Application of nano-hydroxyapatite matrix graft in inter-vertebral fusion therapy: a meta-analysis.

OBJECTIVE: Nano-hydroxyapatite and its composites(nHA) have been widely used as grafts in inter-vertebral fusion. However, the safety and efficacy of the graft in inter-vertebral fusion is controversial. This meta-analysis aimed at evaluating the safety and efficacy of nHA and non-hydroxyapatite grafts (noHA) (autologous bone, etc.) in inter-body fusion. MATERIALS AND METHODS: A comprehensive search was performed in electronic database as follows: PubMed, EMBASE, the Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI) from inception until October 2022. Clinical studies on the effect of nHA and noHA in spinal fusion were collected. Analysis of outcome indicators using RevMan 5.4 statistical software. RESULTS: The meta-analysis showed that the operation time of patients who underwent inter-body fusion with nHA grafts was less than that of patients who underwent noHA (p < 0.05). Compared with the noHA group, the nHA group can achieve similar clinical effects in the fusion rate(OR = 1.29,95%CI: 0.88 to 1.88,p = 0.19),Subsidence rate(OR = 1.2,95%CI:0.44 to 3.28,p = 0.72), inter-vertebral space height(SMD = 0.04,95%CI:-0.08 to 0.15,p = 0.54),Cobb angle(SMD = 0.21,95%CI: 0.18 to 0.6,p = 0.21),Blood loss(SMD = -36.58,95%CI: -81.45 to 8.29,p = 0.11),operative time in 12 months(SMD = -5.82,95%CI: -9.98 to -1.67,p = 0.006) and in the final follow-up(SMD = -0.38,95%CI: -0.51 to -0.26,p < 0.00001),ODI(SMD = 0.68,95%CI: -0.84 to 2.19,p = 0.38), VAS(SMD = 0.17,95%CI: -0.13 to 0.48,p = 0.27) and adverse events(OR = 0.98,95%CI: 0.66 to 1.45,p = 0.92), and the differences are not statistically significant. CONCLUSION: This meta-analysis suggests that nHA matrix grafts are similar to noHA grafts in the safety and efficacy of spinal reconstruction, and are an ideal material for inter-vertebral bone grafting.

Evaluation of basilar artery atherosclerotic plaque distribution by 3D MR vessel wall imaging.

PURPOSE: Basilar artery (BA) atherosclerosis is an important cause of perforator stroke in the brainstem due to plaque involvement of the perforator ostia in BA dorsal or lateral walls. Therefore, to acquire information on plaque distribution is important to better understand and prevent the perforator stroke. This study aimed to comprehensively evaluate BA plaque distribution with 3D magnetic resonance imaging (MRI) vessel wall imaging. MATERIALS AND METHODS: Consecutive patients with cerebrovascular symptoms and stenosis or irregular luminal surface of BA were recruited and underwent BA 3D proton density-weighted volume isotropic turbo spin echo acquisition (VISTA) imaging at 3T. The cross-sectional and longitudinal distribution of BA plaque were analyzed with a custom-developed tool. RESULTS: In all, 85 BA plaques were detected in 61 recruited patients. For cross-sectional distribution, the prevalence of plaque involvement in the ventral, left, dorsal, and right quadrant of BA wall was 74.1%, 70.6%, 67.1%, and 62.4%, respectively. Of the 85 plaques, 17.7% involved one quadrant and 82.3% involved two or more quadrants. The most severe plaque region was more commonly situated at lateral walls (66.1%) as compared to ventral (23.2%, P < 0.001) and dorsal walls (10.6%, P < 0.001). Longitudinally, plaques were more frequently found to occur at BA segment distal than proximal to anterior inferior cerebellar artery (AICA) (63.5% vs. 36.5%). CONCLUSION: Taking advantage of 3D MR vessel wall imaging, BA plaques were found to more likely affect lateral walls and form in BA distal to AICA, where most perforators originate, suggesting that it might be useful to characterize BA plaque distribution before aggressive treatment for prevention of perforator stroke. J. Magn. Reson. Imaging 2016;44:1592-1599.

Effect of interface layer on the enhancement of thermal conductivity of SiC-Water nanofluids: Molecular dynamics simulation.

To investigate the impact of interfacial layer effects on the thermal conductivity of nanofluids and the microscopic mechanisms of enhanced thermal conductivity, this study employed non-equilibrium molecular dynamics to compute the thermal conductivity, number density, radial distribution function, and mean square displacement distribution of SiC nanofluids. The impact of nanoparticle volume fraction and particle size parameters on the thermal conductivity of nanofluids and the structure of interfacial adsorption layers was discussed. The simulation calculation results show that the coefficient of thermal conductivity of nanofluid is positively related to the volume fraction of nanoparticles, increasing from 0.6529 W/(m·K) to 0.8159 W/(m·K), and the enhancement of thermal conductivity by the volume fraction can be up to 33.97 %. The thermal conductivity is inversely correlated with the change in particle size, and the maximum improvement in thermal conductivity by particle size can reach up to 12.05 %. The simulated results of the thermal conductivity of nanofluid are almost consistent with the predicted results of the Yu&Choi model, and the error is controlled within 5 %. Simultaneously, the thickness of the interfacial adsorption layer decreases with an increase in particle size. This reduction arises due to larger particles having a smaller specific surface area, resulting in fewer particle surfaces covered by the interface layer. Moreover, the impact of particle size on the arrangement and affinity of molecules within the interface layer contributes to this decrease. Overall, interface layer effects exhibit a dual impact on the thermal conduction of nanofluids. The structured formation and high-density distribution of the adsorption layer contribute to enhanced heat transfer, while thermal resistance between nanoparticle surfaces and the fluid restricts heat transmission.

Machine Learning in Diagnosis and Prognosis of Lung Cancer by PET-CT.

As a disease with high morbidity and high mortality, lung cancer has seriously harmed people's health. Therefore, early diagnosis and treatment are more important. PET/CT is usually used to obtain the early diagnosis, staging, and curative effect evaluation of tumors, especially lung cancer, due to the heterogeneity of tumors and the differences in artificial image interpretation and other reasons, it also fails to entirely reflect the real situation of tumors. Artificial intelligence (AI) has been applied to all aspects of life. Machine learning (ML) is one of the important ways to realize AI. With the help of the ML method used by PET/CT imaging technology, there are many studies in the diagnosis and treatment of lung cancer. This article summarizes the application progress of ML based on PET/CT in lung cancer, in order to better serve the clinical. In this study, we searched PubMed using machine learning, lung cancer, and PET/CT as keywords to find relevant articles in the past 5 years or more. We found that PET/CT-based ML approaches have achieved significant results in the detection, delineation, classification of pathology, molecular subtyping, staging, and response assessment with survival and prognosis of lung cancer, which can provide clinicians a powerful tool to support and assist in critical daily clinical decisions. However, ML has some shortcomings such as slightly poor repeatability and reliability.

Binding of RAGE and RIPK1 induces cognitive deficits in chronic hyperglycemia-derived neuroinflammation.

AIMS: Chronic hyperglycemia-induced inflammation of the hippocampus is an important cause of cognitive deficits in diabetic patients. The receptor for advanced glycation end products (RAGE), which is widely expressed in the hippocampus, is a crucial factor in this inflammation and the associated cognitive deficits. We aimed to reveal the underlying mechanism by which RAGE regulates neuroinflammation in the pathogenesis of diabetes-induced cognitive impairment. METHODS: We used db/db mice as a model for type 2 diabetes to investigate whether receptor-interacting serine/threonine protein kinase 1 (RIPK1), which is expressed in microglia in the hippocampal region, is a key protein partner for RAGE. GST pull-down assays and AutoDock Vina simulations were performed to identify the key structural domain in RAGE that binds to RIPK1. Western blotting, co-immunoprecipitation (Co-IP), and immunofluorescence (IF) were used to detect the levels of key proteins or interaction between RAGE and RIPK1. Cognitive deficits in the mice were assessed with the Morris water maze (MWM) and new object recognition (NOR) and fear-conditioning tests. RESULTS: RAGE binds directly to RIPK1 via the amino acid sequence (AAs) 362-367, thereby upregulating phosphorylation of RIPK1, which results in activation of the NLRP3 inflammasome in microglia and ultimately leads to cognitive impairments in db/db mice. We mutated RAGE AAs 362-367 to reverse neuroinflammation in the hippocampus and improve cognitive function, suggesting that RAGE AAs 362-367 is a key structural domain that binds directly to RIPK1. These results also indicate that hyperglycemia-induced inflammation in the hippocampus is dependent on direct binding of RAGE and RIPK1. CONCLUSION: Direct interaction of RAGE and RIPK1 via AAs 362-367 is an important mechanism for enhanced neuroinflammation in the hyperglycemic environment and is a key node in the development of cognitive deficits in diabetes.

MKK3 K329 Mutation Attenuates Diabetes-Associated Cognitive Dysfunction by Blocking the MKK3-RAGE Interaction and Inhibiting Neuroinflammation.

The receptor for advanced glycation end products (RAGE) contributes to diabetes-associated cognitive dysfunction (DACD) through the interaction of its C-terminal AAs 2-5 with mitogen-activated protein kinase kinase 3 (MKK3). However, the associated MKK3 binding site is unknown. Here, db/db mice were used as a model for type 2 diabetes. GST pull-down assays and AutoDock Vina simulations were conducted to identify the key RAGE binding site in MKK3. This binding site was mutated to investigate its effects on DACD and to elucidate the underlying mechanisms. The interaction of MKK3 and RAGE, the levels of inflammatory factors, and the activation of microglia and astrocytes were tested. Synaptic morphology and plasticity in hippocampal neurons were assessed via electrophysiological recordings and Golgi staining. Behavioral tests were used to assess cognitive function. In this study, MKK3 bound directly to RAGE via its lysine 329 (K329), leading to the activation of the nuclear factor-κB (NF-κB) signaling pathway, which in turn triggered neuroinflammation and synaptic dysfunction, and ultimately contributed to DACD. MKK3 mutation at K329 reversed synaptic dysfunction and cognitive deficits by downregulating the NF-κB signaling pathway and inhibiting neuroinflammation. These results confirm that neuroinflammation and synaptic dysfunction in the hippocampus rely on the direct binding of MKK3 and RAGE. We conclude that MKK3 K329 binding to C-terminal RAGE (ct-RAGE) is a key mechanism by which neuroinflammation and synaptic dysfunction are induced in the hippocampus. This study presents a novel mechanism for DACD and proposes a novel therapeutic avenue for neuroprotection in DACD.

Treadmill exercise training alleviates diabetes-induced depressive-like behavior and cognitive impairment by improving hippocampal CA1 neurons injury in db/db mice.

Patients with diabetes mellitus (DM) have an increased risk of diabetic encephalopathy symptoms such as depressive-like behaviour and cognitive impairment. Exercise is an effective strategy for preventing and treating DM and diabetic complications. The aim of this study is to investigate the effects and potential mechanisms of treadmill exercise training on diabetes-induced depressive-like behavior and cognitive impairment in db/db mice. In this study, the mice were divided into three groups (n = 10 per group) as follows: healthy-sedentary (db/m), diabetes-sedentary (db/db), and diabetes-treadmill exercise training (db/db-TET). The db/db-TET mice were performed five days per week at a speed of 8 m/min for 60 min/day for 8 weeks, following which body weight, fasting blood glucose, insulin resistance, behavioral, synaptic ultrastructure, oxidative stress, apoptotic signaling, and inflammatory responses were evaluated. As a result, treadmill exercise training significantly decreased body weight and fasting blood glucose levels, increased insulin sensitivity, protected synaptic ultrastructure, reduced depression-like behavior, and improved learning and memory deficits in db/db mice. In addition, treadmill exercise training significantly suppressed NOX2-mediated oxidative stress, resulting in a decrease in NOX2-dependent ROS generation in the db/db mouse hippocampus CA1 region. Reduced ROS generation prevented the apoptotic signaling pathway and NLRP3 inflammasome activation, thereby ameliorating hippocampus neuronal damage. In summary, the results indicated that treadmill exercise training significantly ameliorates hippocampus injury by suppressing oxidative stress-induced apoptosis and NLRP3 inflammasome activation, consequently ameliorating diabetes-induced depressive-like behavior and cognitive impairment in db/db mice.

Aerobic exercise training alleviates renal injury in db/db mice through inhibiting Nox4-mediated NLRP3 inflammasome activation.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, with few therapeutic options available to slow its progression. Aerobic exercise training is an effective strategy for diabetes mellitus and its complications' prevention and treatment. The purpose of this study was to determine the effects of aerobic exercise training on diabetic kidney injury in db/db mice and to characterize the mechanism underlying the renal protective effects. The db/db mice were exercised 5 days a week for 60 min each day for 8 weeks at a speed of 5.6 m/min, after which renal function, morphology, oxidative stress, inflammation, fibrosis, and the expression of the Nox4/ROS/NF-κB/NLRP3 signaling pathway-related protein were assessed. Our results showed that aerobic exercise training significantly reduced body weight and microalbuminuria, improved renal function, and attenuated renal pathological changes in db/db mice independent of hyperglycemic state. Aerobic exercise training was also found to significantly improve oxidative stress and inflammation in the kidneys of db/db mice by decreasing the activity of complex I, the levels of MDA, 8-OHdG, Nox4, ROS, TNF-α, MCP-1, IL-6, and IL-18, increasing the activities of SOD and GSH-Px, the expression of klotho and NPHS2, and decreasing the phosphorylation of NF-κB p65 and IκBα, as well as the expression of NLRP3, ASC, caspase-1 p20, and IL-1ß. Additionally, aerobic exercise training decreased TGF-ß, collagen I, collagen IV, and α-SMA expression, thereby slowing the progression of kidney fibrosis in db/db mice. In conclusion, aerobic exercise training effectively reduces oxidative stress, inflammation, and renal fibrosis by modulating the Nox4/ROS/NF-κB/NLRP3 signaling pathway, implying that aerobic exercise training has significant potential to protect diabetic kidney injury and should be given more emphasis in DKD treatment.

Receptor for advanced glycation end products aggravates cognitive deficits in type 2 diabetes through binding of C-terminal AAs 2-5 to mitogen-activated protein kinase kinase 3 (MKK3) and facilitation of MEKK3-MKK3-p38 module assembly.

In this study, we explored the precise mechanisms underlying the receptor for advanced glycation end products (RAGE)-mediated neuronal loss and behavioral dysfunction induced by hyperglycemia. We used immunoprecipitation (IP) and GST pull-down assays to assess the interaction between RAGE and mitogen-activated protein kinase kinase 3 (MKK3). Then, we investigated the effect of specific mutation of RAGE on plasticity at hippocampal synapses and behavioral deficits in db/db mice through electrophysiological recordings, morphological assays, and behavioral tests. We discovered that RAGE binds MKK3 and that this binding is required for assembly of the MEKK3-MKK3-p38 signaling module. Mechanistically, we found that activation of p38 mitogen-activated protein kinase (MAPK)/NF-κB signaling depends on mediation of the RAGE-MKK3 interaction by C-terminal RAGE (ctRAGE) amino acids (AAs) 2-5. We found that ctRAGE R2A-K3A-R4A-Q5A mutation suppressed neuronal damage, improved synaptic plasticity, and alleviated behavioral deficits in diabetic mice by disrupting the RAGE-MKK3 conjugation. High glucose induces direct binding of RAGE and MKK3 via ctRAGE AAs 2-5, which leads to assembly of the MEKK3-MKK3-p38 signaling module and subsequent activation of the p38MAPK/NF-κB pathway, and ultimately results in diabetic encephalopathy (DE).

Risk factors of postoperative bone cement leakage on osteoporotic vertebral compression fracture: a retrospective study.

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.

Alterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms.

Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.

NLRX1 alleviates lipopolysaccharide-induced apoptosis and inflammation in chondrocytes by suppressing the activation of NF-κB signaling.

Osteoarthritis (OA) is a chronic debilitating disease characterized by joint degeneration. Excessive chondrocyte apoptosis and inflammation contributes to articular cartilage destruction in OA pathology. Nucleotide-binding oligomerization domain (NOD)-like receptor X1 (NLRX1) has emerged as a critical regulator of inflammation that participates in the pathology of diverse diseases. To date, little is known about the role of NLRX1 in OA. In the present study, we aimed to explore the function of NLRX1 in lipopolysaccharide (LPS)-induced injury in chondrocytes, an in vitro model of OA. NLRX1 mRNA was detected by quantitative polymerase chain reaction (qPCR) analysis. Protein expression of NLRX1, phosphorylated IκB kinase ß (IKKß), and phosphorylated nuclear factor-κB (NF-κB) p65 were examined by western blot. Cell viability was assessed by the MTT assay. Cell apoptosis was evaluated by measuring caspase-3 activity. Cytokine release was assessed by enzyme-linked immunosorbent assay (ELISA). NF-κB signaling activation was analyzed with a luciferase reporter assay. Herein, our results revealed that NLRX1 expression was markedly decreased in LPS-treated chondrocytes. Functional experiments demonstrated that NLRX1 overexpression significantly improved cell viability and attenuated LPS-treated chondrocyte apoptosis and inflammation, while NLRX1 silencing caused the opposite effects. Moreover, our results showed that NLRX1 regulated LPS-induced NF-κB signaling activation. Notably, NF-κB signaling inhibition significantly reversed the NLRX1-knockdown-mediated enhanced effects on LPS-induced apoptosis and inflammation. Overall, these results demonstrate that NLRX1 alleviates LPS-induced apoptosis and inflammation in chondrocytes by negatively regulating NF-κB signaling, results that indicate an anti-inflammatory role for NLRX1 in OA. Our findings suggest that NLRX1 may serve as a potential therapeutic target for OA.

Spatiotemporal expression of Ski after rat spinal cord injury.

Ski is an evolutionarily conserved protein and widely participates in the regulation of various pathological and physiological processes such as wound healing, liver regeneration, development of the embryonic nervous system, muscle differentiation, and progression of many kinds of tumors. However, the distribution and function of Ski in central nervous system lesion and disease remain unclear. In this study, we investigated the spatiotemporal expression of Ski in a spinal cord injury (SCI) model in adult rats. Western Blot analysis indicated that Ski was expressed in both normal and injured spinal cord, and showed a significant upregulation after SCI compared with the sham group. Double-labeled immunofluorescence staining showed that Ski was significantly expressed in astrocytes, but not in the neurons. Western Blot analyses of glial fibrillary acidic protein (GFAP) and BBB scores were carried out and correlation analysis showed a positive correlation between them. In addition, the relative expression level of Ski was also positively correlated with the relative expression level of GFAP. Moreover, the conspicuous co-expression band of Ski and GFAP at the lesion border was found in the results of immunofluorescence staining combined with the pattern of glial scar formation reflected by H&E staining; in addition, it was found that Ski was also highly associated with glial scar. On the basis of our data, we speculated that Ski might play an important role in the process of reactive astrogliosis after SCI and our study might provide a basis for further study on the detailed role of Ski in astrocytes.