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ObjectiveTo report the trend changes of the prevalence, incidence, and disability-adjusted life years (DALYs) of knee osteoarthritis (KOA) according to age, sex, sociodemographic index (SDI), and income.MethodsThis analysis used estimates from the broader Global Burden of Disease (GBD) study 2019, which covered 201 countries from 1990 to 2019. National prevalence, incidence, and DALYs were shown by using ggplot2 and maps packages. Five-year intervals were used for age groupings. The Commonwealth and the World Bank income classifications were used for income grouping.ResultsGlobally, there were ~364.58 million prevalent cases (females: 225.16 million), 29.51 million incident cases (females: 17.53 million), and 11.53 million DALYs (females: 7.09 million) due to KOA in 2019. The Western Pacific Region had a high endemicity of ~7,319.87 cases per 100,000 people (7.64%). Japan's prevalence rate (12,610.12 cases per 100,000 population) was 10 times that of Somalia (1,178.23) in 2019. In 200 countries (except the United Arab Emirates), the prevalence, incidence, and DALY rates of KOA in 2019 were higher among females than among males and increased with age up to the oldest age group. The prevalence was highest in the high-middle SDI countries, and the incidence and DALYs were highest in the middle SDI countries.ConclusionThere was a large burden of KOA worldwide, with some notable intercountry variation. Some countries had 10 times the burden of other countries. Increasing population awareness regarding the prevalence, incidence, and DALYs of KOA with a focus on the population in the Western Pacific Region is needed, particularly for older females. informs health policy development, and contributes to improving the efficiency, equity, and effectiveness of healthcare systems.

Electrical stimulation (ES) of the spinal cord is a promising therapy for functional rehabilitation after spinal cord injury (SCI). However, the specific mechanism of action is poorly understood. We designed and applied an implanted ES device in the SCI area in rats and determined the effect of ES on the treatment of motor dysfunction after SCI using behavioral scores. Additionally, we examined the molecular characteristics of the samples using proteomic and transcriptomic sequencing. The differential molecules between groups were identified using statistical analyses. Molecular, network, and pathway-based analyses were used to identify group-specific biological features. ES (0.5 mA, 0.1 ms, 50 Hz) had a positive effect on motor dysfunction and neuronal regeneration in rats after SCI. Six samples (three independent replicates in each group) were used for transcriptome sequencing; we obtained 1026 differential genes, comprising 274 upregulated genes and 752 downregulated genes. A total of 10 samples were obtained: four samples in the ES group and six samples in the SCI group; for the proteome sequencing, 48 differential proteins were identified, including 45 up-regulated and three down-regulated proteins. Combined transcriptomic and proteomic studies have shown that the main enrichment pathway is the hedgehog signaling pathway. Western blot results showed that the expression levels of Sonic hedgehog (SHH) (P

IntroductionGlioblastoma (GBM) is the most invasive type of glioma, is insensitive to radiotherapy and chemotherapy, and has high proliferation and invasive ability, with a 5-year survival rate of

Objective To analyze the efficacy of modified Allgöwer–Donati suture (MADS) technique on cosmetic outcomes compared with vertical mattress suture (VMS) technique in spinal surgery wounds. Methods This randomized controlled trial was conducted at the First Hospital of Lanzhou University (Gansu, China) from September 2019 to August 2020. The patients were randomly divided into two groups, a VMS group and a MADS group, by staff not involved in the treatment using a computer‐based random number table program (no restrictions on age or sex). Both procedures were performed by the same group of physicians as well as assistants. All suture wounds were completed by the same person. The primary endpoint was the scar area, and the postoperative scar area was scored by the Patient and Observer Scar Scale Assessment (POSAS). The scar area was calculated by ImageJ software. The second outcome measure was wound complications, including poor wound healing, wound edge necrosis, and infection. The trial was recorded in the Chinese Clinical Trial Register on 18 August 2019 (ChiCTR1900024548). Results A total of 143 patients were included: 72 in the VMS group and 71 in the MADS group. There was no significant difference in their demographics in terms of age (49.71 ± 8.91 vs 50.15 ± 6.79 years, P = 0.737), sex (M/F, 30/41 vs 31/41, P = 0.923), suture time (3.39 ± 0.22 vs 3.47 ± 0.25 s/mm, P = 0.057), or body mass index (BMI, 23.88 ± 3.50 vs 24.05 ± 3.50, P = 0.765) for MADS to VMS. The postoperative scar area was compared between the two groups transversely on day 12, the MADS wound scars decreased by 58.95% (75,133.24/127,452.58). In the POSAS evaluation, after MADS treatment, surface area score decreased from 5 (4, 5) to 2 (2, 3) (P < 0.0001), observer's overall opinion from 5 (4, 5) to 3 (2, 3) (P < 0.0001), itching from 3 (3, 4) to 3 (2, 3) (P = 0.001), color from 4 (4, 5) to 3 (2–4) (P < 0.0001), stiffness 4 (3–4.75) to 3 (3, 4) (P < 0.0001), or thickness from 4 (3–5) to 4 (3, 4) (P = 0.004). In terms of overall opinion evaluation, the MADS showed a significant difference in observer's overall opinion to the VMS (5 (4, 5) vs 3 (2, 3), P < 0.0001) and in patient's overall opinion 5 (5, 6) to 3 (3, 4), (P < 0.0001). There was no significant statistical difference in poor wound healing (3 vs 0, P = 0.245), wound edge necrosis (3 vs 0, P = 0.245), and infection (1 vs 0, P = 1.000) with the MADS to the VMS. Conclusion The results of this study show that the MADS effectively reduced the surgical scar area to 58.95% with no additional adverse events compared with that of the VMS in spine surgery.

Abstract Background IL-6 plays a pivotal role in resistance to chemotherapeutics, including lobaplatin. However, the underlying mechanisms are still unclear. This study was to investigate the changes in phosphoproteins and their related signaling pathways in the process of IL-6-induced chemoresistance to lobaplain in osteosarcoma cells. Methods We performed a quantitative phosphoproteomic analysis of the response of SaOS-2 osteosarcoma cells to recombinant human IL-6 (rhIL-6) intervention prior to lobaplatin treatment. The cells were divided into the control group (Con), the lobaplatin group (Lob), and the rhIL-6-and-lobaplatin group (IL-6). Three biological replicates of each group were included. The differentially expressed phosphoproteins were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Netphos 3.1 was used for the prediction of kinases, and STRING was used for the visualization of protein–protein interactions. The conserved motifs surrounding the phosphorylated residues were analyzed using the motif-x algorithm. Western blot analysis was performed to verify the differential expression of p-FLNC, its predicted kinase and the related signaling pathway. The results of the bioinformatic analysis were validated by immunohistochemical staining of clinical specimens. Results In total, 3373 proteins and 12,183 peptides, including 3232 phosphorylated proteins and 11,358 phosphorylated peptides, were identified and quantified. Twenty-three significantly differentially expressed phosphoproteins were identified in the comparison between the IL-6 and Lob groups, and p-FLNC ranked second among these phosphoproteins. GO and KEGG analyses revealed the pivotal role of mitogen-activated protein kinase signaling in drug resistance induced by rhIL-6. Four motifs, namely, -SPxxK-, -RxxSP-, -SP-, and -SPK-, demonstrated higher expression in the IL-6 group than in the Lob group. The western blot analysis results verified the higher expression of p-FLNC, AKT1, and p-ERK and the lower expression of p-JNK in the IL-6 group than in the Con and Lob groups. The immunohistochemical staining results showed that p-FLNC, AKT1 and p-ERK1/2 were highly expressed in platinum-resistant clinical specimens but weakly expressed in platinum-sensitive specimens, and platinum-resistant osteosarcoma specimens demonstrated weak expression of p-JNK. Conclusions This phosphoproteomic study is the first to reveal the signature associated with rhIL-6 intervention before lobaplatin treatment in human osteosarcoma cells. p-FLNC, AKT1, and MAPK signaling contributes to resistance to lobaplatin in osteosarcoma SaOS-2 cells and may represent molecular targets to overcome osteosarcoma chemoresistance.

Objective: Spinal cord injury (SCI) often leads to severe physiological and pathological changes in patients. Erxian Decoction (EXD) is effective in the postoperative treatment of spinal cord injury, but its specific mechanism of action is poorly defined. Methods: Network pharmacology and molecular docking were used to predict the potential mechanisms of EXD in SCI. In vivo studies were used to validate the above predictions. For in vivo study, the rats were pretreated with or without EXD (5.76 g/kg, by intragastric gavage). Multiple molecular biological test methods to identify molecular mechanisms. One-way analysis of variance (ANOVA) was used with Bonferroni's post-hoc test to identify the differences between groups. Results: In vivo studies have shown that EXD improved motor function at 7dpi in SCI rats (P < 0.0001), significantly reduced spinal cord edema (P = 0.0139), upregulated 5-HT, GFAP, and TMEM119 expression. Through network pharmacology analysis, we found that Akt1 in EXD plays a role in treating SCI. The underlying mechanism may be the inhibition of apoptosis after activation of Akt1 phosphorylation. Molecular docking revealed that the key compounds could spontaneously bind to the Akt1 protein. Pharmacological inhibition of Akt1 activation by MK-2206, attenuated the anti-apoptotic effect of EXD on SCI in rats (P < 0.0001). Conclusions: EXD inhibits apoptosis by activating Akt1, reduce spinal cord edema and restore behavioral function after SCI in rats.

Spinal cord injury refers to damage to the spinal cord due to trauma, disease, or degeneration; and the number of new cases is increasing yearly. Significant cellular changes are known to occur in the area of spinal cord injury. However, changes in cellular composition, trajectory of cell development, and intercellular communication in the injured area remain unclear. Here, we used single-cell RNA sequencing to evaluate almost all the cell types that constitute the site of spinal cord injury in rats. In addition to mapping the cells of the injured area, we screened the expression of immune autophagy-related factors in cells and identified signaling pathways by the measuring the expression of the receptor−ligand pairs to regulate specific cell interactions during autophagy after spinal cord injury. Our data set is a valuable resource that provides new insights into the pathobiology of spinal cord injury and other traumatic diseases of the central nervous system.

Abstract Purpose To investigate risk factors of bone cement leakage in percutaneous vertebroplasty(PVP)for osteoporotic vertebral compression fracture (OVCF). Methods A total of 236 patients (344 vertebrae) who underwent PVP between November 2016 and June 2020 were enrolled in the study. Clinical and radiological characteristics, including age, gender, course of disease, trauma, type of vertebral fracture, cortical continuity of vertebral body, intervertebral vacuum cleft (IVC), fracture severity, fracture level, basivertebral foramen, bone cement dispersion types, the cement injection volume, the type of cement leakage, puncture approach, and intrusion of the posterior wall, were considered as potential risk factors. Three types of leakage (type-B, type-C, and type-S) were defined and risk factors for each type were analyzed. Logistic analysis was used to study the relationship between each factor and the type of cement leakage. Results The incidences of the three types of leakage were 28.5%, 24.4%, and 34.3%. The multinomial logistic analysis revealed that the factors of type-B leakage were the shape of cement and basivertebral foramen. One significant factor related to type-C leakage was cortical disruption, and the factors of type-S leakage were bone cement dispersion types, basivertebral foramen, cleft, fracture severity, an intrusion of the posterior wall, and gender. Conclusion Different types of cement leakage have their own risk factors, and the analysis of risk factors of these might be helpful in reducing the rate of cement leakage.

Despite increasing evidence to support the relationship between FUBP1 and tumorigenesis in some types of cancers, there have been no analyses from a pan-cancer perspective. Here, we are the first to investigate the putative oncogenic role of FUBP1 in 33 cancer types based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Dysregulated FUBP1 expression was observed in most cancer types, and high FUBP1 expression suggests poor prognosis in cancers such as ACC, KICH, LIHC, LUAD, LUSC, SARC, CESC, and SKCM. Missense mutation is the most common type of FUBP1 mutation, and R430 in KH_4 is a predominant mutation site. Enhanced phosphorylation of FUBP1 at the S120 site has been observed in clear cell RCC, lung adenocarcinoma, and pediatric brain cancer specimens from African-American and Asian individuals. The expression of FUBP1 was found to be negatively correlated with the infiltration of CD8+ T lymphocytes in GBM, HNSC-HPV- and UCEC but positively correlated with that of tumor-associated fibroblasts in CESC, ESCA, HNSC, LIHC, LUAD, PAAD, and THYM. Furthermore, RNA splicing and spliceosome signaling were predominantly enriched in both GO and KEGG analyses of the functional mechanism of FUBP1. Briefly, this pan-cancer analysis comprehensively revealed the multifaceted characteristics and oncogenic role of FUBP1 in different human cancers.

Objective: Spinal cord injury (SCI) is a devastating disease resulting in lifelong disability, but the molecular mechanism remains unclear. Our study was designed to observe the role of excision repair cross-complementing group 6 (ERCC6) following SCI and to determine the underlying mechanism.Methods: SCI mouse models and LPS-induced microglia cell models were established. ERCC6 expression was blocked by ERCC6-siRNA-carrying lentivirus. Nissl staining was utilized for detecting neuronal damage, and apoptosis was analyzed with TUNEL and Western blotting (apoptotic markers). Immunofluorescence was used for measuring macrophage markers (CD68 and F4/80) and astrocyte and microglia markers (GFAP and Iba-1). Pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were measured via ELISA. Senescent cells were estimated via SA-β-Gal staining as well as Western blot (senescent markers p21 and p27). Oxidative stress was investigated by detecting the expression of 4-HNE, Nrf2, and Keap1, and intracellular ROS levels.Results: ERCC6 expression was remarkably upregulated both in the spinal cord of SCI mice and LPS-induced microglia cells. ERCC6 deficiency alleviated neuronal damage and apoptosis. Macrophage infiltration and inflammatory response were suppressed by si-ERCC6 treatment. Moreover, ERCC6 blockage ameliorated astrocyte and microglia activation and cell senescence in the damaged spinal cord. Excessive oxidative stress was significantly decreased by ERCC6 knockdown in SCI.Conclusion: Collectively, ERCC6 exerts crucial functions in mediating physiological processes (apoptosis, inflammation, senescence, and oxidative stress), implying that ERCC6 might act as a prospective therapeutic target against SCI.

Abstract Objective The aim of this systematic review and meta-analysis was to evaluate the efficacy of barbed versus conventional sutures in total knee arthroplasty. Methods Two investigators independently performed data extraction and assessed study quality using the keywords “barbed suture, wound suture, total knee arthroplasty” in two search trials, individual trials, and trials from Systematic Reviews or Meta-analyses in PubMed, Cochrane Library, Web of Science, and EMBASE databases. Result A total of 11 articles (involving 1546 total knee arthroplasties) were included in this study. Comparison was made between barbed and conventional sutures in terms of various measures. No significant differences were identified in superficial infection and deep infection (p > 0.51; odds ratio 0.84 [95% confidence interval, 0.50, 1.4] and p > 0.28; odds ratio 0.50 [95% confidence interval, 0.14, 1.75], respectively). There was no significant difference in time for capsular suture (p 0.05; odds ratio − 1.20 [95% confidence interval, − 2.98, 0.58] and p > 0.05; odds ratio − 1.62 [95% confidence interval, − 4.06, 0.18], respectively). No significant differences were revealed in suture breakage and needle stick injury (p

Introduction: Glioblastoma (GBM) is the most invasive type of glioma, is insensitive to radiotherapy and chemotherapy, and has high proliferation and invasive ability, with a 5-year survival rate of <5%. Cuproptosis-related genes (CRGs) have been successfully used to predict the prognosis of many types of tumors. However, the relationship between cuproptosis and GBM remains unclear. Methods: Here, we sought to identify CRGs in GBM and elucidate their role in the tumor immune microenvironment and prognosis. To that aim, changes in CRGs in The Cancer Genome Atlas (TCGA) transcriptional and Gene Expression Omnibus (GEO) datasets (GEO4290 and GEO15824) were characterized, and the expression patterns of these genes were analyzed. Results: A risk score based on CRG expression characteristics could predict the survival and prognosis of patients with GBM and was significantly associated with immune infiltration levels and the expression of CD47 and CD24, which are immune checkpoints of the “don't eat me “signal. Furthermore, we found that the CDKN2A gene may predict GBM sensitivity and resistance to drugs. Discussion: Our findings suggest that CRGs play a crucial role in GBM outcomes and provide new insights into CRG-related target drugs/molecules for cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

In this study, the effects of background error covariance (BE) using the stream function ψ and unbalanced velocity potential χu as momentum control variables (CV5 scheme) and BE using the velocity U and V as momentum control variables (CV7 scheme) on assimilating radar radial velocity and reflectivity data for short-term forecasts of dispersive convection in a weak environmental field are explored based on the weather research and forecasting model (WRF) model and its 3DVAR assimilation system. The 4 km resolution forecast samples are generated to formulate the CV5 and CV7 BE by the National Meteorological Center (NMC) method. The single-observation experiments reveal that the differences between the two BE statistics are mainly reflected on the momentum control variables. The increment of wind field from CV7 shows more small-scale local characteristics. Comparing with control experiment, real radar observation assimilation tests of CV5 and CV7 both improve the reflectivity and precipitation forecasts. But the CV7 scheme improves the forecasting of strong convective systems in weak environmental fields better than CV5. First, the CV7 scheme improves both reflectivity and dispersive precipitation forecasts and significantly suppresses the spurious precipitation forecasts when compared with the CV5 scheme. In addition, CV7 also significantly reduces the forecast errors of surface variables and the wind analysis from CV7 is more local. Further analysis shows that the CV7 improves the water vapor convergence conditions compared to the CV5 scheme, which may be the reason for its better performance in the subsequent forecasts.

Due to its excellent physical properties, γ-TiAl alloy has been widely used in thin-walled components of aerospace engines. However, issues such as low thermal conductivity, poor machinability, and high cutting temperatures often result in difficulties in ensuring the geometric accuracy and surface integrity of the parts. This paper focuses on the study of the thermal deformation behavior of γ-TiAl alloy within a range of higher temperatures and strain rates. Firstly, by conducting quasi-static tests and Hopkinson bar tests on γ-TiAl alloy, the true stress–strain curves of γ-TiAl alloy are obtained within a temperature range of 20~500 °C and a strain rate range of 3000~11,000/s. Based on the Johnson–Cook model, the true stress–strain curves are fitted and analyzed with consideration of the coupling effect of strain rate, temperature, and strain. The strain rate hardening coefficient C and thermal softening exponent m are polynomialized, improving the Johnson–Cook constitutive model of γ-TiAl alloy. The improved model shows significant improvements in the correlation coefficient and absolute errors between the predicted values and experimental values, providing a better reflection of the thermal deformation behavior of γ-TiAl alloy within a range of higher temperatures and strain rates.

Cutting fluids are often used in the machining of titanium alloys to reduce processing temperature and maximize quality and productivity. The permeability of the cutting fluid in the capillary tube directly influences the effect of lubrication on cooling performance. In this study, supercritical carbon dioxide cryogenic micro-lubrication (scCO2-MQL) is used for the auxiliary machining of titanium alloys. A capillary model for scCO2-MQL-assisted cutting is proposed and established while considering the characteristics of three-phase states produced during the decompression release of scCO2. The injection temperature and characteristics of scCO2 are experimentally investigated, and the dynamic process of scCO2-MQL penetration into the capillary is analyzed. The results show that under the applied experimental conditions, the injection temperature of scCO2-MQL ranges from approximately −45 °C to 60 °C. Because scCO2 presents good solubility in oil, it has the capacity to refine the oil droplets into smaller particles, thus resulting in a higher lubricating oil content in the capillary per unit of time. This leads to enhanced lubricity that can benefit processing applications.

Oxidation and diffusion simulation experiments were conducted to choose the most suitable material for cutting the Inconel 625 superalloy. Three tool materials, WC/Co, coated carbide, and ceramic were used as tool materials in the oxidation simulation experiment. The three tool materials were heated for 30 min in a high-temperature furnace, and the high-temperature oxidation products were examined with scanning electron microscopy and X-ray diffraction (XRD). Tools were heated for 90 min in a vacuum tube furnace. The element diffusion behaviors of Inconel 625 and the tool materials were analysed with energy-dispersive X-ray spectroscopy and XRD. Some of the WC and Co in the WC/Co and coated carbide tool materials was oxidized to WO3, Co3O4, and CoWO4, and the oxidation reaction became more intense as the temperature increased. For the ceramic tool, only TiC was oxidized to TiO2, which indicates good oxidation resistance. In the diffusion couple experiments, the diffusion levels of the three tool materials increased with temperature, but the degree of influence differed. Diffusion of elements was hindered by the (Al, Ti) N coating of the coated carbide and effectively inhibited by the Al2O3 in the ceramic tool. In terms of oxidation and diffusion, the most suitable tool material for cutting Inconel 625 was the ceramic, followed by the coated carbide and then WC/Co.