Activation of Notch Signaling Pathway is involved in Extracellular Matrix Degradation in human induced pluripotent stem cells chondrocytes induced by HT-2 toxin.

Notch signaling regulates cartilage formation and homeostasis. Kashin-Beck Disease (KBD), an endemic osteochondropathy, is characterized by severe cartilage degradation. The etiology of KBD is related to the exposure of HT-2 toxin, a mycotoxin and primary metabolite of T-2 toxin. This study aims to explore the role of HT-2 toxin in the Notch signaling regulation and extracellular matrix (ECM) metabolism of hiPSCs-Chondrocytes. Immunohistochemistry and qRT-PCR were employed to investigate the expression of Notch pathway molecules in KBD articular cartilage and primary chondrocytes. hiPSCs-Chondrocytes, derived from hiPSCs, were treated with 100 ng/mL HT-2 toxin and the γ-secretase inhibitor (DAPT) for 48h, respectively. The markers related to the Notch signaling pathway and ECM were assessed using qRT-PCR and Western blot. Notch pathway dysregulation was prominent in KBD cartilage. HT-2 toxin exposure caused cytotoxicity in hiPSCs-Chondrocytes, and activated Notch signaling by increasing the mRNA and protein levels of NOTCH1 and HES1. HT-2 toxin also upregulated ECM catabolic enzymes and downregulated ECM components (COL2A1 and ACAN), indicating ECM degradation. DAPT-mediated Notch signaling inhibition suppressed the mRNA and protein level of ADAMTS5 expression while enhancing ECM component expression in hiPSCs-Chondrocytes. This study suggests that HT-2 toxin may induce ECM degradation in hiPSCs-Chondrocytes through activating Notch signaling.

Associations between immune cells signatures and osteoarthritis: An integrated analysis of bidirectional Mendelian randomization and Bayesian colocalization.

BACKGROUND: Previous investigations have explored the associations between immune cell signatures and osteoarthritis (OA); however, causality remains unclear. This study employs an integrated analysis, combining bidirectional Mendelian randomization (MR) and Bayesian colocalization (Coloc), to investigate causal relationships between 731 immune cells signatures and OA, identifying shared causal variants. METHODS: Utilizing publicly available summary data, this study primarily employs inverse variance weighting (IVW). Supplementary methods include MR-Egger regression, weighted median, weight mode, and simple mode. Various sensitivity tests, including Cochran's Q test, MR pleiotropy Residual Sum and Outlier, and leave-one-out tests, were conducted to assess the robustness of the analysis results. Coloc was employed to identify shared causal genetic variants among potential associations. RESULTS: IVW analysis revealed 196 immune cell signatures potentially linked to OA across diverse subtypes. Reverse MR analyses indicated the causal impact of OA on the levels of 140 immune cell signatures, with subtype-specific variations. Notably, several specific associations, including CD64 on CD14-CD16 + monocyte for Hip OA (OR = 1.0593, 95 % CI: 1.0260-1.0938, P = 0.0004), HLA-DR on CD14 + CD16- monocyte (OR = 0.9664, 95 % CI: 0.9497-0.9834, P = 0.0001), HLA-DR on CD14 + monocyte (OR = 0.9680, 95 % CI: 0.9509-0.9853, P = 0.0003) in the Knee or Hip OA, PDL-1 on CD14-CD16 + monocyte by All OA (OR = 1.7091, 95 %CI:1.2494-2.3378, P = 0.0008), and herpesvirus entry mediator on effector memory CD4 + T cell by Spine OA (OR = 0.5200, 95 %CI:0.3577-0.7561, P = 0.0006) remained significant post-Bonferroni correction. Sensitivity tests validated the credibility of the IVW analysis. Additionally, Coloc revealed several potential associations among shared genetic variants, including rs115328872, rs1800973, and rs317667. CONCLUSIONS: Our findings provide evidence for the potential involvement of immune cell signatures in OA development, revealing avenues for early prevention and innovative therapeutic strategies.

Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization study.

BACKGROUND: Previous studies have indicated a heightened susceptibility to cataract and glaucoma among rheumatoid arthritis (RA) patients, while it remains uncertain whether RA is causally associated with cataract and glaucoma. A two-sample mendelian randomization (MR) analysis was used to investigate the causal associations between RA, cataract and glaucoma in European and East Asian populations. METHODS: In the European population, genome-wide association study (GWAS) summary statistics for cataract (372,386 individuals) and glaucoma (377,277 individuals) were obtained from the FinnGen consortium (R9), while RA summary data were derived from a meta-analysis of GWAS encompassing 97173 samples. In the East Asian population, summary data for cataract (212453 individuals), glaucoma (212453 individuals), and RA (22515 individuals) were sourced from the IEU Open GWAS project. Inverse-variance weighted (IVW, random-effects) method served as the primary analysis, complemented by MR‒Egger regression, weighted median, weighted mode and simple mode methods. Additionally, various sensitivity tests, including Cochran's Q test, MR‒Egger intercept, MR pleiotropy Residual Sum and Outlier test and leave-one-out test were performed to detect the heterogeneity, horizontal pleiotropy and stability of the analysis results. RESULTS: Following stringent screening, the number of selected instrumental variables ranged from 8 to 56. The IVW results revealed that RA had an increased risk of cataract (OR = 1.041, 95% CI = 1.019-1.064; P = 2.08×10-4) and glaucoma (OR = 1.029, 95% CI = 1.003-1.057; P = 2.94×10-2) in European populations, and RA displayed a positive association with cataract (OR = 1.021, 95% CI = 1.004-1.039; P = 1.64×10-2) in East Asian populations. Other methods also supported those results by IVW, and sensitivity tests showed that our analysis results were credible and stable. CONCLUSIONS: This study revealed a positive causality between RA and the increased risk of cataract and glaucoma, which provides guidance for the early prevention of cataracts and glaucoma in patients with RA and furnishes evidence for the impact of RA-induced inflammation on ophthalmic diseases.

Causal associations between circulating inflammatory cytokines and blinding eye diseases: a bidirectional Mendelian randomization analysis.

Background: Previous studies have explored the associations between circulating inflammatory cytokines and blinding eye diseases, including glaucoma, cataract and macular degeneration. However, the causality of these associations remains controversial. This study employs a bidirectional Mendelian randomization (MR) study to investigate the causal relationships between 41 circulating inflammatory cytokines and these blinding eye diseases. Methods: Summary data for glaucoma, cataract, macular degeneration and 41 circulating inflammatory cytokines were publicly available. The inverse variance weighted (IVW) method was employed as the main analysis method. Additionally, various sensitivity tests, including MR-Egger regression, weighted median, weight mode, Cochran's Q test, MR pleiotropy Residual Sum and Outlier test, and leave-one-out test, were conducted to evaluate sensitivity and stability of results. Results: The IVW analysis identified six circulating inflammatory cytokines causally associated with the risk of blinding eye diseases: Monokine induced by interferon-gamma (MIG) for glaucoma, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-10, and platelet derived growth factor BB (PDGFbb) for cataract, and MIG and hepatocyte growth factor (HGF) for macular degeneration. However, it is noteworthy that none of these associations remained significant after Bonferroni correction (p < 0.0004). Reverse MR analyses indicated that cataract may lead to a decrease in vascular endothelial growth factor (VEGF) levels (OR: 3.326 × 10-04, 95% CI: 5.198 × 10-07 - 2.129 × 10-01, p = 0.0151). Conclusion: This study highlights the potential roles of specific inflammatory cytokines in the development of glaucoma, cataract and macular degeneration. Moreover, it suggests that VEGF is likely to be involved in cataract development downstream. These findings offer insights for early prevention and novel therapeutic strategies for these blinding eye diseases.

Decellularized extracellular matrix scaffold seeded with adipose-derived stem cells promotes neurorestoration and functional recovery after spinal cord injury through Wnt/ß-catenin signaling pathway regulation.

Spinal cord injury (SCI) causes tissue destruction and neuronal apoptosis, which impede neural function recovery. Therefore, promoting neuronal regeneration and neural pathway reconstruction is crucial. In this study, a novel and facile decellularized extracellular matrix (dECM) scaffold seeded with adipose-derived stem cells (ADSCs) (dECM scaffolds/ADSCs) was reported. The dECM scaffold maintained the original three-dimensional network structure of spinal cord tissue and contained various small pores.In vitrostudies demonstrated that dECM scaffolds exhibited excellent biocompatibility, facilitated efficient adhesion and proliferation of ADSCs, and promoted the secretion of neurotrophin-3 and neuronal differentiation in the microenvironment after SCI.In vivostudies further showed that dECM scaffolds/ADSCs could alleviate inflammatory and apoptotic reactions, providing a favorable microenvironment for promoting endogenous nerve regeneration rather than glial scars formation, ultimately achieving recovery of hind limb function in rats. Notably, ICG-001 effectively reversed the therapeutic effect of dECM scaffolds/ADSCs, proving that dECM scaffolds/ADSCs promoted functional recovery after SCI by regulating the Wnt/ß-catenin signaling pathway. Overall, dECM scaffolds/ADSCs can simulate the physiological characteristics of the spinal cord and exert neurorestorative potential, providing a new therapeutic strategy for SCI.

Multifunctional injectable hydrogels with controlled delivery of bioactive factors for efficient repair of intervertebral disc degeneration.

Millions of people worldwide suffer from intervertebral disc degeneration (IVDD), which imposes a significant socioeconomic burden on society. There is an urgent clinical demand for more effective treatments for IVDD because conventional treatments can only alleviate the symptoms rather than preventing the progression of IVDD. Hydrogels, a class of elastic biomaterials with good biocompatibility, are promising candidates for intervertebral disc repair and regeneration. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. This review summarizes the latest findings and developments in using bioactive factors-released bioactive injectable hydrogels for the repair and regeneration of intervertebral discs. It focuses on the analysis and summary of the use of multifunctional injectable hydrogels to delivery bioactive factors (cells, exosomes, growth factors, genes, drugs) for disc regeneration, providing guidance for future study. Finally, we discussed and analyzed the optimal timing for the application of controlled-release hydrogels in the treatment of IVDD to meet the high standards required for intervertebral disc regeneration and precision medicine.

Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis.

BACKGROUND: Spondyloarthritis (SpA) is a group of multifactorial bone diseases influenced by genetic factors, the environment and lifestyle. However, current studies have found a limited number of SpA-related genes, and the genetic and pathogenic mechanisms of SpA are still unclear. METHODS: A tissue-specific transcriptome-wide association study (TWAS) of SpA was performed using GWAS (including 3966 SpA patients and 448,298 controls) summary data and gene expression weights of whole blood and skeletal muscle. The SpA-associated genes identified by TWAS were further compared with the differentially expressed genes (DEGs) identified in the SpA gene expression profile acquired from the Gene Expression Omnibus database (GEO, GSE58667). Finally, functional enrichment and annotation analyses of the identified genes were performed. RESULTS: The TWAS detected 499 suggestive genes associated with SpA in whole blood and skeletal muscle, such as CTNNAL1 (PSM = 3.04 × 10-2, PWB = 9.58 × 10-3). The gene expression profile of SpA identified 20 candidate genes that overlapped in the TWAS data, such as MCM4 (PTWAS = 1.32 × 10-2, PDEG = 2.75 × 10-2) and KIAA1109 (PTWAS = 3.71 × 10-2, PDEG = 4.67 × 10-2). Enrichment analysis of the genes identified by TWAS identified 93 significant GO terms and 33 KEGG pathways, such as mitochondrion organization (GO: 0007005) and axon guidance (hsa04360). CONCLUSION: We identified multiple candidate genes that were genetically related to SpA. Our study may provide novel clues regarding the genetic mechanism, diagnosis, and treatment of SpA.

Polyphosphazene nanodrugs for targeting delivery and inflammation responsive release of curcumin to treat acute lung injury by effectively inhibiting cytokine storms.

An excessive inflammatory response induced by cytokine storms is the primary reason for the deterioration of patients with acute lung injury (ALI). Though natural polyphenols such as curcumin (CUR) have anti-inflammation activity for ALI treatment, they often have limited efficacy due to their poor solubility in water and oxidising tendency. This study investigates a highly cross-linked polyphosphazene nano-drug (PHCH) developed by copolymerisation of CUR and acid-sensitive units (4-hydroxy-benzoic acid (4-hydroxy-benzylidene)-hydrazide, D-HBD) with hexachlorotripolyphosphonitrile (HCCP) for improved treatment of ALI. PHCH can prolong the blood circulation time and targeted delivery into lung inflammation sites by enhancing CUR's water dispersion and anti-oxidant properties. PHCH also demonstrates the inflammation-responsive release of CUR in an inflammation environment due to the acid-responsive degradation of hydrazine bonds and triphosphonitrile rings in PHCH. Therefore, PHCH has a substantial anti-inflammation activity for ALI treatment by synergistically improving CUR's water-solubility, bioavailability and biocompatibility. As expected, PHCH attenuates the cytokine storm syndrome and alleviates inflammation in the infected cells and tissues by down-regulating several critical inflammatory cytokines (TNF-α, IL-1ß, and IL-8). PHCH also decreases the expression of p-p65 and C-Caspase-1, inhibiting NLRP3 inflammasomes and suppressing NF-κB signalling pathways. The administrated mice experiments confirmed that PHCH accumulation was enhanced in lung tissue and showed the efficient scavenging ability of reactive oxygen species (ROS), effectively blocking the cytokine storm and alleviating inflammatory damage in ALI. This smart polyphosphazene nano-drug with targeting delivery property and inflammation-responsive release of curcumin has excellent potential for the clinical treatment of various inflammatory diseases, including ALI.

Curcumin-Containing polyphosphazene nanodrug for Anti-Inflammation and nerve regeneration to improve functional recovery after spinal cord injury.

The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1ß, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/ß-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.

Engineering Multifunctional Polyether Ether Ketone Implant: Mechanics-Adaptability, Biominerialization, Immunoregulation, Anti-Infection, Osteointegration, and Osteogenesis.

Polyether ether ketone (PEEK) has become one of the most promising polymer implants in bone orthopedics, due to the biocompatibility, good processability, and radiation resistance. However, the poor mechanics-adaptability/osteointegration/osteogenesis/antiinfection limits the long-term in vivo applications of PEEK implants. Herein, a multifunctional PEEK implant (PEEK-PDA-BGNs) is constructed through in situ surface deposition of polydopamine-bioactive glass nanoparticles (PDA-BGNs). PEEK-PDA-BGNs exhibit good performance on osteointegration and osteogenesis in vitro and in vivo, due to their multifunctional properties including mechanics-adaptability, biominerialization, immunoregulation, anti-infection, and osteoinductive activity. PEEK-PDA-BGNs can show the bone tissue-adaptable mechanic surface and induce the rapid biomineralization (apatite formation) under a simulated body solution. Additionally, PEEK-PDA-BGNs can induce the M2 phenotype polarization of macrophages, reduce the expression of inflammatory factors, promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and improve the osseointegration and osteogenesis ability of the PEEK implant. PEEK-PDA-BGNs also show good photothermal antibacterial activity and can kill 99% of Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA), suggesting their potential antiinfection ability. This work suggests that PDA-BGNs coating is probably a facile strategy to construct multifunctional (biomineralization, antibacterial, immunoregulation) implants for bone tissue replacement.

Study of Hydroxyapatite-coated High-strength Biodegradable Magnesium-based Alloy in Repairing Fracture Damage in Rats.

BACKGROUND/AIM: Hydroxyapatite (HA) coating can improve the degradation rate and biological activity of metallic implants. This study aimed to fabricate a hydroxyapatite-coated ultrafine-grained biodegradable WE43 magnesium (HA/UFG-WE43 Mg) implant for repairing bone fractures. MATERIALS AND METHODS: A hybrid approach, including parallel tubular-channel angular pressing (PTCAP) and physical vapour deposition (PVD) magnetron sputtering, was employed. The HA/UFG-WE43 Mg samples were tested in terms of their physicochemical and biological properties. RESULTS: The processed tubes exhibited ultrafine structures and the uniformity of microstructures improved following the two-pass PTCAP. The phase composition of the coating formed on UFG-WE43 Mg implant at 250 W for 90 min after heat treatment at 500°C for 60 min confirmed the presence of the HA characteristic peaks. Rat skeletal muscle cells were inoculated on the specimens and cultured for 1, 2, 6, 12, and 24 h, followed by evaluation of cell adhesion and morphology. The growth rates of cells were examined by the Cell Counting Kit8 (CCK-8) and cell survival was observed after 3 days of culture by fluorescence microscopy. The concentration of Mg ions in the blood of rats on 1, 3, 5, 7, and 15 days showed a reduction in Mg concentration after deposition of HA. CONCLUSION: Combination of PTCAP processing followed by surface modification led to tibial fracture healing, and histological analysis of implanted areas demonstrated an efficient biodegradation of the implanted material and a moderate inflammatory reaction.

Comparison of Three Common Intervertebral Disc Discectomies in the Treatment of Lumbar Disc Herniation: A Systematic Review and Meta-Analysis Based on Multiple Data.

OBJECTIVE: Due to recent developments and the wide application of percutaneous transforaminal discectomy (PTED), we herein compare it with microendoscopic discectomy (MED) and traditional open surgery (OD) through surgical indicators and postoperative outcomes to evaluate the advantages and disadvantages of minimally invasive surgery PTED. METHODS: This systematic review and meta-analysis was conducted in line with PRISMA guidelines (PROSPERO2018: CRD42018094890). We searched four English and two Chinese databases from the date of their establishment to May 2022. Randomized controlled trials and case-control studies of PTED versus MED or PTED versus OD in the treatment of lumbar disc herniation were retrieved. RESULTS: A total of 33 studies with 6467 cases were included. When comparing MED with PTED, the latter had less intraoperative blood loss, smaller incision, shorter postoperative bed times, shorter hospitalization times, better postoperative visual analogue scale (VAS) for low back pain, and postoperative dysfunction index (Oswestry Disability Index, ODI) and higher recurrence rates and revision rates. However, operation times, postoperative VAS leg scores and complications, and successful operation rates were similar in both groups. Comparison of PTED with OD revealed in the former less intraoperative blood loss and smaller incision, shorter postoperative bed times, shorter hospitalization times, shorter operation times, and higher recurrence rates and revision rates. Nonetheless, comprehensive postoperative VAS scores, VAS leg pain scores, VAS low back pain, ODI and incidence of complications, and successful operation rates were similar between the two groups. CONCLUSIONS: The therapeutic effect and safety of PTED, MED and OD in the treatment of lumbar disc herniation were comparable. PTED had obvious advantages in that it is minimally invasive, with rapid recovery after surgery, but its recurrence rates and revision rates were higher than MED and OD. Therefore, it is not possible to blindly consider replacing MED and OD with PTED.

Precision medicine strategies for spinal degenerative diseases: Injectable biomaterials with in situ repair and regeneration.

As the population ages, spinal degeneration seriously affects quality of life in middle-aged and elderly patients, and prevention and treatment remain challenging for clinical surgeons. In recent years, biomaterials-based injectable therapeutics have attracted much attention for spinal degeneration treatment due to their minimally invasive features and ability to perform precise repair of irregular defects. However, the precise design and functional control of bioactive injectable biomaterials for efficient spinal degeneration treatment remains a challenge. Although many injectable biomaterials have been reported for the treatment of spinal degeneration, there are few reviews on the advances and effects of injectable biomaterials for spinal degeneration treatment. This work reviews the current status of the design and fabrication of injectable biomaterials, including hydrogels, bone cements and scaffolds, microspheres and nanomaterials, and the current progress in applications for treating spinal degeneration. Additionally, registered clinical trials were also summarized and key challenges and clinical translational prospects for injectable materials for the treatment of spinal degenerative diseases are discussed.

Acute abdomen after vertebroplasty-A rare complication.

Introduction: In recent years, as the concept of minimally invasive treatment has been accepted by the majority of patients, the application of percutaneous vertebroplasty in osteoporotic vertebral compression fractures has gradually increased, and research on the adverse complications of bone cement leakage has gradually deepened. Case: Here, we report a rare case of acute pancreatitis after vertebroplasty. The patient had no previous history of pancreatitis and presented with obvious abdominal pain after vertebroplasty. Abdominal CT examination revealed that the leaking bone cement penetrated the anterior wall of the L1 vertebral body into the diaphragm, and the heat released by the polymerization reaction caused inflammation and damage to the adjacent pancreas, resulting in poor blood flow to the pancreatic tissue and leading to acute pancreatitis. Early postoperative symptomatic treatment was given to the patient, and the corresponding symptoms were gradually relieved. During postoperative follow-up, the leaking cement did not degrade, but the patient had no symptoms. Conclusion: Lesions of adjacent organs caused by bone cement leakage are rare, and clinicians often ignore the association between such complications and vertebroplasty. This case report will provide guidance and a reference for clinicians.

Overexpression of HIF-1α enhances the protective effect of mitophagy on steroid-induced osteocytes apoptosis.

Glucocorticoid (GC; dexamethasone, DEX) -induced osteonecrosis of the femoral head (GIOFH) is a challenging orthopedic disease, and its underlying mechanism remains not clear. This study exposed murine long bone osteocyte-Y4 (MLO-Y4) cells to DEX below normoxic or hypoxic circumstances and found that cell autophagy have been reduced. At the same time, flow cytometry analysis showed increased apoptosis, which was more pronounced in hypoxic environments. Recent research also claimed that GC induces osteoporosis after osteocyte apoptosis, and subsequent microfractures lead to ischemia and hypoxia of the femoral head, resulted in GIOFH. Presently, we found that both mitophagy-related protein hypoxia-inducible factor-1α (HIF-1α) and BNIP3 were up-regulated in the hypoxic environment, and their expression was down-regulated when exposed to DEX. Besides, we demonstrated that overexpressing HIF-1α resisted DEX-induced apoptosis in a hypoxic environment. Here, we demonstrated that overexpression of HIF-1α, through its downstream marker BNIP3, reduced the suppression of DEX on mitophagy induced by hypoxia and protected bone cells from apoptosis. Also, these findings may provide a direction of the promising application for better GIOFH treatment shortly.

Genome-Wide Differentially Methylated Region Analysis to Reveal Epigenetic Differences of Articular Cartilage in Kashin-Beck Disease and Osteoarthritis.

Kashin-Beck disease (KBD) is a degenerative osteoarticular disorder, and displays the significant differences with osteoarthritis (OA) regarding the etiology and molecular changes in articular cartilage. However, the underlying dysfunctions of molecular mechanisms in KBD and OA remain unclear. Here, we primarily performed the various genome-wide differential methylation analyses to reveal the distinct differentially methylated regions (DMRs) in conjunction with corresponding differentially methylated genes (DMGs), and enriched functional pathways in KBD and OA. We identified a total of 131 DMRs in KBD vs. Control, and 58 DMRs in OA vs. Controls, and the results demonstrate that many interesting DMRs are linked to DMGs, such as SMOC2 and HOXD3, which are all key genes to regulate cartilage/skeletal physiologic and pathologic process, and are further enriched in skeletal system and limb-associated pathways. Our DMR analysis indicates that KBD-associated DMRs has higher proportion than OA-associated DMRs in gene body regions. KBD-associated DMGs were enriched in wounding and coagulation-related functional pathways that may be stimulated by trace elements. The identified molecular features provide novel clues for understanding the pathogenetic and therapeutic studies of both KBD and OA.

Clinical characteristics of 14 COVID-19 deaths in Tianmen, China: a single-center retrospective study.

BACKGROUND: The treatment of critically ill patients with COVID-19 who were hospitalized in Wuhan has been reported. However, the clinical characteristics of patients who died of COVID-19 in regions with relatively scarce healthcare resources remain unknown. METHODS: In this retrospective study, a total of 14 patients who were admitted from January 18 to February 11, 2020 and died of COVID-19 were evaluated. The epidemiological, symptomatic, laboratory, radiological and treatment records were reviewed and analyzed. RESULTS: The mean age of the 14 patients was 56.7 (SD 15.3) years, and 8 (57.1%) were older than 50 years. Eight (57.1%) were men, and 11 (78.6%) had one or more high risk factors. The most common chronic diseases among these patients were cardiovascular disease (7, 50.0%), hypertension (6, 42.9%), and chronic kidney disease (5, 35.7%). General symptoms included cough (12, 85.7%), fever (11, 78.6%), and dyspnea (10, 71.4%). The median duration from the onset of symptoms to death was 11 (IQR 6.5-19.5) days, and the median duration from admission to death was 4.5 (1.0-11.8) days. Patients who died within 4.5 days had more severe pulmonary lesions, significantly reduced lymphocytes and elevated C-reactive protein (CRP). Most patients had organ dysfunction, including 13 (92.9%) with acute respiratory distress syndrome (ARDS), 4 (28.6%) with cardiac injury, 3 (21.4%) with acute kidney injury, and 3 (21.4%) with liver dysfunction. CONCLUSIONS: Elderly SARS-CoV-2-infected patients with comorbidities, especially those with ARDS and severe chest CT findings on admission, are at increased risk of death and deserve special attention and quality medical treatment.

Biomechanical effects of reconstruction of the posterior structures after laminectomy with an individualized poly-ether-ether-ketone (PEEK) artificial lamina.

BACKGROUND: Laminectomy is a traditional method for treating lumbar diseases; however, the destruction of the posterior structures may cause postoperative symptoms. An individualized poly-ether-ether-ketone (PEEK) artificial lamina was designed to reconstruct the posterior structures after laminectomy. This study aimed to explore the biomechanical effects of reconstruction of the posterior structures with an individualized PEEK artificial lamina using validated finite element models. OBJECTIVE: To examine the biomechanical effects of individualized PEEK artificial lamina on postlaminectomy lumbar. METHODS: A finite element (FE) model of L3-5 was developed based on computed tomography images. Four surgical models (laminectomy, artificial lamina alone, ligament reconstruction, and osseointegration) were constructed, representing different stages of L4 artificial lamina implantation. The range of motion (ROM), intradiscal pressure (IDP), stresses in the annulus fibrosus at the surgical level and cephalad adjacent level, and stresses in the artificial lamina and screws were measured. RESULTS: The ROM, IDP, and stresses in the annulus fibrosus of the different artificial lamina models decreased compared to those of the laminectomy model at both surgical and adjacent levels for all motion patterns, most notably in the osseointegration model. In addition, the results of the stresses in the implants showed that the artificial lamina could enhance the lumbar isthmus and disperse the abnormally concentrated stresses after laminectomy. CONCLUSION: The application of a PEEK artificial lamina has the potential to stabilize the postlaminectomy lumbar spine and prevent adjacent segment disease (ASD) and iatrogenic lumbar deformities, resulting in a reduction in the incidence of post-lumbar surgery syndrome.

LncRNA SNHG7 alleviates IL-1ß-induced osteoarthritis by inhibiting miR-214-5p-mediated PPARGC1B signaling pathways.

BACKGROUND: As a common joint disease, osteoarthritis (OA) is the main cause of limited joint mobility and disability. The role of lncRNAs in the regulation of OA is increasingly discovered. Therefore, further exploring the function of SNHG7 in OA is of great significance for understanding its occurrence and development. METHODS: We used interleukin-1ß (IL-1ß) to treat to establish an OA model primary on chondrocytes in vitro, and gain- and loss of function assays of SNHG7 and miR-214-5p were conducted. The cell viability and apoptosis of chondrocytes were detected by CCK8 assay, BrdU assay and flow cytometry. The inflammatory cytokines (IL-1ß, IL-6 and TNF-α), NLRP3 inflammasome, protein level of PPARGC1B, PPARγ, P38 and NF-κB were determined by RT-PCR and/or western blot. RESULTS: The results showed that SNHG7 was distinctly downregulated, while miR-214-5p was significantly upregulated in OA patients and primary chondrocytes treated with IL-1ß. In addition, SNHG7 enhanced cell viability, inhibited apoptosis and inflammation of IL-1ß-mediated chondrocytes. In contrast, miR-214-5p upregulation reduced viability, promoted apoptosis and inflammation of chondrocytes. Mechanistically, SNHG7 served as a competitive endogenous RNA by sponging miR-214-5p, which targeted PPARGC1B. Besides, the results of the compensation experiment affirmed that miR-214-5p attenuates SNHG7-mediated protective effects on IL-1ß-mediated chondrocytes against apoptosis and inflammation, and activating PPARγ pathway markedly dampened the cytotoxic effects of miR-214-5p. CONCLUSIONS: Collectively, The above results confirmed that SNHG7 prevents IL-1ß induced OA by inhibiting NLRP3 inflammasome and apoptosis through miR-214-5p/PPARGC1B axis.