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.

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.

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.

Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population.

It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein, a Mendelian randomization study conducted in East Asian population enhances the current clinical cognition that T2DM is not associated with reduction in BMD. PURPOSE: A Mendelian randomization (MR) approach was utilized to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in East Asian populations. METHODS: Genome-wide association study summary data from BioBank Japan were used to identify genetic variants strongly related to T2DM risk (36,614 cases and 155,150 controls) and osteoporosis (7788 cases and 204,665 controls). Heel BMD GWAS data of 1260 East Asian people from ieu open gwas project was considered as a second outcome. Inverse variance-weighted (IVW) analysis was mainly applied; MR-Egger and the weighted median were also used to obtain robust estimates. A series of sensitivity analyses including Cochran's Q test, MR-Egger regression, and leave-one-out analysis were used to detect pleiotropy or heterogeneity. RESULTS: In the main analysis, IVW estimates indicated that T2DM significantly associated with the risk of osteoporosis (odds ratio = 0.92, 95% CI: 0.86-0.99, p = 0.016) and with higher BMD (OR: 1.25, 95% CI: 1.06-1.46, p = 6.49 × 10-3). Results of comprehensive sensitivity analysis were consistent with the main causality estimate. Horizontal pleiotropy and heterogeneity were absent in our MR study. CONCLUSIONS: T2DM is not associated with reduction in BMD in terms of genetic polymorphism in East Asian populations.

Multi-center experience in an optimized right upper lobectomy surgical procedure in China.

BACKGROUND: This multi-center study was aimed at retrospectively evaluating the feasibility, safety, clinical outcomes, and surgical learning curve of an optimized procedure for right upper lobectomy (RUL), which is challenging because of the anatomical structures and features of this lobe. METHODS: This study included 45 RUL cases of robot-assisted thoracoscopy (RATS) in a pilot cohort and 187 RUL cases of video-assisted thoracoscopy (VATS) in three cohorts. A total of 121 and 111 patients underwent traditional and optimized RUL, respectively. The optimized surgical procedure was performed to consecutively transect the superior arterial trunk and bronchus, and finally disconnect the pulmonary vein and posterior ascending artery with interlobar fissures. Clinical and radiological data were reviewed retrospectively. RESULTS: Optimized RUL can be performed successfully by RATS or VATS. The optimized procedure yielded better clinical outcomes than the traditional procedure, including shorter operation times, less blood loss, fewer complications, shorter hospital times, lower costs, and a lower likelihood of postoperative intermedius bronchial kinking. Additionally, for calcified interlobar lymph nodes, the optimized VATS group was less likely to be converted to thoracotomy than the traditional group. The skills required to perform optimized VATS RUL can be gained by surgeons after 12 to 15 cases. The two RUL procedures in the pilot cohort showed similar disease-free survival. CONCLUSIONS: The optimized RUL was safe, economical, and feasible, with a short learning curve and satisfactory disease-free survival.

Incidence of postoperative symptomatic spinal epidural hematoma requiring surgical evacuation: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to determine the incidence of symptomatic spinal epidural hematoma (SSEH) following spine surgery. METHODS: We systematically searched for all relevant articles that mentioned the incidence of SSEH following the spine surgery published in the PubMed, Embase, and Cochrane Library databases through March 2022 and manually searched the reference lists of included studies. The Newcastle-Ottawa quality assessment scale (NOS) was used to assess the quality of the included studies. A fixed-effects or random-effects model was performed to calculate the pooled incidence of the totality and subgroups based on the heterogeneity. The potential publication bias was assessed by Egger's linear regression and a funnel plot. Sensitivity analysis was also conducted. RESULTS: A total of 40 studies were included in our meta-analysis based on our inclusion and exclusion criteria. The overall pooled incidence of SSEH was 0.52% (95% CI 0.004-0.007). In the subgroup analysis, the pooled incidence of SSEH in males and females was 0.86% (95% CI 0.004-0.023) and 0.68% (95% CI 0.003-0.017). Among the different indications, a higher incidence (2.9%, 95% CI 0.006-0.084) was found in patients with deformity than degeneration (1.12%, 95% CI 0.006-0.020) and tumor (0.30%, 95% CI 0.006-0.084). For different surgical sites, the incidences of SSEH in cervical, thoracic and lumbar spine were 0.32% (95% CI 0.002-0.005), 0.84% (95% CI 0.004-0.017) and 0.63% (95% CI 0.004-0.010), respectively. The incidences of SSEH in anterior and posterior approach were 0.24% (95% CI 0.001-0.006) and 0.70% (95% CI 0.004-0.011), respectively. The pooled incidence of SSEH was five times higher with minimally invasive surgery (1.94%, 95% CI 0.009-0.043) than with open surgery (0.42%, 95% CI 0.003-0.006). Delayed onset of SSEH had a lower incidence of 0.16% (95% CI 0.001-0.002) than early onset. There were no significant variations in the incidence of SSEH between patients who received perioperative anticoagulation therapy and those who did not or did not report getting chemopreventive therapy (0.44%, 95% CI 0.006-0.084 versus 0.42%, 95% CI 0.003-0.006). CONCLUSION: We evaluated the overall incidence proportion of SSEH after spine surgery and performed stratified analysis, including sex, surgical indication, site, approach, minimally invasive surgery, and delayed onset of SSEH. Our research would be helpful for patients to be accurately informed of their risk and for spinal surgeons to estimate the probability of SSEH after spine surgery.

IGF2BP1-regulated expression of ERRα is involved in metabolic reprogramming of chemotherapy resistant osteosarcoma cells.

Doxorubicin (Dox) is the standard treatment approach for osteosarcoma (OS), while acquired drug resistance seriously attenuates its treatment efficiency. The present study aimed to investigate the potential roles of metabolic reprogramming and the related regulatory mechanism in Dox-resistant OS cells. The results showed that the ATP levels, lactate generation, glucose consumption and oxygen consumption rate were significantly increased in Dox-resistant OS cells compared with parental cells. Furthermore, the results revealed that the increased expression of estrogen-related receptor alpha (ERRα) was involved in metabolic reprogramming in chemotherapy resistant OS cells, since targeted inhibition of ERRα restored the shifting of metabolic profiles. Mechanistic analysis indicated that the mRNA stability, rather than ERRα transcription was markedly increased in chemoresistant OS cells. Therefore, it was hypothesized that the 3'-untranslated region of ERRα mRNA was methylated by N6-methyladenine, which could further recruit insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress mRNA decay and increase mRNA stability. IGF2BP1 knockdown downregulated ERRα and reversed the metabolic alteration of resistant OS cells. Additionally, the oncogenic effect of the IGF2BP1/ERRα axis on Dox-resistant OS cells was verified by in vitro and in vivo experiments. Clinical analysis also revealed that the expression levels of IGF2BP1 and ERRα were associated with the clinical progression of OS. Collectively, the current study suggested that the IGF2BP1/ERRα axis could regulate metabolic reprogramming to contribute to the chemoresistance of OS cells.

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.

ZIP10 drives osteosarcoma proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway.

BACKGROUND: The zinc transporters Zrt- and Irt-related protein (ZIP/SLC39) are overexpressed in human tumors and correlate with poor prognosis; however, their contributions to carcinogenesis and chemoresistance in osteosarcoma (OS) remain unclear. METHODS: We collected 64 OS patient tissues with (n = 12) or without (n = 52) chemotherapy. The expression levels of ZIP10 were measured by immunohistochemistry and applied to prognostic analysis. ZIP10 was knocked down or overexpressed in OS cell lines to explore its effect on proliferation and chemoresistance. RNA sequencing, quantitative real-time PCR, and western blotting analysis were performed to explore ZIP10-regulated downstream target genes. A xenograft mouse model was established to evaluate the mechanisms by which ZIP10 modulates chemoresistance in OS cells. RESULTS: The expression of ZIP10 was significantly induced by chemotherapy and highly associated with the clinical outcomes of OS. Knockdown of ZIP10 suppressed OS cell proliferation and chemoresistance. In addition, ZIP10 promoted Zn content-induced cAMP-response element binding protein (CREB) phosphorylation and activation, which are required for integrin α10 (ITGA10) transcription and ITGA10-mediated PI3K/AKT pathway activation. Importantly, ITGA10 stimulated PI3K/AKT signaling but not the classical FAK or SRC pathway. Moreover, overexpression of ZIP10 promoted ITGA10 expression and conferred chemoresistance. Treatment with the CREB inhibitor 666-15 or the PI3K/AKT inhibitor GSK690693 impaired tumor chemoresistance in ZIP10-overexpressing cells. Finally, a xenograft mouse model established by subcutaneous injection of 143B cells confirmed that ZIP10 mediates chemotherapy resistance in OS cells via the ZIP10-ITGA10-PI3K/AKT axis. CONCLUSIONS: We demonstrate that ZIP10 drives OS proliferation and chemoresistance through ITGA10-mediated activation of the PI3K/AKT pathway, which might serve as a target for OS treatment.

LncRNA LINC01116 sponges miR-93-5p to promote cell invasion and migration in small cell lung cancer.

BACKGROUND: LINC01116 is a recently identified oncogenic lncRNA in glioma. Differential expression analysis using the public gene expression analysis tool GEPIA revealed the upregulation of LINC01116 in lung cancer. We studied the functions of LINC01116 in small cell lung cancer (SCLC). METHODS: The expression of LINC01116 in several types of cancer tissue and the paired non-tumor tissues was evaluated by GEPIA. The effects of the overexpression of LINC01116 and miR-93-5p on the expression of STAT3 were evaluated. The effects of the overexpression of LINC01116, miR-93-5p and STAT3 on SHP-77 cell behaviors were evaluated by Transwell assays. RESULTS: LINC01116 was highly expressed in SCLC and predicted poor survival. In SCLC tissues, the expression of LINC01116 was positively correlated with STAT3. Bioinformatics analysis revealed that miR-93-5p may target LINC01116. Overexpression of LINC01116 increased STAT3 but did not affect the expression of miR-93-5p. Transwell assay showed that LINC01116 and STAT3 increased cell invasion and migration rates. MiR-93-5p played an suppressed cell behaviors and suppressed the role of LINC01116. CONCLUSION: Therefore, LINC01116 might upregulate STA3 by sponging miR-93-5p, thereby promoting cell invasion and migration in SCLC.

Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression.

Objective: Osteoarthritis (OA) is the most common chronic degenerative joint disease, which represents the leading cause of age-related disability. Here, this study aimed to depict the intercellular heterogeneity of OA synovial tissues. Methods: Single-cell RNA sequencing (scRNA-seq) data were preprocessed and quality controlled by the Seurat package. Cell cluster was presented and cell types were annotated based on the mRNA expression of corresponding marker genes by the SingleR package. Cell-cell communication was assessed among different cell types. After integrating the GSE55235 and GSE55457 datasets, differentially expressed genes were identified between OA and normal synovial tissues. Then, differentially expressed marker genes were overlapped and their biological functions were analyzed. Results: Totally, five immune cell subpopulations were annotated in OA synovial tissues including macrophages, dendritic cells, T cells, monocytes and B cells. Pseudo-time analysis revealed the underlying evolution process in the inflammatory microenvironment of OA synovial tissue. There was close crosstalk between five cell types according to the ligand-receptor network. The genetic heterogeneity was investigated between OA and normal synovial tissues. Furthermore, functional annotation analysis showed the intercellular heterogeneity across immune cells in OA synovial tissues. Conclusion: This study offered insights into the heterogeneity of OA, which provided in-depth understanding of the transcriptomic diversities within synovial tissue. This transcriptional heterogeneity may improve our understanding on OA pathogenesis and provide potential molecular therapeutic targets for OA.

An updated meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer.

AIM OF STUDY: There were many reports published on the relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer in these years. In previous, we conducted a meta-analysis to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer. This study was conducted to update it. MATERIALS AND METHODS: The association studies were identified from PubMed and Cochrane Library on March 1, 2016. RESULTS: Sixty-three reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 21,220 patients with lung cancer and 21,496 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations and in Asians (overall populations: Odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.07-1.28, P = 0.006; Asians: OR = 1.41, 95% CI: 1.23-1.62, P < 0.00001). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population, and Africans. CONCLUSION: GSTT1 null genotype is associated with the lung cancer risk in overall populations and in Asians.

Emodin Alleviates Hydrogen Peroxide-Induced Inflammation and Oxidative Stress via Mitochondrial Dysfunction by Inhibiting the PI3K/mTOR/GSK3ß Pathway in Neuroblastoma SH-SY5Y Cells.

Emodin is an active monomer extracted from rhubarb root, which has many biological functions, including anti-inflammation, antioxidation, anticancer, and neuroprotection. However, the protective effect of emodin on nerve injury needs to be further elucidated. The purpose of this study is to investigate the effect of emodin on the neuroprotection and the special molecular mechanism. Here, the protective activity of emodin inhibiting H2O2-induced apoptosis and neuroinflammation as well as its molecular mechanisms was examined using human neuroblastoma cells (SH-SY5Y cells). The results showed that emodin significantly enhanced cell viability, reduced cell apoptosis and LDH release. Simultaneously, emodin downregulated H2O2-induced inflammatory factors, including IL-6, NO, and TNF-α, and alleviated H2O2-induced oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. In addition, emodin inhibited the activation of the PI3K/mTOR/GSK3ß signaling pathway. What is more, the PI3K/mTOR/GSK3ß pathway participated in the protective mechanism of emodin on H2O2-induced cell damage. Collectively, it suggests that emodin alleviates H2O2-induced apoptosis and neuroinflammation potentially by regulating the PI3K/mTOR/GSK3ß signaling pathway.

B3GNT3, a Direct Target of miR-149-5p, Promotes Lung Cancer Development and Indicates Poor Prognosis of Lung Cancer.

BACKGROUND: B3GNT3 (ß1, 3-N-acetylglucosaminyltransferase-3) belongs to the ß3GlcNAcT family and is essential to form extended core 1 oligosaccharides. Previous studies revealed that B3GNT3 expression was dysregulated in multiple cancers. Here, we aimed to understand the expression profile and function of B3GNT3 in lung cancer. MATERIALS AND METHODS: The expression of B3GNT3 was measured by immunohistochemistry and public database analysis. B3GNT3 was knocked down to evaluate the lung cancer cell proliferation, migration and invasion in in vitro and in vivo tumor formation experiments. miR-149-5p targeting B3GNT3 was identified with TargetScan analysis and confirmed with reporter assay. Overexpression of miR-149-5p was achieved using microRNA mimics and function of microRNA-149-5p/B3GNT3 axis was tested in vitro. RESULTS: B3GNT3 was upregulated in lung cancer, and B3GNT3 overexpression was associated with poor prognosis of lung cancer patients. High expression of B3GNT3 was associated with advanced TNM stages, larger tumor size, tumor metastasis and recurrence. Functionally, we demonstrated that knockdown of B3GNT3 suppressed lung cancer cell growth and invasion in vitro. Knockdown of B3GNT3 suppressed lung cancer development in a xenograft tumor model. Moreover, miR-149-5p was validated to negatively regulate B3GNT3 expression through directly targeting B3GNT3 3'-UTR. Overexpression of miR-149-5p could antagonize the tumorigenesis effect of B3GNT3 in vitro. CONCLUSION: In summary, our study demonstrated that B3GNT3 overexpression was correlated with poor prognosis of lung cancer patient, indicating that B3GNT3 could be a promising prognostic biomarker for lung cancer. miR-149-5p negatively regulated B3GNT3 expression, which might be utilized for therapeutic target in lung cancer.

INSR mediated by transcription factor KLF4 and DNA methylation ameliorates osteoarthritis progression via inactivation of JAK2/STAT3 signaling pathway.

OBJECTIVE: To probe into the role and regulatory mechanisms of INSR in pathogenesis of osteoarthritis (OA). METHODS: KLF4 and INSR expression was detected in cartilage tissues of 40 OA patients and 10 controls using RT-qPCR. IL-1ß-induced OA chondrocytes and anterior cruciate ligament transection (ACLT)-induced OA models were respectively constructed. After overexpressing or silencing KLF4 or INSR, flow cytometry assay was utilized to detect chondrocyte apoptosis. Furthermore, JAK2/STAT3, cartilage markers and OA-related markers were examined by western blot. Dual luciferase report and CHIP assay were carried out to verify the interactions between KLF4 and INSR, followed by functional gain and loss assay. INSR promoter methylation was assessed by MS-PCR. RESULTS: Both KLF4 and INSR were down-regulated both in OA chondrocytes and cartilage tissues. Knockdown of KLF4 or INSR accelerated apoptosis of IL-1ß-induced OA chondrocytes. However, overexpression of KLF4 or INSR ameliorated OA progression both in OA chondrocytes and OA mouse models. Moreover, INSR inactivated JAK2/STAT3 pathway in OA chondrocytes. Dual luciferase report and CHIP assay results confirmed that INSR was transcriptionally regulated by KLF4. As shown in MS-PCR results, INSR expression was mediated by DNA methylation in OA. CONCLUSION: Our findings suggested that INSR, as a key regulator for OA, was regulated by transcription factor KLF4 and DNA methylation, thereby mediating the activation of JAK2/STAT3 signaling, which was considered as an underlying therapeutic target for OA.

Open Broström-Gould Repair vs Arthroscopic Anatomical Repair of the Anterior Talofibular Ligament for Chronic Lateral Ankle Instability.

BACKGROUND: The comparative studies on open vs arthroscopic anterior talofibular ligament (ATFL) repair are limited. This study aimed to compare the early therapeutic efficacy and cost between the traditional open Broström-Gould repair and all-arthroscopic anatomical repair of the ATFL for chronic lateral ankle instability. METHODS: A total of 27 of patients with chronic lateral ankle instability undergoing repair of the ATFL between January 2013 and June 2015 were retrospectively included with a traditional open surgery (n = 10) group and arthroscopy (n = 17) group. The surgery duration, surgical cost, postoperative complications, and the preoperative/postoperative American Orthopaedic Foot & Ankle Society Score (AOFAS) and Karlsson-Peterson score were compared between groups. RESULTS: Compared to the arthroscopy group, the open surgery group had significantly shorter surgery duration and lower surgical cost. However, there was no significant difference in hospitalization duration between groups. At 3 years after operation, the AOFAS and Karlsson scores were significantly improved in both groups. Nevertheless, there was no significant difference in the AOFAS and Karlsson scores between groups at both preoperative and postoperative assessment. No significant difference was found in the incidence of postoperative complications between the 2 groups. CONCLUSION: These results suggest that open Broström-Gould repair and all-arthroscopic anatomical repair of the ATFL have comparable therapeutic efficacy for chronic lateral ankle instability. The arthroscopic surgery had a smaller incision, while the open Broström-Gould had a shorter surgery duration and lower cost. LEVEL OF EVIDENCE: Level III, comparative study.

Bax Targeted by miR-29a Regulates Chondrocyte Apoptosis in Osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease, where chondrocyte apoptosis is responsible for cartilage degeneration. Bax is a well-known proapoptotic protein of the Bcl-2 family, involved in a large number of physiological and pathological processes. However, the regulation mechanisms of Bax underlying chondrocyte apoptosis in OA remain unknown. In the present study, we determined the role of Bax in human OA and chondrocyte apoptosis. The results showed that Bax was upregulated in chondrocytes from the articular cartilage of OA patients and in cultured chondrocyte-like ATDC5 cells treated by IL-1ß. Bax was identified to be the direct target of miR-29a by luciferase reporter assay and by western blotting. Inhibition of miR-29a by the mimics protested and overexpression by miR-29a inhibitors aggravated ATDC5 apoptosis induced by IL-1ß. These data reveal that miR-29a/Bax axis plays an important role in regulating chondrocyte apoptosis and suggest that targeting the proapoptotic protein Bax and increasing expression levels of miR-29a emerge as potential approach for protection against the development of OA.

Emodin inhibits zinc-induced neurotoxicity in neuroblastoma SH-SY5Y cells.

Emodin is a natural anthraquinone derivative with numerous beneficial effects, including antioxidant properties, anti-tumor activities, and protecting the nerves. Zinc-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD) and Parkinson's disease (PD). Here, the protective activity of emodin inhibiting zinc-induced neurotoxicity and its molecular mechanisms such as cellular Zn2+ influx and zinc-induced gene expression were examined using human neuroblastoma cells (SH-SY5Y cells). Our findings showed that emodin obviously enhanced cell viability and reduced cell apoptosis and lactate dehydrogenase release. Bedsides, we detected a decrease of intracellular Zn2+ concentration after SH-SY5Y cells were pretreated with emodin. Simultaneously, the expression of zinc transporter-1, metallothionein-1, and metallothionein-2 were weakened in emodin-pretreated SH-SY5Y cells. In addition, emodin prevented the depletion of NAD+ and ATP induced by zinc. Emodin also reduced intracellular reactive oxygen species and endoplasmic reticulum-stress levels. Strikingly, emodin elevated SH-SY5Y cell viability and inhibited cell apoptosis caused by AMP-activated protein kinase signaling pathway activation. Thus, emodin could protect against neurotoxicity induced by Zn2+ in neuroblastoma SH-SY5Y cells. It is expected to have future therapeutic potential for VD or PD and other neurodegenerative diseases.

Thoracic splenosis presenting as pulmonary space-occupying lesion.

BACKGROUND: Spleen leaves its normal anatomical position and appears in other locations, which is called ectopic spleen. It is most commonly found in the abdomen or pelvis with seeding of the peritoneum, omentum or mesentery. A few of cases of thoracic splenosis associated with traumatic diaphragmatic rupture have been reported. CASE PRESENTATION: We make a report on a case of intrapulmonary thoracic splenosis. A 44-year-old male patient underwent splenectomy due to a high fall accident injury in 2008. After ten years, thoracic splenosis were found in the lungs and chest wall. Clinical diagnosis was unidentified masses, benign tumor of lungs and chest wall. The radiological imaging was suggestive of the thoracic splenosis, After surgery, the diagnosis of thoracic splenosis was confirmed by pathological diagnosis. CONCLUSIONS: Thoracic splenosis may occur after the injury to spleen and surgical treatment may not be the preferred method for asymptomatic or less symptomatic thoracic splenosis.

An updated meta-analysis for association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer.

AIM OF STUDY: The conclusions on the association between glutathione S-transferase P1 (GSTP1) gene polymorphism and lung cancer risk are still debated. This meta-analysis was performed to update the association between GSTP1 and the risk of lung cancer. MATERIALS AND METHODS: The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. RESULTS: Fifty reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and lung cancer susceptibility. The association between GSTPI G allele/GG genotype and lung cancer risk was found in this meta-analysis (G allele: odds ratio [OR] = 1.08, 95% confidence interval [CI]: 1.02-1.14, P = 0.006; GG genotype: OR = 1.09, 95% CI: 1.00-1.18, P = 0.04). However, the AA genotype was not associated with the susceptibility of lung cancer. CONCLUSION: GSTP1 G allele/GG genotype is associated with the lung cancer susceptibility.