Poor Prognosis Research Articles

Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy

Hypoxic ischemic encephalopathy (HIE) refers to neonatal hypoxic brain injury caused by severe asphyxia during the perinatal period. With a high incidence rate and poor prognosis, HIE accounts for 2.4% of the global disease burden, imposing a heavy burden on families and society. Current clinical treatment for HIE primarily focuses on symptomatic management and supportive care. Therefore, the developments of effective treatment strategies and new drug formulations are critical for improving the prognosis of HIE patients. In order to protect the compromised neurovascular units after HIE, we prepared membrane-fused nanovesicles for delivering rapamycin and si EDN1 (TRCAM@RAPA@si EDN1). Due to the homotypic targeting feature of membrane-fused nanovesicles, we employed astrocyte membranes as synthetic materials to improve the targeting of astrocytes in brain while reducing the clearance of nanovesicles by circulatory system. Additionally, the surface of cell membrane was modified with CXCR3 receptors, enhancing the homing of nanovesicles to infarcted lesions. Lipid vesicles were modified with TK and RVG29 transmembrane peptides, enabling responsive release of internal drugs and blood-brain barrier penetration. Internally loaded rapamycin could promote protective autophagy in astrocytes, improve cellular oxidative stress, while si EDN1 could reduce the expression level of endothelin gene, thereby reducing secondary damage to neurovascular units.Graphical

Construction of a prognostic model based on disulfidptosis-related genes and identification of CCNA2 as a novel biomarker for hepatocellular carcinoma

BackgroundDisulfidptosis, identified as an innovative form of cellular death subsequent to cuproptosis, is currently under investigation for its mechanisms in oncological contexts. In-depth analyses exploring the relationship between disulfidptosis-related genes (DRGs) and hepatocellular carcinoma (HCC) are currently limited.MethodsTranscriptomic data and clinical information were retrieved from the TCGA and GEO databases (GSE76427 and GSE54236), concentrating on the expression levels of 24 DRGs. Subsequently, multifactor and LASSO regression analyses were utilized to construct the 5-DRG prognostic signature. Immunohistochemistry (IHC) was employed to assess Cyclin A2 (CCNA2) protein expression levels. Quantitative real-time PCR (qRT-PCR) and western blot analyses were conducted to detect transcriptomic and protein expression of CCNA2-targeting short interfering RNA (siRNA). The Cell Counting Kit-8 (CCK-8) assay, EdU staining, and scratch experiments were employed to observe the proliferation and migration of hepatoma cell lines subsequent to CCNA2 inhibition.ResultsThree HCC patterns were identified, among which pattern B exhibited the the most unfavorable survival outcomes. Five DRGs (STC2, PBK, CCNA2, SERPINE1, and SLC6A1) were involved to establish the 5-DRG prognostic signature. High-risk groups (HRGs) exhibited prolonged survival durations in comparison to low-risk groups (LRGs). Both bioinformatics analyses and experimental methodologies corroborated the association of CCNA2 with poor prognosis in HCC patients. Functional studies elucidated that interference with CCNA2 significantly inhibited proliferation and migration, while simultaneously promoting apoptosis in hepatoma cells and resulting in the downregulation of epithelial-mesenchymal transition (EMT)-related protein markers.ConclusionsThe 5-DRG prognostic signature is proficient in predicting clinical outcomes, informing therapeutic strategies, and elucidating the characteristics of the immune microenvironment in HCC patients. Furthermore, this study elucidates the potential of CCNA2 as an innovative biomarker for HCC.

CMTM6 promotes hepatocellular carcinoma invasion and metastasis and tumor-associated neutrophil immunoinfiltration through the Wnt/β-catenin pathway

BackgroundCMTM6 has been closely associated with the onset and progression of various tumor types. However, the precise mechanism by which CMTM6 operates in hepatocellular carcinoma remains elusive, necessitating further investigation.MethodsExpression levels of CMTM6 in hepatocellular carcinoma tissues and cells were analyzed using immunohistochemistry and quantitative real-time PCR. The correlation between CMTM6 expression in hepatocellular carcinoma tissues and clinical pathological characteristics, as well as patient prognosis, was investigated. Proliferation and apoptosis of hepatocellular carcinoma cells with silenced or overexpressed CMTM6 were assessed, alongside measurements of β-catenin and Wnt1 protein expression levels. In vivo research was conducted utilizing a murine subcutaneous transplantation model. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to elucidate the regulatory mechanism of CMTM6. Additionally, CD66b expression levels in tumor tissue were examined using immunohistochemistry, and the immune infiltration of CMTM6 and tumor-associated neutrophils (TANs) was analyzed.ResultsElevated expression levels of CMTM6 in hepatocellular carcinoma tissues and cells were found to be associated with poor patient prognosis. Overexpression of CMTM6 in hepatocellular carcinoma cells was demonstrated to promote cellular proliferation and inhibit apoptosis. Mechanistically, CMTM6 expression levels in hepatocellular carcinoma tissues were observed to positively correlate with β-catenin expression. GSEA and KEGG analysis revealed significant enrichment of CMTM6 in the Wnt/β-catenin pathway, indicating its involvement in pathway regulation. Furthermore, CMTM6 was found to be associated with immune infiltration of TANs in hepatocellular carcinoma tissues.ConclusionCMTM6 plays a pivotal role in the development and progression of hepatocellular carcinoma through regulation of the Wnt/β-catenin pathway via β-catenin. Moreover, CMTM6 demonstrates the capacity to promote immune infiltration of TANs in hepatocellular carcinoma tissues. Consequently, CMTM6 exhibits potential as both an early diagnostic marker and a novel therapeutic target for patients with hepatocellular carcinoma.

Risk factors of disease severity and mechanical ventilation requirement in childhood Guillain-Barré Syndrome

Background. This study aimed to investigate the risk factors associated with the severity of the disease, the need for mechanical ventilation (MV) and poor prognosis in the early stages of Guillain-Barré Syndrome (GBS). Methods. Data of children who met GBS diagnostic criteria were evaluated retrospectively. The sample was divided into three binary subgroups according to severe GBS (Hughes Functional Grading Scale [HFGS] ≥ 4 at admission), mechanical ventilation (MV) requirement, and poor prognosis (inability to walk independently, HFGS ≥ 3 after six months). Various clinical, laboratory and electrophysiological parameters were compared between these subgroups. Results. The mean age of 63 children with GBS was 91.55±49.09 months. 13 (20.6%) patients required MV and 4 (6.3%) patients died. Associated risk factors for the need for MV in severe GBS were found to be autonomic dysfunction, bulbar palsy, sensory impairment, lowest total Medical Research Council (MRC) scale for muscle strength score at admission, high modified Erasmus GBS respiratory failure score (mEGRIS), high neutrophil-lymphocyte ratios (NLR) and high systemic immune-inflammation index (SII) values (p<0.001, p=0.003, p=0.033, p<0.001, p<0.001, p=0.037 and p=0.042, respectively). The lowest total MRC scale for muscle strength score at admission was a significant indicator of poor prognosis (p<0.001). Conclusions. Autonomic dysfunction, bulbar palsy, sensory impairment, lowest total MRC scale for muscle strength score at admission, high mEGRIS score, high NLR and SII values are potential risk factors for the need for MV in children with severe GBS. The lowest total MRC scale for muscle strength score at admission was associated with poor prognosis.

Genetic overlap between breast cancer and sarcopenia: exploring the prognostic implications of SLC38A1 gene expression

BackgroundSarcopenia, an age-related syndrome characterized by a decline in muscle mass, not only affects patients’ quality of life but may also increase the risk of breast cancer recurrence and reduce survival rates. Therefore, investigating the genetic mechanisms shared between breast cancer and sarcopenia is significant for the prevention, diagnosis, and treatment of breast cancer.MethodsThis study downloaded gene expression datasets and clinical data related to breast cancer and skeletal muscle aging from the GEO database. Data preprocessing, integration, differential gene identification, functional enrichment analysis, and construction of protein-protein interaction networks were performed using R language. Subsequently, COX proportional hazards model analysis and survival analysis were conducted, and survival curves and nomograms were generated. The expression levels of genes in tissues were detected using qRT-PCR, and the Radiant DICOM viewer software was used to delineate the pectoralis major muscle area in CT images.ResultsWe identified 152 differentially expressed genes (P < .05) and 226 sarcopenia-related genes (r > .4) associated with skeletal muscle aging. The TCGA-BRCA dataset revealed 106 genes associated with breast cancer (P < .05, logFC = 1). Functional enrichment analysis indicated significant enrichment in cell proliferation and growth pathways. The PPI network identified critical molecules involved in muscle aging and tumor progression. After dimensionality reduction, a strong correlation was observed between the expression of the muscle aging-related gene set and the prognosis of breast cancer patients (P < .01). The expression of SLC38A1 identified through multivariate COX analysis was significantly associated with poor prognosis in breast cancer patients (P = .03). Incorporating SLC38A1 expression, the prognostic model precisely forecasted breast cancer survival (P < .01). External validation confirmed the higher expression of the SLC38A1 gene in breast cancer tissues compared to adjacent non-cancerous tissues (P < .01). The SLC38A1 index, calculated in combination with the patient’s age and BMI, can optimize the prognostic prediction model, providing a powerful tool for personalized treatment of breast cancer.ConclusionHigh SLC38A1 gene expression was significantly associated with poor prognosis in breast cancer patients. The combination of SLC38A1 expression and the pectoralis major muscle area provided an optimized prognostic prediction model, offering a potential tool for personalized breast cancer treatment.

Active cytomegalovirus infection in mechanically ventilated patients with sepsis

BackgroundActive cytomegalovirus (CMV) infection is associated with poor prognosis in septic patients with critical illness. Patients of septic category are highly likely to benefit from prophylactic antiviral therapy. Nevertheless, the clinical characteristics for CMV reactivation are lacking among septic patients requiring mechanical ventilation. The aim of this study was to investigate the incidence, risk factors, and clinical outcomes regarding active CMV infection in mechanically ventilated patients with sepsis.MethodsA single-center, retrospective cohort study conducted from January 2021 to December 2023 that included septic patients on mechanical ventilation at the intensive care unit (ICU) of a national hospital. Study participants were divided into active and non-active CMV infection groups based on CMV DNAemia within a 28-day hospitalization period in ICU. Clinical features, laboratory findings, treatment measures, and clinical outcomes were compared between the two groups.ResultsAmong 118 septic patients, 21 (17.8%) exhibited active CMV infection within 28-day ICU admission. Hemoglobin served as an independent risk factor and predictor for active CMV infection (P < 0.05). Moreover, the duration of mechanical ventilation and ICU stay in active CMV infection patients were significantly higher than in the comparison group (P < 0.05).ConclusionsActive CMV infection is common and associated with adverse clinical outcomes in mechanically ventilated patients with sepsis. A low level of hemoglobin is an independent risk factor for active CMV infection. Further prospective studies are warranted to assess the efficacy of initiating prophylactic and preemptive antiviral therapies among patients with sepsis disorders.

Radiotherapy & total neoadjuvant therapy for recurrent rectal cancer in previously irradiated patients, (RETRY): a multicenter prospective observational study

BackgroundLocal recurrence of rectal cancer (LRRC) previously treated with radiotherapy is associated with a poor prognosis. Historically, the integration of radiotherapy (RT) with surgery has improved the likelihood of complete resections (R0) and, consequently, enhanced survival. Unfortunately, many LRRC cases are not amenable to surgical intervention. The inclusion of chemotherapy (CHT) alongside advanced RT techniques including proton and carbon ion RT (CIRT) and stereotactic body radiation therapy (SBRT), has generated new treatment options. Therefore, there is a need for improved stratification of LRRC patients to enhance treatment outcomes. The RETRY is an integrated trial with the primary aim to explore if combining CHT with RT in all available modalities can enhance local control (LC) in LRRC patients, consequently improving survival.MethodsExperts from Italian centers specializing in rectal cancer and LRRC management collaborated to design a prospective multicenter observational study within the AIRO group for gastrointestinal malignancies. Eligible participants are adult LRRC patients who previously had pelvic RT, meet specific criteria, and are affiliated with the participating Italian centers. Specific criteria must be met for CIRT referral. A total of 88 patients will be enrolled over three years. The primary objective is to determine the 3-year LC rate. Secondary outcomes include assessing survival, quality of life, and R0 resection rates in surgery cases. A minimum dose of 40 Gy, conventional fractionation with concomitant fluoropyrimidine—with/without oxaliplatin-based CHT (CRT) is prescribed in neoadjuvant setting. Alternatively, the dose will vary from 35 to 40 Gy in 5 fractions based on clinical judgment, by SBRT. Both proton and photon therapies will be evaluated in these approaches. Surgery will be considered if deemed operable. In inoperable cases, CIRT with a dose of 40–60 Gy relative biological effectiveness (RBE) will be administered with a daily dose fraction ranging between 3 and 4.8 Gy RBE.DiscussionThe RETRY trial aims to investigate the combined effects of RT and CHT and when feasible the addition of surgery, to determine whether this comprehensive approach can result in improved survival and quality of life for LRRC patients.Trial registration number ClinicalTrials.gov (No. NCT05984576).

Macrophages promote pre-metastatic niche formation of breast cancer through aryl hydrocarbon receptor activity

Macrophages that acquire an immunosuppressive phenotype play a crucial role in establishing the pre-metastatic niche (PMN), which is essential for facilitating breast cancer metastasis to distant organs. Our study showed that increased activity of the aryl hydrocarbon receptor (AHR) in lung macrophages plays a crucial role in establishing the immunosuppressive PMN in breast cancer. Specifically, AHR activation led to high expression of PD-L1 on macrophages by directly binding to the promoter of Pdl1. This upregulation of PD-L1 promoted the differentiation of regulatory T cells (Tregs) within the PMN, further enhancing immunosuppressive conditions. Mice with Ahr conditional deletion in macrophages had reduced lung metastasis of breast cancer. The elevated AHR levels in PMN macrophages were induced by GM-CSF, which was secreted by breast cancer cells. Mechanistically, the activated STAT5 signaling pathway induced by GM-CSF prevented AHR from being ubiquitinated, thereby sustaining its activity in macrophages. In breast cancer patients, the expression of AHR and PD-L1 was correlated with increased Treg cell infiltration, and higher levels of AHR were associated with a poor prognosis. These findings reveal that the crosstalk of breast cancer cells, lung macrophages, and Treg cells via the GM-CSF-STAT5-AHR-PD-L1 cascade modulates the lung pre-metastatic niche during breast cancer progression.

Dual-specificity phosphatase 23 functions as a promising prognostic biomarker in non-small cell lung cancer.

The mechanical remodeling of tumor microenvironment is critical for non-small cell lung cancer (NSCLC) progression. Dual-specificity phosphatase 23 (DUSP23) has been previously identified as a mechano-responsive gene, but its role in NSCLC progression remains unknown. We aim to elucidate the clinical significance of DUSP23 in NSCLC progression. We analyzed the expression of DUSP23 in cancer using polyacrylamide hydrogels designed to mimic the stiffness of normal (soft; ~0.5kPa) and cancerous (stiff; ~40kPa) tissues. The prognostic significance of DUSP23 expression in patients was examined using public databases. Additionally, we conducted various cell-based assays and transcriptomic analyses in DUSP23-silenced NSCLC cell lines. A risk score prognosis model was constructed using univariate Cox regression and Kaplan-Meier analysis. Our findings show that DUSP23 is upregulated in stiff matrices and is highly associated with poor prognosis in patients with solid cancers such as NSCLC and breast cancer. Silencing of DUSP23 resulted in decreased cell proliferation and invasion. Transcriptomic profiling revealed that 182 genes were downregulated, and 230 genes upregulated following DUSP23-depletion. Notably, 182 downregulated genes were enriched in cancer-related pathways, including cell cycle progression and cytoskeleton organization. Through KEGG pathway analysis, we identified 11 cancer-related genes and developed a prognostic risk model. In this model, the high-risk group of NSCLC patients exhibited significantly shorter overall survival compared to low-risk group, based on public datasets. Our study demonstrates the clinical significance of DUSP23 as a prognostic marker in NSCLC and highlights its potential role of DUSP23 in promoting NSCLC progression.

Epstein-Bar Virus-Positive Lymphoepithelioma-Like Intrahepatic Cholangiocarcinoma: A Case Report and Literature Review.

Intrahepatic cholangiocarcinoma is a primary liver malignancy with poor prognosis and limited treatment options. Lymphoepithelioma-like intrahepatic cholangiocarcinoma is an exceedingly rare variant of intrahepatic cholangiocarcinoma that histologically resembles nasopharyngeal carcinoma, previously known as lymphoepithelioma. It was first reported by Hsu et al in 1996 and they were able to show the presence of Epstein-Barr virus in tumor cells. Even though several risk factors for the development of intrahepatic cholangiocarcinoma have been identified, the association between Epstein-Barr virus and intrahepatic cholangiocarcinoma is relatively rare. This article aims at discussing a female patient's lymphoepithelioma-like intrahepatic cholangiocarcinoma tumor and summarizing the existing literature on Epstein-Barr virus-positiveLymphoepithelioma-like intrahepatic cholangiocarcinoma, including the clinical features, pathogenesis, diagnostic challenges, treatment approaches, prognosis, and histopathologic description.

TFAP2A drives non-small cell lung cancer (NSCLC) progression and resistance to targeted therapy by facilitating the ESR2-mediated MAPK pathway

Cancer is among the leading causes of death related diseases worldwide, and lung cancer has the highest mortality rate in the world. Transcription factors (TFs) constitute a class of structurally and functionally intricate proteins. Aberrant expression or functional deficiencies of transcription factors may give rise to abnormal gene expression, contributing to various diseases, including tumours. In this study, we propose to elucidate the potential role and mechanism of TFAP2A in NSCLC. We found that TFAP2A levels were significantly greater in tumour tissues than para-tumour tissues, and high expression of TFAP2A was associated with poor prognosis in NSCLC patients. Additionally, TFAP2A overexpression promoted NSCLC progression both in vivo and in vitro. Mechanistically, ESR2 is a potential target regulated by TFAP2A and that TFAP2A can bind to the promoter region of ESR2. Furthermore, the overexpression of both TFAP2A and ESR2 in NSCLC cells was associated with the overactivation of MAPK signalling, and the combination of PHTPP and osimertinib had a synergistic effect on suppressing tumour growth.

Fluorescent Polymer Nanocomposites as Novel Drug-Loading and Targeted Delivery Nanocarriers for Glioma Therapy by Modulating ERBB4.

Gliomas are the most common type of tumor in the human central nervous system, characterized by high aggressiveness, elevated mortality, and poor prognosis. Therefore, developing new therapeutic strategies is crucial for improving glioma treatment. Temozolomide (TMZ) is widely used in glioma therapy due to its excellent ability to penetrate the blood-brain barrier. In this study, we synthesized HA-PEG@ICG using hyaluronic acid (HA) and polyethylene glycol (PEG), modified with the fluorescent compound indocyanine green (ICG), and thoroughly characterized the product's structure. Subsequently, compound 1 and TMZ were co-loaded onto this carrier to construct a synergistic drug delivery system (HA-PEG@ICG@1@TMZ). Additionally, we evaluated the inhibitory effects and mechanisms of HA-PEG@ICG@1@TMZ on glioma cell proliferation. Our study lays the foundation for further exploration of TMZ-based therapies for glioma treatment.

Prognostic impact of tumor‑associated stroma in triple-negative breast cancer.

To establish the histological categorization of tumor‑associated stroma (TAS) that reflects the biological behavior of triple-negative breast cancer (TNBC). One-hundred-and-twenty surgically resected cases of TNBC were examined. We histologically categorized the TAS in the invasive frontal region into two groups: mature stroma (MS) and immature stroma (IS). The designation of IS was applied for tumors in which the largest myxoid stroma filled a high-power magnification field. When there were no myxoid stroma that meet the criteria for IS, TAS was categorized as MS. The tumors with type MS were observed in 103 (85.8%) of patients, whereas 17 (14.2%) of patients had tumors with IS. In total, 72 out of 120 patients with TNBC exhibited high tumor-infiltrating lymphocytes (TILs) representing 60% of the cohort. The incidences of high TILs were 66% (68 out of 103) in the MS group but only 23.5% (4 of 17) in the IS group (p = 0.001). Progression-free survival (PFS) and overall survival (OS) curves were different between IS and MS groups (p < 0.001 each), and Cox multivariate regression analysis revealed that IS was an independent indicator for lower PFS and OS rates (p < 0.001; p = 0.008). Our findings suggest that TAS characteristics, particularly the distinction between IS and MS, play a significant role in the prognosis of TNBC. The presence of IS, associated with poor prognosis and low TILs, contrasts with the favorable outcomes observed in cases with MS. Understanding these TAS dynamics could aid in identifying patients with varying prognostic outcomes in TNBC, necessitating further research into the mechanisms behind these observations.

Machine learning-based prognostic model of lactylation-related genes for predicting prognosis and immune infiltration in patients with lung adenocarcinoma

BackgroundHistone lactylation is a novel epigenetic modification that is involved in a variety of critical biological regulations. However, the role of lactylation-related genes in lung adenocarcinoma has yet to be investigated.MethodsRNA-seq data and clinical information of LUAD were downloaded from TCGA and GEO datasets. Unsupervised consistent cluster analysis was performed to identify differentially expressed genes (DEGs) between the two clusters, and risk prediction models were constructed by Cox regression analysis and LASSO analysis. Kaplan–Meier (KM) survival analysis, ROC curves and nomograms were used to validate the accuracy of the models. We also explored the differences in risk scores in terms of immune cell infiltration, immune cell function, TMB, TIDE, and anticancer drug sensitivity. In addition, single-cell clustering and trajectory analysis were performed to further understand the significance of lactylation-related genes. We further analyzed lactate content and glucose uptake in lung adenocarcinoma cells and tissues. Changes in LUAD cell function after knockdown of lactate dehydrogenase (LDHA) by CCK-8, colony formation and transwell assays. Finally, we analyzed the expression of KRT81 in LUAD tissues and cell lines using qRT-PCR, WB, and IHC. Changes in KRT81 function in LUAD cells were detected by CCK-8, colony formation, wound healing, transwell, and flow cytometry. A nude mouse xenograft model and a KrasLSL-G12D in situ lung adenocarcinoma mouse model were used to elucidate the role of KRT81 in LUAD.ResultsAfter identifying 26 lactylation-associated DEGs, we constructed 10 lactylation-associated lung adenocarcinoma prognostic models with prognostic value for LUAD patients. A high score indicates a poor prognosis. There were significant differences between the high-risk and low-risk groups in the phenotypes of immune cell infiltration rate, immune cell function, gene mutation frequency, and anticancer drug sensitivity. TMB and TIDE scores were higher in high-risk score patients than in low-risk score patients. MS4A1 was predominantly expressed in B-cell clusters and was identified to play a key role in B-cell differentiation. We further found that lactate content was abnormally elevated in lung adenocarcinoma cells and cancer tissues, and glucose uptake by lung adenocarcinoma cells was significantly increased. Down-regulation of LDHA inhibits tumor cell proliferation, migration and invasion. Finally, we verified that the model gene KRT81 is highly expressed in LUAD tissues and cell lines. Knockdown of KRT81 inhibited cell proliferation, migration, and invasion, leading to cell cycle arrest in the G0/G1 phase and increased apoptosis. KRT81 may play a tumorigenic role in LUAD through the EMT and PI3K/AKT pathways. In vivo, KRT81 knockdown inhibited tumor growth.ConclusionWe successfully constructed a new prognostic model for lactylation-related genes. Lactate content and glucose uptake are significantly higher in lung adenocarcinoma cells and cancer tissues. In addition, KRT81 was validated at cellular and animal levels as a possible new target for the treatment of LUAD, and this study provides a new perspective for the individualized treatment of LUAD.

Development and validation of a radiomics-based nomogram for predicting pathological grade of upper urinary tract urothelial carcinoma

BackgroundUpper urinary tract urothelial carcinoma (UTUC) is a rare and highly aggressive malignancy characterized by poor prognosis, making the accurate identification of high-grade (HG) UTUC essential for subsequent treatment strategies. This study aims to develop and validate a nomogram model using computed tomography urography (CTU) images to predict HG UTUC.MethodsA retrospective cohort study was conducted to include patients with UTUC who underwent radical nephroureterectomy and received a CTU examination prior to surgery. In the CTU images, tumor lesions located in the renal calyces, renal pelvis and ureter were segmented, and radiomics features from the unenhanced, medullary, and excretory phases were extracted. The maximum relevance minimum redundancy algorithm, least absolute shrinkage and selection operator, and various machine learning (ML) algorithms—including random forest, support vector machine, and eXtreme gradient boosting—were employed to select radiomics features and calculate radiomics scores. Logistic regression (LR) analysis was performed to identify the independent influencing factors of clinical baseline characteristics. Multiple datasets of radiomics features were constructed by integrating single-phase radiomics features with the most significant independent factor. Both LR and ML algorithms were utilized to develop predictive models. The area under the receiver operating characteristic curve (AUC values), accuracy, sensitivity, and specificity were assessed for model performance evaluation. Decision curve analysis was conducted to evaluate the clinical net benefits.ResultsA total of 167 patients were enrolled in this study. Among them, 56 were diagnosed with low-grade UTUC (including papillary urothelial neoplasms with low malignant potential and low-grade urothelial carcinoma) as confirmed by postoperative pathological examination results, and 111 were of HG. These patients were randomly allocated to the training set and the validation set at a ratio of 7:3. The training set comprised 116 patients with a mean age of 63.5 ± 9.38 years and 38 males. The validation set comprised 51 patients with a mean age of 65.6 ± 11.1 years and 18 males. Hydronephrosis was identified as the most significant independent factor in the clinical baseline features. Models that include mixed-phase development achieve better performance compared to models that rely simply on single-phase development. The nomogram model had excellent predictive ability for HG UTUC, with AUC values of 0.844 and an accuracy of 0.793 in the validation sets. The nomogram model can enhance accuracy by 14.1% (79.3% vs. 65.2%) and sensitivity by 32.8% (93.2% vs. 60.4%) compared to urinary cytology.ConclusionsThis study developed a nomogram model, which significantly improved the diagnostic ability for HG UTUC compared to urinary cytology. Furthermore, the results of the decision curve analysis showed that the model had a net benefit and could provide a non-invasive and potentially diagnostic reference tool for HG UTUC.

Endometrial hyperplasia, benign endometrial tumors and endometrial carcinoma: A review study

Background. During the reproductive phase, the endometrium undergoes cyclical structural changes. Endometrial hyperplasia (EH) is a prevalent condition that arises from a combination of estrogen exposure and insufficient progesterone levels. Endometrial cancer (EC) is the second most common gynecologic malignancy, with the likelihood of EH progressing to EC ranging from 1% to 29%. The objective of this study is to conduct a comprehensive assessment of various forms of endometrial hyperplasia, benign endometrial tumors, and endometrial cancer (EC). Methods. A review of published papers from major databases, including PubMed, Scopus, and Google Scholar, was conducted. The search included original research articles and reviews on EH, benign endometrial tumors, and EC. Case reports, series, and clinical images were excluded. Results. Information on the selected topics was summarized, including epidemiology, etiology, histopathological classification, anatomy, biological and molecular characteristics, detection and prevention, clinical manifestations, staging, diagnostic workup, prognostic factors, and management. Conclusion. Endometrial hyperplasia and endometrial cancer are two of the most common problems in women. EH is a major precancerous condition for EC, and EC is associated with a poor prognosis if diagnosed late. The epidemiology and outcomes of both conditions vary according to several factors, including ethnicity, environment, socioeconomic status, heredity, drugs, hormones, and the aging process.

Low Expression of FAM96B is Associated with Poor Prognosis in Hepatocellular Carcinoma.

Recently, studies on FAM96B functions mainly focused on its role in maintaining the normal physiological function of cells. However, the clinical implications of FAM96B in hepatocellular carcinoma (HCC) are still unclear. FAM96B mRNA expression was detected in human HCC tissues and the matched nontumorous tissues by quantitative real-time reverse transcription (qRT-PCR) and then validated in The Cancer Genome Atlas (TCGA) database. Immunohistochemistry assay (IHC) was performed on all 137 cases of HCC samples to examine the protein level of FAM96B. Subsequently, the associations between FAM96B expression and clinicopathological parameters and prognosis were further analyzed. The mRNA level of FAM96B was found to be significantly lower in HCC tissues compared to non-tumorous tissues, as observed in both the local hospital and TCGA database.Immunohistochemistry assay analysis revealed a decrease in FAM96B expression in 78 out of 137 cases, which was significantly associated with larger tumor size, higher Barcelona clinic liver cancer or Child stage, and early distant metastasis. Patients with low FAM96B levels tended to have an unfavorable disease-free and overall survival. Moreover, FAM96B was identified as an independent predictor of patient prognosis in both univariate and multivariate survival analyses. Mechanistically, FAM96B was found to inhibit cancer progression by inducing apoptosis in liver cancer cells and inhibiting their growth. Our findings provide the first evidence suggesting the involvement of FAM96B in the progression of HCC. Additionally, FAM96B could potentially serve as a marker for tumor recurrence and prognosis in HCC patients.

A novel mouse model of upper tract urothelial carcinoma highlights the impact of dietary intervention on gut microbiota and carcinogenesis prevention despite carcinogen exposure.

Animal models of N-butyl-N-(4-hydroxy butyl) nitrosamine (BBN)-induced urothelial carcinoma (UC), particularly bladder cancer (BC), have long been established. However, the rare incidence of BBN-induced upper urinary tract UC (UTUC), which originates from the same urothelium as BC, remains elusive. The scarcity of animal models of UTUC has made it challenging to study the biology of UTUC. To address this problem, we tried to establish a novel mouse model of UTUC by treating multiple mice strains and sexes with BBN. The molecular consistency between the UTUC mouse model and human UTUC was confirmed using multi-omics analyses, including whole-exome, whole-transcriptome, and spatial transcriptome sequencing. 16S ribosomal RNA metagenome sequencing, metabolome analysis, and dietary interventions were employed to assess changes in the gut microbiome, metabolome, and carcinogenesis of UTUC. Of all treated mice, only female BALB/c mice developed UTUC over BC. Multi-omics analyses confirmed that the UTUC model reflected the molecular characteristics and heterogeneity of human UTUC with poor prognosis. Furthermore, the model exhibited increased Tnf-related inflammatory gene expression in the upper urinary tract and a low relative abundance of Parabacteroides distasonis in the gut. Dietary intervention, mainly without alanine, led to P. distasonis upregulation and successfully prevented UTUC, as well as suppressed Tnf-related inflammatory gene expression in the upper urinary tract despite the exposure to BBN. This is the first report to demonstrate a higher incidence of UTUC than BC in a non-engineered mouse model using BBN. Overall, this model could serve as a useful tool for comprehensively investigating UTUC in future studies.

Utility of Oligoclonal Band Testing in Differentiating Immune-Mediated From Infectious Central Nervous System Disorders.

This study aimed to evaluate the clinical utility of oligoclonal bands (OCB) in differentiating between immune and infectious diseases of the central nervous system (CNS). The study enrolled patients hospitalized with suspected autoimmune or infectious CNS disorders between 2021 and 2023. Patients were categorized into diagnostic groups: multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), autoimmune encephalitis (AE), and viral encephalitis (VE). Relevant clinical and laboratory data were collected and subjected to comparative analysis. Comparative analysis among the 4 groups revealed that the immunoglobulin G (IgG) index of patients in the MS group was significantly higher than that of patients in the NMOSD and VE groups (P < 0.05). The 24-hour intrathecal synthesis rate of IgG also differed significantly between the MS and NMOSD groups, the NMOSD and AE groups, as well as the AE and VE groups (P < 0.05). The positive rate of OCB was significantly higher in the MS group than in the other 3 groups (P < 0.05). Functional abilities, measured by scores of the Modified Rankin Scale (mRS) and the Expanded Disability Status Scale (EDSS), were higher in the immune group than in the infection group at 1-week, 1-month, 6-month, and 1-year post-treatment. Among patients with immune diseases, those who were OCB-positive showed significantly smaller ΔmRS and ΔEDSS at 1-month, 6-month, and 1-year post-treatment compared with patients who were OCB-negative (P < 0.05). The IgG index and 24-hour intrathecal synthesis rate of IgG served as valuable early indicators for distinguishing between CNS immune and infectious diseases. Positive OCB findings were more common in patients with MS and often associated with poor prognosis and increased risk of disease recurrence.

The impact of high-risk cytogenetic abnormalities in extramedullary multiple myeloma in the era of novel agents: insights from a multicenter study

PurposeThis study aimed to examine the impact of high-risk cytogenetic abnormalities (HRA) on the survival outcomes of multiple myeloma patients with extramedullary disease (EMD) in the era of novel agents, utilizing the largest dataset of extramedullary multiple myeloma patients in China.MethodsThis study included a total of 371 patients with EMD, comprising 113 patients with de novo EME and 258 patients with EMB.ResultsPatients with one HRA and those with ≥ 2 HRA demonstrated significantly worse overall survival (OS) (P < 0.01) and progression-free survival (PFS) (P < 0.01) compared to patients without HRA. Additionally, 1q21 gain/amplification (1q21 +) remained a predictor of poor prognosis in EMD. CD38 monoclonal antibody-based therapy and single transplantation were less effective in improving survival outcomes for EMD with ≥ 2 HRA. Multivariable analysis identified LDH levels > 250 U/L, creatinine levels > 177 μmol/L, extramedullary extraosseous (EME), 1 HRA, and ≥ 2 HRA as independent adverse prognostic factors in patients with EMD.ConclusionPatients with EMD who had ≥ 2 HRA experienced an extremely poor prognosis, which could not be improved by single transplantation or CD38 monoclonal antibody-based treatment. The number of HRA could serve as an important factor in guiding treatment choices and predicting prognosis in patients with EMD. Furthermore, 1q21 + remained a significant factor associated with worse survival outcomes in EMD.