Analysis and validation of hub genes in neutrophil extracellular traps for the long-term prognosis of myocardial infarction.

INTRODUCTION: The study focuses on the long-term prognosis of myocardial infarction (MI) influenced by neutrophil extracellular traps (NETs). It also aims to analyze and validate relative hub genes in this process, in order to further explore new therapeutic targets that can improve the prognosis of MI. MATERIALS AND METHODS: We established a MI model in mice by ligating the left anterior descending branch (LAD) and conducted an 8-week continuous observation to study the dynamic changes in the structure and function of the heart in these mice. Meanwhile, we administered Apocynin, an inhibitor of NADPH Oxidase, which has also been shown to inhibit the formation of NETs, to mice undergoing MI surgery in order to compare. This study employed hematoxylin-eosin (HE) staining, echocardiography, immunofluorescence, and real-time quantitative PCR (RT-qPCR) to examine the impact of NETs on the long-term prognosis of MI. Next, datasets related to MI and NETs were downloaded from the GEO database, respectively. The Limma package of R software was used to identify differentially expressed genes (DEGs). After analyzing the "Robust Rank Aggregation (RRA)" package, we conducted a screening for robust differentially expressed genes (DEGs) and performed pathway enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to determine the functional roles of these robust DEGs. The protein-protein interaction (PPI) network was visualized and hub genes were filtered using Cytoscape. RESULTS: Immunofluorescence and qPCR results showed an increase in the expression of Myeloperoxidase (MPO) at week 1 and week 8 in the hearts of mice after MI. HE staining reveals a series of pathological manifestations in the heart of the MI group during 8 weeks, including enlarged size, disordered arrangement of cardiomyocytes, infiltration of inflammatory cells, and excessive deposition of collagen fibers, among others. The utilization of Apocynin could significantly improve these poor performances. The echocardiography displayed the cardiac function of the heart in mice. The MI group has a reduced range of heart movement and decreased ejection ability. Moreover, the ventricular systolic movement was found to be abnormal, and its wall thickening rate decreased over time, indicating a progressive worsening of myocardial ischemia. The Apocynin group, on the contrary, showed fewer abnormal changes in the aforementioned aspects. A total of 81 DEGs and 4 hub genes (FOS, EGR1, PTGS2, and HIST1H4H) were obtained. The results of RT-qPCR demonstrated abnormal expression of these four genes in the MI group, which could be reversed by treatment of Apocynin. CONCLUSION: The NETs formation could be highly related to MI and the long-term prognosis of MI can be significantly influenced by the NETs formation. Four hub genes, namely FOS, EGR1, PTGS2, and HIST1H4H, have the potential to be key genes related to this process. They could also serve as biomarkers for predicting MI prognosis and as targets for gene therapy.

Tracking and navigation of a microswarm under laser speckle contrast imaging for targeted delivery.

Micro/nanorobotic swarms consisting of numerous tiny building blocks show great potential in biomedical applications because of their collective active delivery ability, enhanced imaging contrast, and environment-adaptive capability. However, in vivo real-time imaging and tracking of micro/nanorobotic swarms remain a challenge, considering the limited imaging size and spatial-temporal resolution of current imaging modalities. Here, we propose a strategy that enables real-time tracking and navigation of a microswarm in stagnant and flowing blood environments by using laser speckle contrast imaging (LSCI), featuring full-field imaging, high temporal-spatial resolution, and noninvasiveness. The change in dynamic convection induced by the microswarm can be quantitatively investigated by analyzing the perfusion unit (PU) distribution, offering an alternative approach to investigate the swarm behavior and its interaction with various blood environments. Both the microswarm and surrounding environment were monitored and imaged by LSCI in real time, and the images were further analyzed for simultaneous swarm tracking and navigation in the complex vascular system. Moreover, our strategy realized real-time tracking and delivery of a microswarm in vivo, showing promising potential for LSCI-guided active delivery of microswarm in the vascular system.

Multiple Magneto-Optical Microrobotic Collectives with Selective Control in Three Dimensions Under Water.

Inspired by natural swarms, various methods are developed to create artificial magnetic microrobotic collectives. However, these magnetic collectives typically receive identical control inputs from a common external magnetic field, limiting their ability to operate independently. And they often rely on interfaces or boundaries for controlled movement, posing challenges for independent, three-dimensional(3D) navigation of multiple magnetic collectives. To address this challenge, self-assembled microrobotic collectives are proposed that can be selectively actuated in a combination of external magnetic and optical fields. By harnessing both actuation methods, the constraints of single actuation approaches are overcome. The magnetic field excites the self-assembly of colloids and maintains the self-assembled microrobotic collectives without disassembly, while the optical field drives selected microrobotic collectives to perform different tasks. The proposed magnetic-photo microrobotic collectives can achieve independent position and path control in the two-dimensional (2D) plane and 3D space. With this selective control strategy, the microrobotic collectives can cooperate in convection and mixing the dye in a confined space. The results present a systematic approach for realizing selective control of multiple microrobotic collectives, which can address multitasking requirements in complex environments.

Effects of "fixation-fusion" sequence of lumbar surgery on surgical outcomes for patients with lumbar spinal stenosis: study protocol for a multicenter randomized controlled trial.

BACKGROUND: New-onset neurological symptoms such as numbness and pain in lower extremities might appear immediately after conventional lumbar interbody fusion (LIF) surgery performed in patients with lumbar spinal stenosis. METHODS AND ANALYSIS: This is a multicenter, randomized, open-label, parallel-group, active-controlled trial investigating the clinical outcomes of modified LIF sequence versus conventional LIF sequence in treating patients with lumbar spinal stenosis. A total of 254 eligible patients will be enrolled and randomized in a 1:1 ratio to either modified LIF sequence or conventional LIF sequence group. The primary outcome measure is the perioperative incidence of new-onset lower extremity neurological symptoms, including new adverse events of pain, numbness, and foot drop of any severity. Important secondary endpoints include visual analogue scale (VAS) pain score and lumbar Japanese Orthopaedic Association (JOA) recovery rate. Other safety endpoints will also be evaluated. The safety set used for safety data analysis by the actual surgical treatment received and the full analysis set for baseline and efficacy data analyses according to the intent-to-treat principle will be established as the two analysis populations in the study. CONCLUSION: This study is designed to investigate the clinical outcomes of modified LIF sequences in patients with lumbar spinal stenosis. It aims to provide clinical evidence that the modified "fixation-fusion" sequence of LIF surgery is effective in treating lumbar spinal stenosis. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx ID: ChiCTR2100048507.

Bioinspired self-assembled colloidal collectives drifting in three dimensions underwater.

Active matter systems feature a series of unique behaviors, including the emergence of collective self-assembly structures and collective migration. However, realizing collective entities formed by synthetic active matter in spaces without wall-bounded support makes it challenging to perform three-dimensional (3D) locomotion without dispersion. Inspired by the migration mechanism of plankton, we propose a bimodal actuation strategy in the artificial colloidal systems, i.e., combining magnetic and optical fields. The magnetic field triggers the self-assembly of magnetic colloidal particles to form a colloidal collective, maintaining numerous colloids as a dynamically stable entity. The optical field allows the colloidal collectives to generate convective flow through the photothermal effect, enabling them to use fluidic currents for 3D drifting. The collectives can perform 3D locomotion underwater, transit between the water-air interface, and have a controlled motion on the water surface. Our study provides insights into designing smart devices and materials, offering strategies for developing synthetic active matter capable of controllable collective movement in 3D space.

Simple fabrication of cobalt-nickel alloy/carbon nanocomposite fibers for tunable microwave absorption.

A series of CoNi/C nanocomposite fibers with different Co and Ni ratios were successfully prepared by electrospinning and carbonization techniques for the study of electromagnetic microwave (EMW) absorbing materials. We systematically studied the influence of Co and Ni content on the microstructure, chemical composition, magnetic properties, and EMW absorption characteristics of the samples. The results showed that CoNi/C nanocomposite fibers obtained excellent EMW absorption ability through the reasonable design of the composition, and the Co/Ni ratio significantly affected the microstructure and EMW absorption performance. When the Co/Ni ratio was 1/3, the minimum reflection loss (RLmin) is -71.2 dB (2.4 mm, 13.4 GHz), and the maximum effective absorption bandwidth (EAB, RL＜-10 dB) is up to 5.9 GHz (2.2 mm, 12.1-18 GHz), covering almost the entire Ku band. This study demonstrated the enormous potential of one-dimensional structure in the field of EMW absorption. In addition, the CoNi/C nanocomposite fiber synthesized using a straightforward and low-cost method not only has excellent EMW absorption performance but also has the potential for practical application. The results of this study provide a simple and effective approach for designing high-performance EMW absorbing materials.

Acid Radical Tolerance of Silane Coatings on Calcium Silicate Hydrate Surfaces in Aggressive Environments: The Role of Nitrate/Sulfate Ratio.

Silane is known as an effective coating for enhancing the resistance of concrete to harmful acids and radicals that are usually produced by the metabolism of microorganisms. However, the mechanism of silane protection is still unclear due to its nanoscale attributes. Here, the protective behavior of silane on the calcium silicate hydrate (C-S-H) surface is examined under the attack environment of nitrate/sulfate ions using molecular dynamics simulations. The findings revealed that silane coating improved the resistance of C-S-H to nitrate/sulfate ions. This resistance is considered the origin of silane protection against harmful ion attacks. Further research on the details of molecular structures suggests that the interaction between the oxygen in the silane molecule and the calcium in C-S-H, which can prevent the coordination of sulfate and nitrate to calcium on the C-S-H surface, is the cause of the silane molecules' strong adsorption. These results are also proved in terms of free energy, which found that the adsorption free energy on the C-S-H surface followed the order silane > sulfate > nitrate. This research confirms the excellent protection performance of silane on the nanoscale. The revealed mechanism can be further used to help the development of high-performance composite coatings.

Design and synthesis of one-dimensional magnetic composites with Co nanoparticles encapsulated in carbon nanofibers for enhanced microwave absorption.

With the increased usage of electromagnetic microwaves (EM) in wireless communication technology, the problem of electromagnetic radiation pollution has grown dramatically. This study successfully prepared novel Co/C magnetic nanocomposite fibers for EM absorption using the electrospinning and carbonization methods. The morphology, composition, magnetic properties, and EM absorption performance were extensively characterized. This material shows exceptional EM absorption performance, achieving -72.01 dB (at 2.08 mm) for minimum reflection loss (RLmin) and 5.4 GHz (at 1.68 mm) for effective absorption bandwidth (EAB). The performance surpasses not only any single precursor but also stands as the best in similar investigations. It can be attributed to the microstructure of magnetic Co nanoparticles encapsulated in carbon nanofibers and the macrostructure of cross-linked three-dimensional (3D) conductive networks. The combination of these structures resulted in excellent dielectric loss, magnetic loss, and impedance matching. This research offers new insights into the production of one-dimensional (1D) carbon-based absorbers, while also establishing a theoretical foundation for exploring the application potential of this material. These findings may contribute to the development of more efficient and practical EM absorption materials in the future.

Preparation and characterization of soy protein isolate films by pretreatment with cysteine.

The effect of cysteine concentration on the viscosity of soy protein isolate (SPI)-based film-forming solution (FFS) and physicochemical properties of SPI films was investigated. The apparent viscosity of FFS decreased after adding 1 mmol/L cysteine but did not change after adding 2-8 mmol/L cysteine. After treatment with 1 mmol/L cysteine, the film solubility decreased from 70.40% to 57.60%, but the other physical properties did not change. The water vapor permeability and contact angle of SPI films increased as cysteine concentration increased from 4 mmol/L to 8 mmol/L, whereas the film elongation at break decreased. Based on scanning electron microscopy and X-ray diffraction results, cysteine crystallization could be aggregated on the surface of SPI films treated with 4 or 8 mmol/L cysteine. In conclusion, pretreatment with approximately 2 mmol/L cysteine could reduce the viscosity of SPI-based FFS, but did not change the physicochemical properties of SPI films.

Klotho reduces the risk of osteoporosis in postmenopausal women: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Osteoporosis (OP) is one of the diseases that endanger the health of the elderly population. Klotho protein is a hormone with anti-aging effects. A few studies have discussed the relationship between Klotho and OP. However, there is still a lack of research on larger populations. This study aims to evaluate the association between OP and Klotho in American postmenopausal women. METHODS: This is a retrospective study. We searched the National Health and Nutrition Examination Survey (NHANES) database and collected data of 3 survey cycles, finally involving 871 postmenopausal women over 50 years old in the present study. All participants took dual-energy X-ray absorptiometry examination and serum Klotho testing at the time of investigation. After adjusting the possible confounding variables, a multivariate regression model was employed to estimate the relationship between OP and Klotho proteins. Besides, the P for trend and restricted cubic spline (RCS) were applied to examine the threshold effect and calculate the inflection point. RESULTS: Factors influencing the occurrence of OP included age, ethnicity, body mass index and Klotho levels. Multivariate regression analysis indicated that the serum Klotho concentration was lower in OP patients than that in participants without OP (OR[log2Klotho] = 0.568, P = 0.027). The C-index of the prediction model built was 0.765, indicating good prediction performance. After adjusting the above-mentioned four variables, P values for trend showed significant differences between groups. RCSs revealed that when the Klotho concentration reached 824.09 pg/ml, the risk of OP decreased drastically. CONCLUSION: Based on the analysis of the data collected from the NHANES database, we propose a correlation between Klotho and postmenopausal OP. A higher serum Klotho level is related to a lower incidence of OP. The findings of the present study can provide guidance for research on diagnosis and risk assessment of OP.

The deubiquitinase USP11 ameliorates intervertebral disc degeneration by regulating oxidative stress-induced ferroptosis via deubiquitinating and stabilizing Sirt3.

Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening that investigating the exact pathogenesis of IVDD and developing target-specific molecular drugs in the future. Ferroptosis is a new form of programmed cell death characterized by glutathione (GSH) depletion, and inactivation of the regulatory core of the antioxidant system (glutathione system) GPX4. The close relationship of oxidative stress and ferroptosis has been studied in various of diseases, but the crosstalk between of oxidative stress and ferroptosis has not been explored in IVDD. At the beginning of the current study, we proved that Sirt3 decreases and ferroptosis occurs after IVDD. Next, we found that knockout of Sirt3 (Sirt3-/-) promoted IVDD and poor pain-related behavioral scores via increasing oxidative stress-induced ferroptosis. The (immunoprecipitation coupled with mass spectrometry) IP/MS and co-IP demonstrated that USP11 was identified to stabilize Sirt3 via directly binding to Sirt3 and deubiquitinating Sirt3. Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving IVDD by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11-/-) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. In conclusion, the current study emphasized the importance of the interaction of USP11 and Sirt3 in the pathological process of IVDD via regulating oxidative stress-induced ferroptosis, and USP11-mediated oxidative stress-induced ferroptosis is identified as a promising target for treating IVDD.

Horizontal and Vertical Coalescent Microrobotic Collectives Using Ferrofluid Droplets.

Many artificial miniature robotic collectives have been developed to overcome the inherent limitations of inadequate individual capabilities. However, the basic building blocks of the reported collectives are mainly in the solid state, where the morphological boundaries of internal individuals are clear and cannot genuinely merge. Miniature robotic collectives based on liquid units still need to be explored; such on-demand mergeable swarm systems are advantageous for adapting to the changing external environment. Here, a strategy to achieve a coalescent collective system we presented that exploits the ferrofluid droplets' splitting and coalescence properties to trigger the formation of horizontal multimodal and vertical gravity-resistant collectives and unveil pattern-enabled robotic functionalities. When subjected to a time-varying magnetic field, the droplet swarm exhibits a variety of morphologies ranging from horizontal collectives, including vortex-like, chain-like, and crystal-like patterns to vertical layer-upon-layer patterns. Using experiments and simulations, the formation and transformation of different morphological collectives are shown and their robust environmental adaptability are demonstrated. Potential applications of the multimodal droplet collectives are presented, including exploring an unknown environment, targeted object delivery, and fluid flow filtration in a lab-on-a-chip. This work may facilitate the design of microrobotic swarm systems and expand the range of materials for miniature robots.

Antibody responses to COVID-19 vaccination in people with obesity: A systematic review and meta-analysis.

COVID-19 vaccine is critical in preventing SARS-CoV-2 infection and transmission. However, obesity's effect on immune responses to COVID-19 vaccines is still unknown. We performed a meta-analysis of the literature and compared antibody responses with COVID-19 vaccines among persons with and without obesity. We used Pubmed, Embase, Web of Science, and Cochrane Library to identify all related studies up to April 2022. The Stata.14 software was used to analyze the selected data. Eleven studies were included in the present meta-analysis. Five of them provided absolute values of antibody titers in the obese group and non-obese group. Overall, we found that the obese population was significantly associated with lower antibody titers (standardized mean difference [SMD] = -0.228, 95% CI [-0.437, -0.019], P < 0.001) after COVID-19 vaccination. Significant heterogeneity was present in most pooled analyses but was reduced after subgroup analyses. No publication bias was observed in the present analysis. The Trim and Fill method did not change the results in the primary analysis. The present meta-analysis suggested that obesity was significantly associated with decreased antibody responses to SARS-CoV-2 vaccines. Future studies should be performed to unravel the mechanism of response to the COVID-19 vaccine in obese individuals.

Nuanxinkang prevents the development of myocardial infarction-induced chronic heart failure by promoting PINK1/Parkin-mediated mitophagy.

BACKGROUND: Mitochondrial dysfunction is an important pathological feature of chronic heart failure (CHF). Regulation of mitophagy can effectively maintain mitochondrial homeostasis and energy metabolism, thereby inhibiting the development of CHF. Nuanxinkang (NXK), a Chinese herbal compound preparation, has significant cardioprotective effects on CHF; however, its underlying mechanism on mitophagy has not been completely clarified. This research intended to investigate the mechanism of NXK in treating myocardial infarction (MI)-induced CHF. METHODS: The left anterior descending coronary artery (LAD) ligation surgery was performed to establish an MI-induced CHF model in male C57BL/6 mice. From 1 day after surgery, mice were given NXK (0.41, 0.82 or 1.65 g/kg/d), Perindopril (PDPL, 0.607 mg/kg/d), or an equivalent amount of sterile water by gavage for 28 continuous days. Then, mice were examined for cardiac function, myocardial fibrosis, cardiomyocyte apoptosis, mitochondrial structure and mitophagy levels of cardiomyocytes, etc. In addition, a hypoxic injury model was created using HL-1 cardiomyocytes from wild-type (WT) mice. HL-1 cells were pretreated with or without NXK-containing serum. Mitochondrial function and mitophagy levels were examined in HL-1 cells. RESULTS: In MI-induced CHF mice, cardiac dysfunction, severe cardiac remodeling, elevated levels of oxidative stress, reduced ATP levels, and inhibition of PINK1/Parkin-mediated mitophagy were observed. High-dose NXK treatment (1.65 g/kg/d) significantly improved myocardial energy metabolism, inhibited cardiac remodeling, improved cardiac function, and restored cardiac PINK1/Parkin-mediated mitophagy levels to some extent in MI mice. In vitro, elevated levels of mitochondrial reactive oxygen species (ROS) with impaired mitochondrial membrane potential (ΔΨm) were observed in hypoxic HL-1 cells. While NXK treatment significantly protected cardiomyocytes from hypoxia-induced mitochondrial dysfunction, which is consistent with the in vivo results. Further studies showed that NXK could increase PINK1/Parkin-mediated mitophagy levels in cardiomyocytes, which could be blocked by the mitophagy inhibitor Mdivi-1. CONCLUSION: In conclusion, NXK could prevent cardiac mitochondrial dysfunction and improve cardiac function against MI-induced CHF by promoting Pink1/Parkin-mediated mitophagy, which represents a very prospective strategy for the treatment of CHF.

The Effect of Diabetes Mellitus on the Neurological Function of Patients with Cervical Spondylotic Myelopathy.

OBJECTIVE: To evaluate the clinical value of diabetes mellitus for diagnosis and postoperative prognosis in patients with cervical spondylotic myelopathy undergoing anterior decompression and fusion. METHODS: A total of 84 Patients (50 males and 34 females) who underwent anterior decompression and fusion were reviewed in this single-center retrospective study. The patients were divided into two groups (44 patients in the diabetes mellitus group and 40 in the non-diabetic group). Clinical manifestations were evaluated, including characteristics baseline, clinical tests, MRI information, clinical scores, and complications. The predictive effect of diabetes mellitus on clinical scores were assessed via the receiver operating characteristic curve. The correlation between the severity of diabetes mellitus and neurological function recovery was estimated using the Pearson correlation coefficient. RESULTS: Patients with diabetes mellitus exhibited a higher ratio of hyperintensity of the spinal cord (P < 0.05) and worse preoperative clinical scores and neurological recovery (all P < 0.05). Receiver operating characteristic curve results indicated that diabetes mellitus could serve as a good indicator for preoperative evaluation of the Japanese Orthopedic Association (JOA) score (area under curve [AUC] = 0.639), visual analogue score (AUC = 0.642), and Nurick score (AUC = 0.740). In addition, analysis of JOA in isolation suggested that diabetes mellitus correlated closely with the sensory function in the upper and lower limbs (both P < 0.01). The Receiver operating characteristic curve also demonstrated that diabetes mellitus as a clinical test had a reasonable specificity for sensory function in the upper (AUC = 0.654) and lower limbs (AUC = 0.671). Both the level of HbA1c and the duration of diabetes mellitus were negatively correlated with the recovery rate of the JOA score. There was no significant difference between the perioperative complications between the two groups (P > 0.05). CONCLUSION: This present study revealed that the neurological impairment caused by diabetes mellitus in patients undergoing anterior decompression and fusion does not only affect postoperative functional recovery but also interferes with the preoperative clinical manifestations, especially the sensory function in the upper and lower limbs.

The role of nerve fibers and their neurotransmitters in regulating intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) has been the major contributor to chronic lower back pain (LBP). Abnormal apoptosis, senescence, and pyroptosis of IVD cells, extracellular matrix (ECM) degradation, and infiltration of immune cells are the major molecular alternations during IVDD. Changes at tissue level frequently occur at advanced IVD tissue. Ectopic ingrowth of nerves within inner annulus fibrosus (AF) and nucleus pulposus (NP) tissue has been considered as the primary cause for LBP. Innervation at IVD tissue mainly included sensory and sympathetic nerves, and many markers for these two types of nerves have been detected since 1940. In fact, in osteoarthritis (OA), beyond pain transmission, the direct regulation of neuropeptides on functions of chondrocytes have attracted researchers' great attention recently. Many physical and pathological similarities between joint and IVD have shed us the light on the neurogenic mechanism involved in IVDD. Here, an overview of the advances in the nervous system within IVD tissue will be performed, with a discussion on in the role of nerve fibers and their neurotransmitters in regulating IVDD. We hope this review can attract more research interest to address neuromodulation and IVDD itself, which will enhance our understanding of the contribution of neuromodulation to the structural changes within IVD tissue and inflammatory responses and will help identify novel therapeutic targets and enable the effective treatment of IVDD disease.

A Simplified Herbal Formula Improves Cardiac Function and Reduces Inflammation in Mice Through the TLR-Mediated NF-κB Signaling Pathway.

Nuanxinkang tablet (NXK), a Chinese herbal formula, can improve heart function and quality of life in patients with chronic heart failure (CHF). However, the mechanisms of action of NXK are not fully understood. In this study, we investigated the effects of NXK on inflammation in the CHF mouse model. This model was established by transverse aortic constriction (TAC) and treated with NXK for 8 weeks. Then, the cardiac function and myocardial fibrosis were evaluated. The monocytes/macrophages were evaluated by immunofluorescence. The mRNA levels of IL-1ß, IL-6, TNF-α, ICAM-1, and VCAM-1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while TLR4, MyD88, NF-κB p65, P-IκBα, TLR2, TLR7 and TLR9 protein levels were evaluated by Western blot. The results showed that NXK improved the left ventricular ejection fraction (LVEF) and left ventricular end-systolic dimension, reversed myocardial fibrosis, and inhibited pro-inflammatory (CD11b + Ly6C+) monocytes/macrophages in the TAC mouse model. NXK also reduced the mRNA and protein levels of the above markers. Taken together, NXK improved heart function and reduced inflammation through the TLR-mediated NF-κB signaling pathway, suggesting that it might be used as an innovative treatment strategy for CHF.

Nuanxinkang protects against ischemia/reperfusion-induced heart failure through regulating IKKß/IκBα/NF-κB-mediated macrophage polarization.

BACKGROUND: Heart failure (HF) is a leading cause of death worldwide. Nuanxinkang (NXK) is an effective Chinese herbal formula used in treating HF, but its underlying potential mechanisms have not been fully elucidated. PURPOSE: To explore the protective activities of NXK in ischemia/reperfusion (IR)-induced HF through modulating the ratio of proinflammatory (M1) and anti-inflammatory (M2) macrophage populations and leading to the alleviation of inflammation. MATERIALS AND METHODS: In vivo, mice were subjected to myocardial IR to generate HF mouse models. Mice in the NXK group were treated with NXK for 28 days. Cardiac function was detected by echocardiography. Major lesions on mouse hearts were determined by hematoxylin-eosin (HE) staining, Masson staining, and TUNEL staining. Inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and qPCR examination. Flow cytometric analyses and qPCR examination were utilized for monitoring the temporal dynamics of macrophage infiltration following IR. In vitro, two polarized models were established by stimulating RAW264.7 cells with 200 ng/ml lipopolysaccharide (LPS) or 20 ng/ml interleukin-4 (IL-4). The RAW264.7 cells with nuclear factor-κB (NF-κB) overexpression was generated by transient transfection of NF-κB plasmids, and NXK intervention was conducted on this cell model to further clarify the involvement of NF-κB signaling in the NXK-mediated HF process. RESULTS: In the present study, NXK was found to significantly contribute the cardiac function and ameliorate cardiac fibrosis and apoptosis after myocardial IR injury in vivo, which may be partially due to a decrease in inflammation. We therefore hypothesized that NXK reduced inflammatory damage by modulating subtypes of macrophages. And the results demonstrated that the percentage of proinflammatory macrophages infiltrated in the post-IR period was reduced with NXK treatment, and thereby blunting the wave of proinflammatory response and shifting the peak of the anti-inflammatory macrophage-mediated wound healing process towards an earlier time point. The further investigation showed that macrophage polarization was mediated by NXK through inhibiting the phosphorylation and the nuclear translocation of NF-κB. Besides, the phosphorylated IKKß and IκBα, upstream mediators of the NF-κB pathway, also decreased by NXK. Moreover, the overexpression of NF-κB partially reversed the NXK-induced favorable activities; and successfully compensated the suppressive effect on inflammation and the phosphorylation of NF-κB. CONCLUSION: In conclude, our results demonstrated that NXK induced the cardioprotective effects against IR injury through a regulatory axis of IKKß/IκBα/NF-κB-mediated macrophage polarization. The information gained from this study provide a possible natural strategy for anti-inflammatory treatment of HF.

The Risk Factors for Developing Clustered Vertebral Compression Fractures: A Single-Center Study.

OBJECTIVE: Vertebral compression fractures (VCFs) are common among elderly individuals, but clustered VCFs (C-VCFs) are rare and more severe. The risk factors for C-VCFs remain unclear. Thus, we investigated the clinical characteristics of C-VCFs to identify the imminent fracture risk and improve the treatment for such patients. METHODS: We reviewed the records of patients with VCF at a single medical center between January 2011 and September 2020. Patients who had 4 or more VCFs within 1 year were categorized into the C-VCF group, and the remaining patients were paired into the control group at a ratio of 2:1. We collected demographic, clinical, laboratory, and radiologic information regarding these patients. Univariate analyses, stratified analyses, and multivariate logistic regression were performed to identify the risk factors for C-VCFs. RESULTS: A total of 156 patients were enrolled, of whom 52 were patients with C-VCF. Patients with C-VCF had more severe fractures and pain, with fractures occurring at uncommon sites of the spine. The independent risk factors for C-VCFs included glucocorticoid (GC) treatment (P < .001; hazard ratio [HR], 12.7), recent fracture history (P = .021; HR, 5.5), and lower trabecular bone score (TBS) (P = .044; HR, 1.6). TBS and bone mineral density had greater predictive values in patients without GC treatment (P < .001). Sex, age, and bone turnover biomarkers were not independent risk factors for C-VCFs. CONCLUSION: C-VCFs are rare adverse consequences of severe osteoporosis, for which GC treatment, recent fracture history, and lower TBS are unique risk factors that are valuable for the early identification and prevention of C-VCFs.

A Novel Capsule Lumbar Interbody Fusion (CLIF) in Treating Foot Drop due to Lumbar Degenerative Diseases: a Prospective, Observational Study.

OBJECTIVE: This present study aimed to explore the clinical effects of a novel capsule lumbar interbody fusion (CLIF) on foot drop due to lumbar degenerative diseases. METHODS: Between June 2018 and January 2019, a total of 27 patients admitted to our department with lumbar degenerative diseases with associated foot drop were prospectively enrolled. Given the selection of surgical technique, patients were divided into traditional TLIF group and CLIF group. We assessed patients' neurological status using JOA and VAS score, tibialis anterior muscle strength using MMT score, diameter and hemodynamic parameters of the L5 nerve root using intraoperative ultrasonography (IoUS), and related radiological parameters of the lumbar spine. Operation time, blood loss, and surgery-associated complications were also recorded. RESULTS: The median duration of follow-up was 150 (6-1460) months. At the final follow-up, all patients acquired satisfactory improvement of neurological function. However, patients in the CLIF group showed better early recovery of foot drop three months after operation than those in the TLIF group, with 75% excellent rate. In addition, IoUS suggested that the diameter and hemodynamic parameters of the L5 nerve root were improved better in the CLIF group, which may suggest the correlation between the recovery of foot drop and the status of L5 nerve root. No severe complications were encountered with CLIF. CONCLUSIONS: Our preliminary study revealed that the axial tension of L5 nerve root may be involved in the pathological mechanism of foot drop. The novel technique of CLIF can shorten the lumbar spine and can be effective and safe for the treatment of foot drop due to lumbar degeneration-related diseases.