The role of foam cells in spinal cord injury: challenges and opportunities for intervention.

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system (CNS) to form an inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are the main cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foam cell modulation and several potential therapeutic targets that may enhance the treatment of SCI.

Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III.

Paclitaxel is a well known anticancer compound. Its biosynthesis involves the formation of a highly functionalized diterpenoid core skeleton (baccatin III) and the subsequent assembly of a phenylisoserinoyl side chain. Despite intensive investigation for half a century, the complete biosynthetic pathway of baccatin III remains unknown. In this work, we identified a bifunctional cytochrome P450 enzyme [taxane oxetanase 1 (TOT1)] in Taxus mairei that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, which represents a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible for the taxane oxidation of the C9 position (T9αH1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.

Periodic injection of liquefied kitchen and food waste in municipal solid waste: Effects on leachate and gas generation.

With continuous advancements in the zero-waste strategy in China, transportation of fresh municipal solid waste to landfills has ceased in most first-tier cities. Consequently, the production of landfill gas has sharply declined because the supply of organic matter has decreased, rendering power generation facilities idle. However, by incorporating liquefied kitchen and food waste (LKFW), sustainable methane production can be achieved while consuming organic wastewater. In this study, LKFW and water (as a control group) were periodically injected into high and low organic wastes, respectively. The biochemical characteristics of the resulting gas and leachate were analyzed. LKFW used in this research generated 19.5-37.6 L of methane per liter in the post-methane production phase, highlighting the effectiveness of LKFW injection in enhancing the methane-producing capacity of the system. The release of H2S was prominent during both the rapid and post-methane production phases, whereas that of NH3 was prominent in the post-methane production phase. As injection continued, the concentrations of chemical oxygen demand, 5-d biological oxygen demand, total organic carbon, ammonia nitrogen, total nitrogen, and oil in the output leachate decreased and eventually reached levels comparable to those in the water injection cases. After nine rounds of injections, the biologically degradable matter of the two LKFW-injected wastes decreased by 8.2 % and 15.1 %, respectively. This study sheds light on determining the organic load, controlling odor, and assessing the biochemical characteristics of leachate during LKFW injection.

Dickkopf-related protein 1 as a biomarker of local immune status and worse prognosis of Oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an infiltrative malignancy characterized by a significantly elevated recurrence rate. Dickkopf-related protein 1 (DKK1), which plays an oncogene role in many cancers, acts as an inhibitor of the Wingless protein (Wnt) signaling pathway. Currently, there is a lack of consensus regarding the role of DKK1 in OSCC or its clinical significance. OBJECTIVE: To examine the role and effect of DKK1 in OSCC. METHODS: The identification of differentially expressed genes (DEGs) in OSCC was conducted by utilizing databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A comprehensive analysis of gene expression profile interactions (GEPIA) and Kaplan-Meier curve were conducted to investigate the associations among DEGs, patient survival and prognosis in individuals with OSCC. The biological function of DKK1 in OSCC was investigated by using molecular biology approaches. RESULTS: The expression of DKK1 was found to be upregulated in OSCC tissues at various stages. High levels of DKK1 expression exhibited a positive correlation with the overall survival (OS) and progression-free survival (PFS) rates among OSCC patients. DKK1 knockdown suppressed the proliferation and induced apoptotic response in OSCC cells. Moreover, DKK1 exerted a positive regulatory effect on HMGA2 expression, thereby modulating cell growth and apoptosis in OSCC. The expression of DKK1 was found to be positively correlated with the infiltration of immune cells in patients with OSCC. Additionally, higher levels of CD4+ T cells were associated with improved 5-year survival rates. CONCLUSION: DKK1 is a prognostic biomarker for patients with OSCC.

The identification of new roles for nicotinamide mononucleotide after spinal cord injury in mice: an RNA-seq and global gene expression study.

Background: Nicotinamide mononucleotide (NMN), an important transforming precursor of nicotinamide adenine dinucleotide (NAD+). Numerous studies have confirmed the neuroprotective effects of NMN in nervous system diseases. However, its role in spinal cord injury (SCI) and the molecular mechanisms involved have yet to be fully elucidated. Methods: We established a moderate-to-severe model of SCI by contusion (70 kdyn) using a spinal cord impactor. The drug was administered immediately after surgery, and mice were intraperitoneally injected with either NMN (500 mg NMN/kg body weight per day) or an equivalent volume of saline for seven days. The central area of the spinal cord was harvested seven days after injury for the systematic analysis of global gene expression by RNA Sequencing (RNA-seq) and finally validated using qRT-PCR. Results: NMN supplementation restored NAD+ levels after SCI, promoted motor function recovery, and alleviated pain. This could potentially be associated with alterations in NAD+ dependent enzyme levels. RNA sequencing (RNA-seq) revealed that NMN can inhibit inflammation and potentially regulate signaling pathways, including interleukin-17 (IL-17), tumor necrosis factor (TNF), toll-like receptor, nod-like receptor, and chemokine signaling pathways. In addition, the construction of a protein-protein interaction (PPI) network and the screening of core genes showed that interleukin 1ß (IL-1ß), interferon regulatory factor 7 (IRF 7), C-X-C motif chemokine ligand 10 (Cxcl10), and other inflammationrelated factors, changed significantly after NMN treatment. qRT-PCR confirmed the inhibitory effect of NMN on inflammatory factors (IL-1ß, TNF-α, IL-17A, IRF7) and chemokines (chemokine ligand 3, Cxcl10) in mice following SCI. Conclusion: The reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model. RNA-seq and qRT-PCR systematically revealed that NMN affected inflammation-related signaling pathways, including the IL-17, TNF, Toll-like receptor, NOD-like receptor and chemokine signaling pathways, by down-regulating the expression of inflammatory factors and chemokines.

Letter to the editor: Aggressive variant prostate cancer: An exemplary case study and comprehensive literature survey.

This article enthusiastically explores the study of highly aggressive variant prostate cancer (AVPC), acknowledging its relatively rare yet highly menacing presence within the realm of prostate cancer. The paper delves into the pathological characteristics of AVPC, diagnostic and therapeutic challenges, and the potential applications of precision medicine and molecular imaging in the future.

Fabrication of triple-crosslinked gelatin/alginate hydrogels for controlled release applications.

Hydrogels have been demonstrated as smart drug carriers to recognize the tumor microenvironment for cancer treatment, where the dynamic crosslinks in the hydrogel network contribute to the stimuli-responsive features but also result in poor stability and weak mechanical property of the hydrogels. Here, phenylboronic acid-grafted polyethyleneimine (PBA-PEI)-modified gelatin (PPG) was synthesized to crosslink alginate dialdehyde (ADA) through imine bonds and boronate ester bonds, and then calcium ions (Ca2+) were added to introduce the third calcium-carboxylate crosslinking in the network to form the triple-crosslinked PPG/ADA-Ca2+ hydrogels. Given the three types of dynamic bonds in the network, PPG/ADA-Ca2+ hydrogels possessed a self-healing manner, stimuli-responsiveness, and better mechanical properties compared to single- or double-crosslinked hydrogels. The controlled release capability of PPG/ADA-Ca2+ hydrogels was also demonstrated, showing the encapsulated molecules can be rapidly released from the hydrogel network in the presence of hydrogen peroxide while the release rate can be slowed down at acidic pH. Furthermore, PPG/ADA-Ca2+ hydrogels presented selected cytotoxicity and drug delivery to cancer cells due to the regulated degradation by the cellular microenvironment. Taken together, PPG/ADA-Ca2+ hydrogels have been demonstrated as promising biomaterials with multiple desirable properties and dynamic features to perform controlled molecule release for biomedical applications.

Aliidiomarina quisquiliarum sp. nov., isolated from landfill leachate.

Bacterial strain Y-6T, isolated from a landfill site in Yiwu, PR China, was characterized using a polyphasic taxonomy approach. Cells were Gram-stain-negative, aerobic, rod-shaped, motile by means of a single polar flagellum and formed pale beige colonies. Strain Y-6T grew at 4-40 °C (optimal at 30-37 °C), pH 6.5-9.5 (optimal at pH 7.2-8.5) and in the presence of 0.5-10.0 % (w/v) NaCl (optimal at 1.0-3.0 %). Phylogenetic analysis revealed that strain Y-6T was a member of the genus Aliidiomarina and closely related to Aliidiomarina taiwanensis MCCC 1A06493T with a 16S rRNA sequence similarity of 98.2 %. The major cellular fatty acids of the isolate were iso-C15 : 0, C16 : 0, iso-C17 : 0 and summed feature 9 (iso-C17 : 1 ω9c and/or 10-methyl-C16 : 0). Q-8 was the predominant ubiquinone. The major polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, aminoglycophospholipid, aminophospholipid, phospholipid, three glycolipids and two unknown lipids. The genomic DNA G+C content was 46.6 mol%. The digital DNA-DNA hybridization value between Y-6T and A. taiwanensis MCCC 1A06493T was 18.3 %. Strain Y-6T had an average nucleotide identity value of 74.09 % with A. taiwanensis MCCC 1A06493T. Results from the polyphasic taxonomy study support the conclusion that strain Y-6T represents a novel Aliidiomarina species, for which the name Aliidiomarina quisquiliarum sp.nov. is proposed. The type strain is Y-6T (=MCCC 1K06228T=KCTC 82676T).

Oncogenic KPNA2 Serves as a Biomarker and Immune Infiltration in Patients With HPV Positive Tongue Squamous Cell Carcinoma.

Human tongue squamous cell carcinoma (TSCC), the most prevalent type of oral cancer, is associated with human papillomavirus (HPV) infection. Our previous work showed Karyopherin α2 (KPNA2), as an oncogene of TSCC, by relegating the p53/autophagy signaling pathway. Nevertheless, the significance of KPNA2 in TSCC pathogenesis has not been established. KPNA2 levels were evaluated via the TCGA database, and its effects on survival outcomes were assessed by LASSO, Kaplan-Meier, and COX regression analyses. CIBERSORT and ESTIMATE investigated the relationships between KPNA2 and immune infiltration. At the same time, KPNA2 and HPV infection was analyzed by immunohistochemistry. In addition, the association between downstream molecular regulation pathways and KPNA2 levels was determined by GO, GSEA, and WGCNA. In TSCC, KPNA2 levels were associated with clinical prognosis and tumor grade. Moreover, KPNA2 may be involved in cancer cell differentiation and facilitates tumor-related genes and signaling pathways, such as Cell Cycle, Mitotic G1 phase, G1/S transition, DNA Repair, and Transcriptional Regulation TP53 signaling pathways. Nevertheless, regulatory B cells, follicular helper B cells, and immune and stromal scores between low- and high-KPNA2 expression groups were insignificant. These results imply that KPNA2 is highly involved in tumor grade and prognosis of TSCC. KPNA2 levels correct with HPV 16 markedly regulated cell differentiation, several oncogenes, and cancer-related pathways.

A Novel STAT3 Gain-of-Function Mutation in Fatal Infancy-Onset Interstitial Lung Disease.

Signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) mutations cause early-onset immune dysregulation syndrome, characterized by multi-organ autoimmunity and lymphoproliferation. Of them, interstitial lung disease (ILD) usually develops after the involvement of other organs, and the onset time is childhood and beyond rather than infancy. Here, we reported a patient who presented with fatal infancy-onset ILD, finally succumbing to death. Next-generation sequencing identified a novel heterozygous mutation in STAT3 (c.989C>G, p.P330R). Functional experiments revealed it was a gain-of-function mutation. Upon interleukin 6 stimulation, this mutation caused a much higher activation of STAT3 than the wild-type control. In addition, the mutation also activated STAT3 under the steady state. The T helper 17 cell level in the patient was significantly higher than that in normal controls, which may contribute to the autoimmune pathology caused by the STAT3P330R mutation. Apart from Janus kinase (JAK) inhibitors, we also provided experimental evidence of a STAT3 selective inhibitor (Stattic) effectively suppressing the activation of mutant STAT3 in vitro. Collectively, our study expanded the clinical spectrum of STAT3 GOF syndrome. STAT3 GOF mutation appears as a new etiology of ILD and should be considered in patients with early-onset ILDs. In addition to JAK inhibitors, the specific STAT3 inhibitor would be an appealing option for the targeted treatment.

Automated in silico EGFR Peptide Inhibitor Elongation using Self-evolving Peptide Algorithm.

BACKGROUND: The vast diversity of peptide sequences may hinder the effectiveness of screening for potential peptide therapeutics as if searching for a needle in a haystack. This study aims to develop a new self-evolving peptide algorithm (SEPA), for easy virtual screening of small linear peptides (three to six amino acids) as potential therapeutic agents with the collaborative use of freely available software that can be run on any operating system equipped with a Bash scripting terminal. Mitogen-inducible Gene 6 (Mig6) protein, a cytoplasmic protein responsible for inhibition and regulation of epidermal growth factor receptor tyrosine kinase, was used to demonstrate the algorithm. OBJECTIVE: The objective is to propose a new method to discover potential novel peptide inhibitors via an automated peptide generation, docking and post-docking analysis algorithm that ranks short peptides by using essential hydrogen bond interaction between peptides and the target receptor. METHODS: A library of dockable dipeptides were first created using PyMOL, Open Babel and AutoDockTools, and docked into the target receptor using AutoDock Vina, automatically via a Bash script. The docked peptides were then ranked by hydrogen bond interaction-based thorough interaction analysis, where the top-ranked peptides were then elongated, docked, and ranked again. The process repeats until the user-defined peptide length is achieved. RESULTS: In the tested example, SEPA bash script was able to identify the tripeptide YYH ranked within top 20 based on the essential hydrogen bond interaction towards the essential amino acid residue ASP837 in the EGFR-TK receptor. CONCLUSION: SEPA could be an alternative approach for the virtual screening of peptide sequences against drug targets.

Soil heavy metal pollution of industrial legacies in China and health risk assessment.

Rapid urbanization in China has brought about large-scale factory relocation. Severe environmental ecological and human health risks are caused by a large number of contaminated legacies left in the city. To comprehensively review the pollution and assess the health risk of industrial legacies in China, a total of 625 polluted industrial legacies were compiled by document retrieval. Legacies are mainly located in the southwest of China, the North China Plain, Yangtze River Basin, Yangtze River Delta, and Pearl River Delta with a mean operation time of 35 years, and legacies of chemical manufacturing take the biggest proportion of all sites. Health risk assessments considering the uncertainty of exposure and toxic factors reveal that the soil heavy metal pollution in China is serious, with Pb, Cd, Zn, Ni, and As as dominant pollutants. Legacies of chemical manufacturing, ferrous metal processing, non-ferrous metal processing, and mines should be priority controlled for their large number and serious risks. Children are the most vulnerable people with more serious non-carcinogenic and carcinogenic risks, while males are slightly surpassed by females. Insights for better risk management of legacies are provided based on the comprehensive assessment of pollution and human health risk in this study.

Towards ARTEM-IS: Design guidelines for evidence-based EEG methodology reporting tools.

As the number of EEG papers increases, so too do the number of guidelines for how to report what has been done. However, current guidelines and checklists appear to have limited adoption, as systematic reviews have shown the journal article format is highly prone to errors, ambiguities and omissions of methodological details. This is a problem for transparency in the scientific record, along with reproducibility and metascience. Following lessons learned in the high complexity fields of aviation and surgery, we conclude that new tools are needed to overcome the limitations of written methodology descriptions, and that these tools should be developed through community consultation to ensure that they have the most utility for EEG stakeholders. As a first step in tool development, we present the ARTEM-IS Statement describing what action will be needed to create an Agreed Reporting Template for Electroencephalography Methodology - International Standard (ARTEM-IS), along with ARTEM-IS Design Guidelines for developing tools that use an evidence-based approach to error reduction. We first launched the statement at the LiveMEEG conference in 2020 along with a draft of an ARTEM-IS template for public consultation. Members of the EEG community are invited to join this collective effort to create evidence-based tools that will help make the process of reporting methodology intuitive to complete and foolproof by design.

Lateral minimal approach to the terrible triad of the elbow: a treatment protocol in Beijing Jishuitan Hospital.

BACKGROUND: This study aimed to report the surgical techniques and results of treating coronoid process and radial head fracture combined with dislocation of the elbow (terrible triad of the elbow) using a single lateral incision, known as the extensor digitorum communis (EDC) split approach. METHODS: A retrospective analysis was performed of 109 patients with terrible triad of the elbow who had been treated by the authors from January 2013 to December 2019. The participants included 67 males and 42 females, with a mean age of 42.2 years (14-71 years). All participants were treated via a single lateral approach. The coronoid process was fixated with Kirschner wires combined with anterior capsule suture lasso fixation. For the radial head fracture, 58 cases were fixated by AO headless cannulated screw (AO HCS) and 51 cases by acumed radial head replacement. In repair of the lateral collateral ligament (LCL) complex and the common extensor tendon, 28 cases used ETHIBOND suture through bone holes at the humeral lateral epicondyle, and the other 81 cases used suture anchors. No medial collateral ligament was repaired. A total of 46 participants were fixated with a Stryker dynamic joint distractor (DJD) II hinged external fixator to protect the bone and soft tissue. RESULTS: All participants were followed up from 6 to 60 months (mean, 36.1 months). Their elbow range of flexion and extension averaged 123.4°±20.7°, forearm rotation 151.0°±25.6°, and Mayo elbow performance score (MEPS) 92.3±8.8. There were 22 participants (19.5%) with ulnar nerve symptoms, 16 (14.7%) who had elbow stiffness, and 7 underwent secondary surgery, including 6 removals of internal fixation, 5 arthrolyses of the elbow, and 2 ulnar neurolyses. CONCLUSIONS: Coronoid fractures, radial head fractures, and LCL injuries of the terrible triad of the elbow can be treated satisfactorily through a lateral minimal incision, combined with a hinged external fixation if necessary.

[Extraction, Characterization and Immune Effect Analysis of Listeria Monocytogenes Membrane Vesicles].

OBJECTIVE: To establish a method for extracting Listeria monocytogenesmembrane vesicles (LM-MVs) and to analyze the characteristics of LM-MVs and their ability to induce innate immune effect in vitro so as to lay the foundation for research into using LM-MVs as vaccine carrier and drug delivery platform. METHODS: The membrane vesicles secreted by Listeria monocytogenes were extracted through a continuous process, including culturing, centrifugation, filtration, ultrafiltration concentration and ultracentrifugation. The morphological characteristics of LM-MVs were observed with transmission electron microscope, and particle size distribution were measured by dynamic light scattering analysis. SDS-PAGE and Western blot were used to analyze the protein composition of LM-MVs. CCK-8 cell proliferation and toxicity determination experiments were done to analyze their effect on the proliferation of innate immune cells, and qPCR was used to analyze their ability to induce innate immune responses. RESULTS: A method for extracting LM-MVs was successfully established. Under the transmission electron microscope, LM-MVs presented a nearly circular film-like structure, and dynamic light scattering analysis showed that their sizes were between 65 and 190 nm. SDS-PAGE and Western blot showed that LM-MVs contained proteins, including listeriolysin O (LLO). CCK-8 cell proliferation and toxicity experiment showed that after intervention with 10, 20 and 50 µg/mL of LM-MVs for 24 hours, the proliferation rate of DC 2.4 mouse dendritic cell line was higher than that of non-interventional DC 2.4 cells ( P<0.05); after intervention with 0.1, 1, 10, 20 and 50 µg/mL of LM-MVs for 24 hours, the proliferation rate of RAW 264.7 cells was higher than that of non-interventional RAW 264.7 cells ( P<0.01). The results of qPCR showed that, after intervention with 50 µg/mL of LM-MVs, the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 in RAW 264.7 cells were higher than those of non-intervention control cells ( P<0.05). CONCLUSIONS: The method established in the study can be used to extract LM-MVs. The extracted LM-MVs have a diameter of 65-190 nm and a nearly circular membrane-like structure. They can secrete a variety of protein components and stimulate innate immune responses.

Individualized model for predicting COVID-19 deterioration in patients with cancer: A multicenter retrospective study.

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent area under the receiver operating characteristic curve (t-AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points ≤ 9.98) and high-risk (total points > 9.98) group. The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.

Deformation Assessment of the Manually Pre-Bent Titanium Miniplates in Orthognathic Surgery With Finite Element Analysis.

ABSTRACT: This study summarized the literature regarding the application of pre-bent titanium miniplates in orthognathic surgery and evaluated the extra deformation of the manually pre-bent titanium miniplates via finite element analysis for acquiring higher surgical accuracy. The literature was reviewed with a chart. Three models of titanium miniplates with different thicknesses (1.0 mm, 0.8 mm, 0.6 mm) were created using COMSOL Multiphysics software for biomechanical behavior analysis. The 3 models were virtually bent into 5 angles (15 degree, 30 degree, 45 degree, 60 degree, 80 degree). respectively to simulate the preoperative virtual bending, then to simulate the practical manual bending via finite element analysis. The stresses and displacements of these models were recorded. The models from virtual bending simulation and manual bending simulation were registered to analyze the deviations. The results showed that the maximum stress and the displacement deviations between the virtual bending models and the manual bending models increased with the thickness and bending angle of the pre-bent miniplate models. To improve the surgical accuracy, measures should be applied to the manually pre-bent titanium miniplates to reduce the extra deformation when the plate being thicker and the bending angle being larger.

Osteogenesis Differences Around Titanium Implant and in Bone Defect Between Jaw Bones and Long Bones.

The aim of this study is to evaluate the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones in ovariectomized (OVX) animal models. The literature on the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones was reviewed with charts. Fourty-eight rats were randomly divided into OVX group with ovariectomy and SHAM (sham-surgery) group with sham surgery. Titanium implants were inserted in the right mandibles and tibiae; bone defects were created in the left mandibles and tibiae. Two-week postoperatively, mandibles and tibiae of 8 rats were harvested and examined by hematoxylin and eosin staining and histological analysis; 4-week postoperatively, all mandibles and tibiae were harvested and examined by Micro-CT and histological analysis. A total of 52 articles were included in this literature review. Tibial osteogenesis around titanium implant and in bone defect in OVX group were significantly decreased compared with SHAM group. However, osteogenesis differences in the mandible both around titanium implant and in bone defect between groups were not statistically significant. OVX-induced osteoporosis suppresses osteogenesis around titanium implant and in the bone defect or fracture in long bones significantly while has less effect on that in the jaw bones.

Lumbar decompression and lumbar interbody fusion in the treatment of lumbar spinal stenosis: A systematic review and meta-analysis.

BACKGROUND: The goal of this study was to review relevant randomized controlled trials in order to determine the efficacy of decompression and lumbar interbody fusion in the treatment of lumbar spinal stenosis. METHOD: Using appropriate keywords, we identified relevant studies in PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through July 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval to assess and synthesize outcomes. RESULT: Twenty-one randomized controlled trials were eligible for this meta-analysis with a total of 3636 patients. Compared with decompression, decompression and fusion significantly increased length of hospital stay, operative time and estimated blood loss. Compared with fusion, decompression significantly decreased operative time, estimated blood loss and overall visual analogue scale (VAS) scores. Compared with endoscopic decompression, microscopic decompression significantly increased length of hospital stay, and operative time. Compared with traditional surgery, endoscopic discectomy significantly decreased length of hospital stay, operative time, estimated blood loss, and overall VAS scores and increased Japanese Orthopeadic Association score. Compared with TLIF, MIS-TLIF significantly decreased length of hospital stay, and increased operative time and SF-36 physical component summary score. Compared with multi-level decompression and single level fusion, multi-level decompression and multi-level fusion significantly increased operative time, estimated blood loss and SF-36 mental component summary score and decreased Oswestry disability index score. Compared with decompression, decompression with interlaminar stabilization significantly decreased operative time and the score of Zurich claudication questionnaire symptom severity, and increased VAS score. CONCLUSION: Considering the limited number of included studies, we still need larger-sample, high-quality, long-term studies to explore the optimal therapy for lumbar spinal stenosis.

Sevoflurane modulates the cancer stem cell-like properties and mitochondrial membrane potential of glioma via Ca2+-dependent CaMKII/JNK cascade.

AIMS: Gliomas are responsible for the majority of deaths from primary brain tumours. Sevoflurane showed inhibition effects on the tumor progression in vitro. However, whether sevoflurane could affect the stemness of glioma stem cells (GSCs) and the potential molecular mechanism have not been well elucidated. MAIN METHODS: Effects of sevoflurane on cell viability, proliferation and invasion ability of glioma cells as well as tumor growth in vivo were assessed. Sphere formation assay was performed to evaluate the effect of sevoflurane on the stemness of GSCs. Effects of sevoflurane on mitochondrial function was evaluated by intracellular/mitochondrial reactive oxygen species (ROS) level and mitochondrial membrane potential. Expression levels of proliferation-related proteins, stemness markers and proteins in CaMKII/JNK cascade were measured by Western blot. KEY FINDINGS: Sevoflurane inhibited the viability, proliferation and invasion ability of glioma cells (U87MG and U373MG). Western blot showed that sevoflurane decreased the expression levels of proliferation and invasion-related proteins. Sphere formation ability of GSCs, expression levels of stemness markers and mitochondrial function were significantly suppressed by sevoflurane. Moreover, sevoflurane treatment significantly increased the Ca2+ concentration and stimulated phosphorylation of CaMKII, JNK and IRS1. Ca2+ chelator BAPTA-AM combined with sevoflurane synergistically inhibited colony forming ability and the expression levels of proliferation-related proteins and stemness markers. In addition, the in vivo study further confirmed that sevoflurane inhibited tumor growth via Ca2+-dependent CaMKII/JNK cascade. SIGNIFICANCE: The present study demonstrated that sevoflurane inhibited glioma tumorigenesis and modulated the cancer stem cell-like properties and mitochondrial membrane potential via activation of Ca2+-dependent CaMKII/JNK cascade.