Vascular Type Research Articles

Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis.

While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood. Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in 16 588 single cells isolated during atherosclerosis progression in Ldlr-/-Apob100/100 mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study. Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by 3 smooth muscle cells (SMCs), and 3 macrophage subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type proinflammatory/Trem2-high lipid-associated (macrophage) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of 3 arterial wall GRNs: GRN33 (macrophage), GRN39 (SMC), and GRN122 (macrophage) with major contributions to coronary artery disease heritability and strong associations with clinical scores of coronary atherosclerosis severity. The presence and pathophysiological relevance of GRN39 were verified in 5 independent RNAseq data sets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM in cultured human coronary artery SMCs. By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a coronary artery disease framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced, symptomatic atherosclerosis.

The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.

Islets of Langerhans are anatomically dispersed within the pancreas and exhibit regulatory coordination between islets in response to nutritional and inflammatory stimuli. However, within individual islets, there is also multi-faceted coordination of function between individual beta-cells, and between beta-cells and other endocrine and vascular cell types. This is mediated partly through circulatory feedback of the major secreted hormones, insulin and glucagon, but also by autocrine and paracrine actions within the islet by a range of other secreted products, including somatostatin, urocortin 3, serotonin, glucagon-like peptide-1, acetylcholine, and ghrelin. Their availability can be modulated within the islet by pericyte-mediated regulation of microvascular blood flow. Within the islet, both endocrine progenitor cells and the ability of endocrine cells to trans-differentiate between phenotypes can alter endocrine cell mass to adapt to changed metabolic circumstances, regulated by the within-islet trophic environment. Optimal islet function is precariously balanced due to the high metabolic rate required by beta-cells to synthesize and secrete insulin, and they are susceptible to oxidative and endoplasmic reticular stress in the face of high metabolic demand. Resulting changes in paracrine dynamics within the islets can contribute to the emergence of Types 1, 2 and gestational diabetes.

Impact of Vascular Access Type on Inflammatory Biomarkers and Clinical Outcomes in Haemodialysis Patients

Impact of Vascular Access Type on Inflammatory Biomarkers and Clinical Outcomes in Haemodialysis Patients

Hemodialysis-Related Infections: A 4-Year Surveillance

Objective: To analyze the results from the surveillance of hemodialysis-related infections.Material and Methods: Data was prospectively gathered from outpatients attending a hemodialysis unit from April 2019 until March 2023. The National Healthcare Safety Network (NHSN) Dialysis Event Surveillance was used to identify three types of infection-related dialysis events. Event rates were calculated and stratified by vascular access type, standardized infection ratios for bloodstream infections (BSI), intravenous antimicrobial starts, and described pathogens identified among BSI.Results: A total of 2,288 patient-month follow-ups were included. There were 79 infection-related dialysis events (24 BSI; 46 intravenous antimicrobial starts, nine pus, redness, or increased swelling at the vascular access site). The incidence of BSI per 100 patient-months was 1.05 (0.59 arteriovenous fistula, 0.83 arteriovenous graft, and 2.22 central venous catheter). Seventeen BSI were vascular access-related. Access-related BSI per 100 patient-months was 0.74 (0.39 arteriovenous fistula, 0.41 arteriovenous graft, and 1.85 central venous catheter). Intravenous antimicrobial starts per 100 patient-months was 2.01 (0.98 arteriovenous fistula, 2.62 arteriovenous graft, and 3.14 central venous catheter). Most events occurred in patients with a central venous catheter. When benchmarked with the 2014 NHSN, the standardized infection ratio of BSI, access-related BSI, and intravenous antimicrobial starts were 1.40, 1.26, and 0.55, respectively. The most serious outcome was BSI; resulting in 83.3% hospitalizations, 25% loss of vascular access, and 15.8% deaths. Conclusion: Surveillance of infection-related dialysis events is important for prevention. These events were highest among patients with a central venous catheter compared with other vascular access types.

A Preliminary Evaluation of Advanced Oxidation Protein Products (AOPPs) as a Potential Approach to Evaluating Prognosis in Early-Stage Breast Cancer Patients and Its Implication in Tumour Angiogenesis: A 7-Year Single-Centre Study.

Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 μM and 10.39 μM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan-Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 μM and 10.39 μM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice.

Classic Choroidal Neovascularization in Young Man

Introduction : Classic choroidal neovascularization (CNV 2) represent a pathological growth of blood vessels and can result in loss of visual function. The most common cause of CNV 2 in elderly patients is age- related macular degeneration, meanwhile in young age it is frequently due to inflammation, high myopia, angioid disks and hereditary disorders. Hence, the presented case reports the characteristic findings as well the management of the disease.
 Case Illustration : A 37-year-old man had two weeks history of metamorphopsia on both eyes. The left eye (LE) had a worse visual acuity, macular fibrosis with pigment epithelial detachment in funduscopy and Optical Coherence Tomography (OCT). A submacular hemorrhage and exudative lesion were recognized on the right eye (RE) with type 2 choroidal neovascularization. Fundus Fluorescence Angiography (FFA) was also performed. Systemic conditions were unremarkable. Intravitreal anti-VEGF injections on RE were given for three consecutive months and showed significant improvement.
 Discussion : The etiology of CNV 2 includes high myopia, and inflammation. However, none was found in this patient. Nonetheless, CNV type 2 is still uncommon in young age without predisposing conditions. As most common lesions involve the macula, symptoms shown include metamorphopsia, central scotoma and floaters. FFA is still considered to be the gold standard to differentiate the types of choroidal vascularization. Neovascularization and submacular hemorrhage can be treated with intravitreal injection of anti-VEGF, as previous studies reported significant improvement.
 Conclusion : This was a case of bilateral CNV type 2 in a young man without any previous predisposing conditions. Three monthly injections of anti-VEGF showed significant improvement.

Agronomic potential of plant-specific Gγ proteins.

The vascular plant-specific type III Gγ proteins have emerged as important targets for biotechnological applications. These proteins are exemplified by Arabidopsis AGG3, rice Grain Size 3 (GS3), Dense and Erect Panicle 1 (DEP1), and GGC2 and regulate plant stature, seed size, weight and quality, nitrogen use efficiency, and multiple stress responses. These Gγ proteins are an integral component of the plant heterotrimeric G-protein complex and differ from the canonical Gγ proteins due to the presence of a long, cysteine-rich C-terminal region. Most cereal genomes encode three or more of these proteins, which have similar N-terminal Gγ domains but varying lengths of the C-terminal domain. The C-terminal domain is hypothesized to give specificity to the protein function. Intriguingly, many accessions of cultivated cereals have natural deletion of this region in one or more proteins, but the mechanistic details of protein function remain perplexing. Distinct, sometimes contrasting, effects of deletion of the C-terminal region have been reported in different crops or under varying environmental conditions. This review summarizes the known roles of type III Gγ proteins, the possible action mechanisms, and a perspective on what is needed to comprehend their full agronomic potential.

Development of a prototype of a theranostic system based on silica nanoparticles with immobilized fluorescent dyes and VEGF targeting ligand.

Background. Administration of certain drugs causes undesirable effects associated with the systemic effect of the active substance on the entire body. Selective targeting of the drug to the affected tissue promotes a selective increase in the concentration of the substance in the area of interest, thereby reducing the systemic effect and enhancing the local therapeutic effect.Objective. Development of a targeted delivery system for theranostic agents using recombinant human vascular endothelial growth factor type A (rhVEGF-A121) as a targeting ligand.Design and method. To create the theranostic complex, commercially available reagents were used: the recombinant protein rhVEGF-A121 (cat.#: PSG140-10, LLC CyStorLab, Skolkovo, Russia) and fumed silica Aerosil (A-200, Degussa AG, Germany). The tosyl spacer that interconnects both components was synthesized in the laboratory. Protein conjugation with fluorophores was also carried out in-house. Indocyanine green (ICG; Sigma-Aldrich, USA) and rhodamine B (JSC Lenreaktiv, St. Petersburg, Russia) were taken for immobilization.Results. In the course of the work, functionalization of silica nanoparticles (SiNPs) with a tosyl spacer was carried out, conjugates of SiNPs with rhVEGF-A121 were synthesized, and theranostic constructs based on SiNPs were obtained, including rhVEGF-A121 as a targeting ligand, and ICG/Rhodamine B as a visualizing label.Conclusion. In the presented study, a prototype of a complex for targeted delivery of a theranostic agent to tissues with an active angiogenesis process, for example, to tumor and ischemic tissues, was developed. To solve the problem, we immobilized on the surface of SiNP a recombinant protein of human vascular endothelial growth factor (rhVEGF) to use as a guide ligand. Such a synthetic construct will help to deliver diagnostic and/ or medicinal substances packed in SiNP directly to cells that overexpress extracellular specific receptors of the VEGFR family. In subsequent in vivo experiments, delivery efficiency will be assessed by tissue accumulation of the fluorophores ICG and rhodamine B, which have been conjugated to the targeting ligand protein. The physicochemical characteristics of the obtained samples were studied by the methods of spectrophotometry and dynamic light scattering.

Clinical significance of type IV vascularization of laryngeal lesions according to the Ni classification

BackgroundScattered, small, dot-like intraepithelial papillary capillary loops (IPCLs) represent type IV epithelial vascularization according to “Ni classification” and are considered to be nonmalignant. According to the European Laryngological Society classification, these loops are malignant vascular changes. This contradiction has high clinical importance; therefore, clarification of the clinical significance of type IV vascularization according to the Ni classification is needed.MethodsThe study was performed between June 2015 and December 2022. All recruited patients (n = 434) were symptomatic, with macroscopic laryngeal lesions (n = 674). Patients were investigated using the enhanced endoscopic methods of narrow band imaging (NBI) and the Storz Professional Image Enhancement System (IMAGE1 S). The microvascular patterns in the lesions were categorized according to Ni classification from 2011 and all lesions were examined histologically.ResultsA total of 674 lesions (434 patients) were investigated using flexible NBI endoscopy and IMAGE1 S endoscopy. Type IV vascularization was recognized in 293/674 (43.5%) lesions. Among these 293 lesions, 178 (60.7%) were benign (chronic laryngitis, hyperplasia, hyperkeratosis, polyps, cysts, granulomas, Reinkeho oedema and recurrent respiratory papillomatosis); 9 (3.1%) were squamous cell carcinoma; 61 (20.8%) were mildly dysplastic, 29 (9.9%) were moderately dysplastic, 14 (4.8%) were severe dysplastic and 2 (0.7%) were carcinoma in situ. The ability to recognize histologically benign lesions in group of nonmalignant vascular pattern according to Ni (vascularization type I-IV) and distinguish them from precancers and malignancies was with accuracy 75.5%, sensitivity 54.4%, specificity 94.4%, positive predictive value 89.6% and negative predictive value 69.9%.ConclusionLaryngeal lesions with type IV vascularization as defined by Ni present various histological findings, including precancerous and malignant lesions. Patients with type IV vascularization must be followed carefully and, in case of progression mucosal lesion microlaryngoscopy and excision are indicated.

Risk of acute kidney injury in elective percutaneous coronary intervention: A comparative study of radial and femoral access

The impact of vascular access type, specifically transradial versus transfemoral, on the occurrence of acute kidney injury (AKI) in patients undergoing percutaneous coronary intervention (PCI) remains uncertain. In this study, we aimed to compare the incidence of AKI between the two access groups.
 Methods. This prospective observational study involved 164 adult patients undergoing elective PCI. Patients were categorized into transfemoral (n = 100) and transradial (n = 64) groups. Demographic data, including age, sex, body surface area, and preoperative glomerular filtration rate, as well as clinical information such as the presence of baseline ventricular dysfunction, diabetes mellitus, hypertension, postoperative blood loss, and transfusion volume, were recorded. Serum creatinine levels within the first 48-72 hours postoperatively were also documented.
 Results. Out of 100 patients in the transfemoral group, 12 (12%) developed AKI compared with 2 patients out of 64 (3.13%) in the transradial group. In the logistic multivariate analysis, several independent risk factors for AKI in patients undergoing PCI were identified. These factors included age >55 years (OR 2.88, 95% CI 1.09; 11.97, p = 0.046), diabetes (OR 4.82, 95% CI 1.12; 31.65, p = 0.039), preprocedural creatinine levels > 0.85 mg/dL (OR 3.17, 95% CI 1.54; 17.96, p = 0.019), fluoroscopy time > 10 min (OR 6.55, 95% CI 1.65; 26.03, p = 0.008), Mehran score indicating a risk of contrast-induced nephropathy >8 (OR 4.23, 95% CI 1.25; 14.3, p = 0.020), and transfemoral access (OR 3.22, 95% CI 1.08; 18.54, p = 0.044).
 Conclusions. Transradial access is associated with a significant independent reduction in the incidence of post-PCI AKI compared with transfemoral access. Age >55 years, diabetes, preprocedural creatinine > 0.85 mg/dL, fluoroscopy time > 10 min, Mehran score >8, and transfemoral access were identified as independent risk factors for AKI in patients undergoing PCI.

Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms

Brain metastasis (BrM) is a common malignancy, predominantly originating from lung, melanoma, and breast cancers. The vasculature is a key component of the BrM tumor microenvironment with critical roles in regulating metastatic seeding and progression. However, the heterogeneity of the major BrM vascular components, namely endothelial and mural cells, is still poorly understood. We perform single-cell and bulk RNA-sequencing of sorted vascular cell types and detect multiple subtypes enriched specifically in BrM compared to non-tumor brain, including previously unrecognized immune regulatory subtypes. We integrate the human data with mouse models, creating a platform to interrogate vascular targets for the treatment of BrM. We find that the CD276 immune checkpoint molecule is significantly upregulated in the BrM vasculature, and anti-CD276 blocking antibodies prolonged survival in preclinical trials. This study provides important insights into the complex interactions between the vasculature, immune cells, and cancer cells, with translational relevance for designing therapeutic interventions.

Microfluidic model of the alternative vasculature in neuroblastoma

Neuroblastoma (NB) is a highly vascularized pediatric tumor arising from undifferentiated neural crest cells early in life, exhibiting both traditional endothelial-cell-driven vasculature and an intriguing alternative vasculature. The alternative vasculature can arise from cancer cells undergoing transdifferentiation into tumor-derived endothelial cells (TEC), a trait associated with drug resistance and tumor relapse. The lack of effective treatments targeting NB vasculature primarily arises from the challenge of establishing predictive in vitro models that faithfully replicate the alternative vasculature phenomenon. In this study, we aim to recreate the intricate vascular system of NB in an in vitro context, encompassing both types of vascularization, by developing a novel neuroblastoma-on-a-chip model. We designed a collagen I/fibrin-based hydrogel closely mirroring NB’s physiological composition and tumor stiffness. This biomaterial created a supportive environment for the viability of NB and endothelial cells. Implementing a physiological shear stress value, aligned with the observed range in arteries and capillaries, within the microfluidic chip facilitated the successful development of vessel-like structures and triggered transdifferentiation of NB cells into TECs. The vascularized neuroblastoma-on-a-chip model introduced here presents a promising and complementary strategy to animal-based research with a significant capacity for delving into NB tumor biology and vascular targeting therapy.

Radiological classification of the Heidelberg triangle and its application in laparoscopic pancreaticoduodenectomy for malignancies

BackgroundThe TRIANGLE operation benefits patients with pancreatic cancer; however, the Heidelberg triangle, where the operation occurs, contains vessels that can impact safety, especially in laparoscopic pancreaticoduodenectomy (LPD) with the TRIANGLE operation. This study aimed to identify Heidelberg triangle vessel types and their implications in pancreaticoduodenectomy (PD).MethodsRetrospective collection of radiographic data was performed from January 2017 to April 2023. Three-dimensional (3D) CT reconstructions were performed on patients. Vascular types in the Heidelberg triangle were classified based on named vessels crossing its interior. The impact of these types on surgical outcomes and complications in PD with the TRIANGLE operation was assessed.ResultsPreoperative CT reconstruction was conducted on 184 pancreatic surgery patients. The findings revealed 99 patients (53.8%) with the type I Heidelberg triangle, lacking named vessels crossing the interior. Type II (n = 85, 46.2%), with named vessels crossing the interior, was identified. Among reconstructed patients who underwent PD with the TRIANGLE operation (n = 103), they were categorized as type I (n = 57) or type II (n = 46). The results showed that LPD patients with type II had significantly higher median intraoperative blood loss (300 mL vs. 200 mL, P = 0.030) and mean examined lymph nodes (17.2 ± 7.6 vs. 13.4 ± 5.2, P = 0.019) compared to those with type I. No significant differences were found in operative time or postoperative complications.ConclusionThe presence of named vessels crossing the interior of the Heidelberg triangle was associated with increased intraoperative bleeding during LPD combined with the TRIANGLE operation. Therefore, targeted preoperative planning is required before the operation, thus improving the safety of the TRIANGLE operation in minimally invasive surgery.

Predictive values of ultrasound characters associated with malignant thyroid nodules in Yaoundé: a cross-sectional study.

most ultrasound criteria are defined in developed countries and commonly used in practice to assess the malignancy risk of thyroid nodules. This practice does not take into consideration some aspects of our context as delay of consultation and insufficient iodine intake. The objective of this study was to determine the predictive values of ultrasound characters associated with malignant thyroid nodules in our environment. we conducted a cross-sectional, prospective, and analytical study in three hospitals in Yaoundé over a six-month period in 2022. Our sample consisted of thyroid nodules with ultrasound, cytopathological, and histopathological data. The ultrasound characters and histology status of category III thyroid nodules and higher in Bethesda score were analysed in univariate and multivariate statistics to determine their predictive values. eighty-nine nodules were obtained according to our inclusion criteria. The sex ratio was 0.46 and the average age of the patients was 46 years (IQR=42-59). The cancer prevalence in our sample was 22.47%. On ultrasound assessment, the characters associated to malignant histology (p<0.05) were nodules count, echogenicity, echostructure, presence or absence of microcalcifications, margins, and type of vascularization. Positive predictive values ranged from 26.15 to 57.14%, while negative predictive values ranged from 12.5 to 33.3%. taken alone, the ultrasound characters of suspected thyroid nodules have poor predictive values. There was a high variability in sensitivity but that was generally good (60-95%) while specificity was low. The prediction of malignant thyroid nodules is correlated with the association of at least two ultrasound criteria supported by clinical arguments.

Comparative characteristics of neuropsychological and neurometabolic changes in patients with Alzheimer's disease and vascular cognitive impairment

To investigate the pattern and connections of neuropsychological and metabolic indices in patients with cognitive disorders of Alzheimer's and vascular (subcortical-cortical) types of different severity. A total of 177 patients were examined, including 85 patients with Alzheimer's disease (AD) and 92 patients with vascular cognitive impairment (VCI). All patients underwent complex neuropsychological examination; 18F-FDG PET was performed in 17 patients with AD and 15 patients with VCI. The greatest changes in patients with AD were noted in the mnestic sphere, and the indicators significantly differed from the results of the study of patients with VCI already at the pre-dementia stage. Neurodynamic and dysregulatory disorders prevailed in patients with VCI. Patients with AD showed bilateral symmetrical reduction of metabolic activity in the cortex of parietal and temporal lobes, often in combination with marked hypometabolism in the hippocampal region. In patients with VCI, there were areas of decreased brain tissue metabolism of different localization and size, mainly in the projection of the basal ganglia and in the prefrontal and parietal cortex, as well as in the cingulate gyrus, which indirectly confirms the mechanism of disconnection of subcortical and cortical structures. In AD, impaired metabolic activity in the hippocampal region correlated with impaired temporal and spatial orientation (ρ=-0.54, p<0.05), memory impairment (ρ=-0.71, p<0.005). Hypometabolism of the parietal lobe cortex was associated with total MMSE score (ρ=-0.8, p<0.001), 10-word test (ρ=-0.89, p<0.001 and ρ=-0.82, p<0.001), visual-spatial impairment (ρ=-0.64, p<0.01), categorical association test (ρ=-0.73, p<0.005). In patients with VCI, dysregulatory disorders correlated with hypometabolism in the thalamic projection (ρ=-0.56, p<0.05), prefrontal cortex (ρ=-0.64, p<0.05) and in the cingulate gyrus (anterior regions) (ρ=-0.53, p<0.05). The results indicate the presence of differences in cognitive impairment and cerebral metabolism in patients with AD and VCI.

SkinCNN: Classification of Skin Cancer Lesions with A Novel CNN Model

Recently, there has been an increase in the number of cancer cases due to causes such as physical inactivity, sun exposure, environmental changes, harmful drinks and viruses. One of the most common types of cancer in the general population is skin cancer. There is an increase in exposure to the sun's harmful rays due to reasons such as environmental changes, especially ozone depletion. As exposure increases, skin changes occur in various parts of the body, especially the head and neck, in both young and old. In general, changes such as swelling in skin lesions are diagnosed as skin cancer. Skin cancers that are frequently seen in the society are known as actinic keratosis (akiec), basal cell carcinoma (bcc), bening keratosis (bkl), dermatofibroma (df), melanoma (mel), melanocytic nevi (nv), and vascular (vasc) types. It is not possible to consider all possible skin changes as skin cancer. In such a case, the development of a decision support system that can automatically classify the specified skin cancer images will help specialized healthcare professionals. For these purposes, a basic model based on MobileNet V3 was developed using the swish activation function instead of the ReLU activation function of the MobileNet architecture. In addition, a new CNN model with a different convolutional layer is proposed for skin cancer classification, which is different from the studies in the literature. The proposed CNN model (SkinCNN) achieved a 97% success rate by performing the training process 30 times faster than the pre-trained MobileNet V3 model. In both models, training, validation and test data were modelled by partitioning according to the value of cross-validation 3. MobileNet V3 model achieved F1 score, recall, precision, and accuracy metrics of 0.87, 0.88, 0.84, 0.83, 0.84, and 0.83, respectively, in skin cancer classification. The SkinCNN obtained F1 score, recall, precision, and accuracy metrics of 0.98, 0.97, 0.96, and 0.97, respectively. With the obtained performance metrics, the SkinCNN is competitive with the studies in the literature. In future studies, since the SkinCNN is fast and lightweight, it can be targeted to run on real-time systems.

Analysis of immunophenotypic features in hyaline vascular type Castleman disease

BackgroundStudies suggested that the immunophenotype of hyaline vascular type Castleman disease (HVCD) lacked characteristics, which was easy to be confused with other diseases.MethodsFrom January 2010 to June 2022, 17 cases of HVCD were selected from the Department of Pathology of Shaanxi Provincial People’s Hospital and the Department of Pathology of Shaanxi Provincial Cancer Hospital. 13 cases of reactive hyperplastic lymph nodes (RHL) and 11 cases of follicular lymphoma (FL) were selected as the control group. All cases were performed CD3, CD20, CD21 and BCL2 immunohistochemical staining.Results(i) In 17 cases of HVCD, the negative area of BCL2 of germinal center was significantly smaller than the negative area of CD3 of germinal center. However, in 13 cases of RHL, the negative area of CD3 of germinal center was basically consistent with the negative area of germinal center of BCL2 of germinal center. In 11 cases of FL, in neoplastic follicles, the negative area of CD3 was basically consistent with the positive area of BCL2. The difference between HVCD group and other two groups of diseases was statistically significant (P < 0.05). (ii) In 17 cases of HVCD, the negative area of BCL2 of germinal center was significantly smaller than the follicular dendritic cell (FDC) meshworks expressed by CD21. However, in 13 cases of RHL, the FDC meshworks expressed by CD21 were basically consistent with the negative area of BCL2 of germinal center. In 11 cases of FL, in neoplastic follicles, the FDC meshworks expressed by CD21 was basically consistent with the positive area of BCL2. The difference between HVCD group and other two groups of disease was statistically significant (P < 0.05).ConclusionsHVCD has unique immunophenotypic characteristics. The negative area of BCL2 of germinal center is significantly smaller than the negative area of CD3. The negative area of the BCL2 of germinal center is significantly smaller than the FDC meshworks expressed by CD21. These two immunophenotypic features in HVCD are very important in diagnosis and differential diagnosis.

Single cell multi‐omics implicates immune and vascular cells in Alzheimer’s etiology

AbstractBackgroundUnderstanding the genetic etiology of Alzheimer’s disease (AD) is critical to inform effective therapies but remains a challenge. Genetic heritability of late‐onset AD is ∼60‐80%, and genome‐wide association studies (GWAS) have uncovered dozens of noncoding single nucleotide polymorphisms (SNPs) that influence AD risk. Two challenges for the functional interpretation of AD genetic risk are (1) determining the cell types in which SNPs operate and (2) identifying the genes they dysregulate to drive AD pathogenesis. Single‐nucleus sequencing studies of human neurons, microglia, and other brain cell types have begun addressing these challenges. Yet, many AD risk SNPs remain unmapped. One possibility is that they are expressed in immunovascular brain cell types largely missed by current methods.MethodHere, we optimized Vessel Isolation and Nuclei Extraction for Sequencing (VINE‐seq) to capture multimodal gene expression and chromatin accessibility assays across all major brain cell types from 30 cognitively normal, MCI, and AD human prefrontal cortex samples.ResultWe discover early gene dysregulation in immune and vascular cell types along AD progression. We highlight the gene regulatory networks mediating this dysregulation and implicate processes associated with AD pathology and cognitive decline. Finally, we map noncoding AD risk variants to diverse immune and vascular cell types, thereby expanding our understanding of AD etiology.ConclusionDysfunction of diverse human brain immune and vascular cell types mediate the genetic risk for Alzheimer’s disease.

Investigation of Biopsychosocial Status, Fatigue, Sleep Quality, Alexithymia, Cognitive Functions, and Quality of Life in Behçet's Disease.

The aim of this study was to compare the effects of Behçet's disease in terms of anxiety, biopsychosocial status, fatigue, sleep quality, alexithymia, cognitive level, and quality of life according to major and minor organ involvement. The study was planned as a single-centre cohort study. Fifty patients diagnosed with Behçet's (mean age 43±11.96 years) were included in the study. The patients were divided into two groups as major organ involvement (uveitis, neuro-Behçet's, or vascular type Behçet's disease) and minor organ involvement (mucocutaneous type Behçet's disease). Biopsychosocial status was evaluated with Biopsychosocial Questionnaire (BETY-BQ), anxiety with Beck Anxiety Inventory (BAI), fatigue with Multidimensional Assessment of Fatigue (MAF) Scale, sleep quality with Pittsburgh Sleep Quality Index (PSQI), alexithymia with Toronto Alexithymia Scale-20 (TAS-20), cognition level with Mini-Mental State Examination (MMSE), and quality of life with Short Form-36 (SF-36). In the comparison according to minor and major organ involvement, there was no significant difference between the groups in BETY-BQ, BAI, MAF, PSQI, TAS-20, MMSE and SF-36 (p>0.05). Behçet's disease negatively effects in parameters such as biopsychosocial status, fatigue, sleep quality, alexithymia and quality of life. The presence of major or minor organ involvement in the patients did not change these negative effects.

Clinicopathological and computed tomography features associated with recurrence-free survival of patients with small-sized peripheral invasive lung adenocarcinoma after sublobectomy.

Sublobar resection is gradually becoming a standard treatment for small-sized (≤2 cm) peripheral non-small cell lung cancer (NSCLC), with lung adenocarcinoma (LADC) being the most frequent histologic subtype. However, the prognostic predictors for preoperatively determining whether sublobectomy is feasible for patients with early LADC have not yet been well identified. Therefore, this study aimed to investigate the clinicopathological and computed tomography (CT) features associated with the recurrence-free survival (RFS) of patients with small-sized invasive LADC (SILADC) after sublobar resection. This retrospective cohort study analyzed 107 patients with SILADC who underwent preoperative chest CT scan and sublobar resection from December 2012 to March 2019. The Kaplan-Meier survival was used to analyze the relationship between clinicopathological characteristics, preoperative chest CT findings, and RFS. The Cox proportional hazards regression was used to identify independent prognostic factors of poor RFS. For clinicopathological characteristics, RFS was shorter in patients aged ≥70 years, smokers, and those with micropapillary/solid-predominant adenocarcinomas (all P values <0.05). For preoperative CT features, RFS was shorter in patients with tumor size ≥1.4 cm, solid component size ≥1.1 cm, proportion of solid component ≥72%, solid density, spiculation, vascular convergence sign, peripheral fibrosis, and type II pleural tag (all P values <0.05). Multivariate analysis showed proportion of solid component ≥72% [hazard ratio (HR): 5.920; P=0.006; 95% confidence interval (CI): 1.686-20.794], spiculation (HR: 5.026; P=0.001; 95% CI: 2.008-12.581), and type II pleural tag (HR: 4.638; P=0.002; 95% CI: 1.773-12.136) were independent risk factors for poor prognosis in patients with SILADC after sub-lobectomy. Clinicopathological and CT characteristics are helpful for predicting the RFS of patients with SILADC after sublobar resection and can be used as an auxiliary tool for thoracic surgeons to choose the best surgical mode.