Supramolecular 3 in 1: A Lubrication and Co-Delivery System for Synergistic Advanced Osteoarthritis Therapy.

The complexity, heterogeneity, and drug resistance of diseases necessitate a shift in therapeutic paradigms from monotherapy to combination therapy, which could augment treatment efficiency. Effective treatment of advanced osteoarthritis (OA) requires addressing three key factors contributing to its deterioration: chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation. Herein, we present a supramolecular nanomedicine of multifunctionality via molecular recognition and self-assembly. The employed macrocyclic carrier, zwitterion-modified cavitand (CV-2), not only accurately loads various drugs but also functions as a therapeutic agent with lubricating properties for the treatment of OA. Kartogenin (KGN), a drug for articular cartilage regeneration and protection, and flurbiprofen (FP), an anti-inflammatory agent, were coloaded onto CV-2 assembly, forming a supramolecular nanomedicine KGN&FP@CV-2. The three-in-one combination therapy of KGN&FP@CV-2 addresses the three pathological features for treating OA collectively, and thus provides long-term therapeutic benefits for OA through sustained drug release and intrinsic lubrication in vivo. The multifunctional integration of macrocyclic delivery and therapeutics provides a simple, flexible, and universal platform for the synergistic treatment of diseases involving multiple drugs.

Deficiency of Acetyltransferase nat10 in Zebrafish Causes Developmental Defects in the Visual Function.

Purpose: N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification catalyzed by N-acetyltransferase 10 (NAT10), a critical factor known to influence mRNA stability. However, the role of ac4C in visual development remains unexplored. Methods: Analysis of public datasets and immunohistochemical staining were conducted to assess the expression pattern of nat10 in zebrafish. We used CRISPR/Cas9 and RNAi technologies to knockout (KO) and knockdown (KD) nat10, the zebrafish ortholog of human NAT10, and evaluated its effects on early development. To assess the impact of nat10 knockdown on visual function, we performed comprehensive histological evaluations and behavioral analyses. Transcriptome profiling and real-time (RT)-PCR were utilized to detect alterations in gene expression resulting from the nat10 knockdown. Dot-blot and RNA immunoprecipitation (RIP)-PCR analyses were conducted to verify changes in ac4C levels in both total RNA and opsin mRNA specifically. Additionally, we used the actinomycin D assay to examine the stability of opsin mRNA following the nat10 KD. Results: Our study found that the zebrafish NAT10 protein shares similar structural properties with its human counterpart. We observed that the nat10 gene was prominently expressed in the visual system during early zebrafish development. A deficiency of nat10 in zebrafish embryos resulted in increased mortality and developmental abnormalities. Behavioral and histological assessments indicated significant vision impairment in nat10 KD zebrafish. Transcriptomic analysis and RT-PCR identified substantial downregulation of retinal transcripts related to phototransduction, light response, photoreceptors, and visual perception in the nat10 KD group. Dot-blot and RIP-PCR analyses confirmed a pronounced reduction in ac4C levels in both total RNA and specifically in opsin messenger RNA (mRNA). Additionally, by evaluating mRNA decay in zebrafish treated with actinomycin D, we observed a significant decrease in the stability of opsin mRNA in the nat10 KD group. Conclusions: The ac4C-mediated mRNA modification plays an essential role in maintaining visual development and retinal function. The loss of NAT10-mediated ac4C modification results in significant disruptions to these processes, underlining the importance of this RNA modification in ocular development.

Prognostic impact of colorectal cancer patients with bone metastases: a single-center experience.

The incidence of bone metastasis (BM) in colorectal cancer (CRC) patients is low and the prognosis is poor. There is no clear conclusion on the risk factors affecting the survival of CRC patients with BM. The aim of this study was to investigate the factors that may affect the prognosis of CRC patients with BM. The clinical and pathological data of CRC patients with BM were retrospectively analyzed. The overall survival after BM diagnosis was estimated using the Kaplan-Meier method and Log-rank test, and a multivariable cox regression model was used to identify the prognostic factors of overall survival. This study included 178 CRC patients with BM, of whom 151 had left-sided CRC and 27 had right-sided colon cancer. 1124 CRC patients with BM from the SEER database were included to perform a sensitivity analysis of the primary outcome. Multivariate analysis showed that the N staging, site of BM, and primary tumor sidedness (PTS) were independent prognostic factors for CRC with BM. Among them, right-sided colon cancer patients with BM had a poorer prognosis. Sensitivity analyses showed that PTS was an independent prognostic factor in CRC patients with BM. Primary tumor sidedness and N stage may be potential prognostic markers for BM of CRC. The prognosis of N0 stage CRC with BM is better, while the prognosis of right-sided colon cancer is poor.

A Unified Therapeutic-Prophylactic Tissue-Engineering Scaffold Demonstrated to Prevent Tumor Recurrence and Overcoming Infection toward Bone Remodeling.

Osteosarcoma occurs in children and adolescents frequently and leads to a high fatality rate. Although surgical resection is the most common methods in clinic, patients always suffer from tumor metastasis and recurrence and it is difficult for them to self-repair large bone defects. Furthermore, the postoperative infection from bacteria triggers an inflammatory response and hinders the bone-repair process. This work demonstrates a gadolinium (Gd)-complex and molybdenum sulfide (MoS2 ) co-doped N-acryloyl glycinamide (NAGA)/gelatin methacrylate (Gel-MA) multifunctional hydrogel (GMNG). The combination between NAGA and Gel-MA endows the GMNG with attractive mechanical properties and controllable degradation ability. The MoS2 improves the hydrogel system, which has excellent photothermal ability to kill tumor cells and inhibit bacterial infection both in vitro and in vivo. Based on the Gd-complex, the magnetic resonance imaging (MRI) effect can be used to monitor the position and degradation situation of the hydrogel. Notably, accompanied by the degradation of GMNG hydrogel, the gradually released Gd3+ from the hydrogel exhibits osteogenic property and could promote new bone formation efficiently in vivo. Therefore, this strategy supplies a method to prepare multifunctional bone-defect-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for bone tissue engineering.

Comparison of discover cervical disc arthroplasty and anterior cervical discectomy and fusion for the treatment of cervical degenerative disc diseases: A meta-analysis of prospective, randomized controlled trials.

Objective: This study aims to evaluate the clinical efficacy and safety between Discover cervical disc arthroplasty (DCDA) and anterior cervical discectomy and fusion (ACDF) in Cervical degenerative disc diseases. Methods: Two researchers independently conducted a search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trails (CENTRAL) for randomized controlled trials (RCTs) following the Cochrane methodology guidelines. A fixed-effects or random-effects model was applied based on different heterogeneity. Review Manager (Version 5.4.1) software was used to perform data analysis. Results: A total of 8 RCT studies were included in this meta-analysis. The results indicate that the DCDA group had a higher incidence of reoperation (P = 0.03) and a lower incidence of ASD (P = 0.04) than the CDA group. There was no significant difference between two groups regarding NDI score (P = 0.36), VAS ARM score (P = 0.73), VAS NECK score (P = 0.63), EQ-5D score (P = 0.61) and dysphagia incidence (0.18). Conclusion: DCDA and ACDF have similar results in terms of NDI scores, VAS scores, EQ-5D scores, and dysphagia. In addition, DCDA can reduce the risk of ASD but increases the risk of reoperation.

Morroniside ameliorates glucocorticoid-induced osteoporosis and promotes osteoblastogenesis by interacting with sodium-glucose cotransporter 2.

CONTEXT: Morroniside (MOR) possesses antiosteoporosis (OP) effects, but its molecular target and relevant mechanisms remain unknown. OBJECTIVE: We investigated the effects of MOR on glucocorticoid-induced OP and osteoblastogenesis and its underlying mechanisms. MATERIALS AND METHODS: The effects of MOR (10-100 µM) on the proliferation and differentiation of MC3T3-E1 cells were studied in vitro. The glucocorticoid-induced zebrafish OP model was treated with 10, 20 and 40 µM MOR for five days to evaluate its effects on vertebral bone density and related osteogenic markers. In addition, molecular targets prediction and molecular docking analysis were carried out to explore the binding interactions of MOR with the target proteins. RESULTS: In cultured MC3T3-E1 cells, 20 µM MOR significantly increased cell viability (1.64 ± 0.12 vs. 0.95 ± 0.16; p < 0.01) and cell differentiation (1.57 ± 0.01 vs. 1.00 ± 0.04; p < 0.01) compared to the control group. MOR treatment significantly ameliorated vertebral bone loss in the glucocorticoid-induced OP zebrafish model (0.86 ± 0.02 vs. 0.40 ± 0.03; p < 0.01) and restored the expression of osteoblast-specific markers, including ALP, Runx2 and Col-І. Ligand-based target prediction and molecular docking revealed the binding interaction between MOR and the glucose pockets in sodium-glucose cotransporter 2 (SGLT2). DISCUSSION AND CONCLUSIONS: These findings demonstrated that MOR treatment promoted osteoblastogenesis and ameliorated glucocorticoid-induced OP by targeting SGLT2, which may provide therapeutic potential in managing glucocorticoid-induced OP.

Sequential Therapy for Bone Regeneration by Cerium Oxide-Reinforced 3D-Printed Bioactive Glass Scaffolds.

Rational design of multifunctional biomaterials with customized architecture and on demand bioactivity is of great significance for bone tissue engineering (BTE) in modern society. Herein, a versatile therapeutic platform has been established by integrating cerium oxide nanoparticles (CeO2 NPs) into bioactive glass (BG) to fabricate three-dimensional (3D)-printed scaffolds, achieving a sequential therapeutic effect against inflammation and promoting osteogenesis toward bone defect. The antioxidative activity of CeO2 NPs plays a crucial role in alleviating the oxidative stress upon formation of bone defects. Subsequently, CeO2 NPs exert a promotion effect on the proliferation and osteogenic differentiation of rat osteoblasts through enhancing mineral deposition and alkaline phosphatase and osteogenic gene expression. Strikingly, the incorporation of CeO2 NPs bestows on the BG scaffolds greatly reinforced mechanical properties, improved biocompatibility, adequate cell adhesion, elevated osteogenic capability, and multifunctional performance in a single platform. In vivo studies on the treatment of rat tibial defect confirmed the better osteogenic properties of CeO2-BG scaffolds compared with pure BG scaffolds. Additionally, the employment of the 3D printing technique creates a proper porous microenvironment around the bone defect, which further facilitates the cell in-growth and new bone formation. This report provides a systematic study on CeO2-BG 3D-printed scaffolds prepared by simple ball milling method, achieving sequential and integral treatment in BTE based on a single platform.

Predictors of residual low back pain in patients with osteoporotic vertebral fractures following percutaneous kyphoplasty.

Objective: Patients with osteoporotic vertebral fractures (OVFs) often suffer from residual low back pain (LBP) after percutaneous kyphoplasty (PKP). The purpose of this study was to identify risk factors for postoperative residual LBP and to develop a nomogram to predict the occurrence of residual LBP. Methods: We retrospectively reviewed 236 patients who underwent PKP for OVFs and had a minimum follow-up of 12 months. The mean age was 72.1 ± 6.3, 74.3% were female and 25.7% were male. Patients with LBP VAS scores ≥ 3.5 at the 12th month postoperatively were considered to have residual LBP. Risk factors for residual LBP were identified by univariate and multifactorial logistic regression analysis. Then, a predictive nomogram was constructed and validated using the bootstrap method. The discrimination, calibration, and clinical utility of the nomogram were assessed using a receiver operating characteristic curve (ROC), a calibration curve, and a decision curve analysis (DCA). Results: univariate and multifactorial logistic regression analysis identified depression (P = 0.02), intravertebral vacuum cleft (P = 0.01), no anti-osteoporosis treatment (P < 0.001), cement volume <3 ml (P = 0.02), and cement distrubution (P = 0.01) as independent risk factors for residual LBP. The area under the ROC was 0.83 (0.74-0.93) and further validated by bootstrap method was 0.83 (0.73-0.92). The calibration curve illustrated the consistency between the predicted probability and the observed results. DCA showed that nomogram exhibits clinical utility and net benefit when the threshold probability is between 6% and 73%. Conclusions: Our study found that depression, intravertebral vacuum cleft, no anti-osteoporosis treatment, cement volume <3 ml and cement distribution represent independent risk factors for residual LBP. The nomogram containing the above five predictors can accurately predict the risk of residual LBP after surgery.

Long noncoding RNA HCG18 Promotes Extracellular Matrix Degradation of Nucleus Pulposus Cells in Intervertebral Disc Degeneration by Regulating the miR-4306/EPAS1 Axis.

BACKGROUND: Intervertebral disc degeneration is a very common disease worldwide and the leading cause of low back pain. Long noncoding RNAs are novel players in intervertebral disc degeneration and have multiple functions. This study explored the role of long noncoding RNA HCG18 in regulating extracellular matrix (ECM) degradation in nucleus pulposus cells (NPCs) during intervertebral disc degeneration. METHODS: NPCs were subjected to interleukin-1ß to induce a degenerative model of NPCs. Cell viability was assessed using Cell Counting Kit-8 assay. Messenger RNA and protein expressions were examined by real-time quantitative polymerase chain reaction and Western blot. The location of HCG18 was determined by nucleocytoplasmic separation assay. The binding relationships between HCG18, MIR4306, and EPAS1 were verified by dual luciferase reporter gene assay and/or RNA immunoprecipitation assay. RESULTS: HCG18 was highly expressed in interleukin-1ß-induced degenerated NPCs, which was associated with reduced collagen II and aggrecan expression and increased MMP-13 and ADAMTS-4 expression. HCG18 knockdown could remarkably inhibit ECM degradation in IL-1ß-induced degenerated NPCs, while HCG18 overexpression had the opposite effect. Our molecular study further revealed that HCG18 could sponge MIR4306, and HCG18 knockdown could suppress ECM degradation in degenerated NPCs by elevating MIR4306 expression. In addition, EPAS1 was identified as the direct target of MIR4306. As expected, MIR4306 overexpression inhibited ECM degradation in degenerated NPCs by downregulating EPAS1. CONCLUSIONS: HCG18 promoted ECM degradation in degenerated NPCs via regulation of the MIR4306/EPAS1 axis.

Causal effects of homocysteine levels on the components of sarcopenia: A two-sample mendelian randomization study.

Background: Currently, it is unclear whether there is a causal association between genetically predicted plasma homocysteine (Hcy) levels and the risk of sarcopenia. We performed a Mendelian randomization (MR) study to assess the association between circulating Hcy levels and the components [grip strength, walking pace, and appendicular lean mass (ALM)] of sarcopenia. Methods: Independent single nucleotide polymorphisms (SNPs) significantly associated with plasma Hcy levels served as instrumental variables. Summary-level data regarding the components of sarcopenia. Were obtained from the UK Biobank. Inverse variance weighted (IVW) as the primary method was used for Mendelian randomization (MR) analysis. We also use four models, weighted median, MR-Egger regression, Maximum likelihood, and Penalised weighted median, as supplementary methods to IVW. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of the causal association between Hcy levels and the components of sarcopenia. Results: The IVW-MR analysis suggested significant negative associations of increased plasma Hcy levels with grip strength (right: effect = -0.036, SE = 0.032, p = 5.53E-4; left: effect = -0.045, SE = 0.010, p = 1.45E-5), walking pace (effect = -0.038, SE = 0.011, p = 3.18E-4), and ALM (effect = -0.058, 0.013, p = 1.03E-5). However, there were no significant associations of decreased plasma Hcy levels with grip strength (right: effect = 0.005, SE = 0.021, p = 0.82; left: effect = -0.006, SE = 0.014, p = 0.64), walking pace (effect = 0.01, 0.020, p = 0.61), or ALM (effect = -0.034, SE = 0.018, p = 0.06).The accuracy and robustness of these findings were confirmed by sensitivity tests. Conclusion: Increased circulating Hcy levels were associated with lower grip strength, slower walking pace, and decreased ALM.

Predictive models based on machine learning for bone metastasis in patients with diagnosed colorectal cancer.

Background: This study aimed to develop an artificial intelligence predictive model for predicting the probability of developing BM in CRC patients. Methods: From SEER database, 50,566 CRC patients were identified between January 2015 and December 2019 without missing data. SVM and LR models were trained and tested on the dataset. Accuracy, area under the curve (AUC), and IDI were used to evaluate and compare the models. Results: For bone metastases in the entire cohort, SVM model with poly as kernel function presents the best performance, whose accuracy is 0.908, recall is 0.838, and AUC is 0.926, outperforming LR model. The top three most important factors affecting the model's prediction of BM include extraosseous metastases (EM), CEA, and size. Conclusion: Our study developed an SVM model with poly as kernel function for predicting BM in CRC patients. SVM model could improve personalized clinical decision-making, help rationalize the bone metastasis screening process, and reduce the burden on healthcare systems and patients.

The efficacy of platelet-rich plasma applicated in spinal fusion surgery: A meta-analysis.

Objective: The purpose of this meta-analysis is to evaluate the effect of the application of platelet-rich plasma (PRP) in spinal fusion surgery on the fusion rate of the spine. Methods: A comprehensive search of the PubMed, Embase, Cochrane Library, and Science Direct databases was conducted to identify randomized control trials (RCTs) or observational cohort studies that evaluated the efficacy and safety of PRP in spinal fusion. Data on final fusion rate, changes in the visual analog scale (VAS), estimated blood loss (EBL), and operative time was collected from the eligible studies for meta-analysis. Patients were divided into PRP and non-PRP groups according to whether PRP was used during the spinal fusion procedure. Results: According to the selection criteria, 4 randomized controlled trials and 8 cohort studies with 833 patients and 918 levels were included. The outcomes indicated that PRP application is associated with a lower fusion rat (OR = 0.62, 95% CI: (0.43, 0.89), P = 0.009) at final follow-up (>24 months). Subgroup analysis showed a lower rate of spinal fusion in the PRP group compared to the non-PRP group (OR = 0.35, 95% CI: (0.21, 0.58), P < 0.001) when spinal fusion was assessed using only anterior-posterior radiographs. When the bone graft material was a combination of autologous bone + artificial bone, the spinal fusion rate was lower in the PRP group than in the non-PRP group (OR = 0.34, 95% CI: (0.16, 0.71), P = 0.004). The PRP and non-PRP groups showed no significant differences in VAS changes at the 24th postoperative month (WMD = 0.36, 95% CI: (-0.37, 1.09), P = 0.33); Application of PRP does not reduce the estimated blood loss (WMD = -86.03, 95% CI: (-188.23, 16.17), P = 0.10). In terms of operation time, using PRP does not prolong operation time (WMD = -3.74, 95% CI: (-20.53, 13.04), P = 0.66). Conclusion: Compared with bone graft fusion alone, PRP cannot increase the rate of spinal fusion. Inappropriate methods of spinal fusion assessment or mixing PRP with artificial/allograft bone may have been responsible for the lower rate of spinal fusion in the PRP group. Systematic Review Registration: doi: 10.37766/inplasy2022.5.0055.

[Effects and mechanism of morroniside on osteogenic differentiation and proliferation of mouse MC3T3-E1 cells].

Objective: To study the effects of morroniside (MOR) on the proliferation and osteogenic differentiation of mouse MC3T3-E1 cells. Methods: The 4th generation MC3T3-E1 cells were randomly divided into 6 groups: control group (group A), MOR low dose group (10 µmol/L, group B), MOR medium-low dose group (20 µmol/L, group C), MOR medium dose group (40 µmol/L, group D), MOR medium-high dose group (80 µmol/L, group E), and MOR high dose group (100 µmol/L, group F). The proliferation activity of each group was detected by cell counting kit 8 (CCK-8) assay; the bone differentiation and mineralized nodule formation of each group were detected by alizarin red staining; real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect cyclin-dependent kinase inhibitor 1A (P21), recombinant Cyclin D1 (CCND1), proliferating cell nuclear antigen (PCNA), alkaline phosphatase (ALP), collagen type Ⅰ (COL-1), bone morphogenetic protein 2 (BMP-2), and adenosine A2A receptor (A2AR) mRNA expressions; Western blot was used to detecte the expressions of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), and adenosine A2AR protein. Results: The CCK-8 assay showed that the absorbance ( A) values of groups B to F were significantly higher than that of group A at 24 hours of culture, with group C significantly higher than the rest of the groups ( P<0.05). The MOR concentration (20 µmol/L) of group C was selected for the subsequent CCK-8 assay; the results showed that the A values of group C were significantly higher than those of group A at 24, 48, and 72 hours of culture ( P<0.05). Alizarin red staining showed that orange-red mineralized nodules were visible in all groups and the number of mineralized nodules was significantly higher in groups B and C than in group A ( P<0.05). RT-qPCR showed that the relative expressions of P21, CCND1, and PCNA mRNAs were significantly higher in group C than in group A ( P<0.05). The expressions of ALP, BMP-2, COL-1, and adenosine A2AR mRNAs in groups B to E were significantly higher than those in group A, with the expressions of ALP, BMP-2, COL-1 mRNAs in group C significantly higher than the rest of the groups ( P<0.05). Compared with group A, the expressions of OPN and RUNX2 proteins in groups B and C were significantly increased, while those in group D and E were significantly inhibited ( P<0.05). There was no significant difference between groups B and C and between groups D and E ( P>0.05). The relative expression of adenosine A2AR protein in groups B to E was significantly higher than that in group A, with group C significantly higher than the rest of the groups ( P<0.05). Conclusion: MOR can promote the proliferation and osteogenic differentiation of MC3T3-E1 cells; the mechanism of MOR may be achieved by interacting with adenosine A2AR.

Robot-Assisted Kyphoplasty Improves Clinical and Radiological Features Better Than Fluoroscopy-Assisted Kyphoplasty in the Treatment of Vertebral Compression Fractures: A Meta-Analysis.

Purpose: This meta-analysis aimed to determine whether patients treated with robot-assisted kyphoplasty for vertebral compression fractures have superior clinical and radiographic improvement than those treated with fluoroscopy. Methods: A comprehensive search of the PubMed, Embase, Cochrane Library, Science Direct, and CNKI (China National Knowledge Infrastructure) databases was conducted to find randomized control trials (RCTs) or observational cohort studies that compared robotic-assisted kyphoplasty (RA-kyphoplasty) with fluoroscopy-assisted kyphoplasty (FA-kyphoplasty) in treating vertebral compression fractures. Preoperative, postoperative, and final follow-up data on vertebral height (VH), vertebral kyphosis angle (VKA), visual analog scale (VAS) for back pain, and cement leakage rate were collected from eligible studies for meta-analysis. Patients were divided into RA and FA groups depending on whether the operation was robotically or fluoroscopically guided. Results: We included 6 cohort studies with 491 patients and 633 vertebrae. The results of the meta-analysis showed that the RA group had a higher VH than the FA group at both postoperation (p < 0.001) and final follow-up (p < 0.001); the VKA in the RA group was lower than that in the FA group at postoperation (p < 0.001) and final follow-up (p < 0.001); the back pain VAS score was lower in the RA group than in the FA group at postoperation (p = 0.01) and final follow-up (p = 0.03); and the cement leakage rate in the RA group was lower than those in the FA group (p < 0.001). Conclusion: This meta-analysis demonstrated that RA-kyphoplasty outperformed FA-kyphoplasty in vertebral height restoration, kyphosis angle correction, VAS score reduction for back pain, and lower cement leakage rate in the treatment of vertebral compression fractures.

Comparison of radiological and clinical outcomes of 3D-printed artificial vertebral body with Titanium mesh cage in single-level anterior cervical corpectomy and fusion: A meta-analysis.

Propose: This meta-analysis aimed to determine whether 3D-printed artificial vertebral body have superior clinical and radiographic outcome than Titanium Mesh Cage(TMC) in single-level anterior cervical corpectomy and fusion. Methods: A comprehensive search of the PubMed, Embase, Cochrane Library, Web of Science, and CNKI (China National Knowledge Infrastructure) databases was conducted to find randomized control trials (RCTs) or cohort studies that compared 3D-printed artificial vertebral body with conventional Titanium Mesh Cage (TMC) in single-level anterior cervical corpectomy and fusion (SL-ACCF). Operation time; intraoperative blood loss; subsidence of vertebral body; preoperative, and final follow-up C2-C7 Cobb angle, Japanese Orthopedic Association (JOA) scores, and Visual Analog Scale(VAS) scores were collected from eligible studies for meta-analysis. Results: We included 6 cohort studies with 341 patients. The results of the meta-analysis showed that the 3D group has a shorter operation time than the traditional TMC group(p = 0.04) and the TMC group had more severe subsidence(≥3 mm) of vertebral body than the 3D group(p < 0.0001). And the cervical C2-C7 Cobb angle in the 3D group was larger than that in the TMC group at the final follow-up. Conclusion: This meta-analysis demonstrates that 3D-printed artificial vertebral body is superior to traditional TMC in reducing the operation time and maintaining the postoperative vertebral height and restoring sagittal balance to the cervical spine in single-level anterior cervical corpectomy and fusion.

Status, fuzzy integrated risk assessment, and hierarchical risk management of soil heavy metals across China: A systematic review.

Many reviewers have applied bibliometric analysis to conduct research on heavy metals (HMs) in Chinese soil and found that risk management decisions were biased to a certain extent due to case distribution difference and uncertainty. The previous methodologies were optimized integrating further uncertainty control and case identification in this study. A solid database was built, which included 779 cases published from 2009 to 2020. Based on the data features, the weight method was used to objectively shield extreme cases and normalize the concentrations. We conducted fuzzy eco- and health risk models via a triangular fuzzy number, and identified the risks from Pb, Cd, As, and Hg as the priority control metals. However, the national HMs risk had complex spatial heterogeneity and significant uncertainty. Thus, an "integrated risk grade criterion (IRGC)" was coupled with the risk threshold concentrations for the eco- and health risks to classify the each case. The cases above the moderate IRGC grade for Cd or Hg accounted for approximately 50%, and were mainly in the west and north of China, respectively. The high-grade areas were mostly in the south of China, including the Xijiang-Pearl River Basin and the Yangtze River Basin. It was demonstrated that warning health risks were likely a local question and that the ecological risks from Hg and Cd were considerable across China. By reviewing and summarizing the text information, high grades of soil Cd, Pb, and As were frequently reported in the villages associated with the mining industry, and certain soil Cd near suburban industrial complexes also caused warning health risks. Finally, this study proposed priority control objects for hierarchical risk management, including the identified heavy metals, areas, and pilot cities from multi-spatial scales.

Ginsenoside Rb1 Facilitates Browning by Repressing Wnt/ß-Catenin Signaling in 3T3-L1 Adipocytes.

BACKGROUND The discovery of browning in white adipose tissue has provided new ideas for treating obesity. Many studies have reported that ginsenoside Rb1 (G-Rb1) has activity against diabetes, inflammation, and obesity, but further investigation is needed on the effect and mechanism of G-Rb1 on browning. MATERIAL AND METHODS We treated 3T3-L1 adipocytes with 0-200 µM G-Rb1, and 0.5 µM Compound 3f and 30 µM SKL2001 were used to activate Wnt/b-catenin signaling. Adipocyte activity was evaluated by Cell Counting Kit-8. Oil Red O staining was used to detect the lipid droplets. Quantitative real-time polymerase chain reaction was used to measure the expression of Cd-137, Cited-1, Txb-1, Prdm-16, and Ucp-1 mRNA. Western blotting was used to measure the expression of Ucp-1, pGSK-3ß (Ser 9), GSK- 3ß, and ß-catenin proteins. The expression of Ucp-1 was also detected with immunofluorescence. RESULTS Adipocyte activity was not affected by 0-100 µM G-Rb1. However, G-Rb1 dose-dependently reduced the accumulation of lipid droplets; increased the expression of Cd-137, Cited-1, Txb-1, Prdm-16, and Ucp-1 mRNA; and increased the expression of Ucp-1, pGSK-3ß (Ser 9), GSK-3ß, and ß-catenin proteins. The accumulation of lipid droplets and the expression of Ucp-1 protein decreased as b-catenin increased. CONCLUSIONS G-Rb1 at various concentrations (0-100 µM) promoted the browning of adipocytes in a dose-dependent manner. Further, we confirmed that activation of Wnt/ß-catenin signaling could inhibit browning. Therefore, the browning promoted by G-Rb1 may be associated with the inhibition of Wnt/ß-catenin signaling.

Metabolic syndrome increases risk for perioperative outcomes following posterior lumbar interbody fusion.

The present study is a retrospective cohort study. Metabolic syndrome (MetS) is a clustering of clinical findings that has been shown to increase the risk of the surgical outcomes. Our study aimed to evaluate whether MetS was a risk factor for increased perioperative outcomes in patients undergoing posterior lumbar interbody fusion (PLIF).We retrospectively analyzed patients over 18 years following elective posterior lumbar spine fusion from January 2014 to December 2018. Emergency procedures, infections, tumor, fracture, and revision surgeries were excluded. Patients were divided into 2 groups with and without MetS. The MetS was defined by having 3 of the following 4 criteria: obesity (body mass index ≥30 kg/m), dyslipidemia, hypertension, and diabetes. The follow-up period lasted up to 30 days after surgery. The outcomes of demographics, comorbidities, perioperative complications, and length of stay were compared between the 2 groups. Multivariate logistic regression analysis was used to identify perioperative outcomes that were independently associated with MetS.The overall prevalence of MetS was 12.5% (360/2880). Patients with MetS was a significantly higher risk factor for perioperative complications, and longer length of stay cmpared with patients without MetS (P < .05). The MetS group had a higher rate of cardiac complications (P = .019), pulmonary complication (P = .035), pneumonia (P = .026), cerebrovascular event (P = .023), urinary tract infection (P = .018), postoperative ICU admission (P = .02), and deep vein thrombosis (P = .029) than non-MetS group. The patients with MetS had longer hospital stays than the patients without MetS (22.16 vs 19.99 days, P < .001). Logistic regression analysis revealed that patients with MetS were more likely to experience perioperative complications (odds ratio [OR] 1.31; 95% confidence interval [CI]: 1.06-2.07; P < .001), and extend the length of stay (OR: 1.69; 95% CI: 1.25-2028; P = .001).The MetS is a significant risk factor for increased perioperative complications, and extend length of stay after PLIF. Strategies to minimize the adverse effect of MetS should be considered for these patients.

miR-532-3p inhibits osteogenic differentiation in MC3T3-E1 cells by downregulating ETS1.

BACKGROUND: Many studies had identified that MicroRNAs (miRNAs) could affect bone metabolism by regulating the expression of various proteins. This study explored the effect and mechanism of miR-532-3p on osteogenic differentiation. METHODS: We analyzed the content of miR-532-3p in osteoporosis patients, osteoporosis rats, and osteogenic induced MC3T3-E1 cells. MiR-532-3p mimic or inhibitor utilized to alter intracellular miR-532-3p content. MTT method executed to detect the effect of miR-532-3p on osteoblast proliferation. Real-time qPCR, Western blot, alkaline phosphatase staining, and alizarin red staining utilized to ascertain the influence of miR-532-3p on osteogenic differentiation. Then, databases and a dual-luciferase reporter gene assay used to verify the target of miR-532-3p. Furthermore, the lentiviral vector was utilized to overexpress interesting target gene expression and checked whether the target gene was involved in the regulation of osteogenic differentiation by miR-532-3p. RESULTS: MiR-532-3p expression boosted in low bone mineral density (BMD) patients and rats. In MC3T3-E1 cells, miR-532-3p expression gradually decreased as osteogenic induction matures. MiR-532-3p mimic negatively regulated succinate dehydrogenase (SDH) activity, alkaline phosphatase (ALP) activity, mineralization ability, the osteogenic-associated gene (Col1A1, Runx2, ALP, OPN, and OCN) and E-26 transformation specific-1 (ETS1) expression of MC3T3-E1 cells. Things are the opposite of the miR-532-3p inhibitor. ETS1 identified as the miR-532-3p target gene, and miR-532-3p could inhibit its expression. Besides, improved ETS1 expression could rescue the suppressive effect of miR-532-3p mimic on osteogenic differentiation. CONCLUSION: miR-532-3p can suppress osteogenic differentiation by downregulating ETS1 expression.

Comparative clinical efficacy and safety of cortical bone trajectory screw fixation and traditional pedicle screw fixation in posterior lumbar fusion: a systematic review and meta-analysis.

PURPOSE: To compare the clinical efficacy and safety between cortical bone trajectory (CBT) and pedicle screw (PS) in posterior lumbar fusion surgery. METHODS: Five electronic databases were used to identify relevant studies comparing the clinical efficacy and safety between CBT and PS. The main outcomes were postoperative fusion rates and complication (especially in superior facet joint violations, symptomatic ASD, wound infection, dural tear, screw malposition and hematoma). The secondary results included operation time, intraoperative blood loss, length of hospital stay, incision length, ODI, VAS, JOA score, JOA recovery rate, patients' satisfaction and health-related quality of life. RESULTS: The outcomes showed that there was no significant difference in terms of fusion rate (p = 0.55), back and leg VAS score (p > 0.05), JOA score (p = 0.08) and incidence of reoperation (p = 0.07). However, CBT was superior to PS with Oswestry Disability Index (ODI) (p = 0.02), JOA recovery rate (p < 0.00001) and patients' satisfaction (p = 0.001). In addition, CBT was superior to PS with significantly lower incidence of superior facet joint violation and symptomatic ASD. However, there was no significant difference regarding wound infection (p > 0.05) and screw malposition (p > 0.05). CBT group required significant shorter operation time, less blood loss, shorter incision length and shorter length of hospital stay in comparison with PS group (p < 0.05). CONCLUSIONS: Both CBT and PS achieve similar, fusion rate and revision surgery rate. Furthermore, CBT is superior to PS with lower incidence of complications, shorter operation time, less blood loss, shorter incision length and shorter length of hospital stay. These slides can be retrieved under Electronic Supplementary Material.