Opportunistic prediction of osteoporosis in patients with degenerative lumbar diseases: a simplified T12 vertebral bone quality approach.

BACKGROUND: Osteoporosis is one of the risk factors for screw loosening after lumbar fusion. However, the probability of preoperative osteoporosis screening in patients with lumbar degenerative disease is low. Therefore, the aim of this study was to investigate whether a simplified vertebral bone quality (VBQ) score based on T12 T1-MRI could opportunistically predict osteoporosis in patients with degenerative lumbar spine diseases. METHODS: We retrospectively analyzed cases treated for lumbar degenerative diseases at a single institution between August 2021 and June 2022. The patients were divided into three groups by the lowest T-score: osteoporosis group, osteopenia group, and normal bone mineral density (BMD) group. The signal intensity based on the T12 vertebral body divided by the signal intensity of the cerebrospinal fluid was calculated to obtain the simplified VBQ score, as well as the CT-based T12HU value and the traditional L1-4VBQ score. Various statistical analyses were used to compare VBQ, HU and DEXA, and the optimal T12VBQ threshold for predicting osteoporosis was obtained by plotting the receiver operating curve (ROC) analysis. RESULTS: Total of 166 patients were included in this study. There was a statistically significant difference in T12VBQ scores between the three groups (p < 0.001). Pearson correlation showed that there was a moderate correlation between T12VBQ and T-score (r=-0.406, p < 0.001). The AUC value of T12VBQ, which distinguishes between normal and low BMD, was 0.756, and the optimal diagnostic threshold was 2.94. The AUC value of T12VBQ, which distinguishes osteoporosis from non-osteoporosis, was 0.634, and the optimal diagnostic threshold was 3.18. CONCLUSION: T12VBQ can be used as an effective opportunistic screening method for osteoporosis in patients with lumbar degenerative diseases. It can be used as a supplement to the evaluation of DEXA and preoperative evaluation. TRIAL REGISTRATION: retrospectively registered number:1502-009-644; retrospectively registered number date:27 oct 2022.

DPPA2/4 Promote the Pluripotency and Proliferation of Bovine Extended Pluripotent Stem Cells by Upregulating the PI3K/AKT/GSK3ß/ß-Catenin Signaling Pathway.

Developmental pluripotency-associated 2 (DPPA2) and DPPA4 are crucial transcription factors involved in maintaining pluripotency in humans and mice. However, the role of DPPA2/4 in bovine extended pluripotent stem cells (bEPSCs) has not been investigated. In this study, a subset of bEPSC-related differentially expressed genes (DEGs), including DPPA2 and DPPA4, was identified based on multiomics data (ATAC-seq and RNA-seq). Subsequent investigations revealed that double overexpression of DPPA2/4 facilitates the reprogramming of bovine fetal fibroblasts (BFFs) into bEPSCs, whereas knockout of DPPA2/4 in BFFs leads to inefficient reprogramming. DPPA2/4 overexpression and knockdown experiments revealed that the pluripotency and proliferation capability of bEPSCs were maintained by promoting the transition from the G1 phase to the S phase of the cell cycle. By activating the PI3K/AKT/GSK3ß/ß-catenin pathway in bEPSCs, DPPA2/4 can increase the nuclear accumulation of ß-catenin, which further upregulates lymphoid enhancer binding factor 1 (LEF1) transcription factor activity. Moreover, DPPA2/4 can also regulate the expression of LEF1 by directly binding to its promoter region. Overall, our results demonstrate that DPPA2/4 promote the reprogramming of BFFs into bEPSCs while also maintaining the pluripotency and proliferation capability of bEPSCs by regulating the PI3K/AKT/GSK3ß/ß-catenin pathway and subsequently activating LEF1. These findings expand our understanding of the gene regulatory network involved in bEPSC pluripotency.

Discovery of 1H-pyrazolo[3,4-b]pyrazine derivatives as selective allosteric inhibitor of protein tyrosine phosphatase SHP2 for the treatment of KRASG12C-mutant non-small cell lung cancer.

The high expression or mutation of SHP2 can induce cancer, so targeting SHP2 has become a new strategy for cancer treatment. In this study, we used the previously reported SHP2 allosteric inhibitor IACS-13909 as a lead drug for structural derivation and modification, and synthesized three SHP2 inhibitors. Among them, 1H-pyrazolo[3,4-b]pyrazine derivative 4b was a highly selective SHP2 allosteric inhibitor, with an IC50 value of 3.2 nM, and its inhibitory activity was 17.75 times than that of the positive control IACS-13909. The cell proliferation experiment detected that compound 4b would markedly inhibit the proliferation of various cancer cells. Interestingly, compound 4b was highly sensitive to KRASG12C-mutant non-small cell lung cancer NCI-H358 cells, with an IC50 value of 0.58 µM and its antiproliferative activity was 4.79 times than that of IACS-13909. Furthermore, the combination therapy of compound 4b and KRASG12C inhibitor sotorasib would play a strong synergistic effect against NCI-H358 cells. The western blot experiment detected that compound 4b markedly downregulated the phosphorylation levels of ERK and AKT in NCI-H358 cells. Molecular docking study predicted that compound 4b bound to the allosteric site of SHP2 and formed H-bond interactions with key residues Thr108, Glu110, Arg111, and Phe113. In summary, this study aims to provide new ideas for the development of SHP2 allosteric inhibitors for the treatment of KRASG12C mutant non-small cell lung cancer.Communicated by Ramaswamy H. Sarma.

Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis.

BACKGROUND: Hedgehog-Gli1 signaling induces development of two common neurological features seen in pancreatic ductal adenocarcinoma (PDAC): peripheral neural invasion (PNI) and peripheral neural remodeling (PNR). However, the underlying molecular mechanisms in cancer cells and nerves within Gli1-derived PNR have not previously been comprehensively analyzed. METHODS: In this study, RNA sequencing was used to screen meaningful circRNAs in PNR. An in vitro model of PNR was subsequently constructed through a co-culture system comprising PDAC cells and murine dorsal root ganglia (DRG) (as the neuronal element), and the relevant mechanisms were explored using a series of molecular biology experiments. A subcutaneous nude mouse tumorigenesis model was established to further verify the occurrence of PNR that was detected in human PDAC samples. RESULTS: We first confirmed the molecular mechanisms of PNR development through crosstalk between exosomal circ-0011536 and DRG. In Gli1-overpressed PDAC, circ-0011536 is mainly secreted by exosomes. After being ingested by DRG, it can promote the activity of DRG by degrading miR-451a and upregulating the expression of VGF. Overexpression of Gli1 can accelerate the proliferation of subcutaneous tumors in mice and is closely related to the density of nerve plexuses, while downregulating circ-RNA inhibits tumor proliferation and reduces the density of nerve plexuses. In addition, TMA results confirmed that Gli1 overexpression significantly increased the expression of VGF and was closely associated with increased nerve plexus density. CONCLUSION: Hedgehog-Gli1-induced exosomal circ-0011536 promoted PNR via the miR-451a/VGF axis, thereby establishing that it may contribute to PDAC-associated nerve changes with activated Hedgehog signaling.

Modified Kirschner wire percutaneous rotation prying reduction combined with elastic stable intramedullary nailing in children with Judet IV radial neck fracture.

PURPOSE: This study was to investigate the feasibility and treatment effect of using modified Kirschner wire (K-wire) percutaneous rotation prying reduction combined with Elastic Stable Intramedullary Nailing (ESIN) in children with Judet IV radial neck fracture. METHODS: A retrospective analysis was conducted on 47 children with Judet IV radial neck fracture who underwent treatment with modified K-wire percutaneous rotation prying reduction combined with ESIN from April 2019 to November 2022, including 25 males and 22 females, with an average age of 8.79 years old (ranging from 5 to 14). The study recorded the surgical time, fluoroscopy time, reduction time, and reduction quality evaluated according to the Metaizeau radiological standard. During the last follow-up, the flexion-extension and forearm rotation function of the affected and healthy sides were recorded, and the Mayo Elbow Performance index was used to evaluate the elbow joint function. RESULTS: The average duration of the operation was 25.51 min (ranging from 14 to 43 min), with a mode of 2 reset times (ranging from 1 to 5) and 8 fluoroscopic times (ranging from 4 to 15). Based on the Metaizeau radiological standard for assessing reduction quality, 45 cases were deemed excellent, while 2 cases were considered good. Following 3-4 weeks of postoperative long-arm cast immobilization, exercises were performed to promote elbow joint and forearm rotation. The ESIN was removed after satisfactory fracture healing around 4 months postoperatively. The average follow-up period was 26.79 months (ranging from 5 to 48). At the final follow-up, the range of motion for the affected limb in flexion, extension, pronation, and supination was (140.23 ± 4.80)°, (4.43 ± 3.98)°, (84.09 ± 4.97)°, and (83.83 ± 4.55)°, respectively. There was no statistically significant difference compared to the healthy side, which had a range of motion of (141.36 ± 3.27)°, (5.28 ± 2.25)°, (85.66 ± 3.20)°, and (84.98 ± 2.57)° (P > 0.05). According to the Mayo Elbow Performance index, 44 cases were rated as excellent and 1 case was considered good. CONCLUSION: The modified K-wire percutaneous rotation prying reduction combined with ESIN is an effective treatment for severe radial neck fractures in children. This technique offers several advantages, including the ability to easily "capture" significantly displaced radial heads, achieve rapid and accurate reduction, and reduce radiation exposure.

[Computer-simulated osteotomy based on health-side combined with guide plate technique in treatment of cubitus varus deformity in adolescents].

Objective: To explore the feasibility and early effectiveness of computer-simulated osteotomy based on the health-side combined with guide plate technique in the treatment of cubitus varus deformity in adolescents. Methods: The clinical data of 23 patients with cubitus varus deformity who met the selection criteria between June 2019 and February 2023 were retrospectively analyzed. There were 17 males and 6 females, ranging in age from 4 to 16 years with an average of 8.5 years. The time from injury to operation was 1-4 years. The angle of distal humerus rotation was defined by humeral head posterior inclination angle using low radiation dose CT to scan the patient's upper extremity data at one time, and the preoperative rotation of the distal humerus on the affected side was (33.82±4.39)°. The CT plain scan data were imported into 9yuan3D digital orthopaedic system (V3.34 software) to reconstruct three-dimensional images of both upper extremities. The simulated operation was performed with the healthy upper extremity as the reference, the best osteotomy scheme was planned, overlapped and compared, and the osteotomy guide plate was prepared. The patients were followed up regularly after operation, and the formation of callus in the osteotomy area was observed by X-ray examination. Before and after operation, the carrying angle of both upper extremities (the angle of cubitus valgus was positive, and the angle of cubitus varus was negative) and anteversion angle were measured on X-ray and CT images. At the same time, the flexion and extension range of motion of elbow joint and the external rotation range of motion of upper extremity were measured, and Mayo score was used to evaluate the function of elbow joint. Results: The operation time ranged from 34 to 46 minutes, with an average of 39 minutes. All patients were followed up 5-26 months, with a mean of 14.9 months. All the incisions healed by first intention after the operation; 2 patients had nail path irritation symptoms after Kirschner wire fixation, which improved after dressing change; no complication such as breakage and loosening of internal fixators occurred after regular X-ray review. Continuous callus formed at the osteotomy end at 4 weeks after operation, and the osteotomy end healed at 8-12 weeks after operation. At last follow-up, the carrying angle, anteversion angle, external rotation range of motion, and extension and flexion range of motion of the elbow joint of the affected side significantly improved when compared with preoperative ones ( P<0.05). Except for the extension range of motion of the healthy elbow joint ( P<0.05), there was no significant difference in other indicators between the two sides ( P>0.05). At last follow-up, the Mayo elbow score was 85-100, with an average of 99.3; 22 cases were excellent, 1 case was good, and the excellent and good rate was 100%. Conclusion: Computer-simulated osteotomy based on health-side combined with guide plate technique for treating cubitus varus deformity in adolescents can achieve precise osteotomy, which has the advantages of short operation time and easy operation, and the short-term effectiveness is satisfactory.

Systematic analysis of glutamine metabolism family genes and exploration of the biological role of GPT in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignancy of the digestive system with high incidence rate and mortality, and reliable diagnostic and prognostic markers for CRC are still lacking. Glutamine metabolism is crucial to the occurrence and development of CRC. However, no research has systematically analyzed the biological role of glutamine metabolism-related genes (GMRGs) in CRC. METHODS: We downloaded gene expression data and clinical data of CRC patients from the TCGA database. The UCSC database downloads pan-cancer gene expression data and prognosis data. Characteristic GMRGs were screened out using differential analysis and two types of machine learning (SVM-REF and RandomForest). Single-cell RNA-sequencing data from CRC patients were downloaded from GEO data. ROC curve was used to evaluate the diagnostic value. Kaplan-Meier method and univariate Cox regression analysis were used to evaluate the prognostic value. The oncopredict package is used to calculate IC50 values for common drugs in CRC patients. RESULTS: A total of 31 differentially expressed GMRGs were identified, 9 of which were identified as characteristic GMRGs. Further evaluation of diagnostic and prognostic value finally identified GPT as the most important GMRGs in CRC. scRNA-seq analysis revealed that GPT is almost exclusively expressed in epithelial cells. GPT expression is closely related to the tumor microenvironment and can effectively distinguish the sensitivity of different CRC patients to clinical drugs. In addition, pan-cancer analysis showed that GPT is an excellent diagnostic and prognostic marker for multiple cancers. CONCLUSIONS: GPT is a reliable diagnostic, prognostic marker and therapeutic target in CRC.

Fucoidan Ameliorates Ferroptosis in Ischemia-reperfusion-induced Liver Injury through Nrf2/HO-1/GPX4 Activation.

Background and Aims: Liver ischemia-reperfusion (IR) injury is a common pathological process in liver surgery. Ferroptosis, which is closely related to lipid peroxidation, has recently been confirmed to be involved in the pathogenesis of IR injury. However, the development of drugs that regulate ferroptosis has been slow, and a complete understanding of the mechanisms underlying ferroptosis has not yet been achieved. Fucoidan (Fu) is a sulfated polysaccharide that has attracted research interest due to its advantages of easy access and wide biological activity. Methods: In this study, we established models of IR injury using erastin as an activator of ferroptosis, with the ferroptosis inhibitor ferrostatin-1 (Fer-1) as the control. We clarified the molecular mechanism of fucoidan in IR-induced ferroptosis by determining lipid peroxidation levels, mitochondrial morphology, and key pathways in theta were involved. Results: Ferroptosis was closely related to IR-induced hepatocyte injury. The use of fucoidan or Fer-1 inhibited ferroptosis by eliminating reactive oxygen species and inhibiting lipid peroxidation and iron accumulation, while those effects were reversed after treatment with erastin. Iron accumulation, mitochondrial membrane rupture, and active oxygen generation related to ferroptosis also inhibited the entry of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and reduced downstream heme oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPX4) protein levels. However, fucoidan pretreatment produced adaptive changes that reduced irreversible cell damage induced by IR or erastin. Conclusions: Fucoidan inhibited ferroptosis in liver IR injury via the Nrf2/HO-1/GPX4 axis.

Covalent netting restrains dissolution enabling stable high-loading and high-rate iron difluoride cathodes.

Metal fluoride conversion cathodes are promising for the production of cheap, sustainable, and high-energy lithium-ion batteries. Yet, such systems are plagued by active material dissolution that causes capacity fade and hinders commercialization. Here, a covalent netting strategy is proposed to overcome this hurdle. In a proof-of-concept design, polydopamine derived carbon-mediated covalent binding inhibited the dissolution, while the pyrolyzed bacterial cellulose netting structure furnished fast electronic and ionic transport pathways. We demonstrate high-capacity, high-rate and long-lasting stability attained at practical loading levels. Our investigations suggest that the covalent netting-enabled formation of a robust and efficient blocking layer, highly competent in suppressing the leaching, is key for a stable performance. The successful stabilization of metal difluorides in the absence of electrolyte engineering opens an avenue for their practical deployment in future higher-level but lower-cost batteries, and provides a solution to similar challenges encountered by other dissolving energy electrode materials.

Regional differences in bone mineral density biomechanically induce a higher risk of adjacent vertebral fracture after percutaneous vertebroplasty: a case-comparative study.

BACKGROUND: Adjacent vertebral fracture (AVF) is a frequently observed complication after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compressive fracture. Biomechanical deterioration initially induces a higher risk of AVF. Studies demonstrated that the aggravation of regional differences in the elastic modulus of different components might deteriorate the local biomechanical environment and increase the risk of structural failure. Considering the existence of intravertebral regional differences in bone mineral density (BMD) (i.e. elastic modulus), it was hypothesized in the present study that higher intravertebral BMD differences may induce a higher risk of AVF biomechanically. MATERIALS AND METHODS: The radiographic and demographic data of osteoporotic vertebral compressive fracture patients treated using PVP were reviewed in the present study. The patients were divided into two groups: those with AVF and those without AVF. The Hounsfield unit (HU) values of transverse planes from the superior to the inferior bony endplate were measured, and the differences between the highest and lowest HU values of these planes were considered the regional differences of the HU value. The data from patients with and without AVF were compared, and the independent risk factors were identified through regression analysis. PVP with different grades of regional differences in the elastic modulus of the adjacent vertebral body was simulated using a previously constructed and validated lumbar finite element model, and the biomechanical indicators related to AVF were computed and recorded in surgical models. RESULTS: Clinical data on 103 patients were collected in this study (with an average follow-up period of 24.1 months). The radiographic review revealed that AVF patients present a significantly higher regional difference in the HU value and that the increase in the regional difference of the HU value was an independent risk factor for AVF. In addition, numerical mechanical simulations recorded a stress concentration tendency (the higher maximum equivalent stress value) in the adjacent vertebral cancellous bone, with a stepwise aggravation of the adjacent cancellous bony regional stiffness differences. CONCLUSIONS: The aggravation of regional BMD differences induces a higher risk of AVF after PVP surgery through a deterioration of the local biomechanical environment. The maximum differences in the HU value of the adjacent cancellous bone should, therefore, be measured routinely to better predict the risk of AVF. Patients with noticeable regional BMD differences should be considered at high risk for AVF, and greater attention must be paid to these patients to reduce the risk of AVF. EVIDENCE GRADE: Level III b.

Safety and clinical efficacy of endoscopic procedures for the treatment of adjacent segmental disease after lumbar fusion: A systematic review and meta-analysis.

BACKGROUND: Adjacent segment disease (ASD) is a common complication after lumbar fusion and is still traditionally treated by open surgery. In recent years, with the development of minimally invasive techniques, percutaneous endoscopic surgery(PES) has been used for the treatment of ASD after lumbar fusion due to its unique benefits. Nevertheless, it remains unclear about its significant clinical efficacy and advantages over conventional open surgery. OBJECTIVES: To evaluate the clinical efficacy and safety of PES in the treatment of ASD after lumbar fusion. STUDY DESIGN: A systematic review and meta-analysis studies about the role of PES in managing ASD after lumbar fusion. METHODS: A systematic search review was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, VIP, WanFang, and SinoMed databases from the start of their construction to 15 November 2021. Eligible studies included references to clinical trials of PES for ASD after open lumbar fusion. Observations included pain relief, recovery of postoperative function, overall excellent rates, and indicators of the advantages of minimally invasive surgery compared to conventional surgery. Postoperative complications and recurrence rates were also recorded. RESULTS: A total of 24 studies, including 20 single-arm studies and 4 clinical control studies, all involving 928 patients were included. A total of 694 patients were included in the single-arm analysis. The results of the single-arm meta-analysis showed that PES could significantly reduce low back and leg pain and improve the functional status of the lumbar spine in patients with ASD after open lumbar fusion compared to preoperatively, and had good clinical efficacy after surgery. A total of 234 patients were included in the four clinically controlled studies, and the results of the meta-analysis showed that PES could clearly reduce pain and improve lumbar function, with no significant difference in efficacy between PES and open surgery. However, PES has a lower surgical incision, less intraoperative bleeding, and shorter operative time and length of hospital stay compared to open surgery. Moreover, it has a lower rate of postoperative recurrence as well as complications and a longer duration of efficacy. CONCLUSIONS: On the basis of the available clinical literature and the results of this study, PES could achieve satisfactory clinical effects in ASD treatment after lumbar fusion. Compared with conventional open surgery, PES can not only obtain similar clinical results, but also had the advantages of less trauma and faster recovery. Nevertheless, a randomized controlled study is still needed to validate the findings of this study. TRIAL REGISTRATION: Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022298387.

Inhibition Effect and Mechanism Explanation of Perilla Seed Extract as a Green Corrosion Inhibitor on Q235 Carbon Steel.

The development of environmentally friendly corrosion inhibitors has become a research hotspot. Aiming at the potential corrosion inhibition effect of perilla seed extract on Q235 carbon steel, the corrosion inhibition effect was quantitatively evaluated by various research methods, and the effective corrosion inhibition composition and mechanism were discussed. The research methods include potentiodynamic polarization curve method, HPLC-MS, FT-IR, XPS and chemical calculation. The experimental results show that the inhibitor prepared from perilla seed extract is a mixed inhibitor, and its adsorption behavior accords with Langmuir adsorption theory and its adsorption free energy is -22.70 kJ/mol. Combined with the experimental results and theoretical calculation, the effective corrosion inhibiting components are luteolin and apigenin. Theoretical calculation shows that both of them are adsorbed parallel to the surface of carbon steel to form thin films. The adsorption mechanism is that carbonyl O atoms in luteolin and apigenin hybridize with the 3 d empty orbit of Fe. From the point of view of quantum chemistry, the smaller the HOMO value and the energy gap value, the better the adsorption of corrosion inhibitor on the surface of carbon steel. From the point of view of molecular dynamics simulation, the greater the absolute value of adsorption energy, the better the adsorption of corrosion inhibitor on carbon steel surface.

The N6-methyladenosine modification enhances ferroptosis resistance through inhibiting SLC7A11 mRNA deadenylation in hepatoblastoma.

BACKGROUND: Solute carrier family 7 member 11 (SLC7A11) is overexpressed in multiple human tumours and functions as a transporter importing cystine for glutathione biosynthesis. It promotes tumour development in part by suppressing ferroptosis, a newly identified form of cell death that plays a pivotal role in the suppression of tumorigenesis. However, the role and underlying mechanisms of SLC7A11-mediated ferroptosis in hepatoblastoma (HB) remain largely unknown. METHODS: Reverse transcription quantitative real-time PCR (RT-qPCR) and western blotting were used to measure SLC7A11 levels. Cell proliferation, colony formation, lipid reactive oxygen species (ROS), MDA concentration, 4-HNE, GSH/GSSG ratio and cell death assays as well as subcutaneous xenograft experiments were used to elucidate the effects of SLC7A11 in HB cell proliferation and ferroptosis. Furthermore, MeRIP-qPCR, dual luciferase reporter, RNA pulldown, RNA immunoprecipitation (RIP) and RACE-PAT assays were performed to elucidate the underlying mechanism through which SLC7A11 was regulated by the m6A modification in HB. RESULTS: SLC7A11 expression was highly upregulated in HB. SLC7A11 upregulation promoted HB cell proliferation in vitro and in vivo, inhibiting HB cell ferroptosis. Mechanistically, SLC7A11 mRNA exhibited abnormal METTL3-mediated m6A modification, which enhanced its stability and expression. IGF2 mRNA-binding protein 1 (IGF2BP1) was identified as the m6A reader of SLC7A11, enhancing SLC7A11 mRNA stability and expression by inhibiting SLC7A11 mRNA deadenylation in an m6A-dependent manner. Moreover, IGF2BP1 was found to block BTG2/CCR4-NOT complex recruitment via competitively binding to PABPC1, thereby suppressing SLC7A11 mRNA deadenylation. CONCLUSIONS: Our findings demonstrated that the METTL3-mediated SLC7A11 m6A modification enhances HB ferroptosis resistance. The METTL3/IGF2BP1/m6A modification promotes SLC7A11 mRNA stability and upregulates its expression by inhibiting the deadenylation process. Our study highlights a critical role of the m6A modification in SLC7A11-mediated ferroptosis, providing a potential strategy for HB therapy through blockade of the m6A-SLC7A11 axis.

Exosomes derived from fibrinogen-like protein 1-overexpressing bone marrow-derived mesenchymal stem cells ameliorates rheumatoid arthritis.

Rheumatoid arthritis (RA) is a most common chronic joint disease belonging to inflammatory autoimmune disease. The aim of this study was to determine the role and mechanism of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and fibrinogen-like protein 1 (FGL1) overexpression exosomes shuttled by BMSCs (FGL1-Exos) on RA. All of the exosomes were visualized by transmission electron microscope (TEM) and the characteristic proteins were detected by western blot. To investigate the therapeutic effect of FGL1-Exos, RA-FLSs were activated by TNF-α and RA rat model was established by collagen incomplete Freund's adjuvant. Cell viability, apoptosis, inflammation factors, and protein levels were detected by CCK-8, flow cytometry, enzyme-linked immunosorbent assay and western blot, respectively. Hematoxylin and eosin and safranin O staining were used to detect the histopathology changes. Cell apoptosis and FGL1 expression in knee joint were detected by immunofluorescence. The results showed that FGL1-Exos could inhibit the cell viability meanwhile increase the cell apoptosis in RA-FLSs. Meanwhile, FGL1-Exos could effectively suppress the inflammation score, joint destruction, and inflammatory response in RA rat model. FGL1-Exos directly inhibited cell apoptosis of RA-FLSs and RA rat model by suppressing the inflammatory cytokines, specific rheumatoid markers, immunological markers meanwhile meditating the NF-κB pathway. Our results indicate that FGL1 was a therapeutic potential target in RA therapy.

Induction of Bone Remodeling by Raloxifene-Doped Iron Oxide Functionalized with Hydroxyapatite to Accelerate Fracture Healing.

Repairing fractures in the presence of infection is a major challenge that is currently declining using nanotechnology. By producing iron oxide nanoparticles (NPs) containing hydroxyapatite and Raloxifene (R-IONPs-HA), this study tries to target drug delivery, control infection and promotion of the cells proliferation/differentiation to repair damaged tissue. After the production of R-IONPs-HA through co-precipitation, the physicochemical features of the NPs were considered by SEM, TEM, DLS and XRD methods, and the possibility of drug release. The effect of R-IONPs-HA on MC3T3-E1 cell proliferation/differentiation was determined by CCK-assay and microscopic observations. Also, Gram-negative and -positive bacteria were applied to evaluate the antibacterial activity. Finally, cell differentiation biomarkers like an ALP, OCN, and RUNX-2 genes were examined by real time (RT)-PCR. The results showed that R-IONPs-HA was spherical with dimensions of 98.1 ± 1.17 nm. In addition, the results of Zeta and XRD confirmed the loading HA and R on IONPs. Also, the release rate of R and HA in 64 h with pH 6 reached 61.4 and 30.4%, respectively. The anti-bacterial activity of R-IONPs-HA on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacteria showed a significant reduction in infection. Also, MC3T3-E1 cells showed greater proliferation and differentiation by R-IONPs-HA compared to other groups. Increased expression of ossification genes such as OCN, and RUNX-2 confirmed this claim. Finally, R-IONPs-HA with good biocompatibility, antibacterial activity and ossification induction has great potential to repair bone fractures and prevent infection.

[Biomechanical affect of percutaneous transforaminal endoscopic discectomy on adjacent segments with different degrees of degeneration:a finite element analysis].

OBJECTIVE: To investigate the biomechanical affect of percutaneous transforaminal endoscopic discectomy(PTED) on adjacent segments with different degrees of degeneration and related risk of adjacent segment diseases (ASD) caused by this operation. METHODS: A healthy male adult volunteer was selected, and the lumbosacral vertebra image data was obtained by CT scan, and the external contour of the bone structure was reconstructed. On this basis, the external contour of the bone structure was fitted by using the smooth curve in 3D-CAD software, and the complete three-dimensional finite element modelof the non degenerate L3-S1 segment and the degenerative models of the L3-L4 and L5-S1 segment were drawn forward. In L4, L5 segment simulating PTED surgery through the removal of right part of articular process and nucleus pulposus and anulus fibrosus. After PTED was simulated in the L4-L5 segment and the risk of ASD has been evaluated by six changes of biomechanical indicators in flexion, extension, left and right lateral bending, left and right axial rotation conditions. RESULTS: In the finite element model without adjacent segmental disc degeneration, the annulus fibrosus von Mises stress and intradiscal pressure of the PTED model showed only a slight increase under most stress conditions, and a slight decrease in a few conditions, and there was no significant change trend before and after surgery. In the original degenerated adjacent segment disc model, the biomechanical indicators related to disc degeneration in the pre- and post-PTED model showed significant deterioration, leading to an increased risk of potential adjacent spondylopathy. CONCLUSION: PTED surgery will not lead to the significant deterioration of postoperative biomechanical environment of non-degeneration adjacent intervertebral discs, and the original degeneration of adjacent intervertebral discs is a important risk factor for ASD.

Enantioselective Intermolecular Heck and Reductive Heck Reactions of Aryl Triflates, Mesylates, and Tosylates Catalyzed by Nickel.

Nickel-catalyzed intermolecular Heck reaction of cycloalkenes proceeds well with aryl triflates, mesylates and tosylates in excellent enantiomeric ratios. The asymmetric reductive Heck reaction also works with a 2-cyclopentenone ketal, which is equivalent to conjugate arylation of the enone itself.

[Short-term effectiveness of Endobutton plate in reconstruction of Lisfranc ligament].

OBJECTIVE: To observe the short-term effectiveness of Endobutton plate in the reconstruction of Lisfranc ligament in tarsometatarsal joint injury. METHODS: Between March 2015 and July 2018, 18 patients with tarsometatarsal joint injuries were treated with Lisfranc ligament reconstruction by Endobutton plate. There were 12 males and 6 females with an average age of 32.5 years (range, 16-55 years). The causes of injury were traffic accident in 8 cases, falling from height in 3 cases, crushing by a heavy objective in 4 cases, and spraining in 3 cases. There were 10 cases of Myerson type A, 4 of type B1, 2 of type B2, 1 of type C1, and 1 of type C2. The interval between injury and operation ranged from 3 to 9 days (mean, 4.9 days). X-ray examination was performed regularly after operation to measure the distance between the first and the second metatarsal joints, and the visual analogue scale (VAS) score was used to evaluate the pain relief. At last follow-up, the reduction of tarsometatarsal joint was evaluated by measuring and comparing the height of the affected and healthy arches. The foot function was evaluated according to the American Orthopaedic Foot and Ankle Society (AOFAS) score. RESULTS: The average follow-up time was 15.8 months (range, 10-28 months). All incisions healed by first intention. X-ray reexamination showed that there was no screw loosening or plate fracture. There were significant differences in the distance between the first and the second metatarsal joints and VAS score at 3 months after operation, before removal of the internal fixator, and at last follow-up when compared with preoperative values ( P<0.05). There was no significant difference between the time points after operation ( P>0.05). At last follow-up, there was no significant difference in the arch height between affected foot [(5.3±0.2) mm] and healthy foot [(5.4± 0.3) mm] ( t=1.798, P=0.810). The AOFAS score of foot function was 89.5±7.3 with excellent in 12 cases, good in 4 cases, and fair in 2 cases. The excellent and good rate was 88.9%. CONCLUSION: The reconstruction of Lisfranc ligament with Endobutton plate can stabilize the tarsometatarsal joint and achieve satisfactory foot function at early stage.

[Application of self-designed adjustable operation frame in treatment of severe kyphosis secondary to ankylosing spondylitis with posterior osteotomy].

OBJECTIVE: To introduce a self-designed adjustable operation frame and explore the feasibility and safety in the treatment of severe kyphosis secondary to ankylosing spondylitis with posterior osteotomy. METHODS: Between March 2016 and May 2018, 7 cases of severe kyphosis secondary to ankylosing spondylitis were treated with posterior osteotomy using self-designed adjustable operation frame with prone position. There were 5 males and 2 females with an average age of 49.4 years (range, 40-55 years). The disease duration was 10-21 years (mean, 16.7 years). The apical vertebrae of kyphosis were located at T 11 in 2 cases, T 12 in 1 case, L 1 in 1 case, and L 2 in 3 cases. Among the 7 cases, 2 were classified as typeⅠ, 4 as type ⅡB, and 1 as type ⅢA according to 301 classification system. There was no neurological deficit of all cases; but 1 case suffered bilateral hip joints ankylosed in non-functional position. The parameters of chin-brow vertical angle (CBVA), global kyphosis (GK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sagittal vertical axis (SVA) were measured; and the operation time, the intraoperative blood loss, and the complications were also collected and analyzed. RESULTS: All operations completed successfully. The operation time was 310-545 minutes (mean, 409.7 minutes) and the intraoperative blood loss was 1 500-2 500 mL (mean, 1 642.9 mL). There were 2 cases treated with one-level osteotomy of sagittal translation, 1 case of radiculopathy symptom of L 3, and 3 cases of tension of abdominal skin. All patients were followed up 20-35 months (mean, 27.9 months). There were significant differences in CBVA, GK, TLK, LL, and SVA between pre- and post-operation ( P<0.05); but no significant difference between 1 week after operation and last follow-up ( P>0.05). All the osteotomies and bone grafts fused well and no complications of loosening and breakage of internal fixator occurred during the follow-up. CONCLUSION: In the posterior osteotomy for correction of severe kyphosis secondary to ankylosing spondylitis, the self-designed adjustable operation frame is convenient for the patient to be placed in prone position. It is safe, feasible, and effective to perform osteotomy correction with the aid of the self-designed adjustable operation frame.

Sulfidation enhances stability and mobility of carboxymethyl cellulose stabilized nanoscale zero-valent iron in saturated porous media.

Sulfidation can enhance the reactivity and longevity of nanoscale zero-valent iron (nZVI), but little is known about its effect on the fate and transport of nZVI in saturated porous media. This work compared the stability and mobility of carboxymethyl cellulose (CMC) stabilized nZVI (CMC-nZVI) and sulfidated nZVI (CMC-S-nZVI) particles in saturated porous media. After sulfidation, the hydrodynamic size of CMC-S-nZVI was 100-150 nm larger than CMC-nZVI due to enhanced adsorption of CMC onto the S-nZVI surface, which was facilitated by the bidentate bridging interaction between CMC and the FeSx phase on S-nZVI. Of note is that they had a similar core size and zeta potential. In comparison to CMC-nZVI, CMC-S-nZVI exhibited less physical settling (0-5% vs. 5-73%) and chemical dissolution (2-10% vs. 3-27%) within 55 min under the same ionic conditions (Na+, K+ < 200 mM; Al3+ < 0.75 mM). Column breakthrough experiments showed that both CMC-S-nZVI and CMC-nZVI had relatively high mobility in saturated porous media. However, CMC-S-nZVI exhibited greater breakthrough (C/C0 = 0.57-1.0) and corresponding greater mass recovery rates than the corresponding CMC-nZVI (C/C0 = 0.44-1.0) under most of the experimental conditions (e.g., different ion type and concentration, flow rate, and input concentration). The fitted colloid filtration theory model was in good agreement with experiments. This work suggests that in addition to the significant reactivity and longevity improvements demonstrated in other studies, CMC-S-nZVI is also more mobile than CMC-nZVI suggesting that CMC-S-nZVI has many of the characteristics favorable for field application.