ABSTRACT Background Thalassemia trait (TT) and iron deficiency anemia (IDA) represent the most common causes of microcytic hypochromic anemia (MHA) and are challenging to differentiate in clinical settings. Data regarding the genetic and clinical characteristics of TT in Northern China remain insufficient, highlighting an urgent need for rapid and efficient diagnostic strategies for the regional population. Methods This retrospective study enrolled 482 TT and 640 IDA patients from Northern China. Twenty‐seven α‐ and β‐TT mutations were detected by multicolor probe melting curve analysis (MMCA) and further confirmed by Sanger sequencing. A LASSO regression model using routine hematological indices was constructed and further validated. The diagnostic efficacy was compared with other indices (Mentzer, Shine and Lal, and Green and King indices). Results A total of 482 cases with TT mutations were identified. β‐TT mutations were the most prevalent ( n = 261, 54.15%), followed by α‐TT mutations ( n = 209, 43.36%) and α+β complex TT mutations ( n = 12, 2.49%). Among which, eight α‐TT genotypes, eleven β‐TT genotypes, and eight α+β compound genotypes mutations were detected. For α‐TT, the predominant genotype was _α SEA /αα (77.0%), followed by _α 3.7 /αα (14.3%), α SEA /_α 3.7 (3.3%) and the rare HKαα (1.0%). The three most prevalent genotypes among β‐TT mutations were HBB:c.316_197C>T heterozygous ( het ) (35.2%), HBB:c.124_127delTTCT het (29.5%), and HBB:c.52A>T het (23.4%). α‐TT minor (33.82%) and β‐TT minor (53.94%) contributed the predominant phenotypes. The LASSO‐nomogram based on RBC, MCV, MCHC, and RDW‐SD achieved favorable discriminative performance (AUC = 0.94, sensitivity = 90.0%, specificity = 91.8%), showing superior diagnostic efficacy than other indices. Conclusion Our study revealed a distinct β‐TT‐dominant genotypic profile in Northern China and provided a simple, region‐adapted model as a potential tool for differentiating TT from IDA in clinical practice.
ABSTRACT Objective To verify the clinical performance of the Mindray MN2880 system for simultaneous detection of SARS‐CoV‐2, influenza A virus (IAV), influenza B virus (IBV), and respiratory syncytial virus (RSV) nucleic acids. Methods According to the CNAS‐GL039:2019 and CNAS‐GL037:2019 requirements for molecular diagnostic verification, we comprehensively evaluated the Mindray MN2880 multiplex respiratory virus assay across seven critical performance parameters: clinical concordance, limit of detection (LoD), repeatability, precision, cross‐reactivity/interference resistance, daily QC, and contamination control. Results The Mindray MN2880 system demonstrated high diagnostic concordance with the reference method, with total percent agreements of 99.51% (95% CI: 99.00%–99.76%) for SARS‐CoV‐2, 99.93% (95% CI: 99.60%–99.99%) for IAV, and 100% for both IBV and RSV, and achieved clinically verified limits of detection (LoD: SARS‐CoV‐2 at 100 copies/mL, IAV/IBV/RSV at 200 copies/mL). Analytical precision was confirmed through 100% detection across negative/low/medium/high concentration panels with ≤ 3% CV for repeatability (Ct values) and ≤ 5% CV for inter‐run precision. The assay exhibited 100% specificity against 6 clinically relevant pathogens, including Human Rhinovirus, parainfluenza virus, adenovirus, Mycoplasma pneumoniae , Haemophilus influenzae , and Staphylococcus aureus , with no observed cross‐reactivity. Moreover, the MN2880 system demonstrated robust interference resistance (100% detection of weakly‐positive samples spiked with seven interferents), stable daily QC performance (100% valid controls across 115 consecutive runs), and 100% contamination prevention. Conclusion The MN2880 system satisfies key analytical benchmarks required for diagnostic use in respiratory virus multiplex testing, with performance verified against CNAS‐GL039:2019 and CNAS‐GL037:2019 standards.
ABSTRACT Background Pain control in neonates is crucial as inadequate management may impair neuronal development. Dexmedetomidine (DEX), an alpha2 agonist, is approved for intravenous use in ventilated neonates. While intranasal DEX is off‐label in neonates and children, studies show its efficacy for magnetic resonance imaging sedation. Limited pharmacokinetic data exist for intranasal DEX in pre‐term infants and neonates. This study aimed to develop an analytical method for DEX quantification in blood samples (20 μL) of complex patients collected with microsampling technique to enable future pharmacokinetic studies. Methods A liquid–liquid extraction from blood absorbed in microsampling devices (MITRA) and an LC–MS/MS method were developed and validated following EMA/FDA guidelines. The method's suitability was verified by comparing results from nine paediatric blood samples collected in EDTA tubes or using MITRA devices. Results All results obtained for selectivity (no interference at R T of DEX), sensitivity (DEX LLOQ = 0.025 ng/mL), linearity (R 2 > 0.99), intra and inter‐day repeatability (CV % 1.8–11.8), stability, and hematocrit effect met the acceptance criteria for bioanalytical method validation. Compared with plasma samples, the proposed method showed good consistency in detecting DEX in MITRA samples. Conclusion The MITRA microsampling tools reduce the amount of blood needed and the risks of anemisation for neonates hospitalised and simplifies procedures, allowing a reduction of the staff involved in the routine. The analytical and clinical validation of the method demonstrated its suitability to quantify DEX in a range of concentrations potentially useful for pharmacokinetic studies in paediatric patients for approval use and drug monitoring.
Background Given the controversy surrounding anticoagulation therapy in sepsis, this study evaluated the efficacy of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) compared with no anticoagulation in sepsis management, considering their potential benefits beyond anticoagulation. Methods In this retrospective cohort study, 1362 sepsis patients were stratified into no anticoagulation, UFH, or LMWH groups. Propensity score matching balanced baseline characteristics. UFH was administered intravenously and LMWH subcutaneously at standard doses. Twenty-two biomarkers were assessed at baseline and days 1, 3, and 7 post-anticoagulation. Survival and bleeding were evaluated using Kaplan-Meier curves. Generalized linear mixed models identified treatment-associated biomarkers, and mediation analysis evaluated their role in survival benefit. Results After matching, 109 and 394 patients were included in the UFH and LMWH comparisons, respectively. Both UFH and LMWH were associated with significantly improved survival versus the no anticoagulation group (p < 0.001), without increased 90-day bleeding risk. UFH was associated with significant reductions in FDP, D-dimer, IL-6, IL-8, and CRP (FDR-adjusted p < 0.001), whereas LMWH was associated with significant reductions only in FDP and D-dimer. Mediation analysis demonstrated that UFH's survival benefit was partly mediated by IL-6 and IL-8 reduction, accounting for 30.9% (p = 0.012) and 29.6% (p = 0.045) of the total effect. LMWH's survival benefit was not significantly mediated by any measured biomarker. Conclusions Both UFH and LMWH improved survival in sepsis patients without increasing bleeding risk. However, UFH demonstrated broader anti-inflammatory effects, with survival benefit partially explained by IL-6/IL-8 suppression. LMWH's benefit appeared primarily anticoagulant-mediated.Trial Registration Chinese Clinical Trial Registry, ChiCTR2100045167. Registered 06 April 2021, retrospectively registered
ABSTRACT Background Humoral immunity defends via immunoglobulins. This study aimed to evaluate the association between immunoglobulins and CVDs and lipid profiles in a cohort of individuals aged 45 years and older. Methods Data from 982 subjects were analyzed. The cohort had a median age of 61 years (IQR 56–72), was predominantly male (84.8%), and had a high prevalence of CVDs at baseline, including hypertension (30.3%), dyslipidemia (20.7%), arrhythmia (22.3%), coronary heart disease (12.1%), and atrial fibrillation (4.5%). Logistic regression analysis was used to examine the association between baseline and time‐varying serum levels of IgG, IgA, and IgM and the presence of five CVDs: coronary heart disease, atrial fibrillation, arrhythmia, hypertension, and dyslipidemia. We additionally explored the relationship between these immunoglobulin levels and lipid profiles. Results No significant differences in immunoglobulin levels were found between CVD and non‐CVD groups at baseline, and baseline immunoglobulin levels were not associated with any CVD. However, longitudinal changes in IgG and IgA levels were positively associated with changes in free fatty acids (FFAs). Intriguingly, longitudinal increases in IgM levels were positively associated with total cholesterol, LDL‐C, non‐HDL‐C, and HDL‐C. Conclusions This study provides longitudinal evidence that increases in IgG and IgA levels are associated with elevated FFA levels, while increases in IgM are associated with an adverse lipid profile characterized by higher total cholesterol, LDL‐C, and non‐HDL‐C, and lower HDL‐C. These findings suggest a link between humoral immunity and lipid metabolism that warrants further investigation, with potential implications for cardiovascular risk assessment.
