To explore the application and value of chromosomal karyotype analysis combined with Chromosomal Microarray Analysis (CMA) in the amniotic fluid of advanced maternal age. A total of 817 advanced maternal age (AMA) who underwent amniocentesis at the Prenatal Diagnosis Center of Huizhou Central People's Hospital between January 2018 and July 2024 were enrolled in this study. The women were grouped based on different age ranges and prenatal diagnosis factors. These groups were used to compare the detection rates and differences between chromosomal karyotype analysis and CMA. The overall chromosomal abnormality rates detected by karyotype analysis in the 35-39 years age group and the ≥ 40 years age group were 8.81% and 13.79%, respectively, with a statistically significant difference (p < 0.05). For CMA, the overall abnormality rates in the same age groups were 10.79% and 15.33%, respectively, but the difference was not statistically significant (p > 0.05). The non-solely advanced-age group (those with additional factors beyond just advanced age) had higher overall chromosomal abnormality rates, aneuploidy rates, structural abnormality rates, and mosaicism rates compared to the solely advanced-age group, with statistically significant differences (p < 0.05). Additionally, the non-solely advanced-age group had a higher overall abnormality rate detected by CMA compared to the solely advanced-age group, with a statistically significant difference (p < 0.05). However, there were no statistically significant differences between the two groups in terms of the detection of pathogenic, likely pathogenic, and variants of uncertain significance (p > 0.05). In this study, a total of 68 cases were identified where the results of karyotype analysis and CMA were inconsistent. The overall abnormal rate of chromosomal karyotype analysis increases with maternal age, while the overall abnormal rate of CMA shows no significant correlation with maternal age. The abnormal rates are significantly higher in AMA with additional factors. The combination of chromosomal karyotype analysis and CMA can validate and complement each other, thereby improving the detection rates of chromosomal abnormalities in amniotic fluid samples of AMA. This provides a diagnostic basis for subsequent pregnancy choices, which effectively reduces the birth of fetuses with chromosomal abnormalities and enhances population quality.

This retrospective multicenter study is aimed at evaluating the diagnostic accuracy and influence factors of serum des-gamma-carboxy prothrombin (DCP) as a diagnostic biomarker of hepatocellular carcinoma (HCC). Clinical data were collected from 4555 subjects with DCP tests, composed of primary liver cancer (PLC), metastatic liver cancer (MLC), chronic hepatitis (CH), liver cirrhosis (LC), benign liver diseases (BLD), biliary tract diseases (BTD), non-liver cancers (NLC), and non-liver benign diseases (NLBD). The clinical data collected included medical history, treatment records, various serum tests, and imaging examination. Serum DCP was measured with Abbott agents in each center. In HCC, serum DCP concentration was at 9086.00 ± 366.10 mAU/mL, higher than that in other diseases (p < 0.05). At 40.00 mAU/mL recommended by instruction, positive rates of serum DCP were at 85.11% in HCC, 30.12% in intrahepatic cholangiocellular carcinoma (ICC), 31.65% in MLC, 13.95% in BLD, 18.14% in CH, 27.87% in LC, 15.75% in BTD, 35.29% in NLC, and 20.00% in NLBD. In this study, the diagnostic specificity of serum DCP in HCC was affected by liver function. In HCC, serum AFP concentrations also increased compared to non-HCC diseases (p < 0.05), but specificity varied with agents from different providers. Serum DCP decreased after the surgical removal of HCC, but remained elusive in systemic treatment. Serum DCP may serve as an optimal biomarker for the diagnosis of HCC, but its accuracy appears influenced by liver function; attention needs to be paid to the liver function of patients for false positivity.

With the worldwide increase of diabetes mellitus prevalence, ensuring the performance of HbA1c assays is essential. Internal quality control (IQC) and external quality assessment (EQA) serve as critical components of quality assurance systems and provide comprehensive performance assessment. We aimed to evaluate the intra-laboratory and inter-laboratory variations of HbA1c assays using EQA and IQC data. A total of 326 laboratories continuously participating in the HbA1c EQA program from 2020 to 2023 were included, of which 168 laboratories reported IQC data voluntarily. Acceptance rates and bias were evaluated at three levels: per sample, per year, and per manufacturer. Intra-laboratory and inter-laboratory variations were assessed according to biological variation (BV) criteria and clinical guidelines. The mean acceptance rates for 20 EQA samples were 48.5%, 77.8%, 86.7% within optimum, desirable, minimum BV criteria. Annual average acceptance rates increased from 91.8% to 96.9% based on EQA criterion. The absolute manufacturer-specific bias varied from 0.02% to 4.1%. By 2023, the overall inter-laboratory variation significantly decreased to 2.1%-2.6%. The median intra-laboratory variations reduced from 1.6% to 1.4% at the low QC level and from 1.2% to 1.0% at the high QC level. 58.9% and 79.8% of laboratories achieved an intra-laboratory CV < 1.5% for low and high QC levels, respectively. Both inter-laboratory and intra-laboratory variations of HbA1c measurement have significantly decreased over the years. However, the difference among manufacturers still exists, and ongoing efforts are required to fully comply with clinical guideline requirements.

Accurate assessment of liver inflammation and fibrosis is of vital importance in the clinical management of patients with liver diseases. Our aim is to conduct a meta-analysis to evaluate the diagnostic accuracy of serum cytokeratin 18 (CK18) for staging of liver inflammation and fibrosis against a liver biopsy in adults. We systematically searched articles from eight electronic databases. Two authors independently selected included studies, extracted data, and assessed quality. In our meta-analysis, we used the random-effects meta-analysis model. Publication bias, sensitivity analysis, heterogeneity analysis, and post-test probability were used in this meta study. A total of 20 studies with 2235 patients were initially found by the search strategies. The pooled sensitivity, specificity, and area under the curve (AUC) of the summary receiver operating characteristic curve were 0.56, 0.81, and 0.810 for significant fibrosis; 0.64, 0.76, and 0.785 for advanced fibrosis; 0.53, 0.76, and 0.830 for cirrhosis; and 0.68, 0.73, and 0.786 for significant inflammation, respectively. High heterogeneity was observed in our meta-analysis because of factors such as the proportion of males, total number, and antigens of CK-18. Serum CK18 had moderate diagnostic value (AUC > 0.7) in different stages of liver fibrosis and significant inflammation, offering a complementary approach to other non-invasive indicators such as serological biomarkers and imaging techniques. Future research should focus on elucidating the role of CK18 in the occurrence and progression of hepatitis and liver fibrosis, particularly in liver diseases with diverse etiologies.

The rise in carbapenem-resistant Enterobacterales (CRE) has reinforced the global quest for developing effective therapeutics. Traditional drug discovery approaches have been inadequate in overcoming this challenge due to their resource and time constraints. English literature was searched by structured queries related to our review between January 1, 2020, and December 31, 2024. The key resistance mechanisms in CRE, such as enzymatic hydrolysis, decreased permeability, and efflux pump overexpression, have been examined in this review. Computational technologies have become pivotal in discovering novel antimicrobial agents with improved accuracy and efficiency. Besides this, the review highlights the advances in structure- and ligand-based drug discovery approaches for identifying potential drugs against CRE. Recent studies demonstrating the use of such in silico techniques to develop targeted drugs against CRE have also been explored. Moreover, this review also underscores the significance of integrating both in silico and invitro techniques to counter resistance in Enterobacterales, supported by the latest studies. However, these promising computational technologies have a few major drawbacks, such as a lack of standardized parameterization, potentially false positives, and the complexity of effective clinical translations. The drug regulatory barriers also restrict the progress of new antimicrobials for market approval. The use of computational technologies for antimicrobial inhibitor discovery is gaining popularity, and it can be expedited by refining computational techniques and integrating them with reliable invitro validation. The use of innovative hybrid in silico and invitro technologies is the need of the hour to tackle CRE and mitigate the global threat of antimicrobial resistance.

The emergence of COVID-19 has led to a significant public health crisis, and an increase in fungal infections, including candidemia. Candida species are frequently found in intensive care units (ICUs), and it is a common cause of death in many patients. The isolates were identified using polymerase chain reaction-restriction. In this study, We investigated the factors linked to Candida infections in COVID-19 burn patients in the ICU and assessed the antifungal susceptibility of the isolates invitro. Out of 335 burn patients admitted to the ICU, fifty-six with concurrent COVID-19 were included in this study. A total of 133 yeast isolates were obtained from burn wounds, 29 from blood cultures, and 36 from urine cultures. The isolates were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Out of fifty-six patients, twenty-nine had infections and forty-eight had colonization, with Candida parapsilosis being the most common species. Twenty-one patients died during their ICU stay, with mortality rates of 43.8% among colonized patients and 69.0% among infected patients. Fluconazole and itraconazole exhibited the highest minimum inhibitory concentrations, while luliconazole and amphotericin B were identified as the most effective antifungal agents. Our findings indicate that colonization may act as an important prognostic factor prior to the onset of candidemia. In addition, prolonged hospitalization, catheter use, and concurrent COVID-19 infection were identified as key risk factors for candidemia in this patient group. Notably, the rising drug resistance in non-albicans Candida species is a major public health concern.

ABSTRACTBackgroundLittle is known about the relationship between circulating electrolyte concentrations and paroxysmal atrial fibrillation in the emergency department. We aimed to characterize circulating electrolyte concentrations in patients with paroxysmal atrial fibrillation compared with those of nonspecific control patients admitted to the emergency department.MethodsIn total, data from 520 individuals with paroxysmal atrial fibrillation and 1,040 randomly selected 1040 patients without atrial fibrillation (1:2 ratio), all admitted to the emergency department (January 2010–December 2015), were analyzed. A classification model was developed using a tree‐based machine learning algorithm, and the importance of variables was measured.ResultsPatient age, serum glucose, sodium, potassium, calcium, phosphate, and sex were significantly associated with paroxysmal atrial fibrillation (all p &lt; 0.001). For serum magnesium, the difference approached significance (p = 0.096). The model had a moderate performance with a 10‐fold cross‐validation accuracy of 0.728 and a sensitivity, specificity, area under the curve, and likelihood ratio of 0.613, 0.770, 0.692, and 2.67, respectively. Overall, age and glucose were the most important variables followed by serum sodium, potassium, and calcium. Male sex, older age, and a higher serum sodium, calcium, potassium, and magnesium, and a lower serum glucose and phosphate were associated with a higher likelihood of paroxysmal atrial fibrillation in the emergency department.ConclusionSerum electrolyte imbalances, particularly in sodium, potassium, and magnesium, are significantly associated with paroxysmal atrial fibrillation in emergency settings. Emergency physicians should monitor and correct these electrolytes to improve early PAF management and potentially prevent adverse outcomes.

ABSTRACTBackgroundPrimary cilia are organelles formed on the cell surface. They can act as cellular antennae to sense signals and play important roles in various biological processes. Abnormalities in primary cilia lead to a variety of diseases collectively known as ciliopathies. Intraflagellar transport protein 20 (IFT20) has been implicated in ciliogenesis.MethodsIFT20 knockout cell lines were established using the CRISPR‐Cas9 gene editing technology. The GFP‐IFT20 plasmid was constructed with the Gateway cloning system. Protein levels were detected via immunoblotting, and the localization of IFT20, acetylated α‐tubulin, ARL13B, CP110, MKS3, IFT88, and IFT140 in wild‐type and IFT20 knockout cells was examined by immunofluorescence microscopy. The fluorescence intensities were analyzed using ImageJ. Data quantifications and mass spectrometry results were analyzed using GraphPad Prism and Metascape.ResultsThe IFT20 deficiency impaired ciliogenesis and reduced cilium length. IFT20 depletion did not affect the removal of centriolar coiled‐coil protein 110 (CP110) from the mother centriole or the recruitment of Meckel–Gruber syndrome type 3 (MKS3) to the transition zone. Mass spectrometry analysis revealed that proteins interacting with IFT20 were mainly IFT components. IFT20 knockout decreased the levels of both IFT88 and IFT140, and abrogated IFT88 localization at the basal body and ciliary axoneme. IFT20 knockout also impaired IFT140 localization at the ciliary axoneme but did not affect its localization at the basal body.ConclusionsIFT20 is involved in ciliogenesis by regulating the level and localization of other IFT proteins and may have important implications in ciliopathies and related diseases.

ABSTRACTObjectiveTo explore and evaluate the value of chromosomal microarray analysis (CMA) in fetuses with abnormal ultrasound soft markers.MethodsA retrospective study was conducted on 193 fetuses with abnormal ultrasound soft markers who received prenatal diagnosis at Meizhou People's Hospital, between October 2022 and February 2024. Genetic detection of fetal specimens obtained by ultrasound‐guided puncture was carried out. The detection rates of karyotype analysis and CMA for chromosomal abnormalities in different ultrasonic abnormalities were analyzed.ResultsOf the 193 fetuses, there were 77 (39.9%) fetuses with increased nuchal translucency(NT) thickness, 33 (17.1%) with ventriculomegaly, 29 (15.0%) with nasal bone hypoplasia, followed by choroid plexus cyst, pyelic separation, echogenic bowel, single umbilical artery, with persistent left superior vena cava, and persistent right umbilical vein. Aneuploidy was mainly found in fetuses with increased NT thickness or and nasal bone hypoplasia, while P/LP CNVs were mainly concentrated in fetuses with increased NT thickness or ventriculomegaly. The detection rate of karyotype was 5.7% (11/193), the detection rate of aneuploidy plus P/LP CNVs in fetuses with abnormal ultrasonic soft markers by CMA was 10.9% (21/193), and the additional detection rate of CMA was 5.2%.ConclusionsCMA can significantly improve the detection rate of chromosomal abnormalities in fetuses with abnormal ultrasonic soft markers compared with karyotype analysis. There was a significant difference in detection rates of chromosomal abnormality between CMA and karyotype analysis in the single ultrasonic abnormality group, but none in the multiple ultrasonic abnormalities group.

ABSTRACTBackgroundLactate, traditionally viewed as a glycolysis byproduct, has emerged as an important mediator influencing immunity, inflammation, and tissue damage. While PM2.5 exposure is known to cause various metabolic disturbances, the role of lactate metabolism in PM2.5‐induced lung injury remains unclear. This study aims to elucidate the mechanisms underlying PM2.5‐induced lung injury from a metabolic perspective.MethodsLactate and pyruvate assays were performed to assess metabolic changes following PM2.5 exposure. Protein expression and tissue damage were assessed using Western blot, IHC, ELISA, and TUNEL staining. The biological role of USP38 in PM2.5‐induced injury was identified using gain‐ and loss‐of‐function experiments. Co‐immunoprecipitation and ubiquitination assays were conducted to analyze the interaction between USP38 and MCT1, as well as the regulation of MCT1 deubiquitination. The role of MCT1 in lactate metabolism and PM2.5‐induced apoptosis was validated through gene editing. Proteomics revealed the potential mechanisms involved in USP38 regulation of apoptosis.ResultsOur results demonstrated that PM2.5 exposure induced lactate accumulation, leading to cell apoptosis and lung injury. USP38 stabilized MCT1 expression by deubiquitination, facilitating lactate export and reducing apoptosis and lung injury caused by lactate accumulation. Mechanistically, PM2.5 increased lactate production, suppressed AKT/mTOR pathway activation, and promoted apoptosis and lung injury. USP38 promoted lactate export through MCT1, activated the AKT/mTOR pathway, and mitigated PM2.5‐induced lung injury.ConclusionUSP38 reduces lactate accumulation by promoting AKT/mTOR pathway activation through MCT1‐mediated lactate export, thereby alleviating PM2.5‐induced lung injury. These findings reveal a novel mechanism of PM2.5‐related lung injury and highlight potential therapeutic targets.