Facilitating and hindering factors of community nurses' emergency and critical care treatment abilities: A qualitative study.

BACKGROUND: This study adopts a descriptive phenomenological approach to investigate the facilitators and barriers of community nurses' abilities in managing critical and emergency conditions. With the transition of healthcare systems to the community, the evolution of nursing practices, and the attention from policies and practices, community nurses play a crucial role in the management of critical and emergency conditions. However, there is still a lack of comprehensive understanding regarding the factors that promote or hinder their capabilities in this area. AIM: To understand the facilitators and barriers of community nurses in managing critical and emergency conditions, exploring the fundamental reasons and driving forces influencing their treatment capabilities. METHODS: This study utilized the destination sampling method between May 2023 and July 2023. It employed a descriptive phenomenological approach within qualitative research methodologies. Through objective sampling, 17 community nurses from 7 communities in Changning District, Shanghai, were selected as the study subjects. Semi-structured interviews were conducted to gather data, which were subsequently organized and analyzed using Colaizzi's seven-step analysis method, leading to the extraction of final themes. RESULTS: The barrier factors identified from the interviews encompassed three topics: resource allocation, professional factors, and personal literacy. The facilitators comprised three themes: professionalism, management attention, and training and continuing education. We identified that the root causes of the barriers included the lack of practical treatment experience among community nurses, insufficient awareness of self-directed learning, and limited knowledge and technical proficiency. The professional quality of community nurses and management attention serve as motivation for them to enhance their treatment abilities. CONCLUSION: To enhance the capability of community nurses in treating acute and critical patients, it is recommended to bolster training specifically tailored to acute and critical care, raise awareness of first aid practices, and elevate knowledge and skill levels.

Tumor necrosis factor receptor-associated factor 5 protects against intimal hyperplasia by regulation of macrophage polarization via directly targeting PPARγ.

OBJECTIVES: Intimal hyperplasia is a serious clinical problem associated with the failure of therapeutic methods in multiple atherosclerosis-related coronary heart diseases, which are initiated and aggravated by the polarization of infiltrating macrophages. The present study aimed to determine the effect and underlying mechanism by which tumor necrosis factor receptor-associated factor 5 (TRAF5) regulates macrophage polarization during intimal hyperplasia. METHODS: TRAF5 expression was detected in mouse carotid arteries subjected to wire injury. Bone marrow-derived macrophages, mouse peritoneal macrophages and human myeloid leukemia mononuclear cells were also used to test the expression of TRAF5 in vitro. Bone marrow-derived macrophages upon to LPS or IL-4 stimulation were performed to examine the effect of TRAF5 on macrophage polarization. TRAF5-knockout mice were used to evaluate the effect of TRAF5 on intimal hyperplasia. RESULTS: TRAF5 expression gradually decreased during neointima formation in carotid arteries in a time-dependent manner. In addition, the results showed that TRAF5 expression was reduced in classically polarized macrophages (M1) subjected to LPS stimulation but was increased in alternatively polarized macrophages (M2) in response to IL-4 administration, and these changes were demonstrated in three different types of macrophages. An in vitro loss-of-function study with TRAF5 knockdown plasmids or TRAF5-knockout mice revealed high expression of markers associated with M1 macrophages and reduced expression of genes related to M2 macrophages. Subsequently, we incubated vascular smooth muscle cells with conditioned medium of polarized macrophages in which TRAF5 expression had been downregulated or ablated, which promoted the proliferation, migration and dedifferentiation of VSMCs. Mechanistically, TRAF5 knockdown inhibited the activation of anti-inflammatory M2 macrophages by directly inhibiting PPARγ expression. More importantly, TRAF5-deficient mice showed significantly aggressive intimal hyperplasia. CONCLUSIONS: Collectively, this evidence reveals an important role of TRAF5 in the development of intimal hyperplasia through the regulation of macrophage polarization, which provides a promising target for arterial restenosis-related disease management.

Inhibition of P21-activated Kinase 1 Promotes Vascular Smooth Muscle Cells Apoptosis Through Reduction of Phosphorylation of Bad.

BACKGROUND: P21-activated kinase 1 (Pak1) has an effect on cell apoptosis and has recently been reported to play an important role in various cardiovascular diseases, in which vascular smooth muscle cell (VSMC) apoptosis is a key process. Thus, we hypothesized that Pak1 may be a novel target to regulate VSMC behaviors. METHODS AND RESULTS: In the present study, we found that the expression of Pak1 was dramatically upregulated in vascular smooth muscle cells (VSMCs) on H2O2 administration and was dependent on stimulation time. Through a loss-of-function approach, Pak1 knockdown increased apoptosis of VSMCs, as tested by TUNEL (TdT-mediated dUTP Nick-End Labeling) immunofluorescence staining, whereas it inhibited the proliferation of VSMCs examined by EdU staining. Moreover, we also noticed that Pak1 silencing promoted the mRNA and protein levels of pro-apoptosis genes but decreased anti-apoptosis marker expression. Importantly, we showed that Pak1 knockdown reduced the phosphorylation of Bad. Moreover, increased Pak1 expression was also noticed in carotid arteries on the wire jury. CONCLUSIONS: Our study identified that Pak1 acted as a novel regulator of apoptosis of VSMCs partially through phosphorylation of Bad.

N-Acetylcysteine Alleviates Phenylephrine-Induced Cardiomyocyte Dysfunction via Engaging PI3K/AKT Signaling Pathway.

BACKGROUND: Increased reactive oxygen species (ROS) and oxidative stress response lead to cardiomyocyte hypertrophy and apoptosis, which play crucial roles in the pathogenesis of heart failure. The purpose of current research was to explore the role of antioxidant N-acetylcysteine (NAC) on cardiomyocyte dysfunction and the underlying molecular mechanisms. METHODS AND RESULTS: Compared with control group without NAC treatment, NAC dramatically inhibited the cell size of primary cultured neonatal rat cardiomyocytes (NRCMs) tested by immunofluorescence staining and reduced the expression of representative markers associated with hypertrophic, fibrosis and apoptosis subjected to phenylephrine administration examined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Moreover, enhanced ROS expression was attenuated, whereas activities of makers related to oxidative stress response examined by individual assay Kits, including total antioxidation capacity (T-AOC), glutathione peroxidase (GSH-Px), and primary antioxidant enzyme Superoxide dismutase (SOD) were induced by NAC treatment in NRCMs previously treated with phenylephrine. Mechanistically, we noticed that the protein expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) and AKT were increased by NAC stimulation. More importantly, we identified that the negative regulation of NAC in cardiomyocyte dysfunction was contributed by PI3K/AKT signaling pathway through further utilization of PI3K/AKT inhibitor (LY294002) or agonist (SC79). CONCLUSIONS: Collected, NAC could attenuate cardiomyocyte dysfunction subjected to phenylephrine, partially by regulating the ROS-induced PI3K/AKT-dependent signaling pathway.

Safety profile of intravenous digoxin in Chinese patients with acute heart failure with reduced ejection fraction: a small-scale prospective cohort study.

Background: Adverse effects of intravenous digoxin vary from patients and disease status, which should be closely monitored. Aims: To explore the safety profile of intravenous digoxin in acute heart failure with reduced ejection fraction (HFrEF) among Chinese patients. Methods: A clinical prospective, single-center, single-arm, open-label exploratory clinical trial was performed in patients with acute HFrEF at Wuhan Asia Heart Hospital. A fixed dose of 0.5 mg digoxin was used intravenously once per day for 3 days. The normalized dosage of digoxin (NDD), toxic serum digoxin concentration (SDC), and adverse reactions of intravenous digoxin were recorded. Results: A total of 40 patients were recruited in the study. The SDC increased from 1.03 ± 0.34 ng/mL to 1.95 ± 0.52 ng/mL during treatment. 50% (20/40) patients reached a toxic SDC of 2.0 ng/mL, and toxic effects were seen in 30% (12/40) patients. Estimated glomerular filtration rate (eGFR) < 60 mL/min [HR: 5.269; 95% CI: 1.905-14.575, p = 0.001], NDD ≥7 µg/kg [HR: 3.028; 95% CI: 1.119-8.194, p = 0.029], and ischemic cardiomyopathy [HR: 2.658; 95% CI: 1.025-6.894, p = 0.044] were independent risk factors for toxic SDC. Toxic SDC was effectively identified [area under the receiver operating characteristic (ROC) curve = 0.85, p < 0.001] using this model, and patients would have a higher risk of toxicity with more risk factors. Conclusion: Intravenous digoxin of 0.5 mg was safe and effective for initial dose but not suitable for maintenance treatment in Chinese patients with acute HFrEF. Patients who had lower eGFR, received higher NDD, and had ischemic cardiomyopathy should be closely monitored to avoid digoxin toxicity.

Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression.

Recently macrophage polarization has emerged as playing an essential role in the oathogenesis of atherosclerosis, which is the most important underlying process in many types of cardiovascular diseases. Although Nek6 has been reported to be involved in various cellular processes, the effect of Nek6 on macrophage polarization remains unknown. Macrophages exposed to lipopolysaccharide (LPS) or IL-4 were used to establish an in vitro model for the study of regulation of classically (M1) or alternatively (M2) activated macrophage. Bone marrow-derived macrophages (BMDMs) transfected with short hairpin RNA-targeting Nek6 were then in functional studies. We observed that Nek6 expression was decreased in both peritoneal macrophages (PMs) and BMDMs stimulated by LPS. This effect was seen at both mRNA and protein level. The opposite results were obtained after administration of IL-4. Macrophage-specific Nek6 knockdown significantly exacerbated pro-inflammatory M1 polarized macrophage gene expression in response to LPS challenge, but the anti-inflammatory response gene expression that is related to M2 macrophages was attenuated by Nek6 silencing followed by treatment with IL-4. Mechanistic studies exhibited that Nek6 knockdown inhibited the phosphorylated STAT3 expression that mediated the effect on macrophage polarization regulated by AdshNek6. Moreover, decreased Nek6 expression was also observed in atherosclerotic plaques. Collectively, these evidences suggested that Nek6 acts as a crucial site in macrophage polarization, and that this operates in a STAT3-dependent manner.

Methyltransferase-like 3 suppresses phenotypic switching of vascular smooth muscle cells by activating autophagosome formation.

Prevention of neointima formation is the key to improving long-term outcomes after stenting or coronary artery bypass grafting. RNA N6 -methyladenosine (m6 A) methylation has been reported to be involved in the development of various cardiovascular diseases, but whether it has a regulatory effect on neointima formation is unknown. Herein, we revealed that methyltransferase-like 3 (METTL3), the major methyltransferase of m6 A methylation, was downregulated during vascular smooth muscle cell (VSMC) proliferation and neointima formation. Knockdown of METTL3 facilitated, while overexpression of METTL3 suppressed the proliferation of human aortic smooth muscle cells (HASMCs) by arresting HASMCs at G2/M checkpoint and the phosphorylation of CDC2 (p-CDC2) was inactivated by METTL3. On the other hand, the migration and synthetic phenotype of HASMCs were enhanced by METTL3 knockdown, but inhibited by METTL3 overexpression. The protein levels of matrix metalloproteinase 2 (MMP2), MMP7 and MMP9 were reduced, while the expression level of tissue inhibitor of metalloproteinase 3 was increased in HASMCs with METTL3 overexpression. Moreover, METTL3 promoted the autophagosome formation by upregulating the expression of ATG5 (autophagy-related 5) and ATG7. Knockdown of either ATG5 or ATG7 largely reversed the regulatory effects of METTL3 overexpression on phenotypic switching of HASMCs, as evidenced by increased proliferation and migration, and predisposed to synthetic phenotype. These results indicate that METTL3 inhibits the phenotypic switching of VSMCs by positively regulating ATG5-mediated and ATG7-mediated autophagosome formation. Thus, enhancing the level of RNA m6 A or the formation of autophagosomes is the promising strategy to delay neointima formation.

[Relationship between dietary nutrients and hypertension, overweight and obesity in pupil grades 3 to 6 in Wuhan City].

OBJECTIVE: To explore the relationship between children's dietary nutrient intakes and hypertension, overweight and obesity. METHODS: In April 2016, 1033 children aged 9 to 12 from grades 3 to 6 in two primary schools in Hongshan District of Wuhan City were selected by cluster sampling method, with an average age of(10.55±1.10) years, including 545 boys(52.8%) and 488 girls(47.2%), for physical examination and dietary survey. Physical examination included height, weight, blood pressure, etc. Dietary survey was conducted using a 3-day 24 h retrospective method. Principal component factor analysis was used to explore the dietary nutrient patterns of children, and logistic regression was used to analyze the effects of different dietary nutrient patterns on children's hypertension, overweight and obesity. RESULTS: In terms of M(P25, P75), compared with normal blood pressure group, hypertensive group had higher energy intake(1761.97(1617.17, 1940.43)kcal vs.1730.95(1556.06, 1905.71)kcal, P=0.011). Compared with normal weight group, overweight and obese group had higher carbohydrate(250.65(226.55, 281.29)g vs.244.41(220.04, 273.01)g, P=0.011), vitamin B_1(0.29(0.22, 0.36)mg vs.0.27(0.22, 0.34)mg, P=0.022), vitamin B_2(0.45(0.33, 0.60)mg vs.0.39(0.32, 0.51)mg, P=0.001), iron(12.64(11.06, 14.48)mg vs.12.39(10.57, 14.21)mg, P=0.033), zinc(5.11(4.00, 6.77)mg vs.4.60(3.87, 5.84)mg, P<0.001)intakes, lower calcium intake(185.52(136.92, 264.73)mg vs.207.39(141.25, 300.92)mg, P=0.007). Low cholesterol, low vitamin, high calcium pattern(OR=0.644, 95%CI 0.421-0.985) and Q2 of low protein, low fat and low cholesterol(OR=0.626, 95%CI 0.412-0.951) were protective factors for overweight and obesity. CONCLUSION: High carbohydrate may be a risk factor for overweight and obesity, while high calcium, low fat and low cholesterol may be protective factors for overweight and obesity.

JIB-04, a histone demethylase Jumonji C domain inhibitor, regulates phenotypic switching of vascular smooth muscle cells.

BACKGROUND: Vascular smooth muscle cell (VSMC) phenotype switching is critical for neointima formation, which is the major cause of restenosis after stenting or coronary artery bypass grafting. However, the epigenetic mechanisms regulating phenotype switching of VSMCs, especially histone methylation, are not well understood. As a main component of histone lysine demethylases, Jumonji demethylases might be involved in VSMC phenotype switching and neointima formation. METHODS AND RESULTS: A mouse carotid injury model and VSMC proliferation model were constructed to investigate the relationship between histone methylation of H3K36 (downstream target molecule of Jumonji demethylase) and neointima formation. We found that the methylation levels of H3K36 negatively correlated with VSMC proliferation and neointima formation. Next, we revealed that JIB-04 (a pan-inhibitor of the Jumonji demethylase superfamily) could increase the methylation levels of H3K36. Furthermore, we found that JIB-04 obviously inhibited HASMC proliferation, and a cell cycle assay showed that JIB-04 caused G2/M phase arrest in HASMCs by inhibiting the phosphorylation of RB and CDC2 and promoting the phosphorylation of CHK1. Moreover, JIB-04 inhibited the expression of MMP2 to suppress the migration of HASMCs and repressed the expression of contraction-related genes. RNA sequencing analysis showed that the biological processes associated with the cell cycle and autophagy were enriched by using Gene Ontology analysis after HASMCs were treated with JIB-04. Furthermore, we demonstrated that JIB-04 impairs autophagic flux by downregulating STX17 and RAB7 expression to inhibit the fusion of autophagosomes and lysosomes. CONCLUSION: JIB-04 suppresses the proliferation, migration, and contractile phenotype of HASMCs by inhibiting autophagic flux, which indicates that JIB-04 is a promising reagent for the treatment of neointima formation.

MicroRNA-183 as a Novel Regulator Protects Against Cardiomyocytes Hypertrophy via Targeting TIAM1.

BACKGROUND: MicroRNAs serve as important regulators of the pathogenesis of cardiac hypertrophy. Among them, miR-183 is well documented as a novel tumor suppressor in previous studies, whereas it exhibits a downregulated expression in cardiac hypertrophy recently. The present study was aimed to examine the effect of miR-183 on cardiomyocytes hypertrophy. METHODS: Angiotensin II (Ang II) was used for establishment of cardiac hypertrophy model in vitro. Neonatal rat ventricular cardiomyocytes transfected with miR-183 mimic or negative control were further utilized for the phenotype analysis. Moreover, the bioinformatics analysis and luciferase reporter assays were used for exploring the potential target of miR-183 in cardiomyocytes. RESULTS: We observed a significant decreased expression of miR-183 in hypertrophic cardiomyocytes. Overexpression of miR-183 significantly attenuated the cardiomyocytes size morphologically and prohypertrophic genes expression. Moreover, we demonstrated that TIAM1 was a direct target gene of miR-183 verified by bioinformatics analysis and luciferase reporter assays, which showed a decreased mRNA and protein expression in the cardiomyocytes transfected with miR-183 upon Ang II stimulation. Additionally, the downregulated TIAM1 expression was required for the attenuated effect of miR-183 on cardiomyocytes hypertrophy. CONCLUSIONS: Taken together, these evidences indicated that miR-183 acted as a cardioprotective regulator for the development of cardiomyocytes hypertrophy via directly regulation of TIAM1.

Global burden of chronic obstructive pulmonary disease attributable to ambient ozone in 204 countries and territories during 1990-2019.

Ambient ozone becomes one of significant environmental threats to chronic obstructive pulmonary disease (COPD) in recent decades. To date, however, few systematic analyses have been performed to quantify ozone-attributable disease burden, globally and regionally. In this study, we aimed to comprehensively depict the global trend of ozone-related COPD premature deaths and disability-adjusted life years (DALYs). We derived estimates of COPD burden attributable to ambient ozone for 204 countries and territories during 1990-2019 from the Global Burden of Disease Study 2019. We examined the number of deaths and DALYs, as well as age-standardized mortality rate (ASMR) and DALYs rate (ASDR) by sex, socio-demographic index (SDI), countries, and regions. Population attributable fractions (PAFs) were adopted to identify age groups vulnerable to ozone-related COPD. Estimated annual percentage changes (EAPCs) were calculated to assess the temporal trend of ozone-attributable COPD burden (e.g., ASMR and ASDR) between 1990 and 2019, using generalized linear models. Spearman rank correlation was applied to measure the relationships of estimated ASMR, ASDR, and EAPC with SDI. In 2019, COPD attributable to ambient ozone gave rise to 365.22 (95% uncertainty interval: 174.93 to 564.27) thousand deaths and 6.21 (2.99 to 9.63) million DALYs globally, representing a corresponding increase of 76.11% and 56.37% versus 1990. During 1990-2019, however, a yearly decline of 1.07% (0.81 to 1.33) was observed for ASMR and 1.30% (1.07 to 1.52) for ASDR. Considerable gender inequality continues in ozone-attributable COPD burden, with much greater impacts among men, and the gap is enlarged with the increase of age. In all age groups, the fractional contribution of ozone to COPD burden exhibited an overall increasing trend globally for both deaths (8.22% in 1990 versus 11.13% in 2019) and DALYs (6.70% in 1990 versus 8.34% in 2019). The burden of COPD caused by ambient ozone varied substantially by geographical and socioeconomic regions. In 2019, the greatest ASMR and ASDR were seen in South Asia, followed by East Asia and Central Sub-Saharan Africa. Despite the clear drop of age-standardized rates (EAPC<0) in high, high-middle, and middle SDI regions, ASMR and ASDR in low and low-middle SDI regions continuously raised between 1990 and 2019. Higher SDI was found to be associated with lower EAPCs in ASMR (rs=-0.4405, p<0.001) and ASDR (rs=-0.4510, p<0.001). Although the global ASMR and ASDR of COPD attributable to ambient ozone have decreased from 1990 to 2019, there has been an unnegligible increase in some low and low-middle SDI regions such as Southeast Asia, South Asia, and Andean Latin America. Findings may have some implications for formulating targeted plans and policies for future COPD prevention and ambient ozone management in different regions.

PAK1 Silencing Attenuated Proinflammatory Macrophage Activation and Foam Cell Formation by Increasing PPARγ Expression.

Macrophage polarization in response to environmental cues has emerged as an important event in the development of atherosclerosis. Compelling evidences suggest that P21-activated kinases 1 (PAK1) is involved in a wide variety of diseases. However, the potential role and mechanism of PAK1 in regulation of macrophage polarization remains to be elucidated. Here, we observed that PAK1 showed a dramatically increased expression in M1 macrophages but decreased expression in M2 macrophages by using a well-established in vitro model to study heterogeneity of macrophage polarization. Adenovirus-mediated loss-of-function approach demonstrated that PAK1 silencing induced an M2 macrophage phenotype-associated gene profiles but repressed the phenotypic markers related to M1 macrophage polarization. Additionally, dramatically decreased foam cell formation was found in PAK1 silencing-induced M2 macrophage activation which was accompanied with alternation of marker account for cholesterol efflux or influx from macrophage foam cells. Moderate results in lipid metabolism and foam cell formation were found in M1 macrophage activation mediated by AdshPAK1. Importantly, we presented mechanistic evidence that PAK1 knockdown promoted the expression of PPARγ, and the effect of macrophage activation regulated by PAK1 silencing was largely reversed when a PPARγ antagonist was utilized. Collectively, these findings reveal that PAK1 is an independent effector of macrophage polarization at least partially attributed to regulation of PPARγ expression, which suggested PAK1-PPARγ axis as a novel therapeutic strategy in atherosclerosis management.

Association of Clinical and Immunological Characteristics With Disease Severity and Outcomes in 211 Patients With COVID-19 in Wuhan, China.

Background: Coronavirus disease 2019 (COVID-19) has posed a great threat to global public health. There remains an urgent need to address the clinical significance of laboratory finding changes in predicting disease progression in COVID-19 patients. We aimed to analyze the clinical and immunological features of severe and critically severe patients with COVID-19 in comparison with non-severe patients and identify risk factors for disease severity and clinical outcome in COVID-19 patients. Methods: The consecutive records of 211 patients with COVID-19 who were admitted to Zhongnan Hospital of Wuhan University from December 2019 to February 2020 were retrospectively reviewed. Results: Of the 211 patients with COVID-19 recruited, 111 patients were classified as non-severe, 59 as severe, and 41 as critically severe cases. The median age was obviously higher in severe and critically severe cases than in non-severe cases. Severe and critically severe patients showed more underlying comorbidities than non-severe patients. Fever was the predominant presenting symptom in COVID-19 patients, and the duration of fever was longer in critically severe patients. Moreover, patients with increased levels of serum aminotransferases and creatinine (CREA) were at a higher risk for severe and critical COVID-19 presentations. The serum levels of IL-6 in severe and critically severe patients were remarkably higher than in non-severe patients. Lymphopenia was more pronounced in severe and critically severe patients compared with non-severe patients. Lymphocyte subset analysis indicated that severe and critically severe patients had significantly decreased count of lymphocyte subpopulations, such as CD4+ T cells, CD8+ T cells and B cells. A multivariate logistic analysis indicated that older age, male sex, the length of hospital stay, body temperature before admission, comorbidities, higher white blood cell (WBC) counts, lower lymphocyte counts, and increased levels of IL-6 were significantly associated with predicting the progression to severe stage of COVID-19. Conclusion: Older age, male sex, underlying illness, sustained fever status, abnormal liver and renal functions, excessive expression of IL-6, lymphopenia, and selective loss of peripheral lymphocyte subsets were related to disease deterioration and clinical outcome in COVID-19 patients. This study would provide clinicians with valuable information for risk evaluation and effective interventions for COVID-19.

ALK7 Acts as a Positive Regulator of Macrophage Activation through Down-Regulation of PPARγ Expression.

AIM: Activin receptor-like kinase 7 (ALK7) acts as a key receptor for TGF-ß family members, which play important roles in regulating cardiovascular activity. However, ALK7's potential role, and underlying mechanism, in the macrophage activation involved in atherogenesis remain unexplored. METHODS: ALK7 expression in macrophages was tested by RT-PCR, western blot, and immunofluorescence co-staining. The loss-of-function strategy using AdshALK7 was performed for functional study. Oil Red O staining was used to observe the foam cell formation, while inflammatory mediators and genes related to cholesterol efflux and influx were determined by RT-PCR and western blot. A PPARγ inhibitor (G3335) was used to reveal whether PPARγ was required for ALK7 to affect macrophage activation. RESULTS: The results exhibited upregulated ALK7 expression in oxidized low-density lipoprotein (Ox-LDL) induced bone marrow derived macrophages (BMDMs) and mouse peritoneal macrophages (MPMs), isolated from ApoE-deficient mice, while ALK7's strong immunoreactivity in BMDMs was observed. ALK7 knockdown significantly attenuated pro-inflammatory, but promoted anti-inflammatory, macrophage markers expression. Additionally, ALK7 silencing decreased foam cell formation, accompanied by the up-regulation of ABCA1 and ABCG1 involved in cholesterol efflux but the down-regulation of CD36 and SR-A implicated in cholesterol influx. Mechanistically, ALK7 knockdown upregulated PPARγ expression, which was required for the ameliorated effect of ALK7 silencing macrophage activation. CONCLUSIONS: Our study demonstrated that ALK7 was a positive regulator for macrophage activation, partially through down-regulation of PPARγ expression, which suggested that neutralizing ALK7 might be promising therapeutic strategy for treating atherosclerosis.

ALK7 Promotes Vascular Smooth Muscle Cells Phenotypic Modulation by Negative Regulating PPARγ Expression.

As a receptor for transforming growth factor-ß, nodal and activin, activin receptor-like kinase 7 (ALK7) previously acts as a suppressor of tumorigenesis and metastasis, which has emerged to play a key role in cardiovascular diseases. However, the potential effect and molecular mechanism of ALK7 on vascular smooth muscle cells' (VSMCs) phenotypic modulation have not been investigated. Using cultured mouse VSMCs with platelet-derived growth factor-BB administration, we observed that ALK7 showed a significantly increased expression in VSMCs accompanied by decreased VSMCs differentiation marker genes. Loss-of-function study demonstrated that ALK7 knockdown inhibited platelet-derived growth factor-BB-induced VSMCs phenotypic modulation characterized by increased VSMCs differentiation markers, reduced proliferation, and migration of VSMCs. Such above effects were reversed by ALK7 overexpression. Notably, we noticed that ALK7 silencing dramatically enhanced PPARγ expression, which was required for the attenuated effect of ALK7 knockdown on VSMCs phenotypic modulation. Collected, we identified that ALK7 acted as a novel and positive regulator for VSMCs phenotypic modulation partially through inactivation of PPARγ, which suggested that neutralization of ALK7 might act as a promising therapeutic strategy of intimal hyperplasia.

Clinical Features and Short-term Outcomes of 102 Patients with Coronavirus Disease 2019 in Wuhan, China.

BACKGROUND: In December 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, China. In this study, we investigate the clinical and laboratory features and short-term outcomes of patients with coronavirus disease 2019 (COVID-19). METHODS: All patients with COVID-19 admitted to Wuhan University Zhongnan Hospital in Wuhan, China, between 3 January and 1 February 2020 were included. All those patients were with laboratory-confirmed infections. Epidemiological, clinical, and radiological characteristics; underlying diseases; laboratory tests; treatments; complications; and outcomes data were collected. Outcomes were followed up at discharge until 15 February 2020. RESULTS: The study cohort included 102 adult patients. The median age was 54 years (interquartile ranger, 37-67 years), and 48.0% were female. A total of 34 patients (33.3%) were exposed to a source of transmission in the hospital setting (as health-care workers, patients, or visitors) and 10 patients (9.8%) had a familial cluster. There were 18 patients (17.6%) who were admitted to the intensive care unit (ICU), and 17 patients died (mortality, 16.7%; 95% confidence interval, 9.4-23.9%). Those patients who survived were younger, were more likely to be health-care workers, and were less likely to suffer from comorbidities. They were also less likely to suffer from complications. There was no difference in drug treatment rates between the survival and nonsurvival groups. Those patients who survived were less likely to require admission to the ICU (14.1% vs 35.3% of those admitted). Chest imaging examinations showed that patients who died were more likely to have ground-glass opacity (41.2% vs 12.9% in survivors). CONCLUSIONS: The mortality rate was high among the COVID-19 patients described in our cohort who met our criteria for inclusion in this analysis. The patient characteristics seen more frequently in those who died were the development of systemic complications following onset of the illness and a severity of disease requiring admission to the ICU. Our data support those described by others indicating that COVID-19 infection results from human-to-human transmission, including familial clustering of cases, and from nosocomial transmission. There were no differences in mortality among those who did or did not receive antimicrobial or glucocorticoid drug treatments.

Correction to: Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit.

The original version of this article unfortunately contained a mistake. There was an error in Xiaorong Hu's name. The original article has been corrected. The authors apologize for the mistake.

Tollip Negatively Regulates Vascular Smooth Muscle Cell-Mediated Neointima Formation by Suppressing Akt-Dependent Signaling.

BACKGROUND: Tollip, a well-established endogenous modulator of Toll-like receptor signaling, is involved in cardiovascular diseases. The aim of this study was to investigate the role of Tollip in neointima formation and its associated mechanisms. METHODS AND RESULTS: In this study, transient increases in Tollip expression were observed in platelet-derived growth factor-BB-treated vascular smooth muscle cells and following vascular injury in mice. We then applied loss-of-function and gain-of-function approaches to elucidate the effects of Tollip on neointima formation. While exaggerated neointima formation was observed in Tollip-deficient murine neointima formation models, Tollip overexpression alleviated vascular injury-induced neointima formation by preventing vascular smooth muscle cell proliferation, dedifferentiation, and migration. Mechanistically, we demonstrated that Tollip overexpression may exert a protective role in the vasculature by suppressing Akt-dependent signaling, which was further confirmed in rescue experiments using the Akt-specific inhibitor (AKTI). CONCLUSIONS: Our findings indicate that Tollip protects against neointima formation by negatively regulating vascular smooth muscle cell proliferation, dedifferentiation, and migration in an Akt-dependent manner. Upregulation of Tollip may be a promising strategy for treating vascular remodeling-related diseases.

Mindin deficiency in macrophages protects against foam cell formation and atherosclerosis by targeting LXR-ß.

Mindin, which is a highly conserved extracellular matrix protein, has been documented to play pivotal roles in regulating angiogenesis, inflammatory processes, and immune responses. The aim of the present study was to assess whether mindin contributes to the development of atherosclerosis. A significant up-regulation of Mindin expression was observed in the serum, arteries and atheromatous plaques of ApoE-/- mice after high-fat diet treatment. Mindin-/-ApoE-/- mice and macrophage-specific mindin overexpression in ApoE-/- mice (Lyz2-mindin-TG) were generated to evaluate the effect of mindin on the development of atherosclerosis. The Mindin-/-ApoE-/- mice exhibited significantly ameliorated atherosclerotic burdens in the entire aorta and aortic root and increased atherosclerotic plaque stability. Moreover, bone marrow transplantation further demonstrated that mindin deficiency in macrophages was largely responsible for the alleviated atherogenesis. The Lyz2-mindin-TG mice exhibited the opposite phenotype. Mindin deficiency enhanced foam cell formation by increasing the expression of cholesterol effectors, including ABCA1 and ABCG1. The mechanistic study indicated that mindin ablation promoted LXR-ß expression via a direct interaction. Importantly, LXR-ß inhibition largely reversed the ameliorating effect of mindin deficiency on foam cell formation and ABCA1 and ABCG1 expression. The present study demonstrated that mindin deficiency serves as a novel mediator that protects against foam cell formation and atherosclerosis by directly interacting with LXR-ß.