Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt signaling pathway to promote the activation of fibroblasts.

BACKGROUND: Fibroblast plays a major role in tendon-bone healing. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) can activate fibroblasts and promote tendon-bone healing via the contained microRNAs (miRNAs). However, the underlying mechanism is not comprehensively understood. Herein, this study aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets, and to verify their effects as well as mechanisms on fibroblasts. AIM: To identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify their effects as well as mechanisms on fibroblasts. METHODS: BMSC-derived exosomal miRNAs data (GSE71241, GSE153752, and GSE85341) were downloaded from the Gene Expression Omnibus (GEO) database. The candidate miRNAs were obtained by the intersection of three data sets. TargetScan was used to predict potential target genes for the candidate miRNAs. Functional and pathway analyses were conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, by processing data with the Metascape. Highly interconnected genes in the protein-protein interaction (PPI) network were analyzed using Cytoscape software. Bromodeoxyuridine, wound healing assay, collagen contraction assay and the expression of COL I and α-smooth muscle actin positive were applied to investigate the cell proliferation, migration and collagen synthesis. Quantitative real-time reverse transcription polymerase chain reaction was applied to determine the cell fibroblastic, tenogenic, and chondrogenic potential. RESULTS: Bioinformatics analyses found two BMSC-derived exosomal miRNAs, has-miR-144-3p and has-miR-23b-3p, were overlapped in three GSE datasets. PPI network analysis and functional enrichment analyses in the GO and KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling pathway by targeting phosphatase and tensin homolog (PTEN). In vitro experiments confirmed that miR-144-3p and miR-23b-3p stimulated proliferation, migration and collagen synthesis of NIH3T3 fibroblasts. Interfering with PTEN affected the phosphorylation of Akt and thus activated fibroblasts. Inhibition of PTEN also promoted the fibroblastic, tenogenic, and chondrogenic potential of NIH3T3 fibroblasts. CONCLUSION: BMSC-derived exosomes promote fibroblast activation possibly through the PTEN and PI3K/Akt signaling pathways, which may serve as potential targets to further promote tendon-bone healing.

Trend of unplanned reoperation rates after lumbar degenerative surgery from 2011 to 2019: a large patient population study.

BACKGROUND: Unplanned reoperation is commonly performed due to postoperative complications. Previous studies have reported the incidence of unplanned reoperation following lumbar spinal surgery. But few study focused on the trend of reoperation rates, and the reasons of unplanned reoperation were not clear. In this study, we conducted a retrospective study to determine the trend of unplanned reoperation rates after degenerative lumbar spinal surgery from 2011 to 2019, and the reasons and risk factors of unplanned reoperation were also determined. METHODS: Data of patients who were diagnosed with degenerative lumbar spinal disease and underwent posterior lumbar spinal fusion surgery in our institution from January 2011 to December 2019 were reviewed. Those who received unplanned reoperation during the primary admission were identified. The demographics, diagnosis, surgical segments and postoperative complications of these patients were recorded. The rates of unplanned reoperation from 2011 to 2019 were calculated, and the reasons of unplanned reoperation were statistically analysed. RESULTS: A total of 5289 patients were reviewed. Of them, 1.91% (n = 101) received unplanned reoperation during the primary admission. The unplanned reoperation rates of degenerative lumbar spinal surgery firstly increased from 2011 to 2014, with a peak rate in 2014 (2.53%). Then, the rates decreased from 2014 to 2019, with the lowest one in 2019 (1.46%). Patients with lumbar spinal stenosis have a higher rate of unplanned reoperation (2.67%) compared with those diagnosed as lumbar disc herniation (1.50%) and lumbar spondylolisthesis (2.04%) (P < 0.05). The main reasons for unplanned reoperation were wound infection (42.57%), followed by wound hematoma (23.76%). Patients who underwent 2-segment spinal surgery had a higher unplanned reoperation rate (3.79%) than those receiving other segments surgery (P < 0.001). And different spine surgeons had different reoperation rates. CONCLUSIONS: The rates of unplanned reoperation after lumbar degenerative surgery increased at first and then decreased during past 9 years. Wound infection was the major reason for unplanned reoperation. 2-segment surgery and surgeon's surgical skills were related to the reoperation rate.

LRIG2 regulates cell proliferation, migration and apoptosis of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is one of the malignant bone tumors with strong aggressiveness and poor prognosis. Leucine-rich repeats and immunoglobulin-like domains2 (LRIG2) is closely associated with the poor prognosis of a variety of tumors, but the role of LRIG2 in osteosarcoma and the underlying molecular mechanism remains unclear. OBJECTIVE: The aim of this study was to determine the function of LRIG2 in OS and the related molecular mechanism on cell proliferation, apoptosis and migration of OS. METHODS: The mRNA and protein expression of LRIG2 in OS tissues and cells was detected by qRT-PCR, western blot (WB) assay and immunohistochemistry (IHC). The cell counting Kit-8 (CCK-8), clone formation, transwell, TdT-mediated dUTP Nick-End Labeling (TUNEL) and WB assay were applied to determine the proliferation, migration and apoptosis abilities of OS cells and its molecular mechanisms. Spontaneous metastasis xenografts were established to confirm the role of LRIG2 in vivo. RESULTS: LRIG2 exhibited high expression in OS tissues and OS cell lines and the expression of which was significantly correlated with Enneking stage of patients, knockdown LRIG2 expression significantly inhibited OS cell proliferation, migration and enhanced apoptosis. Silencing LRIG2 also suppressed the growth of subcutaneous transplanted tumor in nude mice. Further, the mechanism investigation revealed that the protein level of cell proapoptotic proteins (Bax, caspase9 and caspase3) all increased attributed to LRIG2 deficiency, whereas expression of anti-apoptotic protein BCL2 decreased. LRIG2 silencing led to the decrease phosphorylation of AKT signaling, a decrease expression of vimentin and N-cadherin. Additionally, silencing LRIG2 significantly decreased the rate of tumor growth and tumor size. CONCLUSIONS: LRIG2 acts as an oncogene in osteosarcoma, and it might become a novel target in the treatment of human OS.

Incidences and reasons of postoperative surgical site infection after lumbar spinal surgery: a large population study.

PURPOSE: The purpose of this study was to determine the incidences of postoperative acute surgical site infection (SSI) after lumbar spinal surgery and its possible reasons in our hospital during the past 9 years. METHODS: This is a retrospective study with a large sample size. The medical records of all included patients were reviewed, and patients with acute SSI were identified. The incidence and possible reasons of SSI were determined. RESULTS: A total of 7240 patients who underwent posterior lumbar spinal surgery were included in this study, and the total incidence of postoperative SSI was 1.53% (111/7240). Gram-negative bacteria were found to be dominant in postoperative wound infections after lumbar spinal surgery. And Escherichia coli were the most common pathogen in patients with SSI. The rate of postoperative SSI following lumbar spinal surgery was increased at first and then decreased during the past 9 years. Additionally, from 2011 to 2014, it was mainly deep infection in these patients, and then was mainly superficial infection from 2015 to 2019. Patients with lumbar spinal stenosis had the highest incidence of postoperative SSI (2.39%, P < 0.001). There was also a significant difference for the number of SSI cases among different surgeons. CONCLUSION: Based on a large population analysis, Gram-negative bacteria were the most common pathogen in postoperative SSI after lumbar spinal surgery. And patients with lumbar spinal stenosis had the highest incidence of SSI. Increasing the intervention of Gram-negative may be an important step to reduce the postoperative SSI after lumbar spinal surgery.

Short-segment fixation and transpedicular bone grafting for the treatment of thoracolumbar spine fracture.

Purpose: Thoracolumbar fracture is one of the most common fractures of spine. And short-segment posterior fixation including the fractured vertebra (SSPFI) is usually used for the surgical treatment of it. However, the outcomes of SSPFI for different types of thoracolumbar fractures are not clear, and whether it is necessary to perform transpedicular bone grafting is still controversial. This study was conducted to determine the clinical efficacy of SSPFI for the treatment of different types of single-level thoracolumbar fracture, and make clear what kind of fractures need transpedicular bone grafting during the surgery. Methods: Patients with single-level thoracolumbar fracture undergoing SSPFI surgery between January 2013 and June 2020 were included in this study. The operative duration, intraoperative blood loss, anterior vertebral height ratio (AVHR) and anterior vertebral height compressive ratio (AVHC) of the fractured vertebra, local kyphotic Cobb angle (LKA), vertebral wedge angle (VWA) and correction loss during follow up period were recorded. Outcomes between unilateral and bilateral pedicle screw fixation for fractured vertebra, between SSPFI with and without transpedicular bone grafting (TBG), and among different compressive degrees of fractured vertebrae were compared, respectively. Results: A total of 161 patients were included in this study. All the patients were followed up, and the mean follow-upped duration was 25.2 ± 3.1 months (6-52 months). At the final follow-up, the AVHR was greater, and the LKA and VWA were smaller in patients with bilateral fixation (6-screw fixation) than those with unilateral fixation (5-screw fixation) of AO type A3/A4 fractures (P < 0.001). The correction loss of AVHR, LKA and VWA in fractured vertebra were significantly great when preoperative AVHC was >50% (P < 0.05). For patients with AVHC >50%, the correction loss in patients with TBG were less than those without TBG at the final follow-up (P < 0.05). Conclusions: SSPFI using bilateral fixation was more effective than unilateral fixation in maintaining the fractured vertebral height for AO type A3/A4 fractures. For patients with AVHC >50%, the loss of correction was more obvious and it can be decreased by transpedicular bone grafting.

New-onset depression after hip fracture surgery among older patients: Effects on associated clinical outcomes and what can we do?

BACKGROUND: Hip fracture in the elderly is a worldwide medical problem. New-onset depression after hip fracture has also received attention because of its increasing incidence and negative impact on recovery. AIM: To provide a synthesis of the literature addressing two very important questions arising from postoperative hip fracture depression (PHFD) research: the risk factors and associated clinical outcomes of PHFD, and the optimal options for intervention in PHFD. METHODS: We searched the PubMed, Web of Science, EMBASE, and PsycINFO databases for English papers published from 2000 to 2021. RESULTS: Our results showed that PHFD may result in poor clinical outcomes, such as poor physical function and more medical support. In addition, the risk factors for PHFD were summarized, which made it possible to assess patients preoperatively. Moreover, our work preliminarily suggested that comprehensive care may be the optimal treatment option for PHFDs, while interdisciplinary intervention can also be clinically useful. CONCLUSION: We suggest that clinicians should assess risk factors for PHFDs preoperatively, and future research should further validate current treatment methods in more countries and regions and explore more advanced solutions.

Application of Machine Learning Techniques to Predict Bone Metastasis in Patients with Prostate Cancer.

OBJECTIVE: This study aimed to develop and validate a machine learning model for predicting bone metastases (BM) in prostate cancer (PCa) patients. METHODS: Demographic and clinicopathologic variables of PCa patients in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2017 were retrospectively analyzed. We used six different machine learning algorithms, including Decision tree (DT), Random forest (RF), Multilayer Perceptron (MLP), Logistic regression (LR), Naive Bayes classifiers (NBC), and eXtreme gradient boosting (XGB), to build prediction models. External validation using data from 644 PCa patients of the First Affiliated Hospital of Nanchang University from 2010 to 2016. The performance of the models was evaluated using the area under receiver operating characteristic curve (AUC), accuracy score, sensitivity (recall rate) and specificity. A web predictor was developed based on the best performance model. RESULTS: A total of 207,137 PCa patients from SEER were included in this study. Of whom, 6725 (3.25%) developed BM. Gleason score, Prostate-specific antigen (PSA) value, T, N stage and age were found to be the risk factors of BM. The XGB model offered the best predictive performance among these 6 models (AUC: 0.962, accuracy: 0.884, sensitivity (recall rate): 0.906, and specificity: 0.879). An XGB model-based web predictor was developed to predict BM in PCa patients. CONCLUSION: This study developed a machine learning model and a web predictor for predicting the risk of BM in PCa patients, which may help physicians make personalized clinical decisions and treatment strategy for patients.

Genome-wide characterization and expression profiling of B3 superfamily during ethylene-induced flowering in pineapple (Ananas comosus L.).

BACKGROUND: The B3 superfamily (B3s) represents a class of large plant-specific transcription factors, which play diverse roles in plant growth and development process including flowering induction. However, identification and functional surveys of B3 superfamily have not been reported in ethylene-induced pineapple flowering (Ananas comosus). RESULTS: 57 B3 genes containing B3 domain were identified and phylogenetically classified into five subfamilies. Chromosomal localization analysis revealed that 54 of 57 AcB3s were located on 21 Linkage Groups (LG). Collinearity analysis demonstrated that the segmental duplication was the main event in the evolution of B3 gene superfamily, and most of them were under purifying selection. The analysis of cis-element composition suggested that most of these genes may have function in response to abscisic acid, ethylene, MeJA, light, and abiotic stress. qRT-PCR analysis of 40 AcB3s containing ethylene responsive elements exhibited that the expression levels of 35 genes were up-regulated within 1 d after ethephon treatment and some were highly expressed in flower bud differentiation period in stem apex, such as Aco012003, Aco019552 and Aco014401. CONCLUSION: This study provides a basic information of AcB3s and clues for involvement of some AcB3s in ethylene-induced flowering in pineapple.

Machine learning for the prediction of bone metastasis in patients with newly diagnosed thyroid cancer.

OBJECTIVES: This study aimed to establish a machine learning prediction model that can be used to predict bone metastasis (BM) in patients with newly diagnosed thyroid cancer (TC). METHODS: Demographic and clinicopathologic variables of TC patients in the Surveillance, Epidemiology, and End Results database from 2010 to 2016 were retrospectively analyzed. On this basis, we developed a random forest (RF) algorithm model based on machine-learning. The area under receiver operating characteristic curve (AUC), accuracy score, recall rate, and specificity are used to evaluate and compare the prediction performance of the RF model and the other model. RESULTS: A total of 17,138 patients were included in the study, with 166 (0.97%) developed bone metastases. Grade, T stage, histology, race, sex, age, and N stage were the important prediction features of BM. The RF model has better predictive performance than the other model (AUC: 0.917, accuracy: 0.904, recall rate: 0.833, and specificity: 0.905). CONCLUSIONS: The RF model constructed in this study could accurately predict bone metastases in TC patients, which may provide clinicians with more personalized clinical decision-making recommendations. Machine learning technology has the potential to improve the development of BM prediction models in TC patients.

[Studies of effect of prosaposin on cell proliferation, cell apoptosis and its possible molecular mechanism].

pcDNA3.1 in NIH3T3 and Psap-Myc in NIH3T3 cell strains were used as cell models in order to study the effect of prosaposin on cell proliferation, cell apoptosis and its possible molecular mechanism. MTT assay and Annexin V/PI apoptosis kit were used to detect the effect of prosaposin on cell proliferation and cell apoptosis induced by se-rum-starvation stress, respectively. Western blotting was conducted to detect the phosphorylative level of PI3K/Akt pathway, and real-time PCR was carried out to explore the expression of the genes regulated by PI3K/Akt pathway. Prosaposin pro-tein was proved to activate the PI3K/Akt signal pathway, upregulate the phosphorylative activity of Akt at Serine 473, downregulate the expression of P27(Kip1) gene, upregulate the expression of Cyclin D1 gene and then promote the G1/S tran-sition, and upregulate the expression of survival genes cIAP1 and cIAP2 and then prevent cell apoptosis. These findings suggest that the growth promotion and anti-apoptotic activity of prosaposin may be partly through the PI3K/Akt signal pathway and its downstream targeted genes.