Annals of clinical and laboratory science最新文献

Objective: Coexistence of hydatidiform mole (HM) and normal pregnancy in twin pregnancies is an extremely rare phenomenon. In HM, overproduction of human chorionic gonadotropin (β-hCG) by proliferating trophoblasts often results in extremely high serum β-hCG levels, which in turn causes a hook effect during the detection of β-hCG concentrations using immunochemiluminescent methods. This case highlights the critical role of serial dilution in mitigating hook effect-induced false-negative β-hCG results.

Case report: This article reports a case of a 28-year-old woman presented to our hospital at 12 weeks' gestation with suspected HM and normal fetal coexistence. The patient became pregnant via in vitro fertilization procedure and showed a single gestational sac at 9 weeks' gestation. Unfortunately, at 13 weeks of gestation, the patient was diagnosed with twin pregnancy with HM and a co-existing normal live fetus. The pregnancy ended with a therapeutic abortion.

Conclusions: Individualized diagnosis and treatment are important when HM coexists with a normal fetus. In such cases, we strongly recommend that ancillary tests be performed in addition to traditional imaging evaluation. In particular, the laboratory should be aware of false-negative β-hCG due to the hook effect.

Objective: Sepsis is a life-threatening condition with unclear pathogenesis and limited effective treatments. Mitochondrial dysfunction is considered a key factor in sepsis-induced multiple organ failure. This study aimed to identify essential mitochondria-related genes associated with sepsis to improve diagnosis and treatment strategies.

Methods: High-throughput gene expression data (GSE185263) were analyzed to identify differentially expressed genes (DEGs) in 348 septic patients and 44 healthy controls. Mitochondria-related DEGs were screened using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Two machine-learning algorithms, LASSO and SVM-RFE, were applied to identify mitochondria-associated hub genes.

Results: We identified 548 DEGs and screened 18 mitochondria-related DEGs. LASSO and SVM-RFE analyses identified 11 genes associated with sepsis diagnosis, showing strong diagnostic abilities through ROC assays. The expression of these 11 genes was examined by quantitative real-time polymerase chain reaction in septic patients and healthy participants, and differential expression of arginase 2 (ARG2), B-cell lymphoma 2-related protein A1 (BCL2A1), interferon alpha inducible protein 27 (IFI27), NADH: ubiquinone oxidoreductase subunit B3 (NDUFB3), stomatin (STOM), and translocator protein (TSPO) were observed. Some gene expression differences remained significant after adjusting for neutrophil and platelet counts.

Conclusions: These findings suggest that mitochondrial dysfunction plays a critical role in sepsis progression, and the identified genes may serve as biomarkers for early diagnosis and targeted treatment, potentially improving patient outcomes.

Objective: Allgrove Syndrome (AS), also known as Triple A syndrome (AAAS) is a rare autosomal recessive disorder characterized by a triad of alacrima, achalasia of the cardia, and ACTH-resistant adrenocortical insufficiency. The study aimed to broaden the understanding of AS's pathogenesis and clinical presentations within the Chinese population by identifying a novel mutation in the AAAS gene through genetic analysis.

Case report: A four-year-old girl presented with short stature and recurrent vomiting for over two years. She had never been able to produce tears. Her physical examination showed short stature, undernourishment, dark pigmented dry skin, and reduced subcutaneous fat. The absence of lacrimal gland function was confirmed, and a barium meal test indicated a diagnosis of cardia achalasia. The patient was diagnosed with AS after genetic testing revealed a homozygous mutation, c.904_905delinsG, in exon 9 of the AAAS gene. Both parents were identified as carriers of the mutation, each presenting as heterozygous. Symptomatic supportive care was provided, including anti-inflammatory, hemostatic, acid-suppressive, antispasmodic, and rehydration therapies. A laparoscopic Heller myotomy was performed, which involved incising the muscular layer of the cardia and a gastric fundoplication. Postoperatively, the patient showed smooth feeding, upper gastrointestinal contrast barium passed without obstruction. The patient showed significant improvement and was discharged. The proband's sister was diagnosed with adrenal insufficiency based on hormonal levels and imaging.

Conclusions: Genetic testing is instrumental in diagnosing AS, and prompt diagnosis can significantly enhance the quality of life for affected children. The study documented a novel mutation in AS, extending the diversity of known genetic variants. For patients with esophageal achalasia, the choice between balloon dilation and laparoscopic Heller's surgery should be individualized. Early identification and management of AS can significantly benefit affected children.

Objective: While long noncoding RNAs (lncRNAs) have emerged as critical regulators in hematological malignancies, their clinical significance in pediatric acute leukemia (AL) remains poorly characterized. This study aimed to (1) systematically profile differentially expressed lncRNAs (DE-lncRNAs) in pediatric AL through comparative analysis of bone marrow samples and (2) functionally characterize the oncogenic role of a top candidate, AC002454.1, to identify potential diagnostic markers and therapeutic targets.

Methods: Using Arraystar Human LncRNA Array V3.0, we analyzed bone marrow samples from 43 pediatric AL patients (21 ALL, 22 AML) and 21 healthy donors. Key DE-lncRNAs were validated by qRT-PCR, with AC002454.1 selected for functional investigation. In NB4 leukemic cells, we performed (1) lentiviral knockdown of AC002454.1, (2) cell proliferation assays (CCK-8), (3) cell cycle analysis (PI staining/flow cytometry), (4) apoptosis assessment (Annexin V-FITC/PI dual staining), and (5) Western blot for CDK6 regulation.

Results: Our qRT-PCR validation confirmed 97 differentially expressed lncRNAs (DE-lncRNAs), with lncRNA AC002454.1 showing the most significant differential expression between ALL and AML samples (P=0.040 and P=0.002, respectively, and particular elevation in AML). Functional studies demonstrated that AC002454.1 knockdown in NB4 cells led to (1) reduced cellular viability, (2) G2/M phase cell cycle arrest, and (3) increased apoptosis. Notably, AC002454.1 silencing also down-regulated CDK6 protein expression, suggesting a potential mechanistic link.

Conclusions: We identified AC002454.1 as a functionally significant lncRNA in pediatric AL, demonstrating its oncogenic role through the promotion of proliferation and inhibition of apoptosis in leukemic cells. These findings suggest its potential as both biomarker and therapeutic target.

CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is a rare and highly aggressive subtype of DLBCL, commonly characterized by extranodal involvement, an activated B-cell/non-germinal center B-cell phenotype, and a poor prognosis. Although CD5+ DLBCL frequently presents at an advanced stage, leukemic presentation-defined by the presence of abundant circulating malignant B-cells in the peripheral blood-is exceedingly rare, with only a limited number of cases reported globally. We herein report, to the best of our knowledge, the first reported case in Korea of relapsed CD5+ DLBCL with leukemic presentation. The patient exhibited a high tumor burden, a double-expressor phenotype, and rapid disease progression despite multiple lines of therapy. This case report highlights the diagnostic and therapeutic challenges in managing CD5+ DLBCL with leukemic presentation and emphasizes the need for further studies.

Intravascular fasciitis (IVF) is a rare, benign myofibroblastic proliferation involving arteries or veins that can mimic deep vein thrombosis (DVT). We report the first known case of IVF arising in the setting of May-Thurner syndrome (MTS), a congenital venous anomaly. A 15-year-old male presented with leg pain, swelling, and pulmonary embolism. Imaging showed iliofemoral "thrombosis" and MTS. Mechanical thrombectomy was performed. Histopathology revealed a spindle cell lesion with myxoid stroma, mitoses, focal necrosis, and organizing thrombi. Immunohistochemistry demonstrated smooth muscle actin positivity and desmin negativity. USP6 rearrangement was detected by fluorescence in situ hybridization (FISH), confirming IVF. This case illustrates the clinical and radiologic overlap between IVF and DVT and highlights the importance of histopathologic and molecular evaluation. Unlike prior reports, IVF was successfully managed with an endovascular approach.

Au-Kline syndrome is a rare disease of major pediatric concern, characterized by intellectual disability, facial deformities, heart defects, and abnormal development of connective tissue and bone. Loss-of-function variants of hnRNPK gene have been proven to be significantly related to Au-Kline syndrome. In this report, a novel hnRNPK gene frameshift variant [NM_031263.4:c.1074dupG:p.M359Dfs*4] was found in a 12-week-old fetus with ultrasound abnormalities including cystic hygroma of the neck, bilateral branchial cysts, and a megabladder. This case report describes a novel frameshift duplication variant of hnRNPK and enriches the mutation database of this gene. Moreover, cystic hygroma of the neck and bilateral branchial cysts on prenatal ultrasound were first discovered in patients with Au-Kline syndrome, which provides a reference for the subsequent prenatal diagnosis of Au-Kline syndrome.

Objective: HLA-B*59:01 is associated with severe cutaneous adverse reactions (SCARs) caused by carbonic anhydrase inhibitors, highlighting the need for rapid and reliable genotyping methods. Our previous conventional PCR-based HLA-B*59:01 genotyping required post-PCR electrophoresis, increasing labor and hands-on time.

Methods: We developed a real-time duplex allele-specific PCR with melting curve analysis for HLA-B*59:01 genotyping. Using KOD SYBR qPCR Mix, we differentiated an HLA-B*59:01-specific amplicon (838 bp) and a GNAQ internal control amplicon (912 bp), yielding distinct melting peaks at about 90.3°C and 94.5°C, respectively. Validation was performed on 50 HLA-B*59:01-positive and 100 negative samples with sequence-based typing (SBT) as the reference.

Results: The method demonstrated complete concordance with SBT, achieving 100% sensitivity and specificity. The closed-tube approach eliminated the need for electrophoresis, reducing hands-on time.

Conclusions: This melting curve analysis provides a reliable and labor-efficient alternative for HLA-B*59:01 screening, facilitating clinical implementation for SCAR risk mitigation.