Association between HMGA1 and immunosuppression in hepatocellular carcinoma: A comprehensive bioinformatics analysis.

The high mobility group A1 (HMGA1) gene is overexpressed in malignant tumors, and its expression level correlates with the progression and metastasis of tumors. However, the specific role of HMGA1 in hepatocellular carcinoma (HCC) and relevant influencing approaches in tumor immunity remain unclear. In this study, the expression and clinical significance of HMGA1 in HCC immunity were analyzed. The expression levels of HMGA1 mRNA and protein in HCC tissue and normal liver tissue were analyzed based on the cancer genome atlas, the gene expression omnibus and the Human Protein Atlas databases. The correlation between HMGA1 and clinicopathological factors was analyzed, and survival was estimated based on the expression of HMGA1. Gene set cancer analysis and the TISIDB database were used to identify tumor-infiltrating immune cells and immune inhibitors. Gene set enrichment analysis was performed to determine the involved signaling pathway. The HMGA1 genetic alterations were identified with the cBioPortal for Cancer Genomics. The expression of HMGA1 mRNA and protein was significantly higher in HCC tissue and negatively correlated with survival. Neutrophils, Th17 cells, several immune inhibitors, and signaling pathways were positively correlated with the expression of HMGA1. Amplification was the main type of genetic alteration in HMGA1. These findings demonstrate that HMGA1 can be a therapeutic target and a potential biomarker to predict the prognosis of patients with HCC. HMGA1 may affect the progression of HCC by suppressing the immune function of these patients.

Curcumin- and resveratrol-co-loaded nanoparticles in synergistic treatment of hepatocellular carcinoma.

BACKGROUND: Currently, systemic therapies for patients with advanced-stage hepatocellular carcinoma (HCC) rely mainly on systemic drugs. However, traditional systemic drugs have a high rate of serious adverse events, and the curative effects of some potential anticancer drugs, such as curcumin (CUR) and resveratrol (RSV), are less apparent due to their poor bioavailability. Therefore, it is urgent to develop a highly effective therapy to improve patient prognosis. Herein, an injectable HCC-targeted nanoparticle (NP) was designed to deliver CUR and RSV to hepatoma cells. RESULTS: The molecular self-assembled NPs showed higher tumour retention through the enhanced permeability and retention (EPR) effect of the NPs and surface modification with the HCC-specific peptide moiety SP94 to effectively treat HCC. These HCC-targeted NPs led to a significant reduction in the drug dosage, delayed the rate of drug release and improved the bioavailability of the encapsulated drugs. The drug concentrations in the vicinity of the tumour increased, and a good therapeutic effect was observed without obvious side effects. CONCLUSIONS: These SP94-mediated NPs allowed large amounts of antitumor drugs to accumulate in tumours, providing a novel strategy for innovative HCC therapy. This nanoplatform also offers an idea for exploring other potential chemotherapeutics.

A novel nomogram and risk classification system predicting the Ewing sarcoma: a population-based study.

Ewing sarcoma (ES) is a rare disease that lacks a prognostic prediction model. This study aims to develop a nomogram and risk classification system for estimating the probability of overall survival (OS) of patients with ES. The clinicopathological data of ES were collected from the Surveillance, Epidemiology and Final Results (SEER) database from 2010 to 2018. The primary cohort was randomly assigned to the training set and the validation set. Univariate and multiple Cox proportional hazard analyses based on the training set were performed to identify independent prognostic factors. A nomogram was established to generate individualized predictions of 3- and 5-year OS and evaluated by the concordance index (C-index), the receiver operating characteristic curve (ROC), the calibration curve, the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Based on the scores calculated with the nomogram, ES patients were divided into three risk groups to predict their survival. A total of 935 patients were identified, and a nomogram consisting of 6 variables was established. The model provided better C-indices of OS (0.788). The validity of the Cox model assumptions was evaluated through the Schönfeld test and deviance residual. The ROC, calibration curve, IDI and NRI indicated that the nomogram exhibited good performance. A risk classification system was built to classify the risk group of ES patients. The nomogram compares favourably and accurately to the traditional SEER tumour staging systems, and risk stratification provides a more convenient and effective tool for clinicians to optimize treatment options.

Nomogram for predicting the overall survival of patients with early-onset prostate cancer: A population-based retrospective study.

BACKGROUND: The incidence of early-onset prostate cancer (PCa) has increased significantly over the past few decades. It is necessary to develop a prognostic nomogram for the prediction of overall survival (OS) in early-onset PCa patients. METHODS: A total of 23,730 early-onset PCa patients (younger than 55 years old) between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled for the current study, and randomly separated into the training cohort and the validation cohort. 361 eligible early-onset PCa patients from The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) cohort were obtained as the external validation cohort. Independent predictors were selected by univariate and multivariate Cox regression analysis, and a prognostic nomogram was constructed for 1-, 3-, and 5-year OS. The accurate and discriminative abilities of the nomogram were evaluated by the concordance index (C-index), receiver operating characteristic curve (ROC), calibration plot, net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: Multivariate Cox analysis showed that race, marital status, TNM stage, prostate-specific antigen, Gleason score, and surgery were significantly associated with poor prognosis of PCa. A nomogram consisting of these variables was established, which had higher C-indexes than the TNM system (training cohort: 0.831 vs. 0.746, validation cohort: 0.817 vs. 0.752). Better AUCs of the nomogram than the TNM system at 1, 3, and 5 years were found in both the training cohort and the validation cohort. The 3-year and 5-year AUCs of the nomogram in the TCGA-PRAD cohort were 0.723 and 0.679, respectively. The calibration diagram, NRI, and IDI also showed promising prognostic value in OS. CONCLUSIONS: We developed an effective prognostic nomogram for OS prediction in early-onset PCa patients, which will further assist both the precise clinical treatment and the assessment of long-term outcomes.

Association between socioeconomic status and survival in patients with hepatocellular carcinoma.

BACKGROUND: The effect of socioeconomic status (SES) on hepatocellular carcinoma (HCC) is still unclear, and there is no nomogram integrated SES and clinicopathological factors to predict the prognosis of HCC. This research aims to confirm the effects of SES on predicting patients' survival and to establish a nomogram to predict the prognosis of HCC. METHODS: The data of HCC patients were collected from the Surveillance, Epidemiology, and Final Results (SEER) database from 2011 to 2015. SES (age at diagnosis, race and sex, median family income, education level, insurance status, marital status, residence, cost of living index, poverty rate) and clinicopathological factors were included in univariate and multivariate Cox regression analysis. Nomograms for predicting 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) were established and evaluated by the concordance index (C-index), the receiver operating characteristic curve (ROC), the calibration plot, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI). RESULTS: A total of 33,670 diagnosed HCC patients were involved, and nomograms consisting of 19 variables were established. The C-indexes of the nomograms are higher than TNM staging system, which predicts the CSS (0.789 vs. 0.692, p < 0.01) and OS (0.777 vs. 0.675, p < 0.01). The ROC curve, calibration diagram, IDI, and NRI showed the improved prognostic value in 1-, 3-, and 5-year survival rates. CONCLUSION: SES plays an important role in the prognosis of HCC patients. Therefore, policymakers can make more precise and socially approved policies to improve HCC patients' CSS and OS.

Robot-assisted vs freehand cannulated screw placement in femoral neck fractures surgery: A systematic review and meta-analysis.

BACKGROUND: Several studies have reported that medical robot-assisted method (RA) might be superior to conventional freehand method (FH) in orthopedic surgery. Yet the results are still controversial, especially in terms of femoral neck fractures surgery. Here, 2 methods were assessed based on current evidence. METHODS: Electronic databases including Cochrane Library, PubMed, Web of Science. and EMBASE were selected to retrieved to identify eligible studies between freehand and RAs in femoral neck fractures, with 2 reviewers independently reviewing included studies as well as collecting data. RESULTS: A total of 5 studies with 331 patients were included. Results indicated that 2 surgical methods were equivalent in terms of surgical duration, Harris score, fracture healing time, fracture healing proportion and complications, while RA showed clinical benefits in radiation exposure, intraoperative bleeding, total drilling times, and screw parallelism. CONCLUSIONS: Current literature revealed significantly difference between 2 techniques and suggested that RA might be beneficial for patients than freehand method.

The distribution and psychological distress related to COVID-19 of spine patients in a Grade-A tertiary hospital in Anhui province, China.

The COVID-19 pandemic may cause psychological distress, changes in numbers and distributions of patients in spine surgery patients, which all affect the strategies of spine surgery treatment. These changes may be related to the number of new COVID-19 cases per day since they are visual indicators of the changes in the epidemic and are of interest to the public. This descriptive research took the spine surgery department as an example in a Grade-A tertiary hospital in Anhui province, China. The number and distribution of patients from January 24 to April 2, 2020 was collected and compared with the past 5 years. A psychological scale was constructed to assess the psychological distress of patients and the number of new COVID-19 cases per day in Anhui, China was collected each day from January 24 to April 2, 2020. Also, this research compared these variables with the emergency response or the number of new COVID-19 cases per day. All distributions dropped dramatically during first-level emergency response and then back to normal. The psychological distress of patients was relatively higher at the beginning of the outbreak and then gradually returned to normal. The trends between the psychological distress of patients and the number of new COVID-19 cases per day were similar. The number of new COVID-19 cases per day could be used to predict psychological distress, changes in patient numbers and distributions, which was beneficial for the department of spine surgery to adjust its treatment strategy during the epidemic.

Prevention and control measures of the coronavirus disease 2019 (COVID-19) in low-risk departments: The spine surgery department example.

As the coronavirus disease 2019 (COVID-19) spreads globally, hospital departments will need take steps to manage their treatment procedures and wards. The preparations of high-risk departments (infection, respiratory, emergency, and intensive care unit) were relatively well within this pandemic, while low-risk departments may be unprepared. The spine surgery department in The First Affiliated Hospital of Anhui Medical University in Hefei, China, was used as an example in this study. The spine surgery department took measures to manage the patients, medical staff and wards to avoid the cross-infection within hospital. During the outbreak, no patients or healthcare workers were infected, and no treatment was delayed due to these measures. The prevention and control measures effectively reduced the risk of nosocomial transmission between health workers and patients while providing optimum care. It was a feasible management approach that was applicable to most low-risk and even high-risk departments.

Extracellular vesicles from endothelial progenitor cells prevent steroid-induced osteoporosis by suppressing the ferroptotic pathway in mouse osteoblasts based on bioinformatics evidence.

Abnormal antioxidative capabilities were observed in the pathogenesis of steroid-induced osteoporosis (SIOP). Ferroptosis is a recently discovered type of cell death that is characterized by the overproduction of ROS in response to GPX4 and system Xc- downregulation, which is mediated by an Fe2+ fenton reaction. However, investigations focusing on the relationship between ferroptosis and steroid-induced bone disease remain limited. In the present study, high-dose dexamethasone was used to establish a mouse SIOP model, and extracellular vesicles extracted from bone marrow-derived endothelial progenitor cells (EPC-EVs) alleviated the pathological changes in SIOP via microtomography (micro-CT), with elevations in bone volume (BV), bone surface (BS), trabecular thickness (Tb.Th), and trabecular connectivity density (Conn-D) and decreases in trabecular separation (Tb.sp) and the structure model index (SMI). Histopathological analysis, such as haematoxylin and eosin (HE) and Masson staining, showed that EPC-EVs treatment increased the volume and density of the trabecular bone and bone marrow. RNA sequencing (RNA-seq) and bioinformatics analysis revealed subcellular biological alterations upon steroid and EPC-EVs treatment. Compared with the control, high-dose dexamethasone downregulated GPX4 and system XC-, and the Kyoto Encyclopedia of Genes and Genomes (KEGG)-based gene set enrichment analysis suggested that the ferroptotic pathway was activated. In contrast, combination treatment with EPC-EVs partly reversed the KEGG-mapped changes in the ferroptotic pathway at both the gene and mRNA expression levels. In addition, alterations in ferroptotic marker expression, such as SLC3A2, SLC7A11, and GPX4, were further confirmed by RNA-seq. EPC-EVs were able to reverse dexamethasone treatment-induced alterations in cysteine and several oxidative injury markers, such as malondialdehyde (MDA), glutathione (GSH), and glutathione disulphide (GSSG) (as detected by ELISA). In conclusion, EPC-EVs prevented mouse glucocorticoid-induced osteoporosis by suppressing the ferroptotic pathway in osteoblasts, which may provide a basis for novel therapies for SIOP in humans.

Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex.

BACKGROUND: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. RESULTS: In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. CONCLUSION: These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.

Resveratrol alleviates inflammatory injury and enhances the apoptosis of fibroblast­like synoviocytes via mitochondrial dysfunction and ER stress in rats with adjuvant arthritis.

Resveratrol, a bioactive compound predominantly found in grapes and red wine, provides a wide range of properties that are beneficial for health, including anticancer and anti­inflammatory activities. Previously published studies have addressed the potential therapeutic effects of resveratrol on rheumatoid arthritis (RA); however, the subcellular mechanism remains to be fully elucidated. In the present study, the therapeutic effects of resveratrol on adjuvant arthritis (AA) in Sprague­Dawley rats were investigated, and the mechanisms of resveratrol­induced apoptosis in fibroblast­like synoviocytes (FLSs) were further examined. Based on the findings, resveratrol treatment over a 12­day period led to a reduction in paw swelling and arthritis scores at the macroscopic level, and an attenuation of inflammatory cell infiltration and synovial hyperplasia, upon a histopathological examination of the AA rats. Furthermore, the administration of resveratrol triggered decreases in the expression of interleukin (IL)­1, IL­6, IL­8 and tumor necrosis factor­α (TNF­α) and an increase in the expression of IL­10, alleviating inflammatory injury in AA rats in a dose­dependent manner. In addition, resveratrol was revealed to induce the apoptosis of FLSs when administered with 5 µM H2O2 as determined by elevated levels of Bax, caspase­3, caspase­12 and C/EBP­homologous protein, and the downregulation of B­cell lymphoma 2 (Bcl­2), suggesting that resveratrol is able to induce apoptosis in FLSs via the mitochondrial pathway and endoplasmic reticulum (ER) stress in a milieu containing 5 µM H2O2. Furthermore, JC­1 was used as a fluorescent probe to detect the mitochondrial membrane potential (Δψm), and resveratrol was shown to reduce the Δψm in FLSs in the presence of 5 µM H2O2. However, resveratrol was not able to trigger intracellular calcium overload, although it did suppress ATP­ and thapsigargin­induced calcium release from the ER. In conclusion, the present study revealed that resveratrol was able to alleviate inflammatory injury in AA rats, triggering the apoptosis of FLSs via the mitochondrial pathway and ER stress. These results provide a theoretical basis for future treatments using resveratrol for RA.

Electron Paramagnetic Resonance Study on Oxygen Vacancies and Site Occupations in Mg-Doped BaTiO3 Ceramics.

Nominal (Ba1-xMgx)TiO3 (x = 0.015) (BM1T) and (Ba1-xMgx)TiO3 (x = 0.03-0.20) (BMT) ceramics were prepared by the mixed-oxide route at sintering temperatures (Ts) of 1200-1400 °C and 1200 °C, respectively. The solubility limit of Mg2+ in BMT was determined by XRD to be x = 0.05, and evidence was found for occupation of the A site by Mg2+. Electron paramagnetic resonance (EPR) was employed as a key technique to investigate the effect of Ts on oxygen vacancies in BM1T. The structure of BM1T changed from pseudocubic at Ts = 1200 °C to tetragonal at 1300 °C to mixed phases of hexagonal and tetragonal at 1400 °C. When Ts ≥ 1300 °C, a g = 1.956 EPR signal was observed at T = -188 °C and assigned as ionized oxygen vacancies. Mg2+ exhibited amphoteric behavior of substituting for the double cation sites. When Ts = 1400 °C, B-site Mg2+ and oxygen vacancies mainly existed in the hexagonal phase and A-site Mg2+ was dominant in the tetragonal phase. The higher tan δ was attributed to the higher concentrations of oxygen vacancies and Ti3+ in the hexagonal phase.

Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex

BACKGROUND: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes In adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. RESULTS: In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. CONCLUSION: These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.