Renqing Yan’s research while affiliated with Zunyi Medical University and other places

17α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is challenging due to its low physiological concentration. The high false-positive rates of immunoassays necessitate the development of more accurate methods. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers increased specificity and sensitivity, yet standardized procedures for 17α-OHP measurement are required for clinical application. A candidate reference measurement procedure (cRMP) using isotope dilution LC-MS/MS was developed for 17α-OHP quantification in DBS. By utilizing stable isotope-labeled D8-17α-OHP as an internal standard, the cRMP was optimized, covering sample preparation, calibration, and LC-MS/MS analysis. The method performance was validated across several parameters, including precision, accuracy, specificity, detection limits, and matrix effects. Clinical applicability was further assessed through the establishment of reference intervals for healthy newborns. The developed cRMP exhibited a linear range of 1.00 to 80.00 ng/mL for 17α-OHP, with detection and quantification limits of 0.14 ng/mL and 0.52 ng/mL, respectively. Inter- and intraday precision demonstrated coefficients of variation within 1.27 to 5.69%. The recovery rates and matrix effects were well within acceptable limits, ensuring method reliability. Clinical application showed distinct reference intervals for healthy newborns that were unaffected by sex but influenced by weight and gestational age. This method significantly enhances CAH diagnostic accuracy in newborns, providing a valuable tool for clinical laboratories and improving newborn screening program standardization and traceability. Supplementary Information The online version contains supplementary material available at 10.1007/s00216-024-05411-9.

Abstract Introduction: The severity of Coronavirus Disease 2019 (COVID-19) has been linked to lower levels of lipid profile, including total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. However, the relationship between triglycerides and COVID-19 severity is still controversial. Thus, this study aimed to evaluate the association between triglyceride concentration and COVID-19 severity. Methods: The systematic review adhered to the PRISMA guidelines. Heterogeneity was assessed using Thompson’s I 2 and Tau2 statistics, and the Standardized Mean Difference (SMD) and 95% confidence intervals (CIs) in triglyceride levels were calculated using random-effects models. Publication bias was evaluated using Egger’s test. Results: Our meta-analysis included 12 observational studies with a total of 5,369 confirmed COVID-19 patients. Of these, 3,956 (46%males) had non-severe COVID-19, and 1,513 (59% males) had severe COVID-19 during follow-up. The SMD in triglyceride levels was 0.110 (95% CI=[0.004, 0.217], P=0.042), indicating a significant difference between the non-severe and severe groups. The studies exhibited moderate heterogeneity in the triglyceride levels (I2 =50.7%). A meta-regression analysis showed that the SMD of triglyceride was significantly associated with the risk ratio of hyperlipidemia (coefficient=-1.40, P=0.007). No publication bias was detected in the studies according to Egger’s test. Conclusion: Our systematic review and meta-analysis revealed that lower serum triglyceride concentrations were associated with severe COVID-19 in patients. Further investigation is needed to determine whether lower triglyceride levels increase COVID-19 severity in larger populations. Keywords: COVID-19; Lipids; Prognosis; Severity; Triglycerides

Introduction: Familial hypercholesterolaemia (FH) is a common hereditary genetic disorder, characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] concentrations, leading to atherosclerotic cardiovascular disease (ASCVD). Two types of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors- alirocumab and evolocumab- are efficient drugs in the treatment of FH, which can effectively reduce Lp(a) levels. Material and methods: Embase, MEDLINE, and PubMed up to November 2022 were searched for randomized clinical trials (RCTs) evaluating the effect of alirocumab/evolocumab and placebo treatment on plasma Lp(a) levels in FH. Statistics were analysed by Review Manager (RevMan 5.3) and Stata 15.1. Results: Eleven RCTs involved a total of 2408 participants. Alirocumab/evolocumab showed a significant efficacy in reducing Lp(a) [weighted mean difference (WMD): -20.10%, 95% confidence interval (CI): -25.59% to -14.61%] compared with placebo. In the drug type subgroup analyses, although the efficacy of evolocumab was slightly low (WMD: -19.98%, 95% CI: -25.23% to -14.73%), there was no difference with alirocumab (WMD: -20.54%, 95% CI: -30.07% to -11.02%). In the treatment duration subgroup analyses, the efficacy of the 12-week duration group (WMD: -17.61%, 95% CI: -23.84% to -11.38%) was lower than in the group of ≥ 24 weeks' duration (WMD: -22.81%, 95% CI: -31.56% to -14.07%). In the participants' characteristics subgroup analyses, the results showed that no differential effect of alirocumab/evolocumab therapy on plasma Lp(a) concentrations was observed (heterozygous FH [HeFH] WMD: -20.07%, 95% CI: -26.07% to -14.08%; homozygous FH [HoFH] WMD: -20.04%, 95% CI: -36.31% to -3.77%). Evaluation of all-cause adverse events (AEs) between alirocumab/evolocumab groups and placebo groups [relative risk (RR): 1.05, 95% CI: 0.98-1.12] implied no obvious difference between the 2 groups. Conclusions: Anti-PCSK9 drugs (alirocumab and evolocumab) may be effective as therapy for reducing serum Lp(a) levels in FH, and no differences were observed in treatment durations, participant characteristics, and other aspects of the 2 types of PCSk9 inhibitors. However, further experimental studies and RCTs are warranted to clarify the mechanism of PSCK9 inhibitors to lowering Lp(a) concentrations in FH.