Comparison of traditional and suctioning ureteral access sheath during retrograde intrarenal surgery in the treatment of renal calculi.

PURPOSE: This study aims to compare the efficiency and clinical outcomes between the suctioning ureteral access sheath (UAS) group and the traditional UAS group during retrograde intrarenal surgery (RIRS) for kidney stones and explore the impact of suctioning UAS on postoperative infectious complications. METHODS: We retrospectively reviewed the clinical data of 162 patients with kidney stones who underwent RIRS with a traditional UAS (n = 74) or a suctioning UAS (n = 71) between March 2021 and May 2023. RESULTS: The mean operative time in suctioning UAS group (39.03 ± 18.01 s) was significantly shorter than that (49.73 ± 20.77 s) in the traditional UAS group (P = 0.037). The mean postoperative hospital stay was significantly shorter in the suctioning UAS group (1.57 ± 0.82d) compared with the traditional UAS group (2.30 ± 1.6 2 d) (P = 0.032). The instant SFRs were significantly higher in the suctioning UAS group (88.73%) than in the traditional UAS group (75.68%) (P = 0.040). The overall SFR in suctioning UAS group (92.96%) was slightly higher than the traditional UAS group (85.14%). The incidence of overall complications was significantly higher in the traditional UAS group (35.14%) than in the suctioning UAS group (16.90%) (P = 0.013). In multivariate analysis, female patients (OR 0.053, P = 0.018), positive urine WBC (OR 10.382, P = 0.034), operative time > 60 min (OR 20.231, P = 0.032), and the application of traditional UAS (OR 0.042, P = 0.017) were independent risk factors associated with infectious complications. CONCLUSION: We demonstrated that suctioning UAS provided a higher instant SFR and fewer postoperative infectious complications during RIRS, and patients with predictable risk factors for infectious complications could potentially benefit from the use of the suctioning UAS.

GhbZIP30-GhCCCH17 module accelerates corm dormancy release by reducing endogenous ABA under cold storage in Gladiolus.

Gladiolus hybridus is one of the most popular flowers worldwide. However, its corm dormancy characteristic largely limits its off-season production. Long-term cold treatment (LT), which increases sugar content and reduces abscisic acid (ABA), is an efficient approach to accelerate corm dormancy release (CDR). Here, we identified a GhbZIP30-GhCCCH17 module that mediates the antagonism between sugars and ABA during CDR. We showed that sugars promoted CDR by reducing ABA levels in Gladiolus. Our data demonstrated that GhbZIP30 transcription factor directly binds the GhCCCH17 zinc finger promoter and activates its transcription, confirmed by yeast one-hybrid, dual-luciferase (Dual-LUC), chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and electrophoretic mobility shift assay (EMSA). GhCCCH17 is a transcriptional activator, and its nuclear localisation is altered by surcose and cytokinin treatments. Both GhbZIP30 and GhCCCH17 positively respond to LT, sugars, and cytokinin treatments. Silencing GhbZIP30 or GhCCCH17 resulted in delayed CDR by regulating ABA metabolic genes, while their overexpression promoted CDR. Taken together, we propose that the GhbZIP30-GhCCCH17 module is involved in cold- and glucose-induced CDR by regulating ABA metabolic genes.

Knowledge-infused Global-Local Data Fusion for Spatial Predictive Modeling in Precision Medicine.

The automated capability of generating spatial prediction for a variable of interest is desirable in various science and engineering domains. Take Precision Medicine of cancer as an example, in which the goal is to match patients with treatments based on molecular markers identified in each patient's tumor. A substantial challenge, however, is that the molecular markers can vary significantly at different spatial locations of a tumor. If this spatial distribution could be predicted, the precision of cancer treatment could be greatly improved by adapting treatment to the spatial molecular heterogeneity. This is a challenging task because no technology is available to measure the molecular markers at each spatial location within a tumor. Biopsy samples provide direct measurement, but they are scarce/local. Imaging, such as MRI, is global, but it only provides proxy/indirect measurement. Also available are mechanistic models or domain knowledge, which are often approximate or incomplete. This paper proposes a novel machine learning framework to fuse the three sources of data/information to generate spatial prediction, namely the knowledge-infused global-local data fusion (KGL) model. A novel mathematical formulation is proposed and solved with theoretical study. We present a real-data application of predicting the spatial distribution of Tumor Cell Density (TCD)-an important molecular marker for brain cancer. A total of 82 biopsy samples were acquired from 18 patients with glioblastoma, together with 6 MRI contrast images from each patient and biological knowledge encoded by a PDE simulator-based mechanistic model called Proliferation-Invasion (PI). KGL achieved the highest prediction accuracy and minimum prediction uncertainty compared with a variety of competing methods. The result has important implications for providing individualized, spatially-optimized treatment for each patient.

A nanocomposite consisting of ZnO decorated graphene oxide nanoribbons for resistive sensing of NO2 gas at room temperature.

A composite prepared from zinc oxide and graphene oxide nanoribbons (ZnO/GONR) is demonstrated to enable improved room temperature (RT) detection of nitrogen dioxide (NO2). Low-cost hydrothermal synthesis is used to construct the composite. The properties of the resistive sensor, including the sensitivity, response and recovery times, repeatability and selectivity, were investigated in the NO2 concentration range from 1 to 50 ppm at RT. The sensor, typically operated at a voltage of 5 V, exhibits a low detection limit of 1 ppm, a fast response-recovery time, and excellent repeatability which outperforms that of pure ZnO sensors. The sensing mechanism is explained in terms of a redox reaction between NO2 and oxygen anions on the surface of the ZnO/GONR composite. Graphical abstract Schematic representation of the NO2 sensing mechanisms on the surface of the ZnO/GONR composite and overall improved NO2 gas-sensing performance.

Electrodeposition of Pd-Pt Nanocomposites on Porous GaN for Electrochemical Nitrite Sensing.

In recent years, nitrite pollution has become a subject of great concern for human lives, involving a number of fields, such as environment, food industry and biological process. However, the effective detection of nitrite is an instant demand as well as an unprecedented challenge. Here, a novel nitrite sensor was fabricated by electrochemical deposition of palladium and platinum (Pd-Pt) nanocomposites on porous gallium nitride (PGaN). The obtained Pd-Pt/PGaN sensor provides abundant electrocatalytic sites, endowing it with excellent performances for nitrite detection. The sensor also shows a low detection limit of 0.95 µM, superior linear ampere response and high sensitivity (150 µA/mM for 1 to 300 µM and 73 µA/mM for 300 to 3000 µM) for nitrite. In addition, the Pd-Pt/PGaN sensor was applied and evaluated in the determination of nitrite from the real environmental samples. The experimental results demonstrate that the sensor has good reproducibility and long-term stability. It provides a practical way for rapidly and effectively monitoring nitrite content in the practical application.

Ki67 and TP53 expressions predict recurrence of non-muscle-invasive bladder cancer.

Tumor markers Ki67, TP53, and TP63 are common labels in the diagnosis of bladder cancer (BCa) around the world. The combination of those biomarkers may have advantages in predicting BCa prognosis and non-muscle-invasive bladder cancer (NMIBC) postoperative recurrence. We investigated the immunohistochemical profiles of 313 bladder cancer samples classified under the WHO/ISUP (2004) grading scale and the UICC-TNM (2002) classification. Then we investigated their predictive value in the tumor recurrence of 270 NMIBC patients after TURBT. Expression of Ki67 correlates with grade, stage, tumor size, and tumor numbers. Semiquantitative evaluation of TP53 correlates with grade and invasive conditions. The positive expression rate of TP63 correlated with tumor grade and stage. The combined effect of TP53 and Ki67 revealed a predictive value in NMIBC recurrence. However, the positive TP63 expression did not show any protective effect in NMIBC recurrence. The expression of TP53 and Ki67 could be used to predict the risk of NMIBC recurrence postoperatively.

Functional analysis reveals calcium-sensing receptor gene regulating cell-cell junction in renal tubular epithelial cells.

PURPOSE: Calcium-sensing receptor (CASR) influences the expression pattern of multiple genes in renal tubular epithelial cells. The objective of this inquiry was to explore the molecular mechanisms of CASR in renal tubular epithelial cells and nephrolithiasis. METHODS: HK-2 cells were transfected with lentiviruses carrying either CASR (named CASR) or an empty vector negative control (named NC), as well as shRNA intended to target CASR (named shCASR) or its corresponding negative control (named shNC). CCK-8 assay was used to detect the effect of CASR on the proliferation of HK-2 cells. RNA-Sequencing was applied to explore potential pathways regulated by CASR in HK-2 cells. RESULTS: PCR and western blot results showed that CASR expression was significantly increased in CASR cells and was decreased in shCASR cells when compared to their corresponding negative control, respectively. CCK-8 assay revealed that CASR inhibited the proliferation of HK-2 cells. RNA-Sequencing results suggested that the shCASR HK-2 cells exhibited a significant up-regulation of 345 genes and a down-regulation of 366 genes. These differentially expressed genes (DEGs) were related to cell apoptosis and cell development. In CASR HK-2 cells, 1103 DEGs primarily functioned in mitochondrial energy metabolism, and amino acid metabolism. With the Venn diagram, 4 DEGs (Clorf116, ENPP3, IL20RB, and CLDN2) were selected as the hub genes regulated by CASR. Enrichment analysis revealed that these hub genes were involved in cell-cell junction, and epithelial cell development. CONCLUSIONS: In summary, our investigation has the potential to offer novel perspectives on CASR regulating cell-cell junction in HK-2 cells.

Quantifying intra-tumoral genetic heterogeneity of glioblastoma toward precision medicine using MRI and a data-inclusive machine learning algorithm.

BACKGROUND AND OBJECTIVE: Glioblastoma (GBM) is one of the most aggressive and lethal human cancers. Intra-tumoral genetic heterogeneity poses a significant challenge for treatment. Biopsy is invasive, which motivates the development of non-invasive, MRI-based machine learning (ML) models to quantify intra-tumoral genetic heterogeneity for each patient. This capability holds great promise for enabling better therapeutic selection to improve patient outcome. METHODS: We proposed a novel Weakly Supervised Ordinal Support Vector Machine (WSO-SVM) to predict regional genetic alteration status within each GBM tumor using MRI. WSO-SVM was applied to a unique dataset of 318 image-localized biopsies with spatially matched multiparametric MRI from 74 GBM patients. The model was trained to predict the regional genetic alteration of three GBM driver genes (EGFR, PDGFRA and PTEN) based on features extracted from the corresponding region of five MRI contrast images. For comparison, a variety of existing ML algorithms were also applied. Classification accuracy of each gene were compared between the different algorithms. The SHapley Additive exPlanations (SHAP) method was further applied to compute contribution scores of different contrast images. Finally, the trained WSO-SVM was used to generate prediction maps within the tumoral area of each patient to help visualize the intra-tumoral genetic heterogeneity. RESULTS: WSO-SVM achieved 0.80 accuracy, 0.79 sensitivity, and 0.81 specificity for classifying EGFR; 0.71 accuracy, 0.70 sensitivity, and 0.72 specificity for classifying PDGFRA; 0.80 accuracy, 0.78 sensitivity, and 0.83 specificity for classifying PTEN; these results significantly outperformed the existing ML algorithms. Using SHAP, we found that the relative contributions of the five contrast images differ between genes, which are consistent with findings in the literature. The prediction maps revealed extensive intra-tumoral region-to-region heterogeneity within each individual tumor in terms of the alteration status of the three genes. CONCLUSIONS: This study demonstrated the feasibility of using MRI and WSO-SVM to enable non-invasive prediction of intra-tumoral regional genetic alteration for each GBM patient, which can inform future adaptive therapies for individualized oncology.

Positive KI67 and periodic acid-schiff mandates wider range of excision in scrotal extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) of the scrotum is a rare disease that requires surgical excision. A positive margin is related to recurrence and poorer prognosis. We aimed to investigate the expression of Ki67 and periodic acid-Schiff (PAS) in a biopsy sample and to evaluate their predictive value in true margin status. METHODS: Sixty-four patients with noninvasive scrotal EMPD were included. Immunohistochemical staining of Ki67 and PAS was reviewed and compared statistically with the margin status of intraoperative frozen section examination (FSE). RESULTS: Seventeen of 64 patients had a positive margin discovered at the first FSE. Expression of Ki67 was not significantly different between positive and negative margin status (p = .16). Expression of PAS was higher in samples with positive margins (p = .05). The incidence of positive margins was significantly higher in the double-positive group than in the double-negative group (p = .03). CONCLUSION: Positive expression of both factors in a biopsy sample requires wider excision to ensure negative margins.

Mesenchymal stem cells in prostate cancer have higher expressions of SDF-1, CXCR4 and VEGF.

Our previous study found that the activity of PCa-MSCs, which could stimulate the cell proliferation of RM-1, was significantly different compared to BMMSCs. Our results indicated that it could be mediated in part by growth factors/chemokines, which were involved in the different activity between two kinds of MSCs (PCa-MSCs and BMMSCs). Normal MSCs (BMMSCs) were isolated from the femur, tibia of the normal mice; prostate tumor MSCs (PCa-MSCs) were obtained from the mice implanted with prostate tumor. Analysis of the expression of SDF-1, CXCR4, VEGF、bFGF and vWF of two kinds of MSCs were examined by ELISA, Realtime-PCR and Western blotting. The expressions of SDF-1 and CXCR4 in PCa-MSCs were higher compared to BMMSCs. Expressions of bFGF and vWF were higher in PCa-MSCs yet the difference did not reach statistical significance. The expression of VEGF was significantly higher in PCa-MSCs. Our data showed that activity of PCa-MSCs was significantly improved compared with BMMSCs, which seemed to have an intrinsic, cell-specific capacity localized to PCa. It could be induced by some factors or chemokines such as SDF-1, CXCR4, and VEGF. The possible role of PCa-MSCs in the process of PCa development needed further clarification.

Relationship of TP53 and Ki67 expression in bladder cancer under WHO 2004 classification.

PURPOSE: Tumor markers TP53 and Ki67 are currently common labels used in the diagnosis of bladder cancer throughout the world. In light of the co-existence of both WHO1973 and 2004 classifications for bladder cancer, it is necessary to establish different quantification standards for both labels to better cater for the grading and staging. METHODS: We investigated the immunohistochemical profiles of 280 bladder cancer samples classified under WHO 2004 standards. TP53 was scored semi-quantitatively whilst Ki67 was scored by label index. RESULTS: We found that expression of TP53 was not correlated to either grade or stage, a finding that doesn't agree with most of the literature. Expression of Ki67 was correlated with grade and stage. Expressions of TP53 and Ki67 were correlated with each other. Interestingly, Ki67 expression was higher in females. CONCLUSION: The expression of TP53 could be modified to better suit the WHO 2004 classification.

Butyric acid inhibits oxidative stress and inflammation injury in calcium oxalate nephrolithiasis by targeting CYP2C9.

This study investigates the mechanism by which butyric acid can protect against calcium oxalate (CaOx) nephrolithiasis. To do so, a rat model was used with 0.75% ethylene glycol administration to induce CaOx crystal formation. Histological and von Kossa staining revealed calcium deposits and renal injury, while dihydroethidium fluorescence staining was used to detect reactive oxygen species (ROS) levels. Flow cytometry and TUNEL assays were used to assess apoptosis, respectively. Treatment with sodium butyrate (NaB) was found to partially reverse the oxidative stress, inflammation, and apoptosis associated with CaOx crystallization in the kidney. In addition, in HK-2 cells, NaB reversed the decreased cell viability, increased ROS levels and apoptosis damage caused by oxalate exposure. Network pharmacology was employed to predict the target genes of butyric acid, CYP2C9. Subsequently, NaB was found to significantly reduce CYP2C9 levels in vivo and in vitro, and inhibition of CYP2C9 by Sulfaphenazole (a specific CYP2C9 inhibitor), was able to reduce ROS levels, inflammation injury, and apoptosis in oxalate-induced HK-2 cells. Collectively, these findings suggest that butyric acid may inhibit oxidative stress and reduce inflammation injury in CaOx nephrolithiasis by suppressing CYP2C9.

The optical puncture combined standard percutaneous nephrolithotomy versus the conventional percutaneous nephrolithotomy for kidney stones without hydronephrosis: a comparative study.

PURPOSE: To compare the efficacy and safety of optical puncture combined with standard percutaneous nephrolithotomy (PNL) and conventional PNL for the treatment of patients with complex kidney stones with no or mild hydronephrosis. METHODS: We retrospectively reviewed the data on patients with complex kidney stones treated by PNL in our hospital between May 2019 and February 2022. The patients were divided into two groups according to the puncture techniques applied. In the optical puncture group, 40 patients underwent optical puncture combined with standard PNL. In the control group, 44 patients underwent conventional standard PNL. The demographics and perioperative parameters were analyzed between the two groups. RESULTS: There mean puncture durations were significantly shorter in the optical puncture group (8.2 ± 2.16 min) than in the control group (14.0 ± 6.76 min) (P = 0.001). The re-puncture rates were lower in the optical puncture group (5%) compared with the control group (20.5%) (P = 0.036). The access loss rate in the optical puncture group (2.5%) was significantly lower than that in the control group (11.36%) (P = 0.037). The mean hemoglobin drop was significantly lower in the optical puncture group (12.6 ± 5.36 g/L) compared with the control group (22.3 ± 11.61 g/L) (P = 0.001). The mean hospital stay was significantly shorter in the optical puncture group (3.9 ± 1.65d) compared with the control group (5.1 ± 2.10d) (P = 0.042). The primary stone-free rate in the optical puncture group (87.5%) was similar to the control group (84.1%) (P = 0.656). The overall stone-free rates were 95% in the optical puncture group and 93.2% in the control group (P = 0.725). There were significantly more patients in the control group (18.2%) who suffered collecting system injury than in the optical puncture group (2.5%) (P = 0.020). There were no significant differences between the two groups in terms of blood transfusion (P = 0.292), fever (P = 0.696) and urosepsis (P = 0.946). CONCLUSION: We demonstrated that optical puncture combined with standard PNL could increase the precision and success rate of puncture, and reduce the access-related complications in patients with complex kidney stones without hydronephrosis.

G9a and DNMT1 inhibition modulates CDKN1A promoter methylation and the cell cycle leading to improvement in kidney fibrosis.

BACKGROUND: Epigenetic mechanisms, including histone and DNA methylation, play a key role in kidney fibrosis, but the precise mechanism remains unclear. Concerted action between histone and DNA-methyltransferases like G9a and DNMT1 is a common theme in gene expression regulation. We investigated the role of G9a and DNMT1 in kidney fibrosis pathogenesis and aimed to elucidate key G9a and DNMT1 targets contributing to kidney fibrosis maintenance. METHODS: G9a and DNMT1 were detected in human fibrotic kidneys, UUO mouse kidneys, and TGFß1-induced HK-2 cells. G9a and DNMT1 expression was knocked down by siRNA or inhibited with CM272 in HK-2 and UUO mouse, and transcriptomic responses to CM272 were examined. Antifibrogenic activity and safety of CM272 were studied in UUO mouse. Cell cycle were analyzed with flow cytometry. Gene expression regulation was analyzed by chromatin immunoprecipitation and methylation-specific PCR. RESULTS: G9a and DNMT1 were overexpressed in human fibrotic kidneys, UUO mouse kidneys, and TGFß1-induced HK-2 cells. G9a/DNMT1 inhibition potently alleviated fibrosis in vitro and vivo. G9a/DNMT1 inhibition reduced the expression of E2F targets and altered the methylation status of CDKN1A leading to the attenuated cell-cycle arrest. TGFß1-induced overexpression of G9a or DNMT1 resulted in the enrichment of H3K9me2 and 5-methylcytosine at CDKN1A promoter. CONCLUSIONS: Our data link G9a and DNMT1 to CDKN1A regulatory function and kidney fibrosis. Combined targeting G9a and DNMT1 could be a promising strategy for the treatment of kidney fibrosis.

Pan-cancer analysis reveals the prognostic gene CASR suppresses tumor progression and epithelial-mesenchymal transition in renal clear cell carcinoma.

Calcium-sensing receptor (CASR), primarily found in the parathyroid gland and other tissues, plays a crucial role in sensing and regulating extracellular calcium, which was also aberrantly expressed in human tumors. Nevertheless, a comprehensive analysis of CASR in pan-cancer has yet to be conducted. To gain a better understanding of CASR in pan-cancer, data profiles on CASR cancers were collected from TCGA database. The expression level, clinical significance, prognostic value, and potential mechanisms of CASR in pan-cancer were analyzed via multiple public databases. The functional assays were conducted using human kidney renal clear cell carcinoma (KIRC) cell lines, clinical samples, and nude mice. Our research revealed that the abnormal expression of CASR was found in a variety of tumors. The expression and mutation of CASR were significantly associated with tumor prognosis and stage. Pathway analyses suggested that CASR was involved in the epithelial-mesenchymal transition (EMT) progress. Besides, CASR expression was correlated with immune inhibitory genes and immunotherapy in cancers. Particularly in KIRC, we established that CASR mRNA and protein levels were downregulated in clinical samples and cell lines. Moreover, a Cox regression analysis revealed that CASR was an independent prognostic factor in both TCGA-KIRC samples and clinical samples from our center. In vitro and in vivo experiments revealed that blocking CASR with lentivirus could suppress tumor growth and invasion, and EMT progress in KIRC cells. In summary, our study provides a comprehensive bioinformatic analysis of CASR in pan-cancer, offering deeper insights into its function and the EMT mechanism in KIRC, warranting further investigation.

Untargeted and targeted metabolomics reveal bile acid profile changes in rats with ethylene glycol-induced calcium oxalate nephrolithiasis.

Calcium oxalate (CaOx) nephrolithiasis is a prevalent disorder linked to metabolism. Examining metabolic alterations could potentially give an initial understanding of the origins of CaOx nephrolithiasis. This study aims to determine gut metabolic biomarkers differentiating CaOx nephrolithiasis utilizing untargeted and targeted metabolomics. CaOx nephrolithiasis model rats were built by 1% ethylene glycol administration. Histologic staining and renal function measurement revealed the presence of crystals in the lumen of the renal tubules, the renal injury and interstitial fibrosis in CaOx rats, demonstrating that the models of CaOx were established successfully. Hematoxylin & eosin (H&E) staining showed that CaOx group had inflammation and damage in the ileal tissue. Immunofluorescence and PCR results displayed that the tight junction proteins, ZO-1 and Occludin levels were decreased in the ileal tissues of the CaOx group. The untargeted metabolomic analysis revealed that 269 gut metabolites were differentially expressed between the CaOx group and the control group. Meanwhile, bile secretion, the main metabolic pathway in CaOx nephrolithiasis, was identified. Following, five significant bile acid metabolites were selected utilizing the targeted bile acid metabolomics, including Hyodeoxycholic acid (HDCA), Glycohyodeoxycholic acid (GHDCA), Nor-Deoxycholic Acid, omega-muricholic acid, and Taurolithocholic acid. Among these metabolites, HDCA and GHDCA presented the highest predictive accuracy with AUC = 1 to distinguish the CaOx group from the control group. As a result of network pharmacology, target genes of HDCA and GHDCA in CaOx nephrolithiasis were enriched in oxidative stress and apoptosis pathways. Conclusively, our study provides insight into bile acids metabolic changes related to CaOx nephrolithiasis. Although alterations in biochemical pathways indicate a complex pathology in CaOx rats, bile acid changes may serve as biomarkers of CaOx nephrolithiasis.

Revealing the biology behind MRI signatures in high grade glioma.

Magnetic resonance imaging (MRI) measurements are routinely collected during the treatment of high-grade gliomas (HGGs) to characterize tumor boundaries and guide surgical tumor resection. Using spatially matched MRI and transcriptomics we discovered HGG tumor biology captured by MRI measurements. We strategically overlaid the spatially matched omics characterizations onto a pre-existing transcriptional map of glioblastoma multiforme (GBM) to enhance the robustness of our analyses. We discovered that T1+C measurements, designed to capture vasculature and blood brain barrier (BBB) breakdown and subsequent contrast extravasation, also indirectly reveal immune cell infiltration. The disruption of the vasculature and BBB within the tumor creates a permissive infiltrative environment that enables the transmigration of anti-inflammatory macrophages into tumors. These relationships were validated through histology and enrichment of genes associated with immune cell transmigration and proliferation. Additionally, T2-weighted (T2W) and mean diffusivity (MD) measurements were associated with angiogenesis and validated using histology and enrichment of genes involved in neovascularization. Furthermore, we establish an unbiased approach for identifying additional linkages between MRI measurements and tumor biology in future studies, particularly with the integration of novel MRI techniques. Lastly, we illustrated how noninvasive MRI can be used to map HGG biology spatially across a tumor, and this provides a platform to develop diagnostics, prognostics, or treatment efficacy biomarkers to improve patient outcomes.

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Comprehensive Landscape of RRM2 with Immune Infiltration in Pan-Cancer.

As a crucial subunit of ribonucleotide reductase, RRM2 plays a significant part in DNA synthesis. This study aimed to elucidate the comprehensive landscape of RRM2 in human cancers. With different bioinformatics platforms, we investigated the expression pattern, prognostic significance, mutational landscapes, gene interaction network, signaling pathways and immune infiltration of RRM2 in tumors. We found that RRM2 expression was predominantly up-expressed in tumor tissues in most tumors. Concurrently, RRM2 expression was significantly associated with worse prognosis and tumor stage across TCGA cancers. Moreover, RRM2 high levels were critically associated with the infiltration of natural killer T cells and immune scores. RRM2 was positively related to immune checkpoints, tumor mutation burden, microsatellite instability, neoantigen, and cytotoxic T lymphocyte in several cancers, predicting effective response to immunotherapy. Meanwhile, a strong co-expression of RRM2 with immune-related genes was observed. Additionally, multiple Cox regression analysis showed that RRM2 was an independent prognostic factor in bladder cancer (BLCA). Eventually, we verified that RRM2 was overexpressed in BLCA clinical samples and cell lines. Blocking RRM2 could suppress BLCA cells' growth and proliferation while enhancing sensitivity to cisplatin. This study provided a new perspective for understanding RRM2 in cancers and new strategies for tumor immunotherapy.

Elevated CEA and CA 19-9 Levels within the Normal Ranges Increase the Likelihood of CRC Recurrence in the Chinese Han Population.

Objective: This study aimed to determine if variations in the expression profiles of CA 19-9 and carcinoembryonic antigen (CEA) within the reference range could serve as possible biomarkers for postoperative CRC recurrence. Method: This retrospective cohort investigation enrolled 2,596 cases of CRC that received curative surgery. Serum CEA/CA 19-9 were measured through chemiluminescence immunoassay (CLIA). Results: During follow-up (median follow-up = 5.2 years), in total, 837 patients experienced recurrence. The fully adjusted hazard ratios (HRs) were significantly higher, ≥1 standard deviation (±SD), in patients with upregulated CEA/CA 19-9 levels (HRCEA = 7.06; HRCA 19 - 9 = 3.98) than in those with downregulated CEA/CA 19-9 levels. The likelihood of recurrence remained consistently greater in cases of elevated CEA/CA 19-9 levels during sensitivity analyses. Conclusions: The findings of this analysis showed that variations in CEA/CA 19-9 expression profiles within the reference range impact CRC recurrence.