subunit 3 gene (SPTLC3) and serum lipid profiles. The present study was detected the association of the SPTLC3 rs364585 SNP and several environmental factors with serum lipid profiles in the Han and Jing populations.MethodsGenotyping of the SPTLC3 rs364585 SNP was performed in 824 unrelated individuals of Han and 783 participants of Jing by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThere was no significant difference in either genotypic or allelic frequencies between Han and Jing, or between males and females of the both ethnic groups. The levels of serum low-density lipoprotein cholesterol (LDL-C) and the ratio of apolipoprotein (Apo) A1 to ApoB in Han; and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and LDL-C in Jing were different between the A allele carriers and the A allele non-carriers (P < 0.05-0.001). Subgroup analysis according to sex showed that the levels of LDL-C in Han males; TC and LDL-C in Jing males; and HDL-C and LDL-C in Jing females were different between the A allele carriers and the A allele non-carriers (P < 0.05-0.001), the A allele carriers had higher LDL-C and TC levels, and lower HDL-C levels than the A allele non-carriers. Serum lipid traits were also associated with several environmental factors in the Han and Jing populations, or in males and females of the both ethnic groups.ConclusionsThe present study demonstrates the association between the SPTLC3 rs364585 SNP and serum TC, HDL-C and LDL-C levels in our study populations. These associations might have ethnic- and/or sex-specificity.Trial registrationRetrospectively registered.

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BackgroundMicroRNAs (miRNAs), a class of small non-coding RNAs, are thought to serve as crucial regulators of gene expression. Dysregulated expression of miRNAs has been described in various diseases and may contribute to related pathologic processes. Our aim was to examine circulating miRNA-146a levels in newly diagnosed type 2 diabetes mellitus (new-T2DM) patients from a Chinese Han population.Methodology/Principal FindingsCirculating miRNA-146a was extracted from plasma samples of 90 new-T2DM patients and 90 age- and sex-matched controls. Quantitative PCR assessment revealed that circulating miRNA-146a levels were significantly elevated in new-T2DM patients compared with controls. Participants in the highest tertile of circulating miRNA-146a levels showed a notably higher risk for new-T2DM (crude OR 4.333, 95% CI, 1.935 to 9.705, P = 0.001) than persons in the lowest tertile. Controlling for known risk factors and some biochemical indicators did not attenuate the aforementioned association. In addition, receiver operating characteristic (ROC) curves generated for miRNA-146a revealed an area under the curve (AUC) of 0.725 (95% CI, 0.651 to 0.799, P < 0.001). Moreover, higher circulating miRNA-146a levels were significantly associated with higher plasma heme oxygenase-1 (HO-1) concentrations (β coefficient = 0.131, P < 0.001) and lower HOMA-beta (β coefficient = -0.153, P = 0.015).Conclusions/SignificanceWe found that circulating miRNA-146a levels were significantly elevated in new-T2DM patients compared with healthy controls. Whether expression of circulating miRNA-146a holds predictive value for T2DM warrants further investigations.

This prospective, double-blinded, randomized controlled study aimed to investigate the efficacy and safety of oral tadalafil in patients receiving background ambrisentan therapy. Current treatments for pulmonary arterial hypertension (PAH) remain insufficient, resulting in high mortality rates. The addition of oral tadalafil, a phosphodiesterase-5 inhibitor, to background ambrisentan may provide a safe and effective therapeutic strategy. A total of 124 patients who had been treated with ambrisentan for at least 4 months and had a stable 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC) for at least 1 month were randomized to either the oral tadalafil or placebo group. Treatment differences in 6MWD, changes in FC, clinical worsening (CW) and adverse events were analyzed after 16 weeks of treatment. At week 16, the tadalafil group showed a significantly improved exercise capacity as assessed by the 6MWD (P<0.05). In addition, 5 (8.3%) patients receiving tadalafil add-on therapy had CW vs. 15 (23.4%) with placebo (P<0.05). No significant differences were found in adverse events or changes in hemodynamic parameters between the placebo and tadalafil groups. Tadalafil 40 mg was well-tolerated as add-on therapy to background ambrisentan. However, the data from this study are insufficient to prove the additional therapeutic benefits of tadalafil add-on therapy.