Annals of clinical and laboratory science最新文献

Clear cell renal cell carcinoma (ccRCC) is the prototypical renal tumor with clear cell features in which the clear cell cytoplasm results from the melted lipid of the cytoplasm after fixation. ccRCC can be associated with a high risk of tumor metastasis.

Methods: In recent years, several new renal mass entities such as RCC with fibromyomatous stroma (FMS), clear cell papillary renal cell tumor (CCP-RCT), multilocular cystic renal cell neoplasm of low malignancy potential (MCRCNLMP), and eosinophilic vacuolated tumor (EVT) have been recognized with some clear-appearing cytoplasm.

Results: Previously identified renal tumor entities like chromophobe renal cell carcinoma (Ch-RCC) and translocation renal cell carcinoma (tRCC) often have clear cytoplasmic features as well. While often challenging due to their morphologic similarities, differentiating these renal tumor entities from ccRCC is important given their varying biological behaviors.

Conclusion: This review will provide a comprehensive roadmap to pathologically differentiate the variants of renal masses with clear cytoplasmic features. In addition, their clinical outcomes and management will be briefly discussed.

Objective: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks effective targeted therapies. The interleukin-18 (IL-18) signaling pathway contributes to cancer progression and poor survival outcomes in several tumor types, including TNBC. IL-18 receptor accessory protein chain (IL-18RAcP), binding to the IL18/IL18Rα complex, plays a critical role in initiating and transducing IL-18 signaling. Targeting IL-18RAcP with human antibodies may offer a promising therapeutic strategy for TNBC.

Methods: Human single-chain variable fragment (scFv) antibodies targeting IL-18RAcP were screened via phage display and characterized using ELISA, SPR, and crystallography. The functional assays that were used included qRT-PCR, MTT, Western blotting, flow cytometry, and xenograft models. Binding interactions were further validated through yeast two-hybrid assays and structural analysis.

Results: We found that elevated IL-18RAcP expression in TNBC is associated with poor recurrence-free survival (RFS), suggesting its potential as both a clinical marker and a therapeutic target. Using combinatorial scFv antibody phage display libraries, we identified a human monoclonal antibody, scFvAPC10, which binds IL-18RAcP with high affinity. scFvAPC10 significantly inhibits TNBC cell proliferation in vitro and reduces tumor growth in vivo by inducing apoptosis. Mechanistic studies reveal that scFvAPC10 impairs both NF-κB and MAPK signaling pathways. Structural analysis shows that scFvAPC10 interacts with the D1-D2 domains of IL-18RAcP through three hydrogen bonds, confirming the specificity of the interaction.

Conclusions: Our findings highlight the therapeutic potential of targeting IL-18RAcP in TNBC through modulation of IL-18/IL-18R-mediated signaling pathways. The development of scFvAPC10 offers a promising approach for novel antibody-based therapies in the treatment of TNBC.

Objective: Klotho is relevant to glucose and lipid metabolism and may be involved in insulin resistance (IR), which is a hallmark of type 2 diabetes mellitus (T2DM). This study aimed to elucidate the alterations in serum Klotho levels and their relationship with IR in T2DM with varying C-peptide patterns.

Methods: 690 T2DM subjects with different levels of serum C-peptide were enrolled. Blood samples were analyzed for FPG, HbA1c, C-peptide, FINS, and Klotho. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as HOMA-IR=FINS (μU/ml)×FPG (mmol/L)/22.5. Finally, receiver operating characteristic (ROC) analysis was used to explore the diagnostic performance based on β-cell function in T2DM.

Results: Klotho levels were significantly lower in T2DM patients compared to in controls, with decreasing maximum in the hyper-C-peptidemia group, while the HOMA-IR exhibited an inverse tendency across T2DM subgroups. In addition, Klotho was inversely correlated with HOMA-IR, FINS, FPG, and HbA1c, especially in T2DM with hyper-C-peptidemia. Moreover, the relationship remained significant even after additional adjustment for FGF23 and eGFR. Finally, Klotho displayed a good ability in distinguishing T2DM patients with different C-peptide patterns from controls, although its performance was marginal among T2DM subgroups.

Conclusion: In T2DM, serum Klotho levels were negatively correlated with HOMA-IR, and Klotho showed a good ability in distinguishing T2DM patients with differential C-peptide level patterns from healthy controls.

Objective: We investigated the association between the serum creatinine (SCr) level at admission to an intensive care unit (ICU) for cardiac arrest (CA) and subsequent acute kidney injury (AKI).

Methods: Data were from a previous study that was conducted at a single secondary care institute. Patients were included if they received successful cardiopulmonary resuscitation (CPR) after in-hospital CA (IHCA) or out-of-hospital CA (OHCA) and were admitted to an ICU. Patients were excluded if their SCr level at admission was missing or if they were younger than 18 years old. A total of 435 patients were screened for eligibility. 61 patients were excluded and the records of 374 patients who met the inclusion and exclusion criteria were examined.

Results: Two multivariate models that adjusted for confounding factors showed that the SCr level at admission was independently associated with AKI in patients who received successful CPR. Receiver operating characteristic (ROC) analysis showed that an increased SCr level at admission was associated with subsequent AKI (area under the curve [AUC]: 0.823, 95% CI: 0.781, 0.865), and that the optimal SCr cutoff level was 1.15 mg/dL.

Conclusion: An increased SCr level at ICU admission for CA was independently associated with subsequent AKI without sex-related discrepancies, and the optimal cutoff level was 1.15 mg/dL.

Objective: To investigate the differentiation-inducing activity of triciribine (TCN), alone and in combination with all-trans retinoic acid (ATRA), in acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML) cell lines, including ATRA-resistant HL-60-R2.

Methods: APL (NB4) and AML (HL-60, K052, HL-60-R2) cell lines were treated with TCN and/or ATRA. Cell proliferation was measured using Cell Count Reagent SF. Differentiation was assessed by quantitative PCR, flow cytometry for surface markers, morphological analysis with Wright-Giemsa staining and nuclear-to-cytoplasmic ratio quantification, and nonspecific esterase staining.

Results: TCN and ATRA each inhibited proliferation, with combination treatment producing a significant additive effect. Expression of differentiation markers, particularly CD11b and CD11c, was enhanced under combined treatment. Morphological analyses revealed cytoplasmic expansion, nuclear indentation, peripheral budding, and vacuole formation, with significantly reduced nuclear-to-cytoplasmic ratios. Nonspecific esterase staining confirmed α-naphthyl butyrate esterase positivity, supporting induction of partial myelomonocytic differentiation in all cell lines, including ATRA-resistant HL-60-R2.

Conclusion: TCN augments the differentiation-inducing activity of ATRA and promotes partial myelomonocytic differentiation, even in ATRA-resistant AML cells. Combination of TCN with established differentiation therapy may provide a strategy to overcome differentiation blockade in AML.

Objective: This case presentation offers an in-depth exploration of the complex and multifaceted realm of neonatal eosinophilic vasculitis, an extremely rare entity that has not been reported in the English literature. Only one similar case has been described in an Italian publication in 1995. Our case places an emphasis on the clinical presentation, postmortem findings, and evaluation of the importance of a multidisciplinary approach to this enigmatic disease.

Case report: We report a case of a 33-week neonate born via cesarean section following premature preterm rupture of membranes who died of an unknown etiology within the first 30 minutes of life despite maximal resuscitation efforts. A limited postmortem examination of only the lungs and heart was requested and revealed a necrotizing eosinophilic vasculitis of the lungs; these histopathologic findings are extremely uncommon in the neonate population.

Conclusion: In other patient groups, eosinophilic vasculitis is a hallmark of several interstitial lung diseases. The etiology widely ranges from viral, fungal, parasitic infections, allergic reactions, hypereosinophilic syndrome, and various vasculitis types such as eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) and granulomatosis with polyangiitis. The potentially fatal outcome for neonates and the lack of a clear etiology identified in the neonatal population necessitates urgent attention to this rare condition.

In 2001, the first draft sequence of the human genome was released, the culmination of a decade-long, multibillion-dollar effort. Since then, an OMICs platform has been proposed to further evaluate and edit the human genome for diagnostic and therapeutic purposes. The Human Genome Project opened a Pandora's box, expanding the forensic laboratory physicians' toolbox. Kinship analysis has been used extensively for parentage testing and identifying cases of human remains and missing persons. The Combined DNA Index System has played a significant role in forensic DNA databases. Nanopore sequencing and improved genomic tools aid enormously in identifying amplicons from degraded samples. The application of genomics in determining the potential channelopathies of sudden cardiac death (SCD) has been an enormous step forward in recent years in forensic histopathology. We reviewed the literature. Kong et al.'s meta-analysis of the mean allele frequencies of SCN5A, NOS1AP, KCNH2, KCNE1, and KCNQ1 genes across Black, Caucasian, Asian, and Hispanic ethnicities has been pivotal to forensic science in the last decade. The authors used sequenced genomic data from the Exome Aggregation Consortium to compare allele frequencies between different ethnicities. They found that Asians had the highest overall mean allele frequencies for NOS1AP and SCN5A, Caucasians had the highest KCNH2 frequency, and Hispanics had the highest KCNQ1 frequency. In 2026, the call for increased professionalism in clinico-molecular autopsy and forensic laboratory sciences is driven by rapid technological advancements (e.g., forensic molecular genomic autopsies), critical workforce shortages in some geographical areas, and the increasing complexity of death investigations. This professionalization focuses on standardizing molecular protocols, enhancing ethical frameworks, and addressing the need for specialized interdisciplinary expertise.

Objective: Ectoine is a natural compatible solute known for its cytoprotective properties, though its potential role in alleviating diabetic cardiomyopathy remains largely unexplored. This study aimed to examine the protective effects and underlying mechanisms of Ectoine on H9c2 cardiomyocytes under high-glucose and high-palmitic acid conditions.

Methods: The investigation included assessment of cell viability and lactate dehydrogenase release. Oxidative stress was evaluated through measurements of reactive oxygen species, malondialdehyde levels, and superoxide dismutase activity. Inflammatory responses were analyzed via TNF-α secretion and NF-κB and ERK1/2 pathways. Molecular docking studies were conducted to explore Ectoine-AMPK interaction, while mechanistic insights were gained through examination of AMPK signaling, energy metabolism regulators, autophagic flux markers, and mitochondrial apoptosis.

Results: Ectoine treatment was associated with enhanced cell viability and reduced lactate dehydrogenase release. It appeared to alleviate oxidative stress through decreased reactive oxygen species and malondialdehyde levels, along with increased superoxide dismutase activity. Ectoine also showed suppressive effects on inflammatory responses, including reduced TNF-α secretion and inhibited NF-κB and ERK1/2 pathways. Molecular docking suggested binding affinity between Ectoine and AMPK (-6.4 kcal/mol). Mechanistically, Ectoine demonstrated potential in activating AMPK signaling, modulating energy metabolism, restoring autophagic flux, and attenuating mitochondrial apoptosis.

Conclusion: The findings suggest that Ectoine may protect against HG-PA-induced cardiomyocyte injury. This protective effect was associated with AMPK activation and the coordinated modulation of metabolic, autophagic, anti-inflammatory, and anti-apoptotic pathways. This study suggests the therapeutic potential of Ectoine and provides a basis for further investigation.

Objective: Serum carbohydrate antigen (CA 19-9) and carcinoembryonic antigen (CEA) are common tumor markers that are mainly used in the diagnosis and therapeutic evaluation of malignant tumors. Here, we detail a case of allergic bronchopulmonary aspergillosis (ABPA) presenting with elevation of CEA and CA 19-9 levels.

Case report: A 22-year-old non-asthmatic male presented with recurrent cough, white mucopurulent sputum, and elevated serum CEA (20.55 ng/mL) and CA 19-9 (>1000 U/mL) levels. Investigations revealed Aspergillus-positive sputum culture, central bronchiectasis, mucus plugs on CT, eosinophilia, and migratory pulmonary lesions. Initial voriconazole therapy failed to prevent relapses. ABPA diagnosis was confirmed after re-evaluation. Combined voriconazole and methylprednisolone treatment achieved sustained remission over three years with normalization of tumor markers.

Results: Elevation of CEA and CA 19-9 levels correlated with ABPA disease activity but not IgE/eosinophil levels. Post-treatment normalization of CEA and CA 19-9 levels supports their utility as inflammatory biomarkers. This case expands the ABPA phenotype and cautions against misinterpreting tumor markers as malignancy indicators in benign inflammatory contexts.

Conclusion: ABPA should be considered in non-asthmatic patients with recurrent respiratory symptoms and elevated tumor markers. Serial monitoring of CEA/CA 19-9 may aid therapeutic assessment.