Annals of clinical and laboratory science最新文献

Objective: Subclinical hypothyroidism (SCH) is associated with an increased risk of coronary heart disease (CHD), yet its predictive value for the severity of coronary artery lesions remains unclear. This study aimed to investigate the relationship between SCH and the Gensini score, a quantitative measure of coronary artery lesion severity, in patients with CHD.

Methods: A retrospective single-center study was conducted involving 311 patients with CHD confirmed by coronary angiography, including 166 with SCH (TSH>4.5 mIU/L with normal FT3/FT4) and 165 euthyroid controls. The Gensini score was assessed by blinded cardiologists. Thyroid function parameters (TSH, FT3, FT4) and traditional cardiovascular risk factors were analyzed. Statistical analyses included Spearman correlation, multiple linear regression, and ROC curve analysis.

Results: Patients with SCH had significantly higher median Gensini scores than controls (46 vs. 15, P<0.0001). TSH was strongly positively correlated with the Gensini score (ρ=0.837, P<0.0001). Multiple regression confirmed that SCH independently predicted higher Gensini scores after adjusting for traditional risk factors (β=0.168, P<0.001). ROC analysis showed that SCH status alone had an AUC of 0.968 for predicting high-risk lesions (Gensini ≥40), with an optimal TSH cutoff of >5.8 mIU/L (sensitivity 85%, specificity 83%). The combined model including SCH and traditional factors further improved predictive performance (AUC=0.906, NRI=17.3%, P=0.002).

Conclusion: SCH is independently associated with more severe coronary artery lesions in CHD patients, as quantified by the Gensini score. TSH>5.8 mIU/L may serve as a valuable threshold for identifying high-risk patients. Incorporating thyroid function screening into CHD risk assessment could enhance stratification and guide early intervention.

β-Thalassemia major (β-TM) is an autosomal recessive genetic disorder characterized by a deficiency in the synthesis of β-globin chains, leading to reduced functional hemoglobin and life-threatening chronic anemia. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for β-TM, with outcomes dependent on stable donor engraftment, donor-derived erythropoiesis, and low transplant-related complications. Herein, we report a case of a 27-month-old male patient with β-TM who achieved successful, sustained engraftment using unrelated umbilical cord blood (UCB) following haplo-cord stem cell transplantation. The patient received a combination of 7/12 HLA-matched haploidentical peripheral blood stem cells (haplo-PBSCs) and 5/10 HLA-matched unrelated UCB. Post-transplant monitoring confirmed exclusive engraftment of UCB (full chimerism via short tandem repeat polymerase chain reaction [STR-PCR]) with complete hematopoietic reconstitution. As of the last follow-up, the patient has maintained disease-free survival for over 36 months without significant chronic graft-versus-host disease (GVHD) and with stable hemoglobin levels (90-130 g/L). This case provides evidence that HLA 5/10 mismatched unrelated UCB can achieve effective engraftment in β-TM patients undergoing haplo-cord transplantation, supporting its potential as an alternative donor source for patients lacking fully matched donors.

Objective: Invasive fungal disease (IFD) is characterized by a high misdiagnosis rate, high morbidity, and high mortality. Currently, early and rapid diagnostic methods for IFD remain limited. In this study, we evaluated the clinical value of droplet digital PCR (ddPCR) for the rapid detection and prognostic monitoring of fungal pathogens in invasive fungal infections, aiming to provide a new and practical laboratory method for the rapid diagnosis of invasive fungal disease (IFD).

Methods: This study collected body fluid samples from patients with suspected invasive fungal infections at Quanzhou First Hospital between February 2023 and March 2024. These samples were subjected to both droplet digital PCR (ddPCR) and fungal culture. The diagnostic performance of ddPCR for invasive fungal infections was evaluated. Furthermore, ddPCR was used to detect fungal pathogens in samples from patients with confirmed fungal disease, and its utility in prognostic monitoring was assessed.

Results: Using fungal culture as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of ddPCR for detecting fungal pathogens were 81.13% (43/53), 84.71% (72/85), 76.79% (43/56), 87.80% (72/82), and 83.33% (115/138), respectively.

Conclusion: ddPCR demonstrates high sensitivity, specificity, positive predictive value, and negative predictive value in detecting fungal pathogens of invasive fungal infections. It offers potential advantages for the rapid and accurate diagnosis of IFD and can serve as a valuable supplement to conventional fungal culture. Furthermore, ddPCR shows promise for prognostic assessment through dynamic monitoring of patients with these infections.

Gastric cancer (GC) is a leading cause of cancer-related death worldwide, and insufficient early diagnostic strategies limit patient outcomes. Phospholipase C X-domain containing 3 (PLCXD3) has been implicated in tumor progression, but its role in GC remains unclear. This study aimed to clarify the biological function of PLCXD3 and assess its potential as an early diagnostic biomarker and tumor suppressor in GC.

Methods: An integrated bioinformatics analysis of three Gene Expression Omnibus (GEO) datasets was performed to identify differentially expressed genes in early gastric cancer tissues. PLCXD3 expression levels were validated in clinical samples and AGS gastric cancer cells. Functional assays, including CCK-8, Transwell, wound-healing, and spheroid formation assays, were conducted to assess the effects of PLCXD3 knockdown and overexpression on cell proliferation, migration, invasion, and stemness. The expression of epithelial-mesenchymal transition (EMT) markers and Wnt/β-catenin pathway-related proteins was examined by qRT-PCR, Western blotting, and immunofluorescence.

Results: PLCXD3 expression was significantly downregulated in early gastric cancer tissues and AGS cells. Silencing PLCXD3 markedly promoted cell proliferation, migration, invasion, EMT progression, and upregulated stemness-associated markers (SOX2, Oct4, NANOG, KLF4). Knockdown of PLCXD3 also activated the Wnt/β-catenin signaling pathway, as evidenced by increased β-catenin, WNT3A, and c-MYC expression. Conversely, PLCXD3 overexpression suppressed these malignant phenotypes.

Conclusions: PLCXD3 functions as a tumor suppressor in gastric cancer by inhibiting cell migration, invasion, and stemness through modulation of the Wnt/β-catenin pathway. Its downregulation may serve as a novel early diagnostic biomarker and a promising therapeutic target in gastric cancer management.

Objective: To explore the effects of programmed death-ligand 1 (PD-L1) and clinicopathological features on the outcomes of patients with colorectal cancer (CRC), and to predict their prognosis using a meta-analysis.

Methods: PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP databases were searched from their inception until 10 September 2023. Eligible studies that explore the relationships between PD-L1 and the survival outcomes of patients with CRC were included. The Newcastle-Ottawa scale (NOS) was used for quality assessment; combined hazard ratios (HR) for overall survival (OS), relapse-free survival (RFS) and disease-free survival were calculated.

Results: Eighteen studies (involving 6,160 patients) with an NOS score of >7 were included in this study. The PD-L1 expression was associated with worse OS (HR=1.45; 95% CI: 1.08-1.94) and RFS (HR=1.87; 95% CI: 1.31-2.67). Male gender, poor differentiation, lymph node metastasis, Tumour-Node-Metastasis stage, pathological nodal status, pathological tumour status and vascular invasion were identified as important risk factors for worse survival outcomes in patients with CRC.

Conclusion: The PD-L1 expression and other important clinicopathological features might be biomarkers for worse prognoses in patients with CRC.

Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a rare autosomal recessive leukodystrophy caused by pathogenic variants in the DARS2 gene. Although the clinical phenotype of LBSL involves a wide spectrum, presentations predominantly characterized by exercise intolerance remain infrequently documented.

Case report: A 24-year-old woman presented with exercise-induced fatigue as the initial and predominant symptom. Neurological examination revealed mild resistance in the bilateral lower limbs, slightly hyperactive patellar and Achilles tendon reflexes (grade 2), and absent Babinski signs, with no evidence of cognitive impairment or sensory deficits. Laboratory tests showed an elevated serum lactate level (2.5 mmol/L) following 4-h fasting and 10 min of moderate-intensity exercise. Brain and spinal magnetic resonance imaging (MRI) revealed extensive symmetric white matter abnormalities and long-segment spinal cord involvement. Molecular analysis confirmed the presence of compound heterozygous DARS2 mutations (NM_018122.5:c.228-16C>A and c.521G>A), thereby confirming the diagnosis. Familial genetic testing indicated that each pathogenic variant was inherited from a different parent.

Conclusions: This case highlights the need to include LBSL in the differential diagnosis of young patients presenting with unexplained exercise intolerance, particularly when neuroimaging reveals characteristic white matter and spinal cord involvement. Early identification and genetic confirmation are critical for accurate diagnosis, genetic counseling, and clinical management.

Objective: Urokinase plasminogen activator (uPA), its receptor uPAR, and plasminogen activator inhibitor type 1 (PAI-1), constitute the plasminogen urokinase activation system that is thought to be associated with the malignant biology of cancer cells. Nevertheless, the regulation mechanism of uPAR expression in colorectal cancer remains unclear.

Methods: The effect of uPAR and miR-516-3p on CRC cells was explored through Methyl thiazolyl tetrazolium (MTT) assay, colony formation, Transwell, and Apoptosis assays. Dual-luciferase reporter assays, reverse transcription quantitative PCR (RT-qPCR), and Western blot assay were carried out to determine that uPAR is directly regulated by miR-561-3p. Levels of protein expression were analyzed by Western blot assay.

Results: In the study, we showed that uPAR was upregulated in serum samples from CRC patients and associated with the more advanced stage and distant metastasis in patients with CRC. In CRC cells, uPAR promotes cell growth, migration, and invasion, while inhibiting cell apoptosis. In addition, the expression of uPAR is negatively regulated by miR-561-3p through binging its 3' UTR.

Conclusion: uPAR is downregulated by miR-561-3p, contributing to tumorigenesis in colorectal cancer.