A dynamic online nomogram for predicts delayed postoperative bleeding after colorectal polyp surgery.

This study aims to analyze the risk factors associated with delayed postoperative bleeding (DPPB) following colorectal polyp surgery, develop a dynamic nomogram and evaluate the model efficacy, provide a reference for clinicians to identify the patients at high risk of DPPB. Retrospective study was done on patients who underwent endoscopic colorectal polypectomy at the First Hospital of Lanzhou University from January 2020 to March 2023. Differences between the group with and without DPPB were compared, and independent risk factors for DPPB occurrence were identified through univariate analysis and combination LASSO and logistic regression. A dynamic nomogram was constructed based on multiple logistic regression to predict DPPB following colorectal polyp surgery. Model evaluation included receiver operating characteristic (ROC), Calibration curve, Decision curve analysis (DCA). DPPB occurred in 38 of the 1544 patients included. multivariate analysis showed that direct oral anticoagulants (DOACs), polyp location in the right hemi colon, polyp diameter, drink, and prophylactic hemoclips were the independent risk factors for DPPB and dynamic nomogram were established. Model validation indicated area under the ROC curve values of 0.936, 0.796, and 0.865 for the training set, validation set, and full set, respectively. The calibration curve demonstrated a strong alignment between the predictions of the column-line diagram model and actual observations. The decision curve analysis (DCA) displayed a significant net clinical benefit across the threshold probability range of 0-100%. The dynamic nomogram aids clinicians in identifying high-risk patients, enabling personalized diagnosis and treatment.

Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS).

Background: Teriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use. Objective: To investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference. Methods: FAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals. Results: Out of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%). Conclusion: Our findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide's clinical use.

Preparation and characterization of Iturin A/chitosan microcapsules and their application in post-harvest grape preservation.

Iturin A (IA) encapsulated in chitosan (CS) microcapsules (IA/CS) underwent thorough physicochemical characterization using thermogravimetric analysis (TGA), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). SEM confirmed the smooth, spherical morphology of the IA/CS microcapsules, while FTIR revealed complex intermolecular interactions between IA and CS. TGA demonstrated thermal stability within the 0-100 °C range, while particle size analysis revealed an average diameter of 553.4 nm. To evaluate IA/CS efficacy in post-harvest grape preservation, grapes were treated with sterile water (CK), 10 g/L CS, 0.1 g/L IA/CS, and 0.1 g/L chitosan empty microcapsules (CKM), then stored at 25 °C for 16 days. IA/CS significantly reduced decay and respiration intensity by 52.3 % and 23.8 %, respectively, compared to CK. IA/CS treatment also inhibited abscission rate, weight loss, firmness reduction, total soluble solids consumption, titratable acidity consumption, polyphenol oxidase, and peroxidase activities on par with CS treatment (p > 0.05), but performed better than CK (reductions of 26.9 %, 41.2 %, 25.8 %, 27.2 %, 24.2 %, 19.4 %, and 17.4 %, respectively) and CKM (p < 0.05). Sensory evaluation confirmed that IA/CS effectively suppressed decay, slowed post-harvest metabolic activity, and maintained grape quality. Therefore, IA/CS microcapsules offer a promising method for extending grape shelf life and preserving quality.

Analysis of the Potential Angiogenic Mechanisms of BuShenHuoXue Decoction against Osteonecrosis of the Femoral Head Based on Network Pharmacology and Experimental Validation.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease with a high disability rate. The clinical effect of BuShenHuoXue decoction (BSHX) for ONFH is satisfactory. We aimed to elucidate the potential angiogenic mechanisms of BSHX in a rat femoral osteonecrosis model and bone marrow mesenchymal stem cells (BMSCs). METHODS: With in vivo experiments, we established the steroid-induced osteonecrosis of the femoral head (SONFH) model using Sprague-Dawley (SD) rats (8-week-old). The rats were randomly divided into five group of 12 rats each and given the corresponding interventions: control, model (gavaged with 0.9% saline), BSHX low-, medium- and high-dose groups (0.132 3, 0.264 6, and 0.529 2 g/mL BSHX solution by gavage). After 12 weeks, haematoxylin and eosin (H&E) staining was preformed to evaluate rat osteonecrosis. the expression of angiogenic factors (CD31, VEGFA, KDR, VWF) in rat femoral head was detected by immunohistochemistry, qPCR and western blotting. In cell experiment, BMSCs were isolated and cultured in the femoral bone marrow cavity of 4-week-old SD rats. BMSCs were randomly divided into eight groups and intervened with different doses of BSHX-containing serum and glucocorticoids: control group (CG); BSHX low-, medium-, and high-dose groups (CG + 0.661 5, 1.323, and 2.646 g/kg BSHX gavage rat serum); dexamethasone (Dex) group; and Dex + BSHX low-, medium-, and high-dose groups (Dex + 0.661 5, 1.323, and 2.646 g/kg BSHX gavaged rat serum), the effects of BSHX-containing serum on the angiogenic capacity of BMSCs were examined by qPCR and Western blotting. A co-culture system of rat aortic endothelial cells (RAOECs) and BMSCs was then established. Migration and angiogenesis of RAOECs were observed using angiogenesis and transwell assay. Identification of potential targets of BSHX against ONFH was obtained using network pharmacology. RESULTS: BSHX upregulated the expression of CD31, VEGFA, KDR, and VWF in rat femoral head samples and BMSCs (p < 0.05, vs. control group or model group). Different concentrations of BSHX-containing serum significantly ameliorated the inhibition of CD31, VEGFA, KDR and VWF expression by high concentrations of Dex. BSHX-containing serum-induced BMSCs promoted the migration and angiogenesis of RAOECs, reversed to some extent the adverse effect of Dex on microangiogenesis in RAOECs, and increased the number of microangiogenic vessels. Furthermore, we identified VEGFA, COL1A1, COL3A1, and SPP1 as important targets of BSHX against ONFH. CONCLUSION: BSHX upregulated the expression of angiogenic factors in the femoral head tissue of ONFH model rats and promoted the angiogenic capacity of rat RAOECs and BMSCs. This study provides an important basis for the use of BSHX for ONFH prevention and treatment.

Combination of fractional carbon dioxide laser with recombinant human collagen in periocular skin rejuvenation.

BACKGROUND: The most visible sign of facial aging is often seen in the periocular area. However, periocular rejuvenation remains challenging due to the particularity of periocular anatomic locations. AIMS: We aimed to evaluate the efficacy and safety of the fractional-ablative CO2 laser-facilitated recombinant human collagen permeation in periocular rejuvenation. PATIENTS/METHODS: This 3-month prospective single-blinded and self-controlled trial enrolled 26 patients with periocular aging who underwent the treatments of fractional-ablative CO2 laser along with laser-facilitated recombinant human collagen permeation. Following the treatments, the patients were quantitatively assessed by various periocular skin aging indices before and after the treatment and monitored for any related adverse events. RESULTS: The patients showed significant improvements with the periocular skin aging indices 3 months after the treatments, which were detailed with a 47.3% decrease in lower eyelid skin rhytids, a 41.4% decrease in the lower eyelid skin texture, a 35.0% decrease in the static crow's feet, a 29.3% decrease in the amount of upper eyelid laxity, and a 20.2% increase in the MRD1 as compared with baseline (p < 0.05). Moreover, total skin thickness under ultrasound was increased in both upper and lower eyelids (5.6% and 3.3%, p < 0.05, respectively). Moreover, six patients (23.1%, 6/26) had erythema for 2 weeks, and two (2/26, 7.7%) had mild hyperpigmentation for 3 months. CONCLUSIONS: Fractional-ablative CO2 laser combined with laser-facilitated recombinant human collagen permeation can be a safe and effective treatment for periocular rejuvenation.

Knowledge mapping of programmed cell death in osteonecrosis of femoral head: a bibliometric analysis (2000-2022).

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common, refractory and disabling disease of orthopedic department, which is one of the common causes of hip pain and dysfunction. Recent studies have shown that much progress has been made in the research of programmed cell death (PCD) in ONFH. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hot spots of PCD in ONFH through bibliometrics. METHOD: The literature search related to ONFH and PCD was conducted on the Web of Science Core Collection (WoSCC) database from 2002 to 2021. The VOSviewers, "bibliometrix" R package and CiteSpace were used to conduct this bibliometric analysis. RESULTS: In total, 346 articles from 27 countries led by China and USA and Japan were included. The number of publications related to PCD in ONFH is increasing year by year. Shanghai Jiao Tong University, Xi An Jiao Tong University, Wuhan University and Huazhong University of Science and Technology are the main research institutions. Molecular Medicine Reports is the most popular journal in the field of PCD in ONFH, and Clinical Orthopaedics and Related Research is the most cocited journal. These publications come from 1882 authors among which Peng Hao, Sun Wei, Zhang Chang-Qing, Zhang Jian and Wang Kun-zheng had published the most papers and Ronald S Weinstein was cocited most often. Apoptosis, osteonecrosis, osteonecrosis of the femoral head, glucocorticoid and femoral head appeared are the main topics the field of PCD in ONFH. Autophagy was most likely to be the current research hot spot for PCD in ONFH. CONCLUSION: This is the first bibliometric study that comprehensively summarizes the research trends and developments of PCD in ONFH. This information identified recent research frontiers and hot directions, which will provide a reference for scholars studying PCD in ONFH.

The Effect of the Hip Flexion Angle in Osteonecrosis of the Femoral Head Based on China-Japan Friendship Hospital Classification - A Finite Element Study.

OBJECTIVE: The alteration in the mechanical environment of the necrotic area is the primary cause of the collapse observed in osteonecrosis of the femoral head (ONFH). This study aims to evaluate the biomechanical implications of the China-Japan Friendship Hospital (CJFH) classification system and hip flexion angles on the necrotic area in ONFH using finite element analysis (FEA). The goal is to provide valuable guidance for hip preservation treatments and serve as a reference for clinical diagnosis and therapeutic interventions. METHODS: Hip tomography CT scan data from a healthy volunteer was used to create a 3D model of the left hip. The model was preprocessed and imported into Solidworks 2018, based on the CJFH classification. Material parameters and boundary conditions were applied to each fractal model in ANSYS 21.0. Von Mises stresses were calculated, and maximum deformation values were obtained to evaluate the biomechanical effects of the load on the necrotic area and post-necrotic femur, as well as assess each fractal model's collapse risk. RESULTS: (1) At the same hip flexion angle, maximum deformation followed this order: M Type < C Type < L Type. The L3 type necrotic area experienced the most significant deformation at 0, 60, and 110° angles (1.121, 1.7913, and 1.8239 mm respectively). (2) Under the same CJFH classification, maximum deformation values increased with hip flexion angle (0 < 60 < 110°), suggesting a higher risk of collapse at larger angles. (3) Von Mises stress results showed that the maximum stress was not located in the necrotic area but near the inner and outer edge of the femoral neck, indicating decreased stiffness and strength of the subchondral bone after osteonecrosis. CONCLUSION: The study found that femoral head collapse risk was higher when the necrotic area was located in the lateral column under the same stress load and flexion angle. Mechanical properties of the necrotic area changed, resulting in decreased bone strength and stiffness. Large-angle hip flexion is more likely to cause excessive deformation of the necrotic area; thus, ONFH patients should reduce or avoid large-angle hip flexion during weight-bearing training in rehabilitation activities.

IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head.

PURPOSE: Steroid-induced osteonecrosis of the femoral head (SONFH) was a refractory orthopedic hip joint disease in the young and middle-aged people, but the pathogenesis of SONFH remained unclear. We aimed to identify the potential genes and screen potential therapeutic compounds for SONFH. METHODS: The microarray was obtained for blood tissue from the GEO database, and then it identifies differentially expressed genes (DEGs). The DEGs were analyzed to obtain the differences in immune cell infiltration. The gene functional enrichment analysis of SONFH was analyzed. The PPI of DEGs was identified through the STRING database, and the cluster modules and hub genes were ascertained using MCODE and CytoHubba, and the ROC curve of hub genes was analyzed, and the tissues distribution of hub genes was understood by the HPA, Bgee and BioGPS databases. The hub genes and target miRNAs and corresponding upstream lncRNAs were predicted by TargetScan, miRDB and ENCORI database. Subsequently, we used CMap, DGIdb and L1000FWD databases to identify several potential therapeutic molecular compounds for SONFH. Finally, the AutoDockTools Vina, PyMOL and Discovery Studio were employed for molecular docking analyses between compounds and hub genes. RESULTS: The microarray dataset GSE123568 was obtained related to SONFH. There were 372 DEGs including 197 upregulated genes and 175 downregulated genes by adjusted P value < 0.01 and |log2FC|> 1. Several significant GSEA enrichment analysis and biological processes and KEGG pathway associated with SONFH were identified, which were significantly related to cytoskeleton organization, nucleobase-containing compound catabolic process, NOD-like receptor signaling pathway, MAPK signaling pathway, FoxO signaling pathway, neutrophil-mediated immunity, neutrophil degranulation and neutrophil activation involved in immune response. Activated T cells CD4 memory, B cells naïve, B cells memory, T cells CD8 and T cells gamma delta might be involved in the occurrence and development of SONFH. Three cluster modules were identified in the PPI network, and eleven hub genes including FPR2, LILRB2, MNDA, CCR1, IRF8, TYROBP, TLR1, HCK, TLR8, TLR2 and CCR2 were identified by Cytohubba, which were differed in bone marrow, adipose tissue and blood, and which had good diagnostic performance in SONFH. We identified IRF8 and 10 target miRNAs that was utilized including Targetsan, miRDB and ENCORI databases and 8 corresponding upstream lncRNAs that was revealed by ENCORI database. IRF8 was detected with consistent expression by qRT-PCR. Based on the CMap, DGIdb and L1000FWD databases, the 11 small molecular compounds that were most strongly therapeutic correlated with SONFH were estradiol, genistein, domperidone, lovastatin, myricetin, fenbufen, rosiglitazone, sirolimus, phenformin, vorinostat and vinblastine. All of 11 small molecules had good binding affinity with the IRF8 in molecular docking. CONCLUSION: The occurrence of SONFH was associated with a "multi-target" and "multi-pathway" pattern, especially related to immunity, and IRF8 and its noncoding RNA were closely related to the development of SONFH. The CMap, DGIdb and L1000FWD databases could be effectively used in a systematic manner to predict potential drugs for the prevention and treatment of SONFH. However, additional clinical and experimental research is warranted.

The combination of molecular docking and network pharmacology reveals the molecular mechanism of Danggui Niantong decoction in treating gout.

BACKGROUND: Due to unhealthy diet and living habits, the incidence of gout is on the rise and has become a common disease with a high incidence. Danggui Niantong decoction (DGNTD), as a classic formula composed of 15 common herbs, has been widely used in clinical practice since ancient times to prevent and treat gout. However, the pharmacological mechanism and target of DGNTD are not clear. METHODS: The potential active compounds and targets of DGNTD were obtained by traditional Chinese medicine systems pharmacology (TCMSP) database, and the differential genes of gout patients and controls were analyzed in gene expression omnibus (GEO) database. GSEA analysis of differential genes with GSEA 4.1.0 software and then the differential genes were intersected with the gout-related disease targets searched by GeneCard, CTD and OMIM disease database to obtain the final disease target. The "Traditional Chinese medicine-Active compounds-Targets" network was constructed by Cytoscape3.7.2 software. The R packet is used for enrichment analysis. The molecular docking between the active compound of DGNTD and the core target was verified by AutoDockTools software. RESULTS: Two hundred eighty six and 244 targets of DGNTD-related active components and 652 targets of gout were obtained, of which 13 targets were potential targets of DGNTD in the treatment of gout. GSEA analysis showed that the differential genes were mainly involved in apoptosis, inflammatory reaction, and receptor metabolism and so on. Gene ontology (GO) functional enrichment analysis shows that DGNTD regulates many biological processes, such as the response to purine-containing compound and response to lipopolysaccharide, positive regulation of acute inflammatory response and other cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that DGNTD treatment of gout is mainly related to interleukin-17 (IL-17), Toll-like receptor, rheumatoid arthritis, tumor necrosis factor (TNF) and so on. The results of molecular docking showed that the five active compounds in DGNTD had strong binding activity to core protein receptors. CONCLUSIONS: The active compounds of DGNTD may achieve the purpose of treating gout by acting on the core target (CASP8, CXCL8, FOS, IL1B, IL6, JUN, PTGS2, STAT1, MMP1, TNF) to regulate cell metabolism, proliferation and apoptosis, and improve inflammatory response, which is the result of multi-component, multi-target and multi-pathway interaction. It provides an idea for the development of new combined drugs for gout.

KLF4 suppresses the proliferation and metastasis of NSCLC cells via inhibition of MSI2 and regulation of the JAK/STAT3 signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains an aggresive tumor with poor survival rates. Krüppel-like factor 4 (KLF4) is known to be involved in progression of NSCLC; however, the detailed mechanism by which KLF4 regulates the progression of NSCLC remains unclear. METHODS: In order to investigate the function of KLF4 in NSCLC, cell proliferation was measured by MTT and colony formation assays. The migration and invasion of NSCLC cells were detected via wound healing and Transwell assays, respectively. Then, the interaction between KLF4 and MSI2 was confirmed using a dual-luciferase reporter assay, and the mechanism by which KLF4 regulates the tumorigenesis of NSCLC was assessed by RT-qPCR and Western blotting. RESULTS: The results showed that KLF4 was downregulated, while MSI2 was upregulated in NSCLC. Additionally, KLF4 could inhibit transcription of MSI2, and overexpression of KLF4 or knockdown of MSI2 could inhibit the proliferation, migration and invasion of NSCLC cells. Moreover, KLF4 could inhibit JAK2/STAT3 signalling pathway. CONCLUSIONS: In conclusion, KLF4 significantly inhibited the proliferation, invasion and migration of NSCLC cells via inactivation of MSI2/JAK2/STAT3 signalling pathway. Thereby, our finding might shed new lights on exploring the new strategies against NSCLC.

Identification of potential autophagy-related genes in steroid-induced osteonecrosis of the femoral head via bioinformatics analysis and experimental verification.

PURPOSE: Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory orthopaedic hip joint disease that occurs in young- and middle-aged people. Previous experimental studies have shown that autophagy might be involved in the pathological process of SONFH, but the pathogenesis of autophagy in SONFH remains unclear. We aimed to identify and validate the key potential autophagy-related genes involved in SONFH to further illustrate the mechanism of autophagy in SONFH through bioinformatics analysis. METHODS: The GSE123568 mRNA expression profile dataset, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Autophagy-related genes were obtained from the Human Autophagy Database (HADb). The autophagy-related genes involved in SONFH were screened by intersecting the GSE123568 dataset with the set of autophagy genes. The differentially expressed autophagy-related genes involved in SONFH were identified with R software. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially expressed autophagy-related genes involved in SONFH were conducted by using R software. Then, the correlations between the expression levels of the differentially expressed autophagy-related genes involved in SONFH were confirmed with R software. Moreover, the protein-protein interaction (PPI) network was analysed by using the Search Tool for the Retrieval of Interacting Genes (STRING), significant gene cluster modules were identified with the MCODE Cytoscape plugin, and hub genes among the differentially expressed autophagy-related genes involved in SONFH were screened by using the CytoHubba Cytoscape plugin. Finally, the expression levels of the hub genes of the differentially expressed autophagy-related genes involved in SONFH were validated in hip articular cartilage specimens from necrotic femur heads (NFHs) by using the GSE74089 dataset and further verification by qRT-PCR. RESULTS: A total of 34 differentially expressed autophagy-related genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 25 upregulated genes and 9 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 34 differentially expressed autophagy-related genes involved in SONFH were particularly enriched in death domain receptors, the FOXO signalling pathway and apoptosis. Correlation analysis revealed significant correlations among the 34 differentially expressed autophagy-related genes involved in SONFH. The PPI results demonstrated that the 34 differentially expressed autophagy-related genes interacted with each other. Ten hub genes were identified by using the MCC algorithms of CytoHubba. The GSE74089 dataset showed that TNFSF10, PTEN and CFLAR were significantly upregulated while BCL2L1 was significantly downregulated in the hip cartilage specimens, which was consistent with the GSE123568 dataset. TNFSF10, PTEN and BCL2L1 were detected with consistent expression by qRT-PCR. CONCLUSIONS: Thirty-four potential autophagy-related genes involved in SONFH were identified via bioinformatics analysis. TNFSF10, PTEN and BCL2L1 might serve as potential drug targets and biomarkers because they regulate autophagy. These results expand the autophagy-related understanding of SONFH and might be useful in the diagnosis and prognosis of SONFH.

MiRNA21 and IL-18 levels in left atrial blood in patients with atrial fibrillation undergoing cryoablation and their predictive value for recurrence of atrial fibrillation.

PURPOSE: The recurrence of atrial fibrillation (AF) after cryoablation still needs to be prioritized, including discriminating predictive indicators. METHODS: Eighty-seven patients aged 43-83 years who underwent cryo-balloon ablation were divided into paroxysmal atrial fibrillation (PAF) and non-paroxysmal atrial fibrillation (non-PAF) groups. Baseline data, intraoperative index, and miRNA21, IL-18, NLRP3, and visfatin levels in peripheral venous blood and left atrial blood were assessed. Follow-up was performed for 6 months to observe the recurrence of AF. A Cox risk ratio model was used to analyze indicators for predicting AF recurrence. RESULTS: The non-PAF and PAF group recurrence rates of AF were statistically different (p < 0.05) at 9/22 (40.9%) and 11/65 (16.9%), respectively. Biomarker levels in the left atrial blood were higher in the non-PAF group than in the PAF group (p < 0.05). The effects of non-PAF and levels of miRNA21 and IL-18 in left atrial serum on the recurrence of AF after cryoablation statistically differed (p < 0.05). CONCLUSION: The levels of miRNA21 and IL-18 were higher in left atrial blood than in peripheral blood, which may be related to the severity of AF and recurrence of AF after cryoablation.

A CT-Based Radiomics Nomogram Integrated With Clinic-Radiological Features for Preoperatively Predicting WHO/ISUP Grade of Clear Cell Renal Cell Carcinoma.

OBJECTIVE: This study aims to develop and validate a CT-based radiomics nomogram integrated with clinic-radiological factors for preoperatively differentiating high-grade from low-grade clear cell renal cell carcinomas (CCRCCs). METHODS: 370 patients with complete clinical, pathological, and CT image data were enrolled in this retrospective study, and were randomly divided into training and testing sets with a 7:3 ratio. Radiomics features were extracted from nephrographic phase (NP) contrast-enhanced images, and then a radiomics model was constructed by the selected radiomics features using a multivariable logistic regression combined with the most suitable feature selection algorithm determined by the comparison among least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE) and ReliefF. A clinical model was established using clinical and radiological features. A radiomics nomogram was constructed by integrating the radiomics signature and independent clinic-radiological features. Performance of these three models was assessed using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: Using multivariate logistic regression analysis, three clinic-radiological features including intratumoral necrosis (OR=3.00, 95% CI=1.30-6.90, p=0.049), intratumoral angiogenesis (OR=3.28, 95% CI=1.22-8.78, p=0.018), and perinephric metastasis (OR=2.90, 95% CI=1.03-8.17, p=0.044) were found to be independent predictors of WHO/ISUP grade in CCRCC. Incorporating the above clinic-radiological predictors and radiomics signature constructed by LASSO, a CT-based radiomics nomogram was developed, and presented better predictive performance than clinic-radiological model and radiomics signature model, with an AUC of 0.891 (95% CI=0.832-0.962) and 0.843 (95% CI=0.718-0.975) in the training and testing sets, respectively. DCA indicated that the nomogram has potential clinical usefulness. CONCLUSION: The CT-based radiomics nomogram is a promising tool to predict WHO/ISUP grade of CCRCC preoperatively and noninvasively.

Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression.

BACKGROUND: UCA1 is frequently upregulated in a variety of cancers, including CRC, and it can play an oncogenic role by various mechanisms. However, how UCA1 is regulated in cancer is largely unknown. In this study, we aimed to determine whether RNA methylation at N6-methyladenosine (m6A) can impact UCA1 expression in colorectal cancer (CRC). METHODS: qRT-PCR was performed to detect the level of UCA1 and IGF2BP2 in CRC samples. CRISPR/Cas9 was employed to knockout (KO) UCA1, METTL3 and WTAP in DLD-1 and HCT-116 cells, while rescue experiments were carried out to re-express METTL3 and WTAP in KO cells. Immunoprecipitation using m6A antibody was performed to determine the m6A modification of UCA1. In vivo pulldown assays using S1m tagging combined with site-direct mutagenesis was carried out to confirm the recognition of m6A-modified UCA1 by IGF2BP2. Cell viability was measured by MTT and colony formation assays. The expression of UCA1 and IGF2BP2 in TCGA CRC database was obtained from GEPIA ( http://gepia.cancer-pku.cn ). RESULTS: Our results revealed that IGF2BP2 serves as a reader for m6A modified UCA1 and that adenosine at 1038 of UCA1 is critical to the recognition by IGF2BP2. Importantly, we showed that m6A writers, METTL3 and WTAP positively regulate UCA1 expression. Mechanically, IGF2BP2 increases the stability of m6A-modified UCA1. Clinically, IGF2BP2 is upregulated in CRC tissues compared with normal tissues. CONCLUSION: These results suggest that m6A modification is an important factor contributing to upregulation of UCA1 in CRC tissues.

Molecular mechanism of Wutou Decoction in the treatment of osteoarthritis: a bioinformatics and molecular docking study.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction and periarticular osteophyte formation. One therapeutic option for this condition, the Wutou Decoction (WTD) Chinese medicine formula, is satisfactory in its efficacy. Here, we used bioinformatic and molecular docking techniques to investigate the mechanism of action of WTD in the treatment of OA. METHODS: The active compounds (and their target proteins) of 5 Chinese herbs in WTD were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The action targets of WTD for OA were obtained by searching the Therapeutic Target Database and by mining the microarray data in the Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to identify key targets for OA treatment with the help of Database for Annotation, Visualization, and Integrated Discovery. Based on the Cytoscape software version 3.6.1, the visual networks of the "TCM drugs-Active Compounds-Targets-Diseases" and protein-protein interaction of the key targets of WTD for the treatment of OA were constructed. The core active compounds and the key targets obtained were molecularly docked and validated. RESULTS: Analyses revealed 140 active compounds in WTD, 123 of which had a total of 163 corresponding targets. In addition, 331 differentially expressed genes and 227 OA-related targets were obtained. The interaction networks among 32 key targets were identified. The biological processes of WTD in treating OA mainly involved regulation of inflammatory factors, transcription of genetic materials, cell cycle, angiogenesis, and endocrine regulation. The signaling pathways involved mainly included TNF signaling pathway, rheumatoid arthritis signaling pathway, cancer-related signals, vascular endothelial growth factor signaling pathway, and osteoclast differentiation signaling pathways. Molecular docking showed that 7 core compounds including quercetin and kaempferol had strong affinities with key target proteins for the WTD treatment of OA. CONCLUSIONS: WTD with multi-component can treats OA through multi-pathway. Its active compounds, including quercetin and kaempferol, can exert their therapeutic effects on OA by acting on TNF, PTGS2, MMP2, IL-6, IL-1ß, and other key targets to regulate inflammation, immunity, autophagy, and endocrine-related signaling pathways.

Exogenous 1',4'-trans-Diol-ABA Induces Stress Tolerance by Affecting the Level of Gene Expression in Tobacco (Nicotiana tabacum L.).

1',4'-trans-diol-ABA is a key precursor of the biosynthesis of abscisic acid (ABA) biosynthesis in fungi. We successfully obtained the pure compound from a mutant of Botrytis cinerea and explored its function and possible mechanism on plants by spraying 2 mg/L 1',4'-trans-diol-ABA on tobacco leaves. Our results showed that this compound enhanced the drought tolerance of tobacco seedlings. A comparative transcriptome analysis showed that a large number of genes responded to the compound, exhibiting 1523 genes that were differentially expressed at 12 h, which increased to 1993 at 24 h and 3074 at 48 h, respectively. The enrichment analysis demonstrated that the differentially expressed genes (DEGs) were primarily enriched in pathways related to hormones and resistance. The DEGs of transcription factors were generally up-regulated and included the bHLH, bZIP, ERF, MYB, NAC, WRKY and HSF families. Moreover, the levels of expression of PYL/PYR, PP2C, SnRK2, and ABF at the ABA signaling pathway responded positively to exogenous 1',4'-trans-diol-ABA. Among them, seven ABF transcripts that were detected were significantly up-regulated. In addition, the genes involved in salicylic acid, ethylene and jasmonic acid pathways, reactive oxygen species scavenging system, and other resistance related genes were primarily induced by 1',4'-trans-diol-ABA. These findings indicated that treatment with 1',4'-trans-diol-ABA could improve tolerance to plant abiotic stress and potential biotic resistance by regulating gene expression, similar to the effects of exogenous ABA.

M6A modification of circNSUN2 promotes colorectal liver metastasis.

Circular RNAs (circRNAs) are playing emerging role in the pathogenesis of cancers, but the mechanisms still unknown. In the recent issue of the Nature Communications, Chen and colleagues have demonstrated that YTHDC1 facilitates N6-methyladenosine modified circNSUN2 cytoplasmic export and the circNSUN2/IGF2BP2/HMGA2 complex stabilizes HMGA2 to promote colorectal liver metastasis. These discoveries not only expand our understanding of circRNAs biology in tumor, but also demonstrate that m6A modification plays a key role for circRNAs in RNA metabolism. Therefore, these findings indicate that circRNAs may be a new approach for therapeutic target of cancers.

Oxidative-protective effect of nuclear receptor coactivator 7 on arecoline-induced endothelial-to-mesenchymal transition.

OBJECTIVE: Overproduction of reactive oxygen species (ROS) has been implicated in inflammatory activities and tumorigenesis in oral submucous fibrosis (OSF). Nuclear receptor coactivator 7 (NCOA7) is capable of regulating cellular responses to ROS. The aim of this study was to investigate the expression of NCOA7 in endothelial cells and the role of NCOA7 in areca nut-induced endothelial-to-mesenchymal transition (EndMT). STUDY DESIGN: Immunohistochemistry and immunofluorescence were used to detect the expression of NCOA7 in endothelia. Human umbilical vein endothelial cells (HUVECs) were treated with various dosages of arecoline (0, 5, 10, 20 µg/mL); then NCOA7 expression, the correlation of NCOA7 with EndMT, and the potential signaling were analyzed by using small interfering RNA (siRNA) transfection, reverse transcription polymerase chain reaction, Western blotting, and flow cytometry. RESULTS: NCOA7 was significantly elevated in OSF tissues, as detected with immunohistochemistry and immunofluorescence. After arecoline treatment, NCOA7 expression and EndMT were induced in HUVECs. Transfection of HUVECs with si-NCOA7, which reduced 73% of NCOA7 expression, aggravated the arecoline-induced EndMT process. Inhibition of ROS markedly, but not completely, reverses this arecoline-induced EndMT in si-NCOA7 cells. CONCLUSIONS: This study highlights NCOA7 as a potential target for therapeutic intervention to mediate EndMT via ROS species production.