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Abstract Total neointima implantation (patch neointima technique + triple‐branched stent graft placement) has been performed in proximal aortic repair for acute type A aortic dissection (ATAAD) for more than 10 years at a center. However, there is no report on the mid‐term outcomes with a control group of the surgical procedure. Consequently, the authors aimed to evaluate the safety and efficacy of this technique in this study. Patients who underwent the total neointima implantation were classified as Group A, and those who underwent the conventional aortic root reconstruction with the “sandwich” technique and the total aortic arch replacement were classified as Group B. Furthermore, the authors described the preoperative characteristics, operative data, and patient outcomes. Group A patients experienced a shorter surgery duration, lower volumes of perioperative bleeding, and fewer red blood cell transfusions. The incidence of neurological complications was significantly reduced in Group A. All patients maintained a normal range of proximal aortic sizes after surgery. Kaplan–Meier analysis revealed no significant differences between the patients in the two groups regarding cumulative mortality and the incidence of moderate‐to‐severe aortic insufficiency. In well‐selected patients, total neointima implantation is an alternative procedure for the surgical repair of ATAAD.

Abstract The purposes of this study were to develop and validate a nomogram for predicting postoperative transient neurological dysfunctions (TND) in patients with acute type A aortic dissection (AAAD) who underwent modified triple‐branched stent graft implantation. This retrospective study developed a nomogram‐based model in a consecutive cohort of 146 patients. Patient characteristics, preoperative clinical indices, and operative data were analyzed. Univariate and multivariable analyses were applied to identify the most useful predictive variables for constructing the nomogram. Discrimination and the calibration of the model was evaluated through the receiver operating characteristic curve (ROC), the Hosmer–Lemeshow goodness‐of‐fit test and the decision curve analysis (DCA). At the same time, to identify and compare long‐term cumulative survival rate, Kaplan‐Meier survival curve was plotted. The incidence rate of postoperative TND observed in our cohort were 40.9%. Supra‐aortic dissection with or without thrombosis, creatinine >115 μmol and albumin 7 min and total operation time >303 min, were confirmed as independent predictors that enhanced the likelihood of TND. Internal validation showed good discrimination of the model with under the ROC curve (AUC) of 0.818 and good calibration (Hosmer–Lemeshow test, p > .05). DCA revealed that the nomogram was clinically useful. In the long‐term survival there was no significant difference between patients with or without TND history. The results showed the predict model based on readily available predictors has sufficient validity to identify TND risk in this population, that maybe useful for clinical decision‐making.

Abstract Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin‐1, an actin‐binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin‐1 in ADMA‐induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty‐two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin‐1 small hairpin RNA to interrupt the expression of profilin‐1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin‐1 was tested using real‐time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin‐1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p

Atherosclerosis is a chronic inflammatory disease that triggers severe thrombotic cardiovascular events, such as stroke and myocardial infarction. In atherosclerotic processes, both macrophages and vascular smooth muscle cells (VSMCs) are essential cell components in atheromata formation through proinflammatory cytokine secretion, defective efferocytosis, cell migration, and proliferation, primarily controlled by Ca2+-dependent signaling. Calmodulin (CaM), as a versatile Ca2+ sensor in diverse cell types, regulates a broad spectrum of Ca2+-dependent cell functions through the actions of downstream protein kinases. Thus, this review focuses on discussing how CaM and CaM-dependent kinases (CaMKs) regulate the functions of macrophages and VSMCs in atherosclerotic plaque development based on literature from open databases. A central theme in this review is a summary of the mechanisms and consequences underlying CaMK-mediated macrophage inflammation and apoptosis, which are the key processes in necrotic core formation in atherosclerosis. Another central theme is addressing the role of CaM and CaMK-dependent pathways in phenotypic modulation, migration, and proliferation of VSMCs in atherosclerotic progression. A complete understanding of CaM and CaMK-controlled individual processes involving macrophages and VSMCs in atherogenesis might provide helpful information for developing potential therapeutic targets and strategies.

BackgroundTo summarize the current practice of anesthesia management for Chinese patients undergoing off-pump coronary artery bypass (OPCAB) surgery at a large-volume cardiovascular center.Materials and methodsThe clinical data of consecutive patients undergoing isolated, primary OPCAB surgery during the period from September 2019 to December 2019 were retrospectively analyzed. Patient characteristics, intraoperative data, and short-term outcomes were extracted from the Hospital Information System and the Anesthesia Information Management System.ResultsA total of 255 patients who underwent OPCAB surgery were enrolled in the current study. High-dose opioids and short-acting sedatives were the most commonly administrated anesthetics intraoperatively. Pulmonary arterial catheter insertion is frequently performed in patients with serious coronary heart disease. Goal-directed fluid therapy, a restricted transfusion strategy, and perioperative blood management were routinely used. Rational usages of inotropic and vasoactive agents facilitate hemodynamic stability during the coronary anastomosis procedure. Four patients underwent re-exploration for bleeding, but no death was observed.ConclusionsThe study introduced the current practice of anesthesia management at the large-volume cardiovascular center, and the short-term outcomes indicated the efficacy and safety of the practice in OPCAB surgery.

Objectives: This study aims to determine if complete transthoracic echocardiography (TTE)-guided percutaneous atrial septal defect (ASD) closure without balloon sizing could be safe and efficacious in adult patients. Methods: A total of 551 patients with ASDs were enrolled in this study, of which 438 patients underwent percutaneous ASD closure. Patients who received TTE-guided percutaneous ASD closure were classified into group T, and those who underwent a procedure that was guided by transesophageal echocardiography (TEE) were classified into group E. The clinical characteristics and the outcomes of the patients were analyzed. Results: The characteristics were comparable at baseline, except for the body mass index (BMI) (21.6 ± 5.3 vs. 23.8 ± 7.1, p < 0.001) between group T and group E. No significant difference was observed between the two groups regarding in-hospital outcomes, except for the duration of the procedure (29.8 ± 15.3 min vs. 41.5 ± 20.4 min), the length of stay in the hospital (2.1 ± 2.3 d vs. 2.9 ± 2.6 d), and hospital costs (USD 6233.3 ± 312.4 vs. USD 6673.7 ± 446.9). There were no significant differences in the incidences of long-term complications, cardiac chamber sizes, and tricuspid regurgitation severity between the patients in the two groups during the 10-year follow-up period. Conclusion: TTE may be as safe and efficacious as TEE for the assessment and guidance of percutaneous ASD closure without balloon sizing in adult patients with lower BMIs who are commonly found in East Asia.

Abstract Aim To develop an instrument to investigate geropsychiatric psychological symptoms, health problem nursing knowledge (GPN‐K), geropsychiatric psychological symptoms and health problem nursing attitude scale (GPN‐A) in clinical practice for nursing students. Design Instrument development and cross‐sectional study for psychometric testing. Methods Construct validity was evaluated using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA), and internal consistency was calculated using Cronbach's α. Results A total of 300 students have completed the questionnaires (85.71% response rate). The CFA of GPN‐K showed good fitness and validity. The Kuder‐Richardson 20 (KR‐20) value of the internal consistency reliability is 0.64. The GPN‐A overall content validity index is 0.95. A three‐factor structure was shown by exploratory factor analysis. The three factors are communication and care, helping others improve and problem evaluation tendency. The total variance explained is 59.01%. Cronbach's alpha of GPN‐A equals 0.84, which represents good internal consistency.

Campylobacter jejuni (C. jejuni), a Gram-negative bacterium, belongs to microaerobic bacteria. We reported a 21-year-old male patient diagnosed with hemophagocytic lymphohistiocytosis (HLH) due to C. jejuni infection, who presented with multiple clinical manifestations of peripheral nerve injury, such as ophthalmoplegia, facial paralysis, and urinary retention during the treatment. Electromyography showed neurogenic injury and the final diagnosis was Guillain-Barre Syndrome (GBS). After treatment of dexamethasone combined with immunoglobulin, the patient was discharged from the hospital with partial recovery of neurological symptoms.

Translation of a genetic codon without a cognate tRNA gene is affected by both the cognate tRNA availability and the interaction with non-cognate isoacceptor tRNAs. Moreover, two consecutive slow codons (slow di-codons) lead to a much slower translation rate. Calculating the composition of host specific slow codons and slow di-codons in the viral protein coding sequences can predict the order of viral protein synthesis rates between different virus strains.Comparison of human-specific slow codon and slow di-codon compositions in the genomes of 590 coronaviruses infect humans revealed that the protein synthetic rates of 2019 novel coronavirus (2019-nCoV) and severe acute respiratory syndrome-related coronavirus (SARS-CoV) may be much faster than other coronaviruses infect humans. Analysis of host-specific slow codon and di-codon compositions provides links between viral genomic sequences and capability of virus replication in host cells that may be useful for surveillance of the transmission potential of novel viruses.

Introduction: A previous study has shown that Ala–Thr–Pro–Gly–Asp–Glu–Gly (ATPGDEG) peptide identified from boiled abalone by-products has high antioxidant activities and antihypertensive effect. Objective: In this study, we further investigated its antiphotoaging activities by ultraviolet B (UVB)-induced HaCaT cells. Result: UVB irradiation significantly increased the content of intercellular reactive oxygen species (ROS) and the production of matrix metalloproteinases (MMPs) in HaCaT cells and decreased its content of collagen. First, the generation of intercellular ROS was reduced by abalone peptide in UVB-induced HaCaT cells. And activities of MMP-1 and MMP-9 were reduced by abalone peptide in a dose-dependent manner. Furthermore, western blot analysis demonstrated that abalone peptide downregulated the expression of p38, c-Jun N-terminal kinases, and extracellular signal-regulated kinases via mitogen-activated protein kinases (MAPKs) and NF-κB signaling to protect type I pro collagen and DNA damage. Molecular docking simulation confirms that abalone peptide inhibited activities of MMP-1 and MMP-9 by docking their active site, among them N-terminal Ala, C-terminal Gly, and Pro at the third position of N-terminal made a great contribution. Conclusion and recommendation: Abalone peptide could protect type I procollagen synthesis in UVB-irradiated HaCaT cells, and it is a potential peptide for the treatment of skin photoaging in the future.

Abstract Background Postoperative cerebral complications (PCC) are common and serious postoperative complications for patients with Stanford type A aortic dissection (AAD). The aim of this study was to evaluate the risk factors for PCC in these patients and to provide a scientific basis for effective prevention of PCC. Methods In this retrospective case-control study, 125 patients with AAD who underwent thoracotomy in our department from October 2017 to October 2018 in the department of cardiovascular surgery, Fujian Medical University Union Hospital were divided into two groups: patients with PCC (n = 12), and patients without PCC (n = 113). The general clinical data, the types of corrective surgeries, the intraoperative situations, the postoperative complications, and the midterm outcomes of the patients were analyzed. Results The patients with PCC were significantly older than the patients without PCC (P = 0.016), and the incidence of the preoperative cerebral disease history in the patients with PCC was significantly higher than those of the PCC (−) group (P = 0.024). The Euro SCORE II of patients with PCC was dramatically higher than the patients without PCC (P = 0.005). There were significant differences between the two groups in terms of the duration of cardiopulmonary bypass (CPB) (P = 0.010) and the length of moderate hypothermic circulatory arrest (MHCA) combined with selective cerebral perfusion (SCP) (P = 0.000). The monitoring of rcSO2 indicated that there was significant difference between the two groups in terms of the bilateral baseline (P = 0.000). Patients with PCC were observed to have experienced significantly longer intubation times (P = 0.000), ICU stays (P = 0.001), and postoperative hospital stays (P = 0.009), and they also had dramatically higher rates of pulmonary infection (P = 0.000), multiple organ dysfunction syndrome (P = 0.041) and tracheotomy (P = 0.022) after surgeries. The duration of MHCA+SCP (OR:9.009, P = 0.034) and the average baseline value of rcSO2 (OR:0.080, P = 0.009) were ultimately identified as significant risk factors. Conclusions PCC has a serious influence on the prognoses of patients following surgical treatment with AAD. The duration of MHCA+SCP and the average baseline value of rcSO2 were the independent risk factors for PCC.

In floriculture design, “shaping” is the use of floral materials as media for expressing ideas. Common floriculture techniques include tying, pasting, winding, connecting, overlapping, and weaving. Shaping is also a key factor in the appeal of the final product. Therefore, this study recruited 149 university students to explore how their floriculture material-shaping skills are affected by factors such as creative personality traits, spatial abilities, and shaping creativity. Students were allowed to use three different leaf materials in their floriculture works: planar leaf, linear leaf, and amorphous leaf materials. Representative planar, linear, and amorphous floriculture materials used in the current study were yellow palm (Chrysalidocarpus lutescens), veitch’s screw pine (Pandanus baptistii), and tree fern (Asparagus virgatus), respectively. The average score for creativity in shaping floriculture material was (±sd) 3.26 ± 0.84 (range, 1.33–4.67). Comparisons of the three leaf materials showed that the score for shaping creativity was highest for the planar leaf material (3.70 ± 1.23), followed by the amorphous leaf material (3.18 ± 0.99) and the linear leaf material (2.91 ± 0.94). The chi-square test results indicated that creative personality traits affected the number of shaping skills used, and that spatial abilities and floriculture material-shaping creativity further enhanced skills in floriculture material-shaping. Suggestions for floriculture educators and practitioners are provided accordingly.

Background The innate immune system especially Toll-like receptor (TLR) 7/8 and the interferon pathway, constitutes an important first line of defense against single-stranded RNA viruses. However, large-scale, systematic comparisons of the TLR 7/8-stimulating potential of genomic RNAs of single-stranded RNA viruses are rare. In this study, a computational method to evaluate the human TLR 7/8-stimulating ability of single-stranded RNA virus genomes based on their human TLR 7/8-stimulating trimer compositions was used to analyze 1,002 human coronavirus genomes. Results The human TLR 7/8-stimulating potential of coronavirus genomic (positive strand) RNAs followed the order of NL63-CoV > HKU1-CoV >229E-CoV ≅ OC63-CoV > SARS-CoV-2 > MERS-CoV > SARS-CoV. These results suggest that among these coronaviruses, MERS-CoV, SARS-CoV and SARS-CoV-2 may have a higher ability to evade the human TLR 7/8-mediated innate immune response. Analysis with a logistic regression equation derived from human coronavirus data revealed that most of the 1,762 coronavirus genomic (positive strand) RNAs isolated from bats, camels, cats, civets, dogs and birds exhibited weak human TLR 7/8-stimulating potential equivalent to that of the MERS-CoV, SARS-CoV and SARS-CoV-2 genomic RNAs. Conclusions Prediction of the human TLR 7/8-stimulating potential of viral genomic RNAs may be useful for surveillance of emerging coronaviruses from nonhuman mammalian hosts.

Amyotrophic lateral sclerosis (ALS) is a progressive nervous system disease that causes motor neuron (MN) degeneration and results in patient death within a few years. To recapitulate the cytopathies of ALS patients’ MNs, SOD1G85R mutant and corrected SOD1G85G isogenic-induced pluripotent stem cell (iPSC) lines were established. Two SOD1 mutant ALS (SOD1G85R and SOD1D90A), two SOD1 mutant corrected (SOD1G85G and SOD1D90D), and one sporadic ALS iPSC lines were directed toward MNs. After receiving ~90% purity for MNs, we first demonstrated that SOD1G85R mutant ALS MNs recapitulated ALS-specific nerve fiber aggregates, similar to SOD1D90A ALS MNs in a previous study. Moreover, we found that both SOD1 mutant MNs showed ALS-specific neurite degenerations and neurotransmitter-induced calcium hyperresponsiveness. In a small compound test using these MNs, we demonstrated that gastrodin, a major ingredient of Gastrodia elata, showed therapeutic effects that decreased nerve fiber cytopathies and reverse neurotransmitter-induced hyperresponsiveness. The therapeutic effects of gastrodin applied not only to SOD1 ALS MNs but also to sporadic ALS MNs and SOD1G93A ALS mice. Moreover, we found that coactivation of the GSK3β and IGF-1 pathways was a mechanism involved in the therapeutic effects of gastrodin. Thus, the coordination of compounds that activate these two mechanisms could reduce nerve fiber cytopathies in SOD1 ALS MNs. Interestingly, the therapeutic role of GSK3β activation on SOD1 ALS MNs in the present study was in contrast to the role previously reported in research using cell line- or transgenic animal-based models. In conclusion, we identified in vitro ALS-specific nerve fiber and neurofunctional markers in MNs, which will be useful for drug screening, and we used an iPSC-based model to reveal novel therapeutic mechanisms (including GSK3β and IGF-1 activation) that may serve as potential targets for ALS therapy.

Alcoholic liver disease (ALD) threatens human health, so it is imperative that we find ways to prevent or treat it. In recent years, the study of polysaccharides has shown that they have different kinds of bioactivities. Among them are many biological effects that have been attributed to polysaccharide precursors. D-Isofloridoside (DIF) is one of the polysaccharide precursors from the marine red alga Laurencia undulata. This study evaluated the effect of DIF on alcohol-induced oxidative stress in human hepatoma cells (HepG2). As a result, DIF attenuated alcohol-induced cytotoxicity, reduced the amount of intracellular reactive oxygen species (ROS), and effectively reduced alcohol-induced DNA damage in HepG2 cells. In addition, a western blot showed that, after DIF treatment, the expression levels of glutathione (GSH), superoxide dismutase (SOD), and B-cell lymphoma-2 (bcl-2) increased, while the expression levels of γ-glutamyl transferase (GGT), BCL2-associated X (bax), cleaved caspase-3, and mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase) signal transduction proteins reduced. This showed that DIF may protect cells by reducing the amount of intracellular ROS and inhibiting intracellular oxidative stress and apoptotic processes. Finally, molecular docking demonstrated that DIF can bind to SOD, GGT, B-cell lymphoma-2, and bax proteins. These results indicated that DIF can protect HepG2 cells from alcohol-induced oxidative stress damage, making it an effective potential ingredient in functional foods.

Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-κB may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.

Vasculogenic mimicry (VM) formed by tumor cells plays a vital role in the progress of tumor, because it provides nutrition for tumor cells and takes away the metabolites. Therefore, the inhibition of VM is crucial to the clinical treatment of tumors. In this study, we investigated the anti-tumor effect of a novel peptide, KVEPQDPSEW (AATP), isolated from abalone (Haliotis discus hannai) on HT1080 cells by migration, invasion analysis and the mode of action. The results showed that AATP effectively inhibited MMPs by blocking MAPKs and NF-κB pathways, leading to the downregulation of metastasis of tumor cells. Moreover, AATP significantly inhibited VM and pro-angiogenic factors, including VEGF and MMPs by suppression of AKT/mTOR signaling. In addition, molecular docking was used to study the interaction of AATP and HIF-1α, and the results showed that AATP was combined with an active site of HIF-1α by a hydrogen bond. The effect of AATP on anti-metastatic and anti-vascular in HT1080 cells revealed that AATP may be a potential lead compound for treatment of tumors in the future.

Influenza A virus genomes are composed of eight negative sense RNAs. In total, 16 proteins encoded by eight positive sense RNAs were identified. One putative protein coding sequence (PCS) encoded by genomic strand RNA of segment 8 has been previously proposed. In this study, 95,608, 123,965 and 35,699 genomic strand RNA sequences from influenza A viruses from avian, human and mammalian hosts, respectively, were used to identify PCSs encoded by the genomic strand RNAs. In total, 326,069 PCSs with lengths equal to or longer than 80 amino acids were identified and clustered into 270 PCS groups. Twenty of the 270 PCS groups which have greater than 10% proportion in influenza A viruses from avian, human or mammalian hosts were selected for detailed study. Maps of the 20 PCSGs in the influenza A virus genomes were constructed. The proportions of the 20 PCSGs in influenza A viruses from different hosts and serotypes were analyzed. One secretory and five membrane proteins predicted from the PCS groups encoded by genomic strand RNAs of segments 1, 2, 4, 6, 7 and 8 were identified. These results suggest the possibility of the ambisense nature of the influenza A virus genomic RNAs and a potential coding sequence reservoir encoding potential pan proteomes of influenza A viruses.

Memory retrieval dysfunction is a symptom of schizophrenia, autism spectrum disorder (ASD), and absence epilepsy (AE), as well as an early sign of Alzheimer’s disease. To date, few drugs have been reported to enhance memory retrieval. Here, we found that a coral-derived natural product, excavatolide-B (Exc-B), enhances contextual memory retrieval in both wild-type and Cav3.2−/− mice via repressing the delayed rectifier potassium current, thus lowering the threshold for action potential initiation and enhancing induction of long-term potentiation (LTP). The human CACNA1H gene encodes a T-type calcium channel (Cav3.2), and its mutation is associated with schizophrenia, ASD, and AE, which are all characterized by abnormal memory function. Our previous publication demonstrated that Cav3.2−/− mice exhibit impaired contextual-associated memory retrieval, whilst their retrieval of spatial memory and auditory cued memory remain intact. The effect of Exc-B on enhancing the retrieval of context-associated memory provides a hope for novel drug development.

Memantine, an NMDA receptor antagonist used for treatment of Alzheimer's disease (AD), is known to block the nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). In the present study, we examined by wire myography if memantine inhibited α3β2-nAChRs located on cerebral perivascular sympathetic nerve terminals originating in the superior cervical ganglion (SCG), thus, leading to inhibition of nicotine-induced nitrergic neurogenic dilation of isolated porcine basilar arteries. Memantine concentration-dependently blocked nicotine-induced neurogenic dilation of endothelium-denuded basilar arteries without affecting that induced by transmural nerve stimulation, sodium nitroprusside, or isoproterenol. Furthermore, memantine significantly inhibited nicotine-elicited inward currents in Xenopous oocytes expressing α3β2-, α7- or α4β2-nAChR, and nicotine-induced calcium influx in cultured rat SCG neurons. These results suggest that memantine is a non-specific antagonist for nAChR. By directly inhibiting α3β2-nAChRs located on the sympathetic nerve terminals, memantine blocks nicotine-induced neurogenic vasodilation of the porcine basilar arteries. This effect of memantine is expected to reduce the blood supply to the brain stem and possibly other brain regions, thus, decreasing its clinical efficacy in the treatment of Alzheimer's disease.

Microglia-mediated inflammation is implicated in pathogenesis of neurodegenerative diseases. Oroxylin A, a flavonoid isolated from Scutellariae baicalensis, has been shown to ameliorate microglia activation-mediated neurodegeneration in vivo. The molecular mechanism underlying the inhibitory effects of oroxylin A on microglia activation, however, remains unknown. In the present study, effects of oroxylin A co-treated with lipopolysaccharide (LPS, 100 ng/ml) on LPS-induced activation of cultured microglial BV-2 cells were examined. Nitric oxide (NO) production was determined by Greiss method. Expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-1β and IL-6 was assessed using real-time RT-PCR or Western blot analysis. Furthermore, activation of the nuclear factor κB (NFκB) and the signal transducer and activator of transcription 1 (STAT1) was examined by Western blot analysis and transcription factor DNA-binding activity assay. Our results indicated that oroxylin A (10-100 µM) in a concentration-dependent manner inhibited LPS-induced NO production via blocking iNOS expression at both mRNA and protein levels without affecting the degradation rate of iNOS mRNA. Moreover, oroxylin A significantly attenuated LPS-induced late expression (20 hours after LPS challenge) of IL-1β and IL-6. Furthermore, oroxylin A significantly suppressed LPS-induced JAK2-mediated STAT1 phosphorylation without affecting LPS-induced NFκB-p65 nuclear translocation or NFκB-p65 DNA-binding activity. This is consistent with the finding that AG490, a specific JAK2 inhibitor, significantly inhibited LPS-induced STAT1 phosphorylation with almost completely diminished iNOS expression. These results suggest that oroxylin A, via suppressing STAT1 phosphorylation, inhibits LPS-induced expression of pro-inflammatory genes in BV-2 microglial cells.

BACKGROUND AND PURPOSE: Successful drug treatment for sepsis-related acute lung injury (ALI) remains a major clinical problem. This study was designed to assess the beneficial effects of post-treatment of oroxylin A (OroA), a flavonoid, in ameliorating lipopolysaccharides (LPS)-induced lung inflammation and fatality. EXPERIMENTAL APPROACH: Rats were injected with LPS (10 mg/kg, iv) to induce ALI, and OroA was given (15 mg/kg, iv) 1 hr or 6 hrs after LPS challenge. Twenty four hrs after LPS challenge, biochemical changes in the blood and lung tissues, and morphological/histological alterations in the lung associated with inflammation and injury were examined. Therapeutic effect of OroA was assessed by measuring the survival rate in endotoxemic mice. KEY RESULTS: LPS (10 mg/kg, iv) significantly altered WBC counts, elevated plasma tumor necrosis factor (TNF)-α and nitric oxide (NO), increased pulmonary edema, thickened alveolar septa, and decreased survival rate. These changes were ameliorated by OroA (15 mg/kg, iv) administered 1 hr or 6 hrs after LPS challenge. This post-treatment also significantly attenuated LPS-induced activation of nuclear factor-κB (NF-κB) and the release of high mobility group box 1 (HMGB1) in lung tissues. Furthermore, post-treatment with OroA (60 mg/kg, ip) administered 1 hr or 6 hrs after LPS challenge in mice significantly increased survival rate. CONCLUSION AND IMPLICATION: OroA administered after induction of ALI by LPS significantly prevent and revere lung tissues injuries with increased survival rate. Positive post-treatment effects of OroA suggest that OroA is a potentially useful candidate for managing lung inflammation in LPS-induced endotoxemia and septic shock.

Healthcare systems must embody equity, diversity, and inclusion (EDI) and, in the event of unfairness, appropriate policies / countermeasures should be enacted. The healthcare system response to the COVID-19 pandemic not only highlighted how socioeconomic disparities affect mortality risk but also posed significant challenges to the successful practice of EDI in healthcare. In light of this, this article was written to provide an overview of EDI, analyze the international efforts to promote it, and suggest strategies for promoting EDI in infectious disease healthcare using COVID-19 as an example. In healthcare settings, equity centers on ensuring patients receive fair treatment regardless of race, gender, age, or socioeconomic status; diversity centers on healthcare providers understanding the uniqueness of patients from different cultural backgrounds and the health barriers they face; and inclusion centers on ensuring patients are treated with respect and given the attention they deserve. During pandemics, social determinants of health (SDOH) greatly impact patient health outcomes and hinder the practice of EDI. Reflecting on the impact of COVID-19, healthcare systems can actively apply EDI in clinical practice to provide to all patients equitable access to healthcare opportunities and outcomes. Practical strategies include establishing EDI committees within healthcare systems, monitoring relevant data, conducting staff training, and continuously addressing the SDOH and needs of marginalized groups to achieve EDI in healthcare. [ABSTRACT FROM AUTHOR]

Exercise can effectively slow aging and prevent the onset and reduce the complications of chronic diseases in the elderly. However, roughly one-third of older adults are inactive. Joyful learning is an effective method for promoting physical activity, while using games is a feasible strategy for achieving joyful learning that enables individuals to fully immerse themselves in and enjoy an activity. Therefore, exploring gaming strategies to enhance physical activity among the elderly is worthwhile. In this paper, a set of gaming strategies based on the literature and practical experience is proposed. The name of this strategy, GAME, is an acronym of the following: goal setting and educational content development (G), activity design and game content creation (A), mechanics and dynamics implementation (M), and evaluation of qualitative and quantitative health outcomes (E). This systematic descriptive approach helps clearly demonstrate how gamification strategies can promote physical activity and health in older adults. The aim of this paper is to provide a reference and guide for education, research, and clinical practice in health promotion programs targeting older adults. [ABSTRACT FROM AUTHOR]

Abstract Objectives Hereditary transthyretin (TTR) amyloidosis (ATTRv) is frequently complicated by polyneuropathy (ATTRv‐PN) and cardiomyopathy (ATTRv‐CM). The long‐term efficacy of diflunisal on both polyneuropathy and cardiomyopathy in ATTRv patients, especially those with non‐V30M genotypes, has not been fully investigated and compared with that of tafamidis. Methods We compared the structural and biochemical characteristics of A97S‐TTR complexed with tafamidis with those of diflunisal, and prospectively followed up and compared the progression of polyneuropathy and cardiomyopathy between ATTRv‐PN patients taking diflunisal and those taking tafamidis. Results Both diflunisal and tafamidis effectively bind to the two thyroxine‐binding sites at the A97S‐TTR dimer–dimer interface and equally and almost sufficiently reduce amyloid fibril formation. Thirty‐five ATTRv‐PN patients receiving diflunisal and 22 patients receiving tafamidis were enrolled. Compared with no treatment, diflunisal treatment significantly delayed the transition of FAP Stage 1 to 2 and Stage 2 to 3 and decreased the deterioration in parameters of the ulnar nerve conduction study (NCS). The progression of FAP stage or NCS parameters did not differ between patients treated with diflunisal and those treated with tafamidis. Both diflunisal and tafamidis treatments significantly decreased radiotracer uptake on 99mTc‐PYP SPECT and stabilized cardiac wall thickness and blood pro‐B‐type natriuretic peptide levels. No significant adverse events occurred during diflunisal or tafamidis treatment. Interpretations The binding patterns of both tafamidis and diflunisal to A97S‐TTR closely resembled those observed in the wild type. Diflunisal can effectively delay the progression of polyneuropathy and cardiomyopathy with similar efficacy to tafamidis and may become a cost‐effective alternative treatment for late‐onset ATTRv‐PN.