Clinical Biopsy Research Articles

Childhood Heart Tumors: Detection, Diagnosis, and Treatments

: Childhood cardiac tumors are rare but challenging conditions that can have a significant impact on a child’s health and even be fatal if not detected and diagnosed timely. While various types of tumors can occur in the heart, the most common among children are benign tumors, such as rhabdomyomas. Diagnosis of pediatric cardiac tumors is often challenging and requires a combination of clinical examination, imaging studies and biopsy. In some cases, the tumors may be asymptomatic and discovered incidentally, while in others, they can cause symptoms, such as shortness of breath, chest pain, arrhythmias and congestive heart failure. Treatment options for pediatric cardiac tumors vary depending on the type, size and location of the tumor and may include surgical resection, watchful waiting or a combination of both. The prognosis for children with cardiac tumors is generally good, with a high rate of complete cure in many cases. However, long-term follow-up and monitoring are important to detect and manage any potential complications or recurrence of the tumors.

Accuracy of clinical diagnosis, imaging methods, and biopsy in tumours and pseudo-tumours of the hand

Accuracy of clinical diagnosis, imaging methods, and biopsy in tumours and pseudo-tumours of the hand

Evaluating myocardial involvement in patients with multiple myeloma at different stages a cardiac MR T1 mapping study

Abstract Background At present, the International criteria for diagnosis multiple myeloma（MM） do not specifically highlight the use of cardiac magnetic resonance (CMR) to detect abnormal myocardial infiltration in patients at different clinical stages of MM. Extracellular volume fraction (ECV) based on CMR T1 mapping indicates expansion of the extracellular space or deposition of material in infiltrative heart diseases. Purpose To detect whether myocardial involvement in patients with MM at different clinical stages based on CMR T1 mapping. Methods A cohort consisting of 20 patients with diagnosed MM and 15 sex- and age-matched controls (Cs) were recruited for this study. All participants underwent CMR examination to obtain native T1 and ECV. The patients with MM were stratified into three groups based on the International Staging System (ISS): Stage I (n=5), Stage II (n=7), and Stage III (n=8). Cardiac amyloidosis (CA) is diagnosed based on the patient's clinical presentation and tissue biopsy. The baseline biochemical indices were collected before CMR examination. Result Among patients with MM, there were a total of 9 patients diagnosed with CA, comprising 3 patients in stage II and 6 patients in stage III. The ECV in stage III patients (45.13±11.89%) was significantly higher compared to that in stage I (26.65±4.22%), stage II (34.09±8.90%), and controls (25.40±2.52%) (p < 0.05). Furthermore, the ECV in stage II patients (34.09±8.90%) was higher compared to controls (25.40±2.52%), though not significantly different from stage I patients (26.65±4.22%). Correlation analysis revealed a positive correlation between brain natriuretic peptide (BNP) levels and ECV (r=0.606, p=0.013). Receiver operating characteristic (ROC) curve analysis demonstrated that ECV had good predictive value for CA, with an area under the curve (AUC) of 0.898 (p < 0.01), and the optimal cutoff value for ECV was determined to be 33.7%. Conclusions ECV derived from CRM T1 mapping holds promise for identifying amyloid accumulation, which deteriorates progressively with the advancement of disease stages in patients with MM. It is recommended that patients diagnosed with Stage II and Stage III MM should undergo CMR to facilitate the early detection of myocardial infiltrative damage.

Comparative analysis of the leprosy detection rate regarding its clinical spectrum through PCR using the 16S rRNA gene: a scientometrics and meta-analysis

BackgroundLeprosy is a chronic and disabling infectious disease caused by Mycobacterium leprae. It has a wide clinical spectrum and is operationally classified into paucibacillary (PB) and multibacillary (MB) cases. There is evidence that the 16S rRNA gene can be used in Polymerase Chain Reaction (PCR) for complementary detection with high sensitivity and specificity. However, there is no literature convention on its diagnostic correspondence regarding the particular operational classification of the disease. This study aimed to correlate, through a meta-analysis, the detection rate of leprosy between the PCR method with the 16S rRNA gene in the clinical forms PB and MB in relation to confirmed cases.MethodsThis is a systematic review and meta-analysis study conducted according to the PRISMA 2020 guidelines, using the search descriptors with “AND”: “Leprosy”; “Polymerase Chain Reaction”; “16S rRNA” in the PUBMED, SciELO, LILACS, and Science Direct databases. The search was limited to original observational articles in Portuguese, English, or Spanish, with no defined time frame. The methodological quality assessment of the selected articles was performed using the JBI checklists. A scientometric approach to the article using used the VOS Viewer and Scimago Graphica software. The meta-analysis was conducted using Comprehensive Meta-Analyses software, under Pearson’s Correlation effect test and fixed effect model and subgroup analysis concerning the type of sample analyzed.ResultsThe study was significant from the perspective of the paucibacillary group (Clinical biopsy: -0.45 [95% CI= -0.63 – −0.22], p < 0.001/ Slit smear skin: −0.52 [95% CI= -0.65 – −0.36], p < 0.001 / Overall: −0.50 [95% CI= −0.61 – −0.37], p < 0.001). The PCR diagnostic method for the16S rRNAgene ofM. lepraehas low viability and diagnostic sensitivity in both clinical biopsy samples and leprosy skin smears.ConclusionThis implies little validation of it as a PCR target gene for diagnosing the disease, highlighting limitations in the actual technique.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024588790.

From Diabetes to Dementia: Identifying Key Genes in the Progression of Cognitive Impairment.

To provide a basis for further research on the molecular mechanisms underlying type 2 diabetes-associated mild cognitive impairment (DCI) using two bioinformatics methods to screen key genes involved in the progression of mild cognitive impairment (MCI) and type 2 diabetes. RNA sequencing data of MCI and normal cognition groups, as well as expression profile and sample information data of clinical characteristic data of GSE63060, which contains 160 MCI samples and 104 normal samples, were downloaded from the GEO database. Hub genes were identified using weighted gene co-expression network analysis (WGCNA). Protein-protein interaction (PPI) analysis, combined with least absolute shrinkage and selection operator (LASSO) and receiver operating characteristic (ROC) curve analyses, was used to verify the genes. Moreover, RNA sequencing and clinical characteristic data for GSE166502 of 13 type 2 diabetes samples and 13 normal controls were downloaded from the GEO database, and the correlation between the screened genes and type 2 diabetes was verified by difference and ROC curve analyses. In addition, we collected clinical biopsies to validate the results. Based on WGCNA, 10 modules were integrated, and six were correlated with MCI. Six hub genes associated with MCI (TOMM7, SNRPG, COX7C, UQCRQ, RPL31, and RPS24) were identified using the LASSO algorithm. The ROC curve was screened by integrating the GEO database, and revealed COX7C, SNRPG, TOMM7, and RPS24 as key genes in the progression of type 2 diabetes. COX7C, SNRPG, TOMM7, and RPS24 are involved in MCI and type 2 diabetes progression. Therefore, the molecular mechanisms of these four genes in the development of type 2 diabetes-associated MCI should be studied.

Validation of the performance of a point of care molecular test for leprosy: From a simplified DNA extraction protocol to a portable qPCR.

The study aimed to optimize qPCR reactions using oligonucleotides from the first Brazilian molecular diagnostic kit for leprosy on a portable platform (Q3-Plus). In addition, we sought to develop a simplified protocol for DNA extraction that met point-of-care criteria. During optimization on the Q3-Plus, optical parameters, thresholds, and cutoffs for the 16S rRNA and RLEP targets of M. leprae were established using synthetic DNA, purified DNA from M. leprae, and pre-characterized clinical samples. For the simplified extraction protocol, different lysis solutions were evaluated using chaotropic agents, and purification was carried out by transferring the lysed material to FTA cards. The complete protocol (simplified extraction + qPCR on the portable platform) was then evaluated with pre-characterized clinical skin biopsy samples and compared with standard equipment (QuantStudio-5). LOD95% for the optimized reactions was 113.31 genome-equivalents/μL for 16S rRNA and 17.70 genome-equivalents/μL for RLEP. Among the lysis solutions, the best-performing was composed of urea (2 M), which provided good dissolution of the skin fragment and a lower Ct value, indicating higher concentrations of DNA. The complete technological solution showed a sensitivity of 52% in reactions. Our results highlight the need for additional optimization to deal with paucibacillary samples, but also demonstrate the feasibility of the portable platform for the qPCR detection of M. leprae DNA in low infrastructure settings.

Expanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases.

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders caused by defects in bile secretion or transport usually presenting as cholestasis in pediatric age. Herewith, we describe 3 PFIC cases with diagnostic challenges and highlight the role of genetic analysis. The clinical history, laboratory data, liver biopsy, and molecular analysis for each case were reviewed. Case 1, a Hispanic male from Puerto Rico with hepatomegaly since age 2 months, was eventually diagnosed with PFIC3 following identification of a homozygous splice site variant in ATP binding cassette subfamily B member 4 (ABCB4) (c.2784-12T>C) at age 17 years by whole-exome sequencing (WES). Case 2 was a 37-year-old man with a history of alcoholism, abnormal liver function tests, and ductopenia on biopsy. Molecular testing revealed a pathogenic heterozygous ABCB4 mutation (c.1633C>T) variant leading to a diagnosis of PFIC3. Case 3 was a 2-year-old female initially presenting as a drug-induced liver injury but was diagnosed with PFIC10 following identification of a heterozygous frameshift mutation (p.Asp300Trpfs*19) and a heterozygous missense mutation (c.1357T>C) in myosin VB (MYO5B) by WES. These PFIC cases highlight the heterogenous presentation and diagnostic challenges, and they emphasize the role of next-generation sequencing, particularly the utility of WES.

Enhancing Biomarker Detection in Cancer: A Comparative Analysis of Preanalytical Reverse Transcription Enzymes for Liquid Biopsy Application

Circulating tumor cells and liquid biopsy-based biomarkers might one day play a crucial role in the treatment decision process for patients of several cancer entities. However, clinical studies on liquid biopsy approaches revealed distinct detection rates and thus, different risk scoring for patients. This study delves into the comparison of 2 utilized reverse transcription enzymes, namely, SuperScript IV VILO (VILO) and Sensiscript (SS), aiming to understand their impact on biomarker detection rates. Prostate cancer cell lines were used to assess detection limits, followed by an investigation of biomarker status in clinical liquid biopsy samples of distinct tumor entities. Our findings highlight the superior reverse transcription efficacy of VILO over SS, commonly used in studies employing the AdnaTest platform. The enhanced efficacy of VILO results in a significantly higher number of patients positive for biomarkers. Clinically, the use of a less-sensitive enzyme system may lead to the misclassification of genuinely biomarker-positive patients, potentially altering their prognosis due to inadequate clinical monitoring or inappropriate treatment strategies.

Uncommon neoplasms mistakenly diagnosed as hidradenitis suppurativa: Report of three consecutive cases

Hidradenitis Suppurativa (HS) poses diagnostic challenges due to its clinical overlap with various skin conditions and neoplasms, potentially leading to misdiagnoses. The absence of a definitive diagnostic test and infrequent use of histopathology contribute to diagnostic complexities, exacerbated by the recent increased focus on HS. Three cases initially diagnosed and treated as HS underwent through clinical work-up and skin biopsies to resolve diagnostic complexities. Initially labelled as HS, the cases revealed a breast carcinomaon axillary ectopic tissue, a cutaneous gamma-delta T-cell lymphoma, and an infiltrating squamous cell carcinoma. Delayed recognition led to misguided therapies and adverse outcomes.This report stresses the need to explore alternative diagnoses for chronic skin nodules with or without ulcerations on the flexures. Timely skin biopsies are crucial for accurate diagnoses. Ongoing clinician education is essential to avoid misdiagnosis in challenging cases, where histopathology aids in reaching a correct diagnosis.

Multiplexed immunohistochemical evaluation of small bowel inflammatory and epithelial parameters in environmental enteric dysfunction

BackgroundEnvironmental enteric dysfunction (EED) is characterized by reduced absorptive capacity and barrier function of the small intestine, leading to poor ponderal and linear childhood growth. ObjectivesTo further define gene expression patterns that are associated with EED to uncover new pathophysiology of this disorder. MethodsDuodenal biopsies from cohorts of children with EED from Bangladesh, Pakistan and Zambia were analyzed by immunohistochemistry (IHC) to interrogate gene products that distinguished differentiation and various biochemical pathways in immune and epithelial cells, some identified by prior bulk RNA sequence analyses. Immunohistochemical staining was digitally quantified from scanned images and compared to cohorts of North American children with celiac disease (gluten-sensitive enteropathy) or with no known enteric disease and no pathologic abnormality (NPA) detected in their clinical biopsies. ResultsAfter multivariable statistical analysis, we identified statistically significant (P < 0.05, 2-tailed t-test) elevated signals representing cluster of differentiation 45 (80%; 95% confidence interval [CI]: 24%, 127%), lipocalin 2 (659%; 95% CI: 198%, 1838%), and regenerating family 1 beta (221%; 95% CI: 47%, 600%) and lower signals corresponding to granzyme B (−74%; 95% CI: −82%, −62%), and sucrase isomaltase (−58%; 95% CI: −75%, −29%) in EED biopsies compared with NPA biopsies. Computerized algorithms also detected statistically significant elevation in intraepithelial lymphocytes (49%; 95% CI: 9%, 105%) and proliferation of leukocytes (267%; 95% CI: 92%, 601%) in EED biopsies compared with NPA biopsies. ConclusionsOur results support a model of chronic epithelial stress that decreases epithelial differentiation and absorptive function. The close association of several IHC parameters with manual histologic scoring suggests that automated digital quantification of IHC panels complements traditional histomorphologic assessment in EED.

False Alarms: The Intriguing Cases of Granulomatous Mastitis Mimicking Malignancy along with Review of the Literature

Abstract Background: Granulomatous mastitis is a rare and challenging condition that can mimic malignancy in the breast. This condition often presents with clinical and radiological features that overlap with those of breast cancer, making it difficult to differentiate between the two based solely on clinical assessment. Aims and Objective: The objective of this study is to highlight the diagnostic dilemmas, the clinico-pathological profile of such cases and what enables a correct diagnosis in such cases. Materials and Methods: A retrospective study of 5 patients with histologically proven granulomatous mastitis attending OPD/IPD at a tertiary care center in south India during a period of 18 months from Jan 2022 – Jul 23. We present five cases of granulomatous mastitis highlighting the inconsistency of the clinical, imaging and initial biopsy findings, briefly review the relevant literature and discuss the challenges associated with its diagnosis. Results and Conclusion: This study highlights the importance of awareness of granulomatous mastitis and its clinicopathological characterstics. The study also emphasizes that a multidisciplinary approach involving Surgeons, radiologists, pathologists, and medical oncologists is crucial to accurately diagnose and manage this condition. Review of literature revealed few studies highlighting the clinic-radiological and histopathological profile of such cases of granulomatous mastitis mimicking malignancy however such studies are far less and encompass only isolated single case reports or occasional series of 2-3 cases. To our knowledge this is one of the largest case series with 5 cases highlighting the clinicopathological details and the diagnostic dilemmas.

Focusing on non-responders to infliximab with ulcerative colitis, what can we do first and next?

BackgroundUlcerative colitis (UC) is a chronic immune-mediated inflammation of the colorectum, for which infliximab (IFX) is currently the mainstay of treatment. However, one-third of patients with UC still fail to benefit from the IFX therapy, and early exposure to IFX impairs the efficacy of other subsequent biologics. Therefore, personalized therapeutic system is urgently needed to assist in clinical decision-making and precision treatment. MethodsFour microarray datasets of colonic biopsies from UC patients treated with IFX were obtained from the GEO database to form the Training Cohort and Validation Cohort. Differentially expressed genes (DEGs) in Training Cohort were identified and enriched for GO, KEGG and immune cell infiltration analysis. A prediction model for IFX efficacy was developed based on the LASSO and Logistic regression. The predictive accuracy of the model was verified by the Validation Cohort, and the model-genes/proteins were validated by immunohistochemistry. Gene-drug, gene-ncRNA interaction analysis were performed to identify drugs or non-coding RNAs (ncRNAs) that potentially interacted with the model-genes. Homology Modeling and Molecular Docking were conducted to filter the optimal candidate as the subsequent adjuvant or alternative for IFX in predicted non-responders. At last, the down-regulation of the key model-gene/protein CYP24A1 by the drug candidate Deferasirox was verified by Western Blot and qRT-PCR Assay based on cellular experiments. ResultsA total of 113 DEGs were identified in the Training Cohort, mainly enriched in inflammatory cell chemotaxis, migration, and response to molecules derived from intestinal microbiota. Activated pro-inflammatory innate immune cells, including neutrophils, M1 macrophages, activated dendritic cells and mast cells, were significantly enriched in colons of non-responders. The prediction model based on three model-genes (IFI44L, CYP24A1, and RGS1) exhibited strong predictive efficacy, with AUC values of 0.901 and 0.80 in the Training and Validation Cohorts, respectively. Higher expression of the three model-genes/proteins in colons of non-responders to IFX was confirmed by clinical colonic mucosal biopsies. 4 Drugs (Calcitriol, Lunacalcipol, Deferasirox, Telaprevir), 15 miRNAs and 66 corresponding lnRNAs interacting with model-genes were identified. The protein 3D structure of the key model-gene/protein (human-derived CYP24A1) was developed. Through the Molecular Docking and cellular experimental validation, Deferasirox, which significantly down-regulated both the RNA and protein expression of CYP24A1, was identified as the optimal adjuvant or alternative for IFX in predicted non-responders with UC. ConclusionThis study developed a novel prediction model for pre-assessing the efficacy of IFX in patients with UC, as the first step towards personalized therapy. Meanwhile, drugs and non-coding RNAs were provided as potential candidates to develop the next-step precise treatment for the predicted non-responders. In particular, Defeasirox appears to hold promise as an adjuvant or alternative to IFX for the optimization of UC therapy.

Towards Preanalytical Best Practices for Liquid Biopsy Studies: A BLOODPAC Landscape Analysis.

BLOODPAC is a public-private consortium that develops best practices, coordinates clinical and translational research, and manages the BLOODPAC Data Commons to broadly support the liquid biopsy community and accelerate regulatory review to aid patient accessibility. BLOODPAC previously recommended 11 preanalytical minimal technical data elements (MTDEs) for BLOODPAC-sponsored studies and data submitted to BLOODPAC Data Commons. The current landscape analysis evaluates the overlap of the BLOODPAC MTDEs with current best practices, guidelines, and standards documents related to clinical and research liquid biopsy applications. Our findings indicate an existing high degree of concordance among these documents. Where differences exist, the BLOODPAC preanalytical MTDEs can be considered a minimal practicable set for organizations to utilize. These MTDEs were developed following extensive examination of best practices and iterative conversations with the U.S. FDA. BLOODPAC recommends the use of these MTDEs in submissions to data commons and to support liquid biopsy clinical trials and research globally.

Frequency of Peptic Ulcer Disease in Patients with Chronic Liver Disease Presenting with Upper Gastrointestinal Bleeding

Background: Peptic ulcer disease (PUD) is a significant cause of morbidity and mortality worldwide, particularly in patients with chronic liver disease (CLD). The occurrence of upper gastrointestinal bleeding (UGIB) in CLD patients presents a serious complication, often requiring urgent medical intervention. Objective: The main objective of this study was to determine the frequency of peptic ulcer disease in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Methods: This retrospective observational study was conducted at Ayub Teaching Hospital, Abbottabad, from 2021 to 2023. Data were collected from 105 patients diagnosed with chronic liver disease who presented with symptoms of upper gastrointestinal bleeding. The diagnosis of CLD was confirmed through clinical evaluation, biochemical tests, imaging studies, and/or liver biopsy. Patients included were aged 18 years and above and presented with UGIB evidenced by hematemesis, melena, or both. Exclusion criteria were individuals with bleeding disorders unrelated to CLD and those who did not undergo endoscopic evaluation. Data collection involved demographic information, clinical history, duration and etiology of CLD, comorbid conditions, and UGIB presentation. Upper gastrointestinal endoscopy was performed on all patients to identify the source of bleeding. Statistical analysis was performed using SPSS version 25, with a p-value of less than 0.05 considered statistically significant. Results: The study included 105 patients, with a mean age of 55.3±3.27 years; 65 (61.9%) were male, and 40 (38.1%) were female. The etiologies of CLD were viral hepatitis (42.9%), alcoholic liver disease (28.6%), non-alcoholic fatty liver disease (19.0%), and other causes (9.5%). Clinical presentations of UGIB included hematemesis (66.7%), melena (23.8%), and both (9.5%). Endoscopic findings revealed that 35 patients (33.3%) had peptic ulcer disease, with 20 (57.1%) having duodenal ulcers and 15 (42.9%) having gastric ulcers. Other sources of UGIB included esophageal varices (38.1%), gastric varices (14.3%), erosive gastritis (9.5%), and malignancies (4.8%). Associated risk factors for PUD included NSAID use (42.9%), smoking (28.6%), and coexisting portal hypertension (71.4%). The mean size of ulcers was 10.2 mm. Endoscopic therapy was utilized in 71.4% of cases, with pharmacological treatment primarily including proton pump inhibitors (85.7%). Complications included rebleeding within 7 days (14.3%) and the need for surgical intervention (5.7%). The mean hospital stay was 7.8 days, and in-hospital mortality was observed in 8.6% of patients. Conclusion: Peptic ulcer disease represents a substantial yet manageable complication in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Prompt recognition and targeted therapeutic interventions are crucial for optimizing outcomes in this high-risk population.

Novel biomimetic hybrid plasmonic nanocavity-based ECL strategy for the detection of extracellular vesicles

Tumor-derived extracellular vesicles detection has emerged as an important clinical liquid biopsy approach for cancer diagnosis. In this work, we developed a novel hybrid plasmonic nanocavity consisting of hexagonal Au nanoplates nanoarray, SnS2/Au nanosheet layer and biomimetic lipid bilayer. Firstly, the hybrid plasmonic nanocavity combined the optical confinement for the ECL regulation and the biological recognition for the detection of extracellular vesicles. Secondly, MXene-derived Ti2N QDs have been prepared as ECL nanoprobe to label extracellular vesicles. Moreover, biomimetic lipid bilayer with specific aptamer was used to identify extracellular vesicles and integrate Ti2N QDs into the nanocavity with membrane fusion strategy. Due to the significant electromagnetic field enhancement at the cavity region, the hybrid plasmonic nanocavity provided strong field confinement to concentrate and redistribute the ECL emission of QDs with a 9.3-fold enhancement. The hybrid plasmonic nanocavity-based ECL sensing system improved the spatial controllability of EVs analysis and the accurate resolution of specific protein. It achieved the sensitive detection of extracellular vesicles in ascites and successfully distinguished the peritoneal metastasis of gastric cancer.

Genetic testing and new variants in diagnosis of congenital ichthyoses.

The aim of this study was to evaluate how diagnostic practice in congenital ichthyoses has evolved during the years 2000-2020 and what kind of gene variants of congenital ichthyosis have been found. The study cohort of this register-based research consisted of a total of 88 patients, whose diagnostic testing was conducted, and ichthyosis diagnoses set at the Department of Dermatology and the Department of Clinical Genetics at Tampere University Hospital during the years 2000-2020. Diagnosis of ichthyosis was confirmed with genetic testing in 33 cases, and with conventional diagnostic methods, such as clinical findings, skin biopsy and family history of ichthyoses, in 55 cases. We observed four novel variants in patients with the clinical diagnoses of congenital ichthyoses. When genetic testing became available, it was offered primarily to patients with severe forms of ichthyosis. During the study period next-generation sequencing became the genetic testing method of choice providing new opportunities in diagnostics.

Pericytes recruited by CCL28 promote vascular normalization after anti-angiogenesis therapy through RA/RXRA/ANGPT1 pathway in lung adenocarcinoma

BackgroundIt has been proposed that anti-angiogenesis therapy could induce tumor "vascular normalization" and further enhance the efficacy of chemotherapy, radiotherapy, target therapy, and immunotherapy for nearly twenty years. However, the detailed molecular mechanism of this phenomenon is still obscure.MethodOverexpression and knockout of CCL28 in human lung adenocarcinoma cell line A549 and murine lung adenocarcinoma cell line LLC, respectively, were utilized to establish mouse models. Single-cell sequencing was performed to analyze the proportion of different cell clusters and metabolic changes in the tumor microenvironment (TME). Immunofluorescence and multiplex immunohistochemistry were conducted in murine tumor tissues and clinical biopsy samples to assess the percentage of pericytes coverage. Primary pericytes were isolated from lung adenocarcinoma tumor tissues using magnetic-activated cell sorting (MACS). These pericytes were then treated with recombinant human CCL28 protein, followed by transwell migration assays and RNA sequencing analysis. Changes in the secretome and metabolome were examined, and verification of retinoic acid metabolism alterations in pericytes was conducted using quantitative real-time PCR, western blotting, and LC–MS technology. Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) was employed to validate the transcriptional regulatory ability and affinity of RXRα to specific sites at the ANGPT1 promoter.ResultsOur study showed that after undergoing anti-angiogenesis treatment, the tumor exhibited a state of ischemia and hypoxia, leading to an upregulation in the expression of CCL28 in hypoxic lung adenocarcinoma cells by the hypoxia-sensitive transcription factor CEBPB. Increased CCL28 could promote tumor vascular normalization through recruiting and metabolic reprogramming pericytes in the tumor microenvironment. Mechanistically, CCL28 modified the retinoic acid (RA) metabolism and increased ANGPT1 expression via RXRα in pericytes, thereby enhancing the stability of endothelial cells.ConclusionWe reported the details of the molecular mechanisms of "vascular normalization" after anti-angiogenesis therapy for the first time. Our work might provide a prospective molecular marker for guiding the clinical arrangement of combination therapy between anti-angiogenesis treatment and other therapies.

Three-dimensional imaging of upper tract urothelial carcinoma improves diagnostic yield and accuracy.

Upper tract urothelial carcinoma (UTUC) is a rare form of urothelial cancer with a high incidence of recurrence and a low survival rate. Almost two-thirds of UTUCs are invasive at the time of diagnosis; therefore, improving diagnostic methods is key to increasing survival rates. Histopathological analysis of UTUC is essential for diagnosis and typically requires endoscopy biopsy, tissue sectioning, and labeling. However, endoscopy biopsies are minute, and it is challenging to cut into thin sections for conventional histopathology; this complicates diagnosis. Here, we used volumetric 3-dimensional (3D) imaging to explore the inner landscape of clinical UTUC biopsies, without sectioning, revealing that 3D analysis of phosphorylated ribosomal protein S6 (pS6) could predict tumor grade and prognosis with improved accuracy. By visualizing the tumor vasculature, we discovered that pS6+ cells were localized near blood vessels at significantly higher levels in high-grade tumors than in low-grade tumors. Furthermore, the clustering of pS6+ cells was associated with shorter relapse-free survival. Our results demonstrate that 3D volume imaging of the structural niches of pS6 cells deep inside the UTUC samples improved diagnostic yield, grading, and prognosis prediction.

18F]-florbetaben PET/CT is sensitive for cardiac AL amyloidosis.

Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.

Helicobacter Pylori: Beyond The Gut - Insights Into Its Association With Dermatological Conditions

Introduction: Helicobacter pylori (H. pylori) is a Gram-negative bacterium associated with gastrointestinal diseases and extra-gastrointestinal manifestations, including dermatological conditions. Understanding the precise mechanisms and clinical implications of the H. pylori skin disorder association is essential. Materials and methods: A cross-sectional observational study was conducted at a private dermatology center in Ahmedabad, Gujarat, from January 2021 to August 2023. Patients coming with various dermatological conditions and with suspected H. pylori infection underwent clinical examination, laboratory tests, and skin biopsy to confirm the diagnosis of disease. The statistical analysis assessed associations between demographics, dermatological conditions, and H. pylori antibody test results. Laboratory Investigation: H. pylori antibody levels were measured using serology by doing H.pylori IgG antibody level testing and cut-off values of &gt;0.90 were considered positive. Statistical Analysis: Data entry and analysis involved Microsoft Excel 360, calculating proportions, and percentages, and drawing appropriate inferences. Results: Of 1131 enrolled patients (male-female ratio 1:1.43), 22% tested positive for H. pylori, with higher positivity rates in patients aged &gt;60 years and 40-60 years. Analysis revealed varying proportions of H. pylori positivity across dermatological conditions, with alopecia areata and chronic urticaria showing the highest rates. Conclusions: While studies suggest H. pylori’s involvement in dermatological diseases, further research is needed to understand this relationship fully. Systematic investigations into the impact of eradication therapy are essential to inform clinical management strategies and guide future research directions.