Distribution Of Cells Research Articles

Structural characteristics of the epidermis in marine and freshwater finless porpoises adapted to distinct osmotic environments

Abstract The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, Pilleri & Gihr, 1972; YFP) is an exclusively freshwater cetacean species inhabiting the Yangtze River and its connecting large lakes. As the primary line of defense in maintaining physiological equilibrium, the epidermis of the porpoise is expected to have undergone structural adaptations due to the shift from the marine to the freshwater environment. This study compared the microstructural and ultrastructural features of the epidermis of YFP and its marine counterpart, the East Asian finless porpoise (Neophocaena asiaeorientalis sunameri, Pilleri & Gihr, 1975; EAFP). Microscopic structural observations and statistical analyses of the epidermal thickness demonstrated no significant differences in the cell structure or distribution between the two porpoise species. However, the epidermis of the YFP contained more abundant stratum basale cells. The outermost lipid stratum corneum exhibited a thinner cell layer with wider neutral lipid droplets to resist the passive entry of water molecules in the hypotonic environment. In contrast, for the EAFP, a more uniformly arranged stratum basale in the epidermis led to denser keratin fibers and robust desmosomes within each epidermal layer at the ultrastructural level. This tight arrangement of cells can reduce transepidermal water loss (TEWL) in an environment with higher osmotic pressure. In conclusion, the 2 finless porpoise species appear to employ different epidermal mechanisms to adapt to their distinct osmotic environments. The YFP appears to possess a “lipid waterproofing” epidermal structure, while the EAFP possesses a “thick and compact water-retaining” epidermal structure to cope with potential water loss.

A nomogram for predicting short-term mortality in ICU patients with coexisting chronic obstructive pulmonary disease and congestive heart failure

ObjectiveThis study aimed to develop and validate a nomogram for predicting 28-day and 90-day mortality in intensive care unit (ICU) patients who have chronic obstructive pulmonary disease (COPD) coexisting with congestive heart failure (CHF). MethodsAn extensive analysis was conducted on clinical data from the Medical Information Mart for Intensive Care IV database, covering patients over 18 years old with both COPD and CHF, who were were first-time ICU admissions between 2008 and 2019. The least absolute shrinkage and selection operator (LASSO) regression method was employed to screen clinical features, with the final model being optimized using backward stepwise regression guided by the Akaike Information Criterion (AIC) to construct the nomogram. The predictive model's discrimination and clinical applicability were evaluated via receiver operating characteristic (ROC) curves, calibration curves, the C-index, and decision curve analysi s (DCA). ResultsThis analysis was comprised of a total of 1948 patients. Patients were separated into developing and validation cohorts in a 7:3 ratio, with similar baseline characteristics between the two groups. The ICU mortality rates for the developing and verification cohorts were 20.8 % and 19.5 % at 28 days, respectively, and 29.4 % and 28.3 % at 90 days, respectively. The clinical characteristics retained by the backward stepwise regression include age, weight, systolic blood pressure (SBP), respiratory rate (RR), oxygen saturation (SpO2), red blood cell distribution width (RDW), lactate, partial thrombosis time (PTT), race, marital status, type 2 diabetes mellitus (T2DM), malignant cancer, acute kidney failure (AKF), pneumonia, immunosuppressive drugs, antiplatelet agents, vasoactive agents, acute physiology score III (APS III), Oxford acute severity of illness score (OASIS), and Charlson comorbidity index (CCI). We developed two separate models by assigning weighted scores to each independent risk factor: nomogram A excludes CCI but includes age, T2DM, and malignant cancer, while nomogram B includes only CCI, without age, T2DM, and malignant cancer. Based on the results of the AUC and C-index, this study selected nomogram A, which demonstrated better predictive performance, for subsequent validation. The calibration curve, C-index, and DCA results indicate that nomogram A has good accuracy in predicting short-term mortality and demonstrates better discriminative ability than commonly used clinical scoring systems, making it more suitable for clinical application. ConclusionThe nomogram developed in this study offers an effective assessment of short-term mortality risk for ICU patients with COPD and CHF, proving to be a superior tool for predicting their short-term prognosis.

Construction of a clinical prediction model for the diagnosis of immune thrombocytopenia based on clinical laboratory parameters

PurposePrimary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by isolated thrombocytopenia that is often misdiagnosed due to the lack of a gold standard for diagnosis and currently relies on exclusionary approaches. This project combines several laboratory parameters to construct a clinical prediction model for adult ITP patients.MethodsA total of 428 patients with thrombocytopenia who visited the West China Hospital of Sichuan University between January 2021 and March 2023 were enrolled. Based on the diagnostic criteria, we divided those patients into an ITP group and a non-ITP group. A total of 34 laboratory parameters were analyzed via univariate analysis and correlation analysis, and the least absolute shrinkage and selection operator regression analysis was used to establish the model. The training and validation sets were divided at a ratio of 7:3, and we used a fivefold cross-validation method to construct the model.ResultsThe model included the following variables: red blood cell, mean corpuscular hemoglobin concentration, red blood cell distribution width-standard deviation, platelet variability index score, immature platelet fraction, lymphocyte absolute value. The prediction model exhibited good performance, with a sensitivity of 0.89 and a specificity of 0.83 in the training set and a sensitivity of 0.90 and a specificity of 0.87 in the validation set.ConclusionThe clinical prediction model can assess the probability of ITP in thrombocytopenic patients and has good predictive accuracy for the diagnosis of ITP.

Contributions of mirror-image hair cell orientation to mouse otolith organ and zebrafish neuromast function.

Otolith organs in the inner ear and neuromasts in the fish lateral-line harbor two populations of hair cells oriented to detect stimuli in opposing directions. The underlying mechanism is highly conserved: the transcription factor EMX2 is regionally expressed in just one hair cell population and acts through the receptor GPR156 to reverse cell orientation relative to the other population. In mouse and zebrafish, loss of Emx2 results in sensory organs that harbor only one hair cell orientation and are not innervated properly. In zebrafish, Emx2 also confers hair cells with reduced mechanosensory properties. Here, we leverage mouse and zebrafish models lacking GPR156 to determine how detecting stimuli of opposing directions serves vestibular function, and whether GPR156 has other roles besides orienting hair cells. We find that otolith organs in Gpr156 mouse mutants have normal zonal organization and normal type I-II hair cell distribution and mechano-electrical transduction properties. In contrast, gpr156 zebrafish mutants lack the smaller mechanically-evoked signals that characterize Emx2-positive hair cells. Loss of GPR156 does not affect orientation-selectivity of afferents in mouse utricle or zebrafish neuromasts. Consistent with normal otolith organ anatomy and afferent selectivity, Gpr156 mutant mice do not show overt vestibular dysfunction. Instead, performance on two tests that engage otolith organs is significantly altered - swimming and off-vertical-axis rotation. We conclude that GPR156 relays hair cell orientation and transduction information downstream of EMX2, but not selectivity for direction-specific afferents. These results clarify how molecular mechanisms that confer bi-directionality to sensory organs contribute to function, from single hair cell physiology to animal behavior.

Regulation of Lead Iodide Crystallization and Distribution for Efficient Perovskite Solar Cells.

At present, the power conversion efficiency (PCE) of perovskite solar cells (PSCs) has reached 26.1%. Polycrystalline perovskite films prepared by sequential deposition are often accompanied by excess PbI2. Although excess PbI2 can reduce the internal defects of the perovskites and promote charge transfer, excess PbI2 is unevenly distributed in the perovskites and easily decomposed into the composite center of charge. Therefore, the growth and distribution of PbI2 crystals can be regulated by introducing 4-fluoroaniline (4-FLA) as an additive into the precursor of PbI2. We observe that the presence of an amino group in 4-FLA leads to a reduction in the strength of van der Waals forces between PbI2 layer structures, thereby facilitating the uniform dispersion of excess PbI2 within the perovskites. Additionally, 4-FLA is restricted from being embedded in the PbI2 layer due to the steric hindrance of 4-FLA and the hydrogen bond interaction between nitrogen atoms and PbI2. Therefore, it leads to better dispersion of PbI2, resulting in better passivation and device efficiency. Based on the hydrophobicity of the benzene ring, the modified perovskite film shows excellent hydrophobicity. Ultimately, we achieved 21.63% PCE and 1.16V VOC. This provides an effective strategy for regulating excess PbI2 to achieve efficient and stable PSCs.

A novel histopathological feature of spatial tumor-stroma distribution predicts lung squamous cell carcinoma prognosis.

We used a mathematical approach to investigate the quantitative spatial profile of cancer cells and stromain lung squamous cell carcinoma tissues and its clinical relevance. The study enrolled 132 patients with 3-5 cm peripheral lung squamous cell carcinoma, resected at the National Cancer Center Hospital East. We utilized machine learning to segment cancer cells and stroma on cytokeratin AE1/3 immunohistochemistry images. Subsequently, a spatial form of Shannon's entropy was employed to precisely quantify the spatial distribution of cancer cells and stroma. This quantification index was defined as the spatial tumor-stroma distribution index (STSDI). The patients were classified as STSDI-low and -high groups for clinicopathological comparison. The STSDI showed no significant association with baseline clinicopathological features, including sex, age, pathological stage, and lymphovascular invasion. However, the STSDI-low group had significantly shorter recurrence-free survival (5-years RFS: 49.5% vs. 76.2%, p < 0.001) and disease-specific survival (5-years DSS: 53.6% vs. 81.5%, p < 0.001) than the STSDI-high group. In contrast, the application of Shannon's entropy without spatial consideration showed no correlation with patient outcomes. Moreover, low STSDI was an independent unfavorable predictor of tumor recurrence and disease-specific death (RFS; HR = 2.668, p < 0.005; DSS; HR = 3.057, p < 0.005), alongside the pathological stage. Further analysis showed a correlation between low STSDI and destructive growth patterns of cancer cells within tumors, potentially explaining the aggressive nature of STSDI-low tumors. In this study, we presented a novel approach for histological analysis of cancer tissues that revealed the prognostic significance of spatial tumor-stroma distribution in lung squamous cell carcinoma.

EVALUATION OF HEMATOLOGICAL PARAMETERS AND DIAGNOSTIC SIGNIFICANCE IN H. PYLORI INFECTION: A COMPARATIVE STUDY

Helicobacter pylori (H. pylori) infection is globally recognized for its role in various gastrointestinal diseases and extra gastric conditions, including hematological anomalies. Understanding the correlation between H. pylori infection and hematological parameters could provide insights into its broader health impacts. Objective: This study evaluated the correlation between H. pylori infection and various demographic, socioeconomic, and hematological parameters. Methods: A cross-sectional study enrolled patients diagnosed with H. pylori and a matched control group without the infection. Blood samples were collected and analyzed for hematological parameters, including white blood cell count, red blood cell count, hemoglobin (HGB), hematocrit (HCT), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW). Statistical analyses were performed using t-tests and chi-square tests where appropriate, with significance set at p &lt; 0.05. Results: The study included patients with statistically significant differences in hematological parameters between the H. pylori-infected and healthy groups. Notably, the infected group showed lower mean HGB (12.41±1.38 g/dl vs. 14.32±1.46 g/dl), RBC count (4.12±0.62x10^6/µL vs. 4.87±0.53x10^6/µL), and HCT (39.17±3.87% vs. 44.52±4.51%), and higher RDW (13.51±2.10% vs. 13.87±1.32%) compared to the control group (all p &lt; 0.05). Conclusion: The findings indicate significant hematological changes associated with H. pylori infection, suggesting a potential impact on the overall health status of affected individuals. These results highlight the importance of considering H. pylori infection in the differential diagnosis of hematological abnormalities and underscore the need for further research to explore the underlying mechanisms and potential therapeutic interventions.

Biomarkers for hypertrophic chondrocyte differentiation are associated with spatial cellular organisation and suggest endochondral ossification-like processes in osteoarthritic cartilage: An exploratory study

BackgroundIn healthy articular cartilage, chondrocytes are found along arcades of collagen fibers as Single Strings. With onset of cartilage degeneration this pattern changes to Double Strings. In the course of osteoarthritis Small Clusters, and finally Big Clusters form. In highly degenerated articular cartilage, another poorly understood pattern is found where chondrocyte morphology differs considerably, and the distribution of cells is diffuse. Progression of osteoarthritis is accompanied by key processes such as chondrocyte proliferation, apoptosis, hypertrophic differentiation, inflammation, and angiogenesis. The aim of this exploratory study was to identify biomarkers for these processes in the context of spatial cellular organizational changes in articular cartilage. MethodsCartilage explants (n = 166 patients) were sorted according to their predominant cellular pattern. Quantitative or semi-quantitative analysis of 39 biomarkers were performed by multiplex assay (31) or ELISA (8), and qualitative analysis on 12 immunohistochemical markers. ResultsHypertrophic differentiation (e.g. type-X collagen, osteopontin, osteocalcin and interleukin-6) and angiogenesis were associated with changes in chondrocyte organisation. First changes take place already at the transition from Single Strings to Double Strings. Drastic changes in the appearance of numerous biomarkers are found at the transition from Big Clusters to Diffuse. ConclusionKey processes in osteoarthritis and their biomarkers seem to depend on the spatial distribution of chondrocytes in articular cartilage. Abrupt changes in biomarker occurrence were observed between Big Clusters and Diffuse insinuating that the Diffuse pattern is composed of a different cell population or at least a different form of chondrocyte morphology. The Translational Potential of this ArticleIn situ identification of the different spatial chondrocyte patterns by fluorescence microscopy has already been established in the recent past. Analysing human in-situ cartilage explants rather than isolated OA chondrocytes closes the gap between in vitro and in vivo studies and as such, stretches a big step towards translation of the observed findings. The direct association between tissue biomarker profile and cellular arrangements representing different states of OA sheds new light on the molecular and cellular physiopathology, especially in the context of larger processes such as angiogenesis, cellular proliferation, differentiation, and apoptosis. This also opens an interesting perspective for future investigation of such biomarkers and processes in clinical studies.

LINC01857 promotes cell proliferation and migration while dampening cell apoptosis in pancreatic cancer by upregulating CDC42EP3 via miR-450b-5p

BackgroundPancreatic cancer (PC) is a devastating human malignancy with a poor survival outcome (5-year survival less than 10%). In recent years, the regulatory roles of long non-coding RNAs (lncRNAs) in various types of cancers have been widely reported. Based on bioinformatics analysis, LINC01857 is shown to be highly expressed in PC tissue. Nevertheless, the role of LINC01857 in PC is limitedly reported. Hence, this study aimed to explore the effects of lncRNA LINC01857 on PC cell process and the related mechanism. MethodsRT-qPCR and fluorescence in situ hybridization (FISH) assay were conducted to measure LINC01857 expression and distribution in PANC-1 and MIA PaCa-2 cells. Colony formation and wound healing assays as well as flow cytometry analyses were employed to estimate the proliferation, migration, and apoptosis of PC cells transfected with pcDNA3.1-LINC01857 or si-LINC01857 compared with the behavior of PC cells transfected with empty pcDNA3.1 vector (control) or si-negative control (NC). Furthermore, RNA pulldown and luciferase reporter assays were utilized to demonstrate the interaction of LINC01857 and miR-450b-5p or to validate the binding of miR-450b-5p and cell division cycle 42 effector protein 3 (CDC42EP3). ResultsLINC01857 was highly expressed in PANC-1 and MIA PaCa-2 cells in contrast to its expression in pancreatic ductal epithelial cells (8.9 folds and 7.1 folds, p<0.001). Silencing LINC01857 significantly reduced cell proliferation and migration while enhancing apoptosis (p<0.0005). In contrast, overexpression of LINC01857 markedly (p<0.05) accelerated these malignant behavior of PC cells. MiR-450b-5p was targeted and inversely regulated by LINC01857. Moreover, CDC42EP3 was verified to be targeted by miR-450b-5p, and CDC42EP3 was correlated to LINC01857 in a positive manner (p<0.001). Rescue experiments manifested that silencing CDC42EP3 effectively (p<0.05) reversed the promoting effect of LINC01857 on malignant behavior of PC cells. ConclusionLINC01857 promotes PC cell proliferation and migration while obstructing cell apoptosis by binding to miR-450b-5p and thus regulating CDC42EP3 expression. The study presents a novel and promising regulatory axis, which holds potential for the identification of biomarkers and development of therapeutic strategies for PC treatment.

Regional Analysis of the Immune Microenvironment in Human Endometrium.

Endometrial immune cells are essential for maintaining homeostasis and the endometrial receptivity to embryo implantation. Understanding regional variations in endometrial immune cell populations is crucial for comprehending normal endometrial function and the pathophysiology of endometrial disorders. Despite previous studies focusing on the overall immune cell composition and function in the endometrium, regional variations in premenopausal women remain unclear. Endometrial biopsies were obtained from four regions (anterior, posterior, left lateral, and right lateral) of premenopausal women undergoing hysteroscopy with no abnormalities. A 15-color human endometrial immune cell-focused flow cytometry panel was used for analysis. High-dimensional flow cytometry combined with a clustering algorithm was employed to unravel the complexity of endometrial immune cells. Additionally, multiplex immunofluorescent was performed for further validation. Our findings revealed no significant variation in the distribution and abundance of immune cells across different regions under normal conditions during the proliferative phase. Each region harbored similar immune cell subtypes, indicating a consistent immune microenvironment. However, when comparing normal regions to areas with focal hemorrhage, significant differences were observed. An increase in CD8+ T cells highlights the impact of localized abnormalities on the immune microenvironment. Our study demonstrates that the endometrial immune cell landscape is consistent across different anatomical regions during the proliferative phase in premenopausal women. This finding has important implications for understanding normal endometrial function and the pathophysiology of endometrial disorders.

Novel single-cell measurements suggest irreversibly sickled cells are neither dense nor dehydrated

In sickle cell anemia, deoxygenation causes erythrocytes to distort, while reoxygenation permits them to recover a normal biconcave disk shape. Irreversibly sickled cells (ISCs) remain distorted when reoxygenated and have been thought to have among the highest intracellular hemoglobin concentrations of the sickle red cell population and therefore the greatest vulnerability to vasoocclusion. Using a new optical method, which we describe, we have made precise measurements of the intracellular hemoglobin concentration, and intracellular O2 saturation, of ISCs, as well as oxygenated sickle cells with a normal biconcave disc shape, and cells with shapes distorted by the sickle fibers they contain. This method also provides good estimates of cell volumes, and hemoglobin per red cell. The concentration distribution of the ISCs is found to be similar to normal, discoid cells. Average ISC volumes exceed their discoid counterparts, with a much broader distribution, arguing against dehydration as their origin. The concentration distribution of the polymer-laden sickled cells is significantly higher in mean value, and their volume distributions indicate some dehydration. Previous assumptions about ISCs may have thus been colored by the presence of sickle cells that did contain polymer, and that true ISCs may be much more benign than once thought, which underscores the importance of accurate measurement on individual cells. This method could be used to follow changes in individual cell properties under various specific perturbations, and where characterization by flow cytometry is infeasible.

Deciphering EIF3D's Role in Immune Regulation and Malignant Progression: A Pan-Cancer Analysis with a Focus on Colon Adenocarcinoma.

EIF3D, a key component of the eukaryotic translation initiation factor 3 (EIF3) complex, is critical in selectively translating mRNAs with atypical cap structures. Its relationship with colon adenocarcinoma (COAD) development and immune infiltration, however, remains under-explored. This study delves into EIF3D's role in COAD using bioinformatics and in vitro experimentation. We analyzed EIF3D expression levels utilizing TCGA, GTEx, CPTAC, and TISIDB databases. The TISCH database and ssGSEA method helped in assessing EIF3D's link with the tumor immune microenvironment. EIF3D expression in CRC cells was gauged via real-time PCR. Cell proliferation was assessed using CCK8 and colony formation assays, while migration capabilities were tested through Transwell assays. Flow cytometry facilitated cell cycle distribution and apoptosis analysis. ChIP-qPCR identified transcription factors regulating EIF3D, and bulk sequencing explored EIF3D's pathways in promoting COAD. EIF3D upregulation is a common feature in various tumors, especially in COAD, correlating with poor prognosis in many cancer types. It showed significant associations with immune cell and cancer-associated fibroblast (CAF) infiltration across multiple tumors. Additionally, it is closely associated with molecular and immune subtypes of multiple tumors, including COAD. Single-cell analyses depicted EIF3D's distribution and proportion in CRC immune cells. In vitro findings indicated EIF3D knockdown curtailed proliferation and migration, inducing G0/G1 arrest in COAD cells. Moreover, bulk sequencing revealed EIF3D knockdown interferes with multiple cancer-related pathways, likely by curtailing cell cycle and DNA replication activities to regulate cell proliferation. EIF3D emerges as a potential prognostic biomarker for tumor progression and immune infiltration, particularly in COAD, potentially predicting immunotherapy efficacy. Additionally, EIF3D represents a multifaceted target implicated in COAD's malignant progression.

Single-Cell RNA Sequencing Deconstructs the Distribution of Immune Cells Within Abdominal Aortic Aneurysms in Mice.

Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited. Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them. Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA. Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.

Super-resolved highly multiplexed immunofluorescence imaging for precise protein localization and podocyte ultrastructure.

Deep insights into the complex cellular and molecular changes occurring during (patho-)physiological conditions are essential for understanding the interactions and regulation of proteins. This understanding is crucial for research and diagnostics. However, the effectiveness of conventional immunofluorescence and light microscope, tools for visualizing the spatial distribution of cells or proteins, are limited both in resolution and multiplexity in complex tissues. This is mainly due to challenges such as the spectral overlap of fluorophore wavelengths, a limited range of antibody types, the inherent variability of samples and the optical resolution limit. The herein demonstrated combination of multiplex immunofluorescence imaging and super resolution microscopy offers a solution to these limitations by enabling the identification of different cell types and precise subcellular localization of proteins in tissue sections. In this study, we demonstrate the cyclic staining and de-staining of paraffin kidney sections, making it suitable for routine use and compatible with super-resolution microscopy for podocyte ultrastructural studies. We have further developed a computerized workflow for data processing which is accessible through available reagents and open-access code. As a proof of principle, we identified CDH2 as a marker for cellular lesions of sclerotic glomeruli in the nephrotoxic serum nephritis mouse model and cross-validated this finding with a human Nephroseq dataset indicating its translatability. In summary, our work represents an advance in multiplex imaging, which is crucial for understanding the localization of numerous proteins in a single FFPE kidney section and the compatibility with super-resolution microscopy to study ultrastructural changes of podocytes.

Red cell distribution width/albumin ratio and mortality risk in rheumatoid arthritis patients: Insights from a NHANES study.

Despite the established negative regulatory effects observed in various diseases like cardiovascular disease and diabetes, the distinct impact of red cell distribution width (RDW) to albumin ratio (RAR) on mortality within the realm of rheumatoid arthritis (RA) remains obscure. This study sought to explore the relationship between RAR and mortality in RA patients. A cohort of 2151 adults with RA from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2016 was analyzed for RAR levels derived from red cell distribution width and albumin concentrations. Utilizing Cox regression analysis, Kaplan-Meier curves, and Restricted Cubic Spline (RCS) models, we assessed the association between RAR levels and RA mortality while adjusting for potential confounding variables. Participants with higher RAR had a twofold to threefold increased risk of all-cause (HR = 3.10, 95% CI: 2.26-4.24) and cardiovascular mortality (HR = 2.46, 95%CI: 1.26-4.79) versus lower RAR. Kaplan-Meier analysis revealed that the higher RAR group had a significantly lower survival rate compared to the lower RAR group for both all-cause and cardiovascular mortality (both p < .0001), with a more pronounced effect observed for all-cause mortality. Furthermore, the RCS-fitted Cox regression model illustrated a nonlinear positive correlation between RAR levels and RA mortality. Overall, a higher RAR was associated with an increased risk mortality in RA patients. These findings underscore the potential of RAR as a prognostic biomarker in predicting outcomes in RA.

Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.

New dimension in viral hepatitis research

Chronic hepatitis B is the leading cause of hepatocellular carcinoma and a significant global health issue, affecting over 296 million people worldwide, with 15 million people coinfected with hepatitis delta...

Determination of the Relationship between Red Cell Distribution Width, NT-proBNP and cTnT in Acute Myocardial Infarction Patients

Determination of the Relationship between Red Cell Distribution Width, NT-proBNP and cTnT in Acute Myocardial Infarction Patients

Value of the red blood cell distribution width (RDW) and neutrophil lymphocyte ratio (NLR) in the prediction of functional recovery and 3-month mortality following endovascular treatment for acute anterior circulation ischemic stroke

ObjectivesThe red blood cell distribution width (RDW) and neutrophil to lymphocyte ratio (NLR) have been linked to poor prognosis in patients with ischaemic stroke. However, no study has yet evaluated the prognostic role of RDW and NLR, or their combined effect on reperfusion in patients with endovascularly-treated acute ischaemic stroke. This study therefore aimed to analyse the impact of RDW and NLR on poor functional outcomes and failed reperfusion following endovascular treatment in patients with acute anterior circulation ischaemic stroke. MethodsA total of 275 patients with acute anterior circulation ischaemic stroke treated endovascularly between 2015 and 2018 were enrolled in this study. The relationships between RDW, NLR, and poor outcomes were analysed using univariate and multivariate logistic regression models and receiver operating characteristic (ROC) curve analysis. The Youden Index was applied to determine the cut-off value. ResultsMultivariate logistic regression analysis identified RDW (p = 0.015) and NLR (p = 0.015) as independent predictors of mortality at the 3rd month. ROC curve analysis of RDW revealed a cutoff value of 14.25 (p = 0.009) for poor clinical outcomes (modified Rankin scale [mRS] 3–6). Similarly, a cutoff value of 14.25 was found for mortality prediction (p = 0.003). The cutoff value for poor clinical outcome (mRS 3–6) in the NLR was determined as 5.93 (p = 0.003), whereas the cutoff value for mortality was set at 5.17 (p = 0.028). RDW also predicted failed reperfusion, with a cutoff value of 17.75 (p = 0.048). ConclusionsHigh RDW and NLR upon admission were identified as independent indicators of mortality in endovascularly treated acute anterior circulation ischemic stroke patients. Furthermore, the RDW could potentially predict failed reperfusion.

Diagnostic sensitivity of immune-inflammatory cell proportion in early diagnosis of endometrial cancer

BackgroundPrevious studies have shown that inflammation is closely linked to the occurrence and progression of cancer. While the role of immune-inflammatory cell proportions in cancer prognosis has been demonstrated, further research is required to fully understand their predictive value. This study aims to investigate the potential of immune-inflammatory cell proportions, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red blood cell distribution width-to-platelet ratio (RPR), and monocyte-to-lymphocyte ratio (MLR), in predicting endometrial cancer (EC). MethodsIn this study, 18 patients with EC were included to create receiver operating characteristic (ROC) curves for NLR, MLR, PLR, and RPR, and the area under the curve (AUC) was calculated. Binary LOGISTIC regression analysis was then used to develop composite indicators. Subsequently, ROC curves were generated for the combined indicators, and the corresponding AUCs were calculated to evaluate the diagnostic efficacy of NLR, MLR, PLR, and RPR individually and in combination. The model was validated in an additional cohort. ResultIn the single-indicator ROC analysis, the baseline AUC for NLR was 0.724, with a significance level of p ​< ​0.05, indicating good predictive power. For the two-indicator combined ROC analysis, the combined AUC of NLR with each of the three other indicators was greater than 0.724 with a significance level of p ​< ​0.05. In the three-indicator combined ROC analysis, the baseline AUC of the combined indicators (including NLR) was greater than 0.766, and a p value of 0.001. Moreover, the baseline AUC of the validation set was 0.726. ConclusionOur findings suggest that the immune-inflammatory cell ratios, especially NLR, have a good predictive value for EC. Furthermore, the combined predictive value of the immune-inflammatory cell ratio is more effective than using individual applications.