Differential diagnostic value of radiomics models in benign versus malignant vertebral compression fractures: A systematic review and meta-analysis.

PURPOSE: Early diagnosis of benign and malignant vertebral compression fractures by analyzing imaging data is crucial to guide treatment and assess prognosis, and the development of radiomics made it an alternative option to biopsy examination. This systematic review and meta-analysis was conducted with the purpose of quantifying the diagnostic efficacy of radiomics models in distinguishing between benign and malignant vertebral compression fractures. METHODS: Searching on PubMed, Embase, Web of Science and Cochrane Library was conducted to identify eligible studies published before September 23, 2023. After evaluating for methodological quality and risk of bias using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), we selected studies providing confusion matrix results to be included in random-effects meta-analysis. RESULTS: A total of sixteen articles, involving 1,519 vertebrae with pathological-diagnosed tumor infiltration, were included in our meta-analysis. The combined sensitivity and specificity of the top-performing models were 0.92 (95 % CI: 0.87-0.96) and 0.93 (95 % CI: 0.88-0.96), respectively. Their AUC was 0.97 (95 % CI: 0.96-0.99). By contrast, radiologists' combined sensitivity was 0.90 (95 %CI: 0.75-0.97) and specificity was 0.92 (95 %CI: 0.67-0.98). The AUC was 0.96 (95 %CI: 0.94-0.97). Subsequent subgroup analysis and sensitivity test suggested that part of the heterogeneity might be explained by differences in imaging modality, segmentation, deep learning and cross-validation. CONCLUSION: We found remarkable diagnosis potential in correctly distinguishing vertebral compression fractures in complex clinical contexts. However, the published radiomics models still have a great heterogeneity, and more large-scale clinical trials are essential to validate their generalizability.

Orchestrating apoptosis and ferroptosis through enhanced sonodynamic therapy using amorphous UIO-66-CoOx.

The development of efficient and multifunctional sonosensitizers is crucial for enhancing the efficacy of sonodynamic therapy (SDT). Herein, we have successfully constructed a CoOx-loaded amorphous metal-organic framework (MOF) UIO-66 (A-UIO-66-CoOx) sonosensitizer with excellent catalase (CAT)- and glutathione-oxidase (GSH-OXD)-like activities. The A-UIO-66-CoOx exhibits a 2.6-fold increase in singlet oxygen (1O2) generation under ultrasound (US) exposure compared to crystalline UIO-66 sonosensitizer, which is attributed to its superior charge transfer efficiency and consistent oxygen (O2) supply. Additionally, the A-UIO-66-CoOx composite reduces the expression of glutathione peroxidase (GPX4) by depleting glutathione (GSH) through Co3+ and Co2+ valence changes. The high levels of highly cytotoxic 1O2 and deactivation of GPX4 can lead to lethal lipid peroxidation, resulting in concurrent apoptosis and ferroptosis. Both in vitro and vivo tumor models comprehensively confirmed the enhanced SDT antitumor effect using A-UIO-66-CoOx sonosensitizer. Overall, this study emphasizes the possibility of utilizing amorphization engineering to improve the effectiveness of MOFs-based sonosensitizers for combined cancer therapies.

Comparing perioperative outcomes between regional anesthesia and general anesthesia in patients undergoing hip fracture surgery: a systematic review and meta-analysis.

PURPOSE: Nearly all patients with hip fractures undergo surgical treatment. The use of different anesthesia techniques during surgery may influence the clinical outcomes. The optimal anesthetic technique for patients undergoing hip fracture surgery is still controversial. We performed this updated systematic review and meta-analysis to compare clinical outcomes of patients undergoing hip fracture surgery with different anesthesia techniques. SOURCE: Articles published from 2000 to May 2023 were included from MEDLINE, Embase, Web of Science, and the Cochrane Library. We included randomized controlled trials and observational studies comparing general anesthesia (GA) with regional anesthesia (RA) for the outcomes of 30-day mortality, 90-day mortality, in-hospital mortality, perioperative complications, length of hospital stay, and length of surgery in patients undergoing hip fracture surgery. Subgroup analyses were performed for the outcomes based on study design (randomized controlled trials or observational studies). We used a random-effects model for all analyses. PRINCIPAL FINDINGS: In this meta-analysis, we included 12 randomized controlled trials. There was no difference in postoperative 30-day mortality between the two groups (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.44 to 1.74; I2 = 0%). The incidence of intraoperative hypotension was lower in patients who received RA vs GA (OR, 0.52; 95% CI, 0.38 to 0.72; I2 = 0%). No significant differences were observed in 90-day mortality, in-hospital mortality, postoperative delirium, pneumonia, myocardial infarction, venous thromboembolism, length of surgery, and length of hospital stay. CONCLUSION: In this updated systematic review and meta-analysis, RA did not reduce postoperative 30-day mortality in hip fracture surgery patients compared to GA. Fewer patients receiving RA had intraoperative hypotension than those receiving GA did. Apart from intraoperative hypotension, the data showed no differences in complications between the two anesthetic techniques. STUDY REGISTRATION: PROSPERO (CRD42023411854); registered 7 April 2023.

RéSUMé: OBJECTIF: Presque toutes les personnes ayant subi une fracture de la hanche se font opérer. L'utilisation de différentes techniques d'anesthésie pendant la chirurgie peut influencer les issues cliniques. La technique d'anesthésie optimale pour la patientèle bénéficiant de chirurgie de fracture de la hanche est encore controversée. Nous avons réalisé cette mise à jour par revue systématique et méta-analyse pour comparer les issues cliniques des personnes bénéficiant d'une chirurgie de fracture de la hanche avec différentes techniques d'anesthésie. SOURCES: Les articles publiés de 2000 à mai 2023 ont été inclus à partir des bases de données MEDLINE, Embase, Web of Science et Cochrane Library. Nous avons inclus des études randomisées contrôlées et des études observationnelles comparant l'anesthésie générale (AG) à l'anesthésie régionale (AR) pour les issues de mortalité à 30 jours, de mortalité à 90 jours, de mortalité intrahospitalière, de complications périopératoires, de durée de séjour à l'hôpital et de durée de la chirurgie pour les personnes bénéficiant d'une chirurgie de fracture de la hanche. Des analyses de sous-groupes ont été réalisées pour les issues en fonction de la méthodologie utilisée (étude randomisée contrôlée ou étude observationnelle). Un modèle à effets aléatoires a été utilisé pour toutes les analyses. CONSTATATIONS PRINCIPALES: Dans cette méta-analyse, nous avons inclus 12 études randomisées contrôlées. Il n'y avait pas de différence dans la mortalité postopératoire à 30 jours entre les deux groupes (rapport de cotes [RC], 0,88; intervalle de confiance à 95 % [IC], 0,44 à 1,74; I2 = 0 %). L'incidence d'hypotension peropératoire était plus faible chez les patient·es ayant reçu une AR vs une AG (RC, 0,52; IC 95 %, 0,38 à 0,72; I2 = 0 %). Aucune différence significative n'a été observée dans les issues de mortalité à 90 jours, de mortalité intrahospitalière, de delirium postopératoire, de pneumonie, d'infarctus du myocarde, de thromboembolie veineuse, de durée de la chirurgie, et de durée du séjour à l'hôpital. CONCLUSION: Dans cette revue systématique avec méta-analyse, l'anesthésie régionale n'a pas réduit la mortalité postopératoire à 30 jours chez les personnes ayant bénéficié d'une chirurgie de fracture de la hanche par rapport à l'anesthésie générale. Une proportion moindre de patient·es ayant reçu une AR présentaient une hypotension peropératoire par rapport aux personnes ayant reçu une AG. En dehors de l'hypotension peropératoire, les données n'ont montré aucune différence dans les complications entre les deux techniques anesthésiques. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42023411854); enregistrée le 7 avril 2023.

Review of the Protective Mechanism of Curcumin on Cardiovascular Disease.

Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.

Application of functional magnetic resonance imaging for evaluation of cartilage injury effect on knee joint function by recurrent patellar dislocation.

Explore the therapeutic effect of vastus medialis oblique plasty and the reliability and applicability of functional magnetic resonance imaging as a diagnostic method for early cartilage degeneration and injury diagnosis. From July 2020 to July 2022, there were 53 patients with recurrent patellar dislocation who met the inclusion criteria for surgery, including 34 women and 19 men, aged 11 to 53 years, with an average age of 24.4 years. After patient selection, functional magnetic resonance imaging was performed before surgery. According to the presence or absence of cartilage injury, they were divided into cartilage injury group (n = 28) and non-cartilage injury group (n = 25), and underwent vastus medialis oblique plasty. Preoperative patellar axial radiographs were performed in both groups of patients to measure the patellar tilt angle and lateral patellofemoral angle. The Lysholm, Kujala, and VAS (visual analogue scale) scores were applied to assess changes in knee joint function and anterior knee pain. All patients were postoperatively followed up. The patellar tilt angle and lateral patellofemoral angle of the 2 groups were significantly improved postoperatively (P < .05), with no statistical difference between the 2 groups (P > .05). Significant differences were observed in the VAS changes between the cartilage injury group and the non-cartilage injury group before and after operation (P < .05). There was a statistical difference in VAS score between the groups (P < .05). The changes in the Lysholm and Kujala scores before and after the operation in the cartilage injury and the non-cartilage injury groups were statistically different (P < .05). There was statistical difference between the 2 groups in Lysholm score and Kujala score after operation (P < .05). Vastus medialis oblique plasty significantly improved knee joint function and pain. Patients with cartilage injury had worse preoperative and postoperative knee function than patients without cartilage injury. Functional magnetic resonance imaging can reflect the early-stage changes in the biochemical cartilage components caused by recurrent patellar dislocation.

Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data.

PURPOSE: Tenosynovial giant cell tumour (TGCT) is a benign hyperplastic and inflammatory disease of the joint synovium or tendon sheaths, which may be misdiagnosed due to its atypical symptoms and imaging features. We aimed to identify biomarkers with high sensitivity and specificity to aid in diagnosing TGCT. METHODS: Two scRNA-seq datasets (GSE210750 and GSE152805) and two microarray datasets (GSE3698 and GSE175626) were downloaded from the Gene Expression Omnibus (GEO) database. By integrating the scRNA-seq datasets, we discovered that the osteoclasts are abundant in TGCT in contrast to the control. The single-sample gene set enrichment analysis (ssGSEA) further validated this discovery. Differentially expressed genes (DEGs) of the GSE3698 dataset were screened and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were conducted. Osteoclast-specific up-regulated genes (OCSURGs) were identified by intersecting the osteoclast marker genes in the scRNA-seq and the up-regulated DEGs in the microarray and by the least absolute shrinkage and selection operator (LASSO) regression algorithm. The expression levels of OCSURGs were validated by an external dataset GSE175626. Then, single gene GSEA, protein-protein interaction (PPI) network, and gene-drug network of OCSURGs were performed. RESULT: 22 seurat clusters were acquired and annotated into 10 cell types based on the scRNA-seq data. TGCT had a larger population of osteoclasts compared to the control. A total of 159 osteoclast marker genes and 104 DEGs (including 61 up-regulated genes and 43 down-regulated genes) were screened from the scRNA-seq analysis and the microarray analysis. Three OCSURGs (MMP9, SPP1, and TYROBP) were finally identified. The AUC of the ROC curve in the training and testing datasets suggested a favourable diagnostic capability. The PPI network results illustrated the protein-protein interaction of each OCSURG. Drugs that potentially target the OCSURGs were predicted by the DGIdb database. CONCLUSION: MMP9, SPP1, and TYROBP were identified as osteoclast-specific up-regulated genes of the tenosynovial giant cell tumour via bioinformatic analysis, which had a reasonable diagnostic efficiency and served as potential drug targets.

Insulin-Like Growth Factor 1 Receptor Deficiency Alleviates Angiotensin II-Induced Cardiac Fibrosis Through the Protein Kinase B/Extracellular Signal-Regulated Kinase/Nuclear Factor-κB Pathway.

Background The renin-angiotensin system plays a crucial role in the development of heart failure, and Ang II (angiotensin II) acts as the critical effector of the renin-angiotensin system in regulating cardiac fibrosis. However, the mechanisms of cardiac fibrosis are complex and still not fully understood. IGF1R (insulin-like growth factor 1 receptor) has multiple functions in maintaining cardiovascular homeostasis, and low-dose IGF1 treatment is effective in relieving Ang II-induced cardiac fibrosis. Here, we aimed to investigate the molecular mechanism of IGF1R in Ang II-induced cardiac fibrosis. Methods and Results Using primary mouse cardiac microvascular endothelial cells and fibroblasts, in vitro experiments were performed. Using C57BL/6J mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-mediated IGF1R heterozygous knockout (Igf1r+/-) mice, cardiac fibrosis mouse models were induced by Ang II for 2 weeks. The expression of IGF1R was examined by quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Mice heart histologic changes were evaluated using Masson and picro sirius red staining. Fibrotic markers and signal molecules indicating the function of the Akt (protein kinase B)/ERK (extracellular signal-regulated kinase)/nuclear factor-κB pathway were detected using quantitative reverse transcription polymerase chain reaction and Western blot. RNA sequencing was used to explore IGF1R-mediated target genes in the hearts of mice, and the association of IGF1R and G-protein-coupled receptor kinase 5 was identified by coimmunoprecipitation. More important, blocking IGF1R signaling significantly suppressed endothelial-mesenchymal transition in primary mouse cardiac microvascular endothelial cells and mice in response to transforming growth factor-ß1 or Ang II, respectively. Deficiency or inhibition of IGF1R signaling remarkably attenuated Ang II-induced cardiac fibrosis in primary mouse cardiac fibroblasts and mice. We further observed that the patients with heart failure exhibited higher blood levels of IGF1 and IGF1R than healthy individuals. Moreover, Ang II treatment significantly increased cardiac IGF1R in wild type mice but led to a slight downregulation in Igf1r+/- mice. Interestingly, IGF1R deficiency significantly alleviated cardiac fibrosis in Ang II-treated mice. Mechanistically, the phosphorylation level of Akt and ERK was upregulated in Ang II-treated mice, whereas blocking IGF1R signaling in mice inhibited these changes of Akt and ERK phosphorylation. Concurrently, phosphorylated p65 of nuclear factor-κB exhibited similar alterations in the corresponding group of mice. Intriguingly, IGF1R directly interacted with G-protein-coupled receptor kinase 5, and this association decreased ≈50% in Igf1r+/- mice. In addition, Grk5 deletion downregulated expression of the Akt/ERK/nuclear factor-κB signaling pathway in primary mouse cardiac fibroblasts. Conclusions IGF1R signaling deficiency alleviates Ang II-induced cardiac fibrosis, at least partially through inhibiting endothelial-mesenchymal transition via the Akt/ERK/nuclear factor-κB pathway. Interestingly, G-protein-coupled receptor kinase 5 associates with IGF1R signaling directly, and it concurrently acts as an IGF1R downstream effector. This study suggests the promising potential of IGF1R as a therapeutic target for cardiac fibrosis.

Exploration of diagnostic biomarkers, microenvironment characteristics, and ursolic acid's therapeutic effect for benign prostate hyperplasia.

Benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PC) have similar symptoms, making it challenging to differentially diagnose these two conditions. The study used Weighted Gene Co-Expression Network Analysis, as well as two machine learning strategies to identify BPH-specific biomarkers based on an integrated transcriptome data from 922 samples. Eight prognostic genes (ALCAM, COL6A2, CRISP2, FOXF2, IGF1, PTN, SCN7A, and UAP1) were identified to be BPH-specific biomarkers with high accuracy and specificity. Moreover, we constructed a seven-gene diagnostic classifier to distinguish BPH from PC. The infiltrations of plasmacytoid dendritic cells and neutrophil cells showed distinct differences between BPH and non-BPH groups. Additionally, ursolic acid can reverse transcriptional features associated with the occurrence and progression of BPH. Both in vivo and in vitro experiments have confirmed that it induces apoptosis of BPH cells and inhibits cell proliferation by promoting cell cycle S-phase arrest. The diagnostic biomarkers, microenvironment characteristics, and therapeutic effect of ursolic acid explored in this study offer new diagnostic and therapeutic strategies for BPH.

Comparison of surface microscopy coil and ankle joint special phased array coil magnetic resonance imaging in assessing preoperative osteochondral lesions of the talus.

Background: Lesion size is a major determinant of treatment strategies and predictor of clinical outcomes for osteochondral lesions of the talus (OLTs). Although magnetic resonance imaging (MRI) has been commonly used in the preoperative evaluation of OLTs, MRI has low reliability and usually overestimates or underestimates lesion size compared with intraoperative assessment. This study aims to determine whether the surface microscopy coil (SMC) can improve the accuracy of assessment of preoperative OLTs compared with conventional coil MRI, ankle joint special phased array coil (ASC). Methods: A total of 43 patients diagnosed with OLTs undertook preoperative MRI examination with both SMC and ASC were included in this prospective study from 2019 to 2022. The diameter of the lesion was measured in sagittal plane and coronal plane at its widest point and then the lesion area was calculated. Then MRI measurements were compared with arthroscopy or open-surgery measurements. Results: The mean lesion area measured with ASC was significantly greater than that measured intraoperatively (95.07±44.60 vs. 52.74±29.86 mm2, P<0.001), while there was no significant difference between lesion area measured in SMC and intraoperatively (55.28±36.06 vs. 52.74±29.86 mm2, P=0.576). Diameter measured in ASC was significantly greater than that measured intraoperatively in both coronal plane (8.95±2.48 vs. 6.67±1.81, P<0.001) and sagittal plane (13.12±3.76 vs. 9.58±3.98, P<0.001). No significant difference between lesion diameter measured in SMC and intraoperatively in both coronal plane (6.44±2.59 vs. 6.67±1.81, P=0.608) or sagittal plane (10.23±3.69 vs. 9.58±3.98, P=0.194). Compared with surgical assessment, 39 of 43 cases were consistent with SMC assessment while only 26 of 43 cases were consistent with ASC assessment (39/43 vs. 26/43, P=0.002). Conclusions: Diameter measured with SMC was much more accurate than ASC MRI. Compared with ASC MRI, the SMC had a much higher concordance rate between preoperative assessment and surgical assessment.

Better timing for HoLEP: a retrospective analysis of patients treated with HoLEP over a 10-year period with a 1-year follow-up.

The aim of this study was to explore the optimal timing of holmium laser enucleation of the prostate (HoLEP) in patients presenting benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). A retrospective analysis was conducted based on the perioperative and postoperative outcome data of 1212 patients who underwent HoLEP in Shanghai Ninth People's Hospital (Shanghai, China) between January 2009 and December 2018. According to the preoperative International Prostate Symptom Score (IPSS), all patients whom we analyzed were divided into Group A (IPSS of 8-18) and Group B (IPSS of 19-35). Peri- and postoperative outcome data were obtained during the 1-year follow-up. IPSS changes were the main postoperative outcomes. The postoperative IPSS, quality of life, peak urinary flow rate, postvoid residual, and overactive bladder symptom score (OABSS) improved significantly. The IPSS improved further in the group with severe LUTS symptoms, but the postoperative IPSS was still higher than that in the moderate LUTS group. OABSSs showing moderate and severe cases after follow-up were more frequent in Group B (9.1%) than in Group A (5.2%) (P < 0.05). There were no significant intergroup differences in the intraoperative American Society of Anesthesiologists or hospitalization expense scores, and the medication costs, as well as the total costs, were significantly higher in Group B. In this retrospective study, HoLEP was an effective treatment for symptomatic BPH. For patients with LUTS, earlier surgery in patients with moderate severity may result in a marginally better 12-month IPSS than that in men with severe symptoms.

Deep learning empowered volume delineation of whole-body organs-at-risk for accelerated radiotherapy.

In radiotherapy for cancer patients, an indispensable process is to delineate organs-at-risk (OARs) and tumors. However, it is the most time-consuming step as manual delineation is always required from radiation oncologists. Herein, we propose a lightweight deep learning framework for radiotherapy treatment planning (RTP), named RTP-Net, to promote an automatic, rapid, and precise initialization of whole-body OARs and tumors. Briefly, the framework implements a cascade coarse-to-fine segmentation, with adaptive module for both small and large organs, and attention mechanisms for organs and boundaries. Our experiments show three merits: 1) Extensively evaluates on 67 delineation tasks on a large-scale dataset of 28,581 cases; 2) Demonstrates comparable or superior accuracy with an average Dice of 0.95; 3) Achieves near real-time delineation in most tasks with <2 s. This framework could be utilized to accelerate the contouring process in the All-in-One radiotherapy scheme, and thus greatly shorten the turnaround time of patients.

Understanding the scope of intracardiac echocardiography in catheter ablation of ventricular arrhythmia.

Over the last few decades, catheter ablation has emerged as the first-line treatment for ventricular arrhythmias. However, detailed knowledge of cardiac anatomy during the surgery remains the prerequisite for successful ablation. Intracardiac echocardiography (ICE) is a unique imaging technique, which provides real-time visualization of cardiac structures, and is superior to other imaging modalities in terms of precise display of cardiac tissue characteristics as well as the orientation of anatomical landmarks. This article aimed to introduce the various advantages and limitations of ICE in the ablation of ventricular arrhythmias.

Identification of cuproptosis-related patterns and construction of a scoring system for predicting prognosis, tumor microenvironment-infiltration characteristics, and immunotherapy efficacy in breast cancer.

Background: Cuproptosis, a recently discovered refreshing form of cell death, is distinct from other known mechanisms. As copper participates in cell death, the induction of cancer cell death with copper ionophores may emerge as a new avenue for cancer treatment. However, the role of cuproptosis in tumor microenvironment (TME) cell infiltration remains unknown. Methods: We systematically evaluated the cuproptosis patterns in The Cancer Genome Atlas (TCGA) database in breast cancer (BRCA) samples based on 10 cuproptosis-related genes (CRGs), and correlated these patterns with the prognosis and characteristics of TME cell infiltration. A principal component analysis algorithm was used to construct a cuproptosis score to quantify the cuproptosis pattern in individual tumors. Further, the relationships between the cuproptosis score and transcription background, clinical features, characteristics of TME cell infiltration, drug response, and efficacy of immunotherapy were assessed. Results: Two distinct cuproptosis patterns with distinct prognoses were identified; their TME characteristics were found to be consistent with the immune-excluded and immune-inflamed phenotypes, respectively. The cuproptosis patterns in individual patients were evaluated using the cuproptosis score based on the cuproptosis phenotype-related genes, contributing to distinguishing biological processes, clinical outcome, immune cell infiltration, genetic variation, and drug response. Univariate and multivariate Cox regression analyses verified this score as an independent prognostic predictor in BRCA. A high cuproptosis score, characterized by immune activation, suggests an inflamed tumor and immune-inflamed phenotype with poor survival and a low cuproptosis score, characterized by immune suppression, indicates a non-inflamed tumor and immune-excluded phenotype with better survival. Significant differences were observed in the IC50 between the high and low cuproptosis score groups receiving chemotherapy and targeted therapy drugs. In the two immunotherapy cohorts, patients with a higher cuproptosis score experienced considerable therapeutic advantages and clinical benefits. Conclusions: This study is the first to elucidate the prominent role of cuproptosis in the clinical outcome and the formation of TME diversity and complexity in BRCA. Estimating cuproptosis patterns in tumors could help predict the prognosis and characteristics of TME cell infiltration and guide more effective chemotherapeutic and immunotherapeutic strategies.

MAFG-AS1 is a prognostic biomarker and facilitates prostate cancer progression.

Long Noncoding RNAs (LncRNAs) have recently been identified as key regulator in tumor progression. The LncRNA MAFG-AS1 has been reported to facilitate the progression of multiple cancers, however, its role in prostate cancer is still unknown. Here, we reported that MAFG-AS1 was upregulated in prostate cancer. Importantly, high expression of MAFG-AS1 indicated advanced stage prostate cancer. Univariate and Multivariate Cox regression analyses showed that high MAFG-AS1 expression was independently correlated with poor progression-free interval (PFI). According to the result of The Cancer Genome Atlas (TCGA) database and tissue microarray, high MAFG-AS1 expression indicated a poor prognosis in prostate cancer patients. In addition, gene functional enrichment analysis revealed that MAFG-AS1 may be involved in ribosome biogenesis, ribonucleoprotein complex subunit organization, ribonucleoprotein complex assembly, rRNA metabolic process, structural constituent of ribosome, and ribonucleoprotein complex binding. Furthermore, MAFG-AS1 knockdown by siRNA markedly impaired prostate cancer cell proliferation, migration, and invasion.

Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis.

BACKGROUND: Human mesenchymal stem cells (hMSCs) have been proven to have inherent chondrogenic differentiation potential, which appears to be used in cartilage regeneration. Increasing evidence suggests that irisin enhances osteoblast differentiation of MSCs, but little is known about its potential on chondrogenic differentiation. METHODS: In the study, we investigated the effects of irisin on chondrogenic differentiation of hMSCs using a high-density pellet culture system. The cartilage pellets were evaluated by morphology, and the metabolism of cartilage matrix was detected by qPCR, western blot and immunohistochemistry. Next, RNA-seq was performed to explore the underlying mechanism. Furthermore, using the transduction of plasmid, miRNAs mimics and inhibitor, the activation of Rap1/PI3K/AKT axis, the expression level of SIPA1L2, and the functional verification of miR-125b-5p were detected on day 7 of chondrogenic differentiation of hMSCs. RESULTS: Compared with the controls, we found that irisin treatment could significantly enhance the chondrogenic differentiation of hMSCs, enlarge the induced-cartilage tissue and up-regulate the expression levels of cartilage markers. RNA-seq indicated that irisin activated the Rap1 and PI3K/AKT signaling pathway, and the lower expression level of SIPA1L2 and the higher expression level of miR-125b-5p were found in irisin-treated group. Further, we found that irisin treatment could up-regulate the expression level of miR-125b-5p, targeting SIPA1L2 and consequently activating the Rap1/PI3K/AKT axis on the process of chondrogenic differentiation of hMSCs. CONCLUSIONS: Collectively, our study reveals that irisin can enhance chondrogenic differentiation of hMSCs via the Rap1/PI3K/AKT pathway, suggesting that irisin possesses prospects in cartilage regeneration.

A prospective randomized controlled trial comparing the effect and safety of Piranha and VersaCut morcellation devices in transurethral holmium laser enucleation of the prostate.

PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is reported to be widely used in the surgical treatment of benign prostatic hyperplasia (BPH), which consists of two procedures: enucleation and morcellation. This study is to examine the efficiency and safety of two different morcellator systems within a cohort of men undergoing HoLEP for BPH. METHODS: A total of 210 consecutive patients undergoing HoLEP and morcellation procedures were enrolled. Individuals were randomly divided into 2 separated groups: the first group (105 patients) was performed with a nephroscope using a mechanical Versacut morcellator and the second (105 patients) was performed with the new morcellation system, nephroscopes and Piranha morcellator. Perioperative characteristics were studied and analyzed. RESULTS: The morcellation time and the morcellation rate was similar when the prostate volume (PV) ≤ 60 mL while the morcellation time was significantly shorter and the morcellation rate was higher in the Piranha group with PV > 60 mL. No significant difference was observed according to the bladder irrigation time, indwelling catheter time, and discharge time. CONCLUSION: Piranha morcellator presents a higher efficiency for the prostate over 60 mL.

Individual Surgical Treatment of Stage IV Müller-Weiss Disease According to CT/MRI Examination: A Retrospective Study of 12 Cases.

Background: This study reported the individual surgical treatment of 12 cases with stage IV Müller-Weiss disease (MWD) according to CT/MRI examination. Methods: In total, 12 cases diagnosed with stage IV MWD in our hospital from 2015 to 2019 were included in the retrospective study. Relevant clinical outcomes were evaluated preoperatively and postoperatively. Results: The follow-up results showed satisfactory outcomes in all cases. All the cases were presented with tenderness and chronic pain on the midfoot dorsum, and three cases were also presented with tenderness and pain on the lateral side of the midfoot, in which calcaneal cuboid arthritis was revealed by CT/MRI. The American Orthopedic Foot and Ankle Society (AOFAS) scores elevated from 62.5 ± 6.8 (range: 53-74) preoperatively to 95.3 ± 7.2 (range: 73-100) postoperatively (P < 0.005). The Visual Analog Scale (VAS) scores declined from 4.2 ± 0.9 (range: 3-5.5) preoperatively to 0.5 ± 0.3 (range: 0-2) postoperatively (P < 0.001). On the weight-bearing lateral view of the foot, the Tomeno-Méary angle (TM lat) changed from -11.2 ± 4.2 (range: -17.2 to -2.8) degrees preoperatively to -2.4 ± 3.9 (range: -10.2 to 5.2) degrees postoperatively (P < 0.001). Conclusions: The fusion of the talus-navicular joint and the adjacent affected joint provide good clinical outcomes. The CT/MRI scans are helpful to identify the adjacent joint arthritis and provide indications for individual treatment for Stage IV MWD.

"Fenestration and Tunnel Method" a Modification for the Holmium Laser Transurethral Prostatectomy of Large-Volume Prostates >80 ml: A Retrospective Study Based on 1-Year Follow-Up.

The purpose of this study was to promote the holmium laser enucleation of the prostate (HoLEP) technology for large-volume prostates (>80 ml) and compare it with the traditional method, we modified the technique and applied this technology to clinical practice. A retrospective study comprising 118 patients who underwent HoLEP surgery from February 2018 to December 2019 was conducted in our center. Group A consisted of 57 patients with large-volume prostate (>80 ml) who received modified "fenestration and tunnel method" from February 2019 till December 2019, while group B consisted of 61 patients who received the traditional trivalvular operation method from February 2018 to December 2018 for comparison. Control subjects are selected such that they match the cases concerning certain characteristics, and perioperative data, voiding outcomes, and complications were evaluated at 1- and 12-month follow-up. The international prostatic symptomatic score (IPSS), quality of life (QoL), and maximum flow rate (Qmax) at 1 month and 12 months were both significantly improved compared with the preoperative baseline, and no significant differences were found between Groups A and B. The mean enucleation time, operation time, catheter indwelling duration, and hemoglobin decrease during the operation of Group A showed superiority compared with Group B (p<.05). The modified "fenestration and tunnel method" of HoLEP was statistically superior to the traditional trivalvular method in terms of the operation time, enucleation time, catheter indwelling duration, and hemoglobin decrease. For large-volume prostates (>80 ml), modified HoLEP was suggested to be a better treatment option.

Melatonin reverses tumor necrosis factor-alpha-induced metabolic disturbance of human nucleus pulposus cells via MTNR1B/Gαi2/YAP signaling.

Background: Intervertebral disc degeneration (IDD), the main cause of low back pain, is closely related to the inflammatory microenvironment in the nucleus pulposus (NP). Tumor necrosis factor-α (TNF-α) plays an important role in inflammation-related metabolic disturbance of NP cells. Melatonin has been proven to regulate the metabolism of NP cells, but whether it can protect NP cells from TNF-α-induced damage is still unclear. Therefore, this study aims to investigate the role and specific mechanism of melatonin on regulating the metabolism of NP cells in the inflammatory microenvironment. Methods: Western blotting, RT-qPCR and immunohistochemistry were used to detect the expression of melatonin membrane receptors (MTNR1A/B) and TNF-α in human NP tissues. In vitro, human primary NP cells were treated with or without vehicle, TNF-α and melatonin. And the metabolic markers were also detected by western blotting and RT-qPCR. The activity of NF-κB signaling and Hippo/YAP signaling were assessed by western blotting and immunofluorescence. Membrane receptors inhibitors, pathway inhibitors, lentiviral infection, plasmids transfection and immunoprecipitation were used to explore the specific mechanism of melatonin. In vivo, the rat IDD model was constructed and melatonin was injected intraperitoneally to evaluate its therapeutical effect on IDD. Results: The upregulation of TNF-α and downregulation of melatonin membrane receptors (MTNR1A/B) were observed in degenerative NP tissues. Then we demonstrated that melatonin could alleviate the development of IDD in a rat model and reverse TNF-α-impaired metabolism of NP cells in vitro. Further investigation revealed that the protective effects of melatonin on NP cells mainly rely on MTNR1B, which subsequently activates Gαi2 protein. The activation of Gαi2 could upregulate the yes-associated protein (YAP) level, resulting in anabolic enhancement of NP cells. In addition, melatonin-mediated YAP upregulation increased the expression of IκBα and suppressed the TNF-α-induced activation of the NF-κB pathway, thereby inhibiting the catabolism of NP cells. Conclusions: Our results revealed that melatonin can reverse TNF-α-impaired metabolism of NP cells via the MTNR1B/Gαi2/YAP axis and suggested that melatonin can be used as a potential therapeutic drug in the treatment of IDD.

E2F transcription factor 2-activated DLEU2 contributes to prostate tumorigenesis by upregulating serum and glucocorticoid-induced protein kinase 1.

Long noncoding RNAs (lncRNAs) participate in biological processes in multiple types of tumors. However, the regulatory patterns of lncRNAs in prostate cancer remain largely unclear. Here, we evaluated the expression and roles of the lncRNA DLEU2 in prostate cancer. Our results showed that DLEU2 was upregulated in advanced prostate cancer tissues. Patients with prostate cancer displaying high expression of DLEU2 had a poor prognosis. Moreover, we demonstrated that overexpression of DLEU2 facilitated the proliferation, migration, and invasion of prostate cancer in vitro. Mechanistically, DLEU2 promoted serum and glucocorticoid-induced protein kinase 1 (SGK1) expression by acting as an miR-582-5p sponge, and the transcription of DLEU2 was activated by the dysregulation of E2F transcription factor 2 (E2F2) expression in prostate cancer. Furthermore, knockdown of DLEU2 attenuated prostate cancer tumorigenesis in vivo. Notably, these findings suggested that E2F2-activated DLEU2 may function as a competing endogenous RNA to facilitate prostate cancer progression by targeting the miR-582-5p/SGK1 axis.