Axin2 depletion in macrophages alleviated senescence and increased immune response after myocardial infarction.

OBJECTIVE AND DESIGN: This study aimed to investigate Axin2 effects on myocardial infarction (MI) using a macrophage Axin2 conditional knockout (cKO) mouse model, RAW264.7 cell line, and human subepicardial tissues from patients with coronary artery bypass graft (CABG). MATERIAL OR SUBJECTS: Axin2 cKO mice showed decreased cardiac function, reduced edema, increased lymphangiogenesis, and improved repair in MI Few studies border zones. Hypoxic macrophages with Axin2 depletion exhibited decreased senescence, elevated IL6 expression, and increased LYVE1 transcription. Senescent macrophages decreased in patients with CABG and low Axin2 expression. TREATMENT: Treatment options included in this study were MI induction in Axin2 cKO mice, in vitro experiments with RAW264.7 cells, and analysis of human subepicardial tissues. METHODS: Assays included MI induction, in vitro experiments, and tissue analysis with statistical tests applied. RESULTS: Axin2 cKO improved cardiac function, reduced edema, enhanced lymphangiogenesis, and decreased senescence. Hypoxic macrophages with Axin2 depletion showed reduced senescence, increased IL6 expression, and elevated LYVE1 transcription. Senescent macrophages decreased in patients with CABG and low Axin2 expression. CONCLUSION: Targeting Axin2 emerges as a novel therapeutic strategy for regulating cardiac lymphatics and mitigating cell senescence post-MI, evidenced by improved outcomes in Axin2-deficient conditions.

Is Takotsubo syndrome induced by patent ductus arteriosus occlusion?

Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role. Genetic factors, hormonal influences like estrogen, and inflammatory processes also contribute, unveiling potential gender-specific differences in its occurrence. Understanding these multifaceted aspects of TTS is crucial for refining clinical approaches and therapies. Continued research efforts will not only deepen our understanding of this syndrome but also pave the way for more targeted and effective diagnostic and treatment strategies. In this report, we conduct an in-depth analysis of a case involving a TTS patient, examining the illness progression and treatment procedures. The aim of this analysis is to enhance the understanding of TTS among primary care physicians. By delving into this case, we aspire to prevent misdiagnosis of typical TTS cases that patients may present, thereby ensuring a more accurate diagnosis and appropriate treatment.

Optimal ultrasonic treatment frequency and duration parameters were used to detect the pathogenic bacteria of orthopedic implant-associated infection by ultrasonic oscillation.

INTRUDUCTON: The most accurate method for detecting the pathogen of orthopedic implant-associated infections (OIAIs) is sonication fluid (SF). However, the frequency and duration of ultrasound significantly influence the number and activity of microorganisms. Currently, there is no consensus on the selection of these two parameters. Through this study, the choice of these two parameters is clarified. METHODS: We established five ultrasonic groups (40kHz/10min, 40kHz/5min, 40 kHz/1min, 20kHz/5min, and 10kHz/5min) based on previous literature. OIAIs models were then developed and applied to ultrasound group treatment. Subsequently, we evaluated the efficiency of bacteria removal by conducting SEM and crystal violet staining. The number of live bacteria in the SF was determined using plate colony count and live/dead bacteria staining. RESULTS: The results of crystal violet staining revealed that both the 40kHz/5min group and the 40kHz/10min group exhibited a significantly higher bacterial clearance rate compared to the other groups. However, there was no significant difference between the two groups. Additionally, the results of plate colony count and fluorescence staining of live and dead bacteria indicated that the number of live bacteria in the 40kHz/5min SF group was significantly higher than in the other groups. CONCLUSION: 40kHz/5min ultrasound is the most beneficial for the detection of pathogenic bacteria on the surface of orthopedic implants.

Experimental evidence to understand mechanical causes of retinal detachment following blunt trauma.

PURPOSE: This study aimed to perform an in vitro experiment to simulate retinal detachment caused by blunt impact, and provide experimental evidence to understand mechanical causes of traumatic retinal detachment. METHODS: The experiment was conducted on twenty-two fresh porcine eyes using a bespoke pendulum testing device at two energy levels (0.1J for low energy and 1.0J for high energy). We examined dynamic forces and mechanical responses to the impact, including global deformations, intraocular pressure changes and the energy absorption. Another set of twenty-two eyes underwent pathological examination immediately after being subjected to blunt impact. Twelve additional intact eyes were examined as controls. All pathological sections were scored to indicate whether retinal detachment had occurred. RESULTS: A dynamic variation in intraocular pressure was detected following impact and exhibited an approximate sinusoidal oscillation-attenuation profile. The peaks of impact force were 12.9 ± 1.9 N at low-energy level and 34.8 ± 9.8 N at high-energy level, showing a significant difference (p < 0.001). The positive and negative peaks of intraocular pressure were 149.4 ± 18.9 kPa and -10.9 ± 7.2 kPa at low-energy level, and 274.5 ± 55.2 kPa and -35.7 ± 23.7 kPa at high-energy level, showing significant differences (p < 0.001 for both levels). Retinal detachments were observed in damaged eyes while few detachments were found in control eyes. The occurrence rate of retinal detachment differed significantly (p < 0.05) between the high- and low-energy impact groups. CONCLUSIONS: This study provided experimental evidence that shockwaves produced by blunt trauma break the force equilibrium and lead to the oscillation and negative pressure, which mainly contribute to traumatic retinal detachment.

Lymphocyte-to-monocyte ratio associated with severe post-stenotic aortic dilation in a case-control study.

BACKGROUND: Calcific aortic valve stenosis (CAVS) represents a serious health threat to elderly patients. Post-stenotic aortic dilation, a common feature in CAVS patients, might progress into aneurysm and even dissection, potential consequences of CAVS, and predicts a poor prognosis. This study sought to investigate the association of lymphocyte-to-monocyte ratio (LMR), an inflammatory biomarker, with severe post-stenotic aortic dilation in a case-control study in Chinese population. MATERIALS AND METHODS: 208 consecutive patients with CAVS were recruited retrospectively in a case-control study in Chinese population, from July 1, 2015 to June 31, 2018. LMR was statistically analyzed using the ROC curve and binary logistic regression analyses for its prognostic value in severe post-stenotic aortic dilation. RESULTS: LMR was significantly reduced in patients with severe post-stenotic aortic dilation (2.72 vs. 3.53, p = 0.002 < 0.05) compared to patients without severe post-stenotic aortic dilation. There was an inverse correlation observed between the maximal diameter of ascending aorta and LMR in the overall patients (r = - 0.217, p = 0.002 < 0.05). For post-stenotic aortic dilation, the prevalence of high-LMR group was statistically lower than that of low-LMR group (19.7% vs. 43.9%, p < 0.001). The maximal diameter of ascending aorta was significantly reduced in the high-LMR group (4.35 vs. 4.76, p = 0.003 < 0.05) compared to low-LMR group. Additionally, LMR was identified in the multivariate analysis independently associated with severe post-stenotic aortic dilation (AUC 0.743, 95% CI: [0.573-0.964], p = 0.025). CONCLUSIONS: This study provided the evidence of an inverse correlation between severe post-stenotic aortic dilation and LMR. LMR is potentially independently associated with severe post-stenotic aortic dilation.

Metformin suppresses UHMWPE particle-induced osteolysis in the mouse calvaria by promoting polarization of macrophages to an anti-inflammatory phenotype.

BACKGROUND: Implant failure remains a major obstacle to successful treatment via TJA. Periprosthetic osteolysis and aseptic loosening are considered as proof of wear debris-induced disruption of local regulatory mechanisms related to excessive bone resorption associated with osteolysis and the damage at the bone-prosthesis interface. Therefore, there is an immediate need to explore strategies for limiting and curing periprosthetic osteolysis and aseptic loosening. METHODS: We analyzed the in vitro cytokine production by primary mouse bone marrow macrophages (BMMs) that were exposed to ultra-high molecular weight polyethylene (UHMWPE) particles and treated with metformin at different concentrations with or without 5-aminoimidazole-4-carboxamide ribonucleoside to activate or inhibit AMPK. A mouse calvarial model was used to examine the in vivo effects of metformin on UHMWPE particle-induced osteolysis. RESULTS: With particles, primary mouse BMMs secreted more pro-inflammatory cytokines tumor necrosis factor-α and interleukin (IL)-6. Treatment with metformin inhibited these variations and promoted the release of cytokine IL-10 with anti-inflammatory capability. In vivo, metformin reduced the production of pro-inflammatory cytokines, osteoclastogenesis, and osteolysis, increasing IL-10 production. Metformin also promoted the polarization of macrophages to an anti-inflammatory phenotype in vivo via AMPK activation. DISCUSSION: A crucial point in limiting and correcting the periprosthetic osteolysis and aseptic loosening is the inhibition of inflammatory factor production and osteoclast activation induced by activated macrophages. The ability of metformin to attenuate osteolysis induced in mouse calvaria by the particles was related to a reduction in osteoclast number and polarization of macrophages to an anti-inflammatory functional phenotype. CONCLUSIONS: Metformin could limit the osteolysis induced by implant debris. Therefore, we hypothesized that metformin could be a potential drug for osteolysis induced by implant debris.

Effects of Pore Size on the Osteoconductivity and Mechanical Properties of Calcium Phosphate Cement in a Rabbit Model.

Calcium phosphate cement (CPC) porous scaffold is widely used as a suitable bone substitute to repair bone defect, but the optimal pore size is unclear yet. The current study aimed to evaluate the effect of different pore sizes on the processing of bone formation in repairing segmental bone defect of rabbits using CPC porous scaffolds. Three kinds of CPC porous scaffolds with 5 mm diameters and 12 mm length were prepared with the same porosity but different pore sizes (Group A: 200-300 µm, Group B: 300-450 µm, Group C: 450-600 µm, respectively). Twelve millimeter segmental bone defects were created in the middle of the radius bone and filled with different kinds of CPC cylindrical scaffolds. After 4, 12, and 24 weeks, alkaline phosphatase (ALP), histological assessment, and mechanical properties evaluation were performed in all three groups. After 4 weeks, ALP activity increased in all groups but was highest in Group A with smallest pore size. The new bone formation within the scaffolds was not obvious in all groups. After 12 weeks, the new bone formation within the scaffolds was obvious in each group and highest in Group A. At 24 weeks, no significant difference in new bone formation was observed among different groups. Besides the osteoconductive effect, Group A with smallest pore size also had the best mechanical properties in vivo at 12 weeks. We demonstrate that pore size has a significant effect on the osteoconductivity and mechanical properties of calcium phosphate cement porous scaffold in vivo. Small pore size favors the bone formation in the early stage and may be more suitable for repairing segmental bone defect in vivo.

The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells.

Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cell cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs.

Estrogen improves the proliferation and differentiation of hBMSCs derived from postmenopausal osteoporosis through notch signaling pathway.

Estrogen deficiency is the main reason of bone loss, leading to postmenopausal osteoporosis, and estrogen replacement therapy (ERT) has been demonstrated to protect bone loss efficiently. Notch signaling controls proliferation and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Moreover, imperfect estrogen-responsive elements (EREs) were found in the 5'-untranslated region of Notch1 and Jagged1. Thus, we examined the molecular and biological links between estrogen and the Notch signaling in postmenopausal osteoporosis in vitro. hBMSCs were obtained from healthy women and patients with postmenopausal osteoporosis. Notch signaling molecules were quantified using real-time polymerase chain reaction (real-time PCR) and Western Blot. Luciferase reporter constructs with putative EREs were transfected into hBMSCs and analyzed. hBMSCs were transduced with lentiviral vectors containing human Notch1 intracellular domain (NICD1). We also used N-[N-(3, 5-diflurophenylacetate)-l-alanyl]-(S)-phenylglycine t-butyl ester, a γ-secretase inhibitor, to suppress the Notch signaling. We found that estrogen enhanced the Notch signaling in hBMSCs by promoting the expression of Jagged1. hBMSCs cultured with estrogen resulted in the up-regulation of Notch signaling and increased proliferation and differentiation. Enhanced Notch signaling could enhance the proliferation and differentiation of hBMSCs from patients with postmenopausal osteoporosis (OP-hBMSCs). Our results demonstrated that estrogen preserved bone mass partly by activating the Notch signaling. Because long-term ERT has been associated with several side effects, the Notch signaling could be a potential target for treating postmenopausal osteoporosis.

Distinct effects of CDK8 module subunits on cellular growth and proliferation in Drosophila.

The Mediator complex, composed of about 30 conserved subunits, plays a pivotal role in facilitating RNA polymerase II-dependent transcription in eukaryotes. Within this complex, the CDK8 kinase module (CKM), comprising Med12, Med13, CDK8, and CycC (Cyclin C), serves as a dissociable subcomplex that modulates the activity of the small Mediator complex. Genetic studies in Drosophila have revealed distinct phenotypes of CDK8-CycC and Med12-Med13 mutations, yet the underlying mechanism has remained unknown. Here, using Drosophila as a model organism, we show that depleting CDK8-CycC enhances E2F1 target gene expression and promotes cell-cycle progression. Conversely, depletion of Med12-Med13 affects the expression of ribosomal protein genes and fibrillarin, indicating a more severe reduction in ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. Moreover, we found that the stability of CDK8 and CycC relies on Med12 and Med13, with a mutually interdependent relationship between Med12 and Med13. Furthermore, CycC stability depends on the other three CKM subunits. These findings reveal distinct roles for CKM subunits in vivo , with Med12-Med13 disruption exerting a more pronounced impact on ribosome biogenesis and cellular growth compared to the loss of CDK8-CycC. Significance: The CDK8 kinase module (CKM), comprising CDK8, CycC, Med12, and Med13, is essential in the Mediator complex for RNA polymerase II-dependent transcription in eukaryotes. While expected to function jointly, CKM subunit mutations result in distinct phenotypes in Drosophila . This study investigates the mechanisms driving these differing effects. Our analysis reveals the role of Med12-Med13 pair in regulating ribosomal biogenesis and cellular growth, contrasting with the involvement of CDK8-CycC in E2F1-dependent cell-cycle progression. Additionally, an asymmetric interdependence in the stability of CDK8-CycC and Med12-Med13 was observed. CKM mutations or overexpression are associated with cancers and cardiovascular diseases. Our findings underscore the distinct impacts of CKM mutations on cellular growth and proliferation, advancing our understanding of their diverse consequences in vivo .

Aucubin protects against myocardial ischemia-reperfusion injury by regulating STAT3/NF-κB/HMGB-1 pathway.

The main characteristics of the myocardial ischemia/reperfusion injury (MI/RI) are oxidative stress, apoptosis, and an inflammatory response. Aucubin (AU) is an iridoid glycoside that possesses various biological properties and has been discovered to demonstrate antioxidant and anti-inflammatory impacts in pathological processes, such as ischemia-reperfusion. The objective of this research was to investigate if AU treatment could mitigate myocardial inflammation and apoptosis caused by ischemia/reperfusion (I/R) in both laboratory and animal models, and to elucidate its underlying mechanism. By ligating the coronary artery on the left anterior descending side, a successful MI/RI rat model was created. Additionally, H9C2 cells were subjected to hypoxia/reoxygenation (H/R) in order to imitate the injury caused by ischemia/reperfusion (I/R). Furthermore, various concentrations of AU were administered to H9C2 cells or rats before H/R stimulation or myocardial I/R surgery, respectively. In vitro, the assessment was conducted on cardiac function, inflammatory markers, and myocardial pathology. In vivo, we examined the viability of cells, as well as factors related to apoptosis and oxidative stress. Furthermore, the presence of proteins belonging to the STAT3/NF-κB/HMGB1 signaling pathway was observed both in vivo and in vitro. AU effectively improved cardiomyocyte injury caused by H/R and myocardial injury caused by I/R. Furthermore, AU suppressed the production of reactive oxygen species and inflammatory molecules (TNF-alpha, IL-1ß, and IL-6) and proteins associated with cell death (caspase-3 and Bax), while enhancing the levels of anti-inflammatory agents (IL-10) and the anti-apoptotic protein Bcl-2.AU mechanistically affected the phosphorylation of STAT3 at the Ser727 site and Tyr705 following H/R by modulating the signaling pathway involving signal transducer and activator of transcription 3 (STAT3)/nuclear factor-κB (NF-κB)/high mobility group box 1 (HMGB1), while also suppressing the nuclear translocation of NF-κB p65 and HMGB1 exonucleation. In conclusion, the use of AU treatment might offer protection against myocardial infarction and injury by reducing oxidative stress, suppressing apoptosis, and mitigating inflammation. The regulation of the STAT3/NF-κB/HMGB-1 pathway may contribute to this phenomenon by affecting STAT3 phosphorylation and controlling NF-κB and HMGB-1 translocation. Contributes to identifying possible objectives for myocardial ischemia/reperfusion damage.

Glycyrrhizic acid alleviated MI/R-induced injuries by inhibiting Hippo/YAP signaling pathways.

BACKGROUND: Previous research has demonstrated that glycyrrhizic acid (GA) exhibits antioxidant, anti-inflammatory, and antiapoptotic characteristics. Using myocardial ischemia/reperfusion injury as a case study, this study aims to clarify the functional significance of GA and to elucidate the mechanisms involved. MATERIALS AND METHODS: In this study, an MI/R injury model was established both in vivo and in vitro to investigate the impact of GA on MI/R injury. The viability of H9c2 cells was evaluated using the Cell Counting Kit-8. Myocardial damage was assessed through the measurement of creatine kinase myocardial band (CK-MB) levels and lactate dehydrogenase (LDH), HE staining, and MASSON staining. Inflammatory cytokine levels (IL-6, IL-1ß, IL-10, and TNF-α) were measured to determine the presence of inflammation. Cellular oxidative stress was evaluated by measuring ROS and MMP levels, while cardiac function was assessed using cardiac color Doppler ultrasound. Immunofluorescence staining to determine the nuclear translocation of YAP, TUNEL to determine apoptosis, and western blotting to determine gene expression. RESULTS: GA treatment effectively alleviated myocardial injury induced by MI/R, as evidenced by reduced levels of inflammatory cytokines (IL-1ß, IL-6, IL-10, and TNF-α) and cardiac biomarkers (CK-MB, LDH) in MI/R rats. Moreover, There was a significant increase in cell viability in vitro after GA treatment and inhibited reactive oxygen species (ROS) during oxidative stress, while also increasing mitochondrial membrane potential (MMP) in vitro. The Western blot findings indicate that GA treatment effectively suppressed apoptosis in both in vivo and in vitro settings. Additionally, GA demonstrated inhibitory effects on the activation of the Hippo/YAP signaling pathway triggered by MI/R and facilitated YAP nuclear translocation both in vitro and in vivo. It has been found, however, in vitro, that silencing the YAP gene negates GA's protective effect against hypoxia/reoxygenation-induced myocardial injury. CONCLUSION: This study suggests that GA regulates YAP nuclear translocation by inhibiting the Hippo/YAP signaling pathway, which protects ists against MI/R injury. This finding may present a novel therapeutic approach for the treatment of MI/R.

[Contrast-enhanced ultrasonography for detecting testicular perfusion in acute testis contusion in rabbits].

OBJECTIVE: To evaluate contrast-enhanced ultrasonography (CEUS) in detecting testicular perfusion in acute testis contusion. METHODS: We established the model of testis contusion in 11 healthy male New Zealand rabbits by randomly hitting one side of the scrotum under general anesthesia. We examined the bilateral scrotums of all the animals before, immediately after and at 2, 4 and 6 hours after modeling by color Doppler flow imaging (CDFI) and CEUS, and analyzed the time-intensity curve (TIC), arriving time (AT), time to peak intensity (TTP), peak intensity (PI), half time of descending peak intensity (HT) and area under the curve (AUC) in the healthy and injured testis, respectively. RESULTS: CEUS exhibited a higher sensitivity in detecting tissue perfusion than CDFI. The mode of contrast agent perfusion in testicular contusion was fast in and slow out. There were no evident differences between the contused and the healthy testis in AT, TTP and PI before modeling. The contused testis showed significantly earlier AT and TTP, higher PI and larger AUC (P < 0.05) than the healthy one at different time points after modeling, but no statistically significant difference was found in HT (P > 0.05). CONCLUSION: Accurate parameters of testicular perfusion in acute testis contusion can be quantitatively obtained by CEUS, which are of important value for the diagnosis of testis contusion.

α-Lipoic acid alleviates myocardial injury and induces M2b macrophage polarization after myocardial infarction via HMGB1/NF-kB signaling pathway.

BACKGROUND: Myocardial infarction (MI) is a serious cardiovascular disease with a poor prognosis. Macrophages are the predominant immune cells in patients with MI and macrophage regulation during the different phases of MI has important consequences for cardiac recovery. Alpha-lipoic acid (ALA) plays a critical role in MI by modulating the number of cardiomyocytes and macrophages. METHODS: MI mice were generated by ligating the left anterior descending coronary artery. Macrophages were exposed to hypoxia to establish a hypoxia model and M1 polarization was induced by LPS and IFN-γ. Different groups of macrophages and MI mice were treated with ALA. The cardiomyocytes were treated with various macrophage supernatants and the cardiac function, cytokine levels, and pathology were also analyzed. Factors related to apoptosis, autophagy, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) were assessed. Finally, the HMGB1/NF-κB pathway was identified. RESULTS: ALA promoted M2b polarization in normal cells and suppressed inflammatory cytokines during hypoxia. ALA inhibited ROS and MMP production in vitro. Supernatants containing ALA inhibited apoptosis and autophagy in hypoxic cardiomyocytes. Moreover, ALA suppressed the HMGB1/NF-κB pathway in macrophages, which may be a potential mechanism for attenuating MI. CONCLUSION: ALA alleviates MI and induces M2b polarization via the HMGB1/NF-κB pathway, impeding inflammation, oxidation, apoptosis, and autophagy, and might be a potential strategy for MI treatment.

Role of BLACAT1 in IL-1ß-Induced Human Articular Chondrocyte Apoptosis and Extracellular Matrix Degradation via the miR-149-5p/ HMGCR Axis.

BACKGROUND: Osteoarthritis (OA) is an inflammatory joint disorder with high incidence rates. Long non-coding RNAs (LncRNAs) influence OA development. OBJECTIVES: In this research, we attempt to figure out the functions of lncRNA BLACAT1 in human articular chondrocyte (HAC) apoptosis and extracellular matrix (ECM) degradation in OA. METHODS: Interleukin (IL)-1ß was employed to induce HAC damage. Cell viability and apoptosis were detected, with expression patterns of lncRNA BLACAT1, miR-149-5p, and HMGCR, and levels of Caspase-3, Caspase-9, BAX, Bcl-2, COL2A1, and SOX9 determined. Then, lncRNA BLACAT1 was silenced in IL-1ß-treated HACs to analyze its role in HAC damage. The target relations of lncRNA BLACAT1 and miR-149-5p and miR-149-5p and HMGCR were verified. In addition, combined experiments were performed as a miR-149-5p inhibitor or HMGCR overexpression was injected into cells with lncRNA BLACAT1 silencing. RESULTS: In IL-1ß-treated HACs, lncRNA BLACAT1 and HMGCR were overexpressed while miR- 149-5p was poorly expressed, along with reduced cell viability, enhanced apoptosis, elevated Caspase-3 and Caspase-9 activities, increased BAX level, decreased Bcl-2 level, and declined levels of COL2A1 and SOX9, which were reversed by lncRNA BLACAT1 silencing. LncRNA BLACAT1 targeted miR-149-5p, and miR-149-5p targeted HMGCR. miR-149-5p knockout or HMGCR overexpression annulled the inhibitory role of lncRNA BLACAT1 silencing in HAC apoptosis and ECM degradation. CONCLUSION: LncRNA BLACAT1 was overexpressed in IL-1ß-treated HACs, and the lncRNA BLACAT1/miR-149-5p/HMGCR ceRNA network promoted HAC apoptosis and ECM degradation.

Sodium alginate-hydrogel coatings on extracorporeal membrane oxygenation for anticoagulation.

Thromboembolism caused by the use of extracorporeal membrane oxygenation (ECMO) remains common among patients with existing heart diseases and contributes to significant morbidity and mortality during the COVID-19 pandemic. Various surface modification strategies have been proposed, showing that the methacrylated alginate (MA-SA) hydrogel layer is transparent, which aids the observation of the thromboembolism from the inner wall of the tubing. In the combined dynamic and static blood of ECMO tubing inner surface in vitro experiments, it was also demonstrated that the adhesion of blood clots to the surface of vessels was remarkably reduced, and the MA-SA-based hydrogel coating could significantly prolong the activated partial thrombin time and block the endogenous coagulation. The favorable properties of natural polysaccharides of hydrogel coatings make them the best surface material choices to be applied for blood-contacting medical devices and significantly improve anticoagulant performance.

The impact of unified discharge standards on the clinical efficacy and prognosis of hemiarthroplasty in elderly patients with hip fractures.

OBJECTIVES: The aim of this study was to investigate the impact of unified discharge standards on the clinical efficacy and prognosis of hemiarthroplasty in elderly patients with hip fractures. METHODS: Retrospective study of 158 elderly patients with hip fractures who underwent artificial femoral head replacement in our hospital from March 2016 to July 2019 were enrolled. According to the unified discharge standards, patients were divided into the observation (65 cases who met discharge criteria) and control group (93 cases who failed to meet all discharge criteria). Histopathological feature, operation status, postoperative Harris Hip score, therapeutic outcome, postoperative complications, readmission and mortality rate were compared between the two groups. RESULTS: Surgery duration and intraoperative blood loss exhibited no difference between the two groups, while transfusion volume and length of hospital stay were significantly increased in the observation group. There was no significant difference in the Harris Hip score between the two groups 12 months postoperatively. The incidence of postoperative complications during the follow-up period was notably lower in the observation group. In addition, the three-month readmission rate and one-year mortality rate were significantly lower in the observation group. CONCLUSIONS: For elderly patients with hip fractures undergoing artificial femoral head replacement, the incidence of postoperative complications and postoperative readmission/mortality rate could be reduced through the establishment of unified discharge standards, which should be used in future clinical practice.

Ferroptosis and Autophagy-Related Genes in the Pathogenesis of Ischemic Cardiomyopathy.

Background: Obesity plays an important role in type 2 diabetes mellitus (T2DM) and myocardial infarction (MI). Ferroptosis and ferritinophagy are related to metabolic pathways, such as fatty acid metabolism and mitochondrial respiration. We aimed to investigate the ferroptosis- and autophagy-related differentially expressed genes (DEGs) that might be potential targets for MI progression. Methods: GSE116250 was analyzed to obtain DEGs. A Venn diagram was used to obtain the overlapping ferroptosis- and autophagy-related DEGs. The enrichment pathway analysis was performed and the hub genes were obtained. Pivotal miRNAs, transcription factors, and drugs with the hub genes interactions were also predicted. The MI mice model was constructed, and qPCR analysis and single-cell sequencing were used to validate the hub genes. Results: Utilizing the limma package and the Venn diagram, 26 ferroptosis-related and 29 autophagy-related DEGs were obtained. The list of ferroptosis-related DEGs was analyzed, which were involved in the cellular response to a toxic substance, cellular oxidant detoxification, and the IL-17 signaling pathway. The list of autophagy-related DEGs was involved in the regulation of autophagy, the regulation of JAK-STAT signaling pathway, and the regulation of MAPK cascade. In the protein-protein interaction network, the hub DEGs, such as IL-6, PTGS2, JUN, NQO1, NOS3, LEPR, NAMPT, CDKN2A, CDKN1A, and Snai1, were obtained. After validation using qPCR analysis in the MI mice model and single-cell sequencing, the 10 hub genes can be the potential targets for MI deterioration. Conclusion: The screened hub genes, IL-6, PTGS2, JUN, NQO1, NOS3, LEPR, NAMPT, CDKN2A, CDKN1A, and Snai1, may be therapeutic targets for patients with MI and may prevent adverse cardiovascular events.

Macrophages-Related Genes Biomarkers in the Deterioration of Atherosclerosis.

Background: The macrophages are involved in all stages of cardiovascular diseases, demonstrating the correlation between inflammation, atherosclerosis, and myocardial infarction (MI). Here, we aim to investigate macrophages-related genes in the deterioration of atherosclerosis. Methods: GSE41571 was downloaded and the abundance of immune cells was estimated by utilizing the xCell. By utilizing the limma test and correlation analysis, differentially expressed macrophages-related genes (DEMRGs) were documented. The functional pathways and the protein-protein interaction (PPI) network were analyzed and the hub DEMRGs were obtained. The hub DEMRGs and their interactions were analyzed using NetworkAnalyst 3.0 and for validation, the expressions of hub DEMRGs were analyzed using the GSE135055 and GSE116250 datasets as well as atherosclerosis and MI mice model. Results: A total of 509 differentially expressed genes (DEGs) were correlated with the abundance of macrophages and were identified as DEMRGs (Pearson correlation coefficients (PCC) > 0.6), which were mainly enriched in extracellular structure organization, lysosomal membrane, MHC protein complex binding, and so on. After screening out, 28 hub DEMRGs were obtained with degrees ≥20, including GNAI1 (degree = 113), MRPS2 (degree = 56), HCK (degree = 45), SOCS3 (degree = 40), NET1 (degree = 28), and so on. After validating using Gene Expression Omnibus (GEO) datasets and the atherosclerosis and MI mice model, eight proteins were validated using ApoE-/- and C57 mice. The expression levels of proteins, including SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, and PPP4C were positively correlated to left ventricular ejection fraction (LVEF), while that of EIF4EBP1 was negatively correlated to LVEF. Conclusion: The screened hub DEMRGs, SYNJ2, NET1, FZD7, LCP2, HCK, GNB2, EIF4EBP1, and PPP4C, may be therapeutic targets for treatment and prediction in the patients with plaque progression and MI recurrent events. The kit of the eight hub DEMRGs may test plaque progression and MI recurrent events and help in the diagnosis and treatment of MI-induced heart failure (HF), thus decreasing mortality and morbidity.

[Analysis of risk factors for readmission in elderly patients with hip fractures undergoing hip hemiarthroplasty].

OBJECTIVE: To explore the incidence and risk factors of readmission of elderly patients with hip fracture after hip hemiarthroplasty. METHODS: A retrospective analysis of 237 elderly hip fracture patients who underwent hip hemiarthroplasty from February 2015 to October 2020 were performed. According to the readmission status of the patients at 3 months postoperatively, the patients were divided into readmission group (39 cases)and non-readmission group(198 cases). In readmission group, there were 7 males and 32 females with an average age of(84.59±4.34) years old, respectively, there were 34 males and 164 females with average age of (84.65±4.17) years old in non-readmission group. The general information, surgical status, hip Harris score and complications of patients in two groups were included in univariate analysis, and multivariate Logistic regression was used to analyze independent risk factors of patients' readmission. RESULTS: The proportion of complications(cerebral infarction and coronary heart disease) in readmission group was significantly higher than that of non-readmission group (P<0.05), and intraoperative blood loss in readmission group was significantly higher than that of non-readmission group(P<0.05). Harris score of hip joint was significantly lower than that of non-readmission group(P<0.05). The proportion of infection, delirium, joint dislocation, anemia and venous thrombosis in readmission group were significantly higher than that of non-readmission group (all P<0.05). Multivariate Logistic regression analysis showed that the risk factors for readmission of elderly patients with hip fracture after hip hemiarthroplasty included cerebral infarction, infection, delirium, dislocation, anemia and venous thrombosis (all P<0.05). CONCLUSION: The complications of the elderly patients who were readmission after hip hemiarthroplasty for hip fractures were significantly higher than those who were non-readmission. Cerebral infarction, infection, delirium, dislocation, anemia and venous thrombosis are risk factors that lead to patient readmission. Corresponding intervention measures can be taken clinically based on these risk factors to reduce the incidence of patient readmissions.