Annals of clinical and laboratory science最新文献

Objective: Given the extreme rarity of primary diffuse large B-cell lymphoma of the prostate (P-DLBCL-P), medical institutions face challenges in accumulating a sufficient number of cases. Thus, investigating the clinical manifestations of this disease and exploring potential therapeutic strategies holds significant importance.

Case report: We present three cases of P-DLBCL-P, all admitted to our hospital with symptoms of lower urinary tract obstruction. Following pathological examination of the prostate, all three patients were definitively diagnosed with P-DLBCL-P.

Discussion: Case 1 discharged himself from the hospital after refusing treatment. Case 2 received eight courses of R-CDOP regimen chemotherapy but died of rectovesical fistula. Case 3 developed obstructive nephropathy due to urinary tract obstruction and died soon after emergency dialysis.

Conclusions: P-DLBCL-P is an extremely rare disease that is prone to misdiagnosis, emphasizing the need to pay close attention to its clinical manifestations for prompt and accurate diagnosis. All three patients in this study received timely diagnoses, but one refused treatment, and the other two experienced disease progression despite appropriate intervention. Given the limited clinical data on this disease, more cases are required to explore the prognosis of patients and the efficacy of various therapeutic strategies, including emerging treatment options.

Objective: Lung cancer's high global burden necessitates early diagnosis. Serum biomarkers (NSE, CYFRA 21-1, SCC) aid screening, but accurate interpretation requires reliable reference intervals (RIs). Most Chinese labs use Western population-based RIs, lacking age-stratification for the elderly and increasing misdiagnosis risk. This study established age- and sex-specific RIs for these biomarkers in Chinese elderly.

Methods: A cohort of 77,123 healthy individuals undergoing physical examinations was screened using strict exclusion criteria to identify healthy reference individuals. Serum biomarker levels were measured using the Roche Cobas e801 fully automated immunoassay analyzer. RIs were established using the nonparametric percentile method (P2.5-P97.5), stratified by sex (Male vs. Female) and age group (50-59, 60-69, 70-79, 80-100 years).

Results: Results revealed that NSE levels increased stepwise with age and were higher in females than males. CYFRA 21-1 levels increased linearly with age, while SCC exhibited a sharp rise in the 80-100-year group. The current manufacturer-provided standards significantly increased misdiagnosis rates in the elderly, highlighting the necessity for localized RIs.

Conclusion: The newly established RIs demonstrated excellent performance in an independent validation cohort, significantly outperforming existing standards. This study provides the first age- and sex-stratified RIs for lung cancer serum biomarkers in the Chinese elderly population, filling a critical gap. These results offer a reliable tool for precise diagnosis and provide essential evidence for optimizing early lung cancer screening and clinical decision-making in the elderly.

Objective: To investigate the effect of Dexmedetomidine (Dex) on myocardial cell pyroptosis by regulating HK-2 cell-derived exosomes and analyze its underlying mechanism.

Methods: An in vitro model of Renal ischemia-reperfusion injury (RIRI) was created by exposing human proximal renal tubule epithelial cells (HK-2) to hypoxia/reoxygenation (H/R) and Dex treatment. We extracted HK-2 cell-derived exosomes using a kit and distinguished them through transmission electron microscopy and nanoparticle tracking analysis. These exosomes were co-cultured with cardiomyocytes AC16. The uptake of AC16 cell-derived exosomes was observed using fluorescent labeling. Cell activity and death rates were examined utilizing cell counting kit-8 and flow cytometry, respectively. The enzyme-linked immunosorbent assay was adopted for the evaluation of the release of inflammatory factors in the cell culture supernatant. Western blot was employed to assess the expression levels of HK-2 cell-derived exosome marker protein, AC16 cell pyroptosis-related protein, high mobility group box 1 (HMGB1), and the TLR4 signaling pathway.

Results: H/R considerably hindered the activity and elevated the death rate of HK-2 cells, elevated the release of inflammatory factors, and significantly up-regulated HMGB1 expression in HK-2 cells. Dex exhibited a protection influence on HK-2 cells under H/R conditions, partially restoring cell activity, reducing cell death rate and the secretion of inflammatory molecules, and down-regulating HMGB1 expression in HK-2 cell-derived exosomes. AC16 cells could internalize exosomes derived from HK-2 cells, and the HMGB1 carried by these exosomes affected the activity of AC16 cells. Dex treatment down-regulated HMGB1 expression in HK-2 cell-derived exosomes under H/R conditions, thereby enhancing AC16 cell activity, reducing AC16 cell death rate and inflammatory factor release, and inhibiting AC16 cell pyroptosis. Furthermore, the use of cell pyroptosis inhibitor VX-765 and the TLR4 signaling pathway inhibitor Resatorvid proved that Dex exerted its protective properties on AC16 cells by modulating the TLR4 signaling pathway through its effects on HMGB1 carried by HK-2 cell-derived exosomes.

Conclusion: Dex can significantly inhibit the expression of HMGB1 in HK-2 cell-derived exosomes exposed to H/R and inhibit AC16 cell pyroptosis through exosome uptake and the effect of HMGB1 on the TLR4 signaling pathway.

Objective: This study was carried out with an objective to clarify the mechanism of mitochondrial transcription termination factor 1 (MTERF1) in regulating mitochondrial DNA (mtDNA) replication and mitochondrial function of podocytes in diabetic nephropathy (DN).

Methods: To establish a type I diabetes model, C57BL/6J mice were injected intraperitoneally with streptozotocin (STZ). Eight weeks after STZ injection, blood glucose levels and renal function were assessed in mice. Mouse renal tissues were analyzed via hematoxylin-eosin, periodic acid-Schiff, and TdT-mediated dUTP nick-end labeling staining. Immunohistochemistry/Western blot were employed for the detection of MTERF1 expression. MPC-5 cells were treated with high glucose (HG) (30 mM) to establish the cellular model. MTERF1-overexpressing MPC-5 cells were constructed and treated with HG and the AMP-activated protein kinase (AMPK) inhibitor compound C (CC) for 24 h. Cell apoptosis was assessed by flow cytometry, cell viability by the cell counting kit-8 assay, mtDNA copy number by real-time quantitative PCR, adenosine triphosphate (ATP) production by ultraviolet spectrophotometric method, mitochondrial reactive oxygen species (mtROS) by MitoSox, and mitochondrial membrane potential (MMP) by JC-1. MTERF1 protein expression and AMPK/mammalian target of rapamycin (mTOR) signaling pathway activity were measured via Western blot.

Results: The model group (relative to the control group) exhibited a significant rise in blood glucose, urine volume, urinary albumin, and urine albumin-creatinine ratio, along with significantly aggravated glomerular injury and markedly increased glycogen deposition and decreased MTERF1 expression in mouse renal tissue. In in vitro experiments, compared with the normal glucose (NG) group, the HG group showed increased apoptosis and reduced cell activity, accompanied by significantly decreased MTERF1 protein expression, mtDNA copy number, and ATP content. Compared to the HG+oe-NC group, the HG+oe-MTERF1 group showed significant increases in mtDNA copy number, ATP content, MMP, and AMPK/mTOR signaling pathway activity, while demonstrating decreased mtROS production. The HG+oe-MTERF1+CC group exhibited significant reductions in mtDNA copy number, ATP production, and AMPK/mTOR signaling pathway activity compared to the HG+oe-MTERF1 group, but displayed elevated mtROS levels.

Conclusion: Over-expression of MTERF1 can alleviate HG-induced damage of mtDNA replication and mitochondrial dysfunction in podocytes via activating the AMPK/mTOR signaling pathway, thus improving DN.

Objective: To clarify the clinical manifestations of X-linked sideroblastic anemia (XLSA) and the mutational profiles of the aminolevulinate synthase 2 (ALAS2) gene, thereby optimizing treatment and prognosis.

Case report: The proband, a 16-year-old male student, presented with microcytic hypochromic anemia, with hemoglobin (Hb) 55 g/L, red cell distribution width (RDW) 22.5%, mean corpuscular hemoglobin concentration (MCHC) 314 g/L, mean corpuscular hemoglobin (MCH) 23.9 pg, and mean corpuscular volume (MCV) 76.1 fL. Next-generation sequencing followed by Sanger sequencing of his family identified a de novo heterozygous nonsense mutation in ALAS2 (c.224C>A); this identification led to the final diagnosis of XLSA with a novel ALAS2 mutation.

Discussion: Incorporating genetic analyses into diagnostic algorithms can improve the precision of XLSA diagnosis and support personalized treatment strategies for patients and families.

Conclusions: Our findings expand the mutational spectrum of ALAS2 and highlight that integrating next-generation sequencing (NGS) with Sanger validation into diagnostic workflows can significantly improve the diagnostic accuracy of XLSA.

Objective: Colorectal cancer (CRC) remains a leading cause of cancer mortality globally, necessitating novel biomarkers for early intervention. Although FAM111B - a gene implicated in DNA repair and cell cycle control - exhibits dysregulation in multiple malignancies, its CRC-specific relevance is underexplored.

Methods: Integrative analysis of five CRC cohorts (TCGA/GEO) was conducted. Differential FAM111B expression was assessed using Wilcoxon tests (paired/unpaired samples). Spearman's correlation determined associations with clinical/molecular features. Prognostic performance of FAM111B combined with AJCC-TNM staging was evaluated via univariate/multivariate Cox regression. Functional characterization employed PPI networks, GO/KEGG, GSEA, and immune deconvolution (ssGSEA).

Results: FAM111B demonstrated consistent overexpression in tumors versus controls across all datasets (P<0.001), showing diagnostic capability (AUC=0.87). Elevated expression independently predicted poor survival (HR=1.82; 95%CI:1.3-2.5). Its integration with TNM staging improved prognostic stratification (ΔAUC=0.17; P=0.006). Functional studies linked FAM111B to oncogenesis through: 1. DNA damage response dysregulation; 2. Metabolic reprogramming (lipid/RNA metabolism); 3. Immunosuppressive microenvironment (reduced CD8+ T-cell infiltration; P=0.003).

Conclusion: This multilevel analysis establishes FAM111B as a CRC biomarker with dual diagnostic-prognostic utility. Its roles in genomic stability, metabolic adaptation, and immune evasion highlight therapeutic potential. Clinical validation using probe ID1557129_a_at is warranted.

We present an 18-month-old boy with an exophytic mass in an unusual location, the right anterior-superior gingiva between deciduous teeth 5.3 and 5.4. Histopathologic and immunohistochemical investigations revealed a mesenchymal hamartoma (MH). Collagen fibers were haphazardly distributed in the dermis, admixed with nerve twigs and inflammatory cells. Twelve months of follow-up did not disclose any local relapse or evidence of oncological disease. To the best of our knowledge, this is the first case of gingival MH in an infant.

Objective: Gestational diabetes mellitus (GDM) affects the health of pregnant women and their fetuses. Poly(C)-binding protein 1 (PCBP1), a multifunctional RNA-binding protein, is pivotal in maintaining cytosolic iron homeostasis. This study aims to explore the role and mechanism of PCBP1 in glucose and lipid metabolism dysregulation in GDM.

Methods: To establish via a high-fat diet-induced GDM mouse model and a palmitic acid (PA)-triggered insulin resistance (IR) model in HepG2 cells, glucose tolerance and insulin tolerance tests were performed in GDM mice, with lipid metabolism evaluated via hematoxylin-eosin (HE) staining, Oil Red O staining, as well as biochemical assay kits. Glucose content was quantified using the glucose oxidase method, while cell viability was evaluated trough the cell counting kit-8(CCK-8) assay. Apoptotic activity was examined through Terminal deoxynucleotidyl transferase dutp nick end labeling (TUNEL) staining, and the expression levels of key proteins, including phosphorylated AKT (p-AKT), phosphorylated IRS1 (p-IRS1), PCBP1, transforming growth factor β-activated kinase 1(TAK1), and Peroxisome proliferator-activated receptor gamma (PPARγ), were analyzed through Western blotting.

Results: The results demonstrated that GDM mice exhibited profound glucose and lipid metabolism disorders, characterized by significant lipid droplet accumulation in hepatic cells and disrupted insulin signaling pathways. Furthermore, hepatic expression of PCBP1 and TAK1 was notably upregulated, whereas PPARγ expression was significantly reduced. In vitro experiments revealed that silencing PCBP1 alleviated glucose and lipid metabolism abnormalities and improved insulin signaling in PA-induced insulin-resistant HepG2 (IR-HepG2) cells. This intervention also enhanced cell viability and suppressed apoptosis. Further mechanistic studies indicated that inhibition of TAK1 expression facilitated PPARγ upregulation, while TAK1 overexpression negated these effects. Additionally, silencing PPARγ in TAK1-silenced cells reversed the metabolic improvements in IR-HepG2 cells, whereas overexpression of PPARγ mitigated the adverse effects of PCBP1 overexpression.

Conclusion: The foregoing findings demonstrate that PCBP1 exerts its effects on glucose and lipid metabolism in GDM via the TAK1/PPARγ signaling axis. Our study highlights the important function of the PCBP1/TAK1/PPARγ signaling pathway in mediating glucose and lipid metabolism in GDM, providing valuable insights into possible therapeutic targets for GDM treatment.

Objective: Organophosphorus pesticide poisoning (AOPP) leads to high mortality among patients. Hemoperfusion can remove organophosphates in the blood circulation and is the treatment of choice in these patients. However, studies on mortality risk factors in AOPP patients undergoing hemoperfusion are limited.

Methods: A retrospective study was conducted on AOPP patients undergoing hemoperfusion between January 2016 and August 2023. Baseline characteristics, laboratory test results, and in-hospital mortality data were collected. The relationships between risk factors and survival status were analyzed. A nomogram predictive model was constructed and evaluated.

Results: Of 216 patients included, 183 and 33 were in the survival and non-survival groups, respectively. Univariate and multivariate analyses revealed that the Glasgow Coma Scale (GCS) at admission, age, white blood cell count, total protein, pH, and cholinesterase change after first hemoperfusion were statistically significantly associated with in-hospital death (odds ratios with 95% CI were 0.71, 0.58-0.85; 1.10, 1.04-1.16; 1.13, 1.03-1.24; 0.88, 0.81-0.96; 0.00, 0.00-0.64; and 0.17, 0.05-0.66, respectively). A nomogram incorporating these six variables demonstrated an area under the curve of 0.966 in the receiver operating characteristic curve. Bootstrap self-sampling internal validation showed a strong correlation between the predicted and actual results of the nomogram (C-index 0.966). The decision curve analysis also indicated satisfactory model performance.

Conclusion: The admission GCS, age, white blood cell count, total protein, pH, and cholinesterase change after the first hemoperfusion could predict in-hospital mortality in AOPP patients undergoing hemoperfusion. A nomogram model based on these six variables could provide accurate mortality prediction in these patients.