ObjectiveWe sought to explore the prevalence and immediate clinical implications of acute myocardial injury in a cohort of patients with COVID-19 in a region of China where medical resources are less ...stressed than in Wuhan (the epicentre of the pandemic).MethodsWe prospectively assessed the medical records, laboratory results, chest CT images and use of medication in a cohort of patients presenting to two designated covid-19 treatment centres in Sichuan, China. Outcomes of interest included death, admission to an intensive care unit (ICU), need for mechanical ventilation, treatment with vasoactive agents and classification of disease severity. Acute myocardial injury was defined by a value of high-sensitivity troponin T (hs-TnT) greater than the normal upper limit.ResultsA total of 101 cases were enrolled from January to 10 March 2020 (average age 49 years, IQR 34–62 years). Acute myocardial injury was present in 15.8% of patients, nearly half of whom had a hs-TnT value fivefold greater than the normal upper limit. Patients with acute myocardial injury were older, with a higher prevalence of pre-existing cardiovascular disease and more likely to require ICU admission (62.5% vs 24.7%, p=0.003), mechanical ventilation (43.5% vs 4.7%, p<0.001) and treatment with vasoactive agents (31.2% vs 0%, p<0.001). Log hs-TnT was associated with disease severity (OR 6.63, 95% CI 2.24 to 19.65), and all of the three deaths occurred in patients with acute myocardial injury.ConclusionAcute myocardial injury is common in patients with COVID-19 and is associated with adverse prognosis.
In this study, we have prepared novel pyrrole–formaldehyde polymers through polymerizing pyrrole and formaldehyde in the mixture solvent of water and ethanol by using hydrochloric acid as a catalyst. ...The as-synthesized polymers possess a nitrogen content of 6.7 atom % and are composed of spherical particles with the diameter of approximately 1–3 μm. A series of nitrogen-doped porous carbons with high specific surface areas (680–2340 m2 g–1) were successfully obtained through the activation treatment of the polymer spheres. The porous properties and surface chemistry of the as-prepared porous carbons are tuned by choosing different activating agents and changing the activation temperature. The morphology, porous properties, and chemical composition of the obtained nitrogen-doped porous carbons are revealed by various characterization methods, such as scanning electron microscopy, nitrogen sorption measurement, and X-ray photoelectron spectroscopy. The as-prepared nitrogen-doped porous carbons as gas adsorbents display high carbon dioxide uptake capacities of 3.80–5.81 mmol g–1 at 273 K and 1.0 bar. They also show excellent carbon dioxide adsorption capacities (2.40–3.37 mmol g–1 at 1.0 bar) and good gas selectivities (CO2/N2 selectivities of 16.9–70.2) at 298 K.
The tyrosine kinase inhibitor (TKI) gefitinib exerts good therapeutic effect on NSCLC patients with sensitive EGFR-activating mutations. However, most patients ultimately relapse due to the ...development of drug resistance after 6–12 months of treatment. Here, we showed that a HIF-1α inhibitor, YC-1, potentiated the antitumor efficacy of gefitinib by promoting EGFR degradation in a panel of human NSCLC cells with wild-type or mutant EGFRs. YC-1 alone had little effect on NSCLC cell survival but significantly enhanced the antigrowth and proapoptotic effects of gefitinib. In insensitive NSCLC cell lines, gefitinib efficiently inhibited the phosphorylation of EGFR but not the downstream signaling of ERK, AKT and STAT3; however, when combined with YC-1 treatment, these signaling pathways were strongly impaired. Gefitinib treatment induced EGFR arrest in the early endosome, and YC-1 treatment promoted delayed EGFR transport into the late endosome as well as receptor degradation. Moreover, the YC-1-induced reduction of HIF-1α protein was associated with the enhancement of EGFR degradation. HIF-1α knockdown promoted EGFR degradation, showing synergistic antigrowth and proapoptotic effects similar to those of the gefitinib and YC-1 combination treatment in NSCLC cells. Our findings provide a novel combination treatment strategy with gefitinib and YC-1 to extend the usage of gefitinib and overcome gefitinib resistance in NSCLC patients.
The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage ...dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH
, for the co-delivery of anti-inflammatory drug curcumin (CCM) and small interfering RNA (siRNA) for hypoxia inducible factor (HIF-2α). CCM and siRNA were loaded via encapsulation and surface coordination ability of MIL-101-NH
. Our vitro tests showed that MIL-101-NH
protected siRNA from nuclease degradation by lysosomal escape. The pH-responsive MIL-101-NH
gradually collapsed in an acidic OA microenvironment to release the CCM payloads to down-regulate the level of pro-inflammatory cytokines, and to release the siRNA payloads to cleave the target HIF-2α mRNA for gene-silencing therapy, ultimately exhibiting the synergetic therapeutic efficacy by silencing HIF-2α genes accompanied by inhibiting the inflammation response and cartilage degeneration of OA. The hybrid material reported herein exhibited promising potential performance for OA therapy as supported by both in vitro and in vivo studies and may offer an efficacious therapeutic strategy for OA utilizing MOFs as host materials.
Metabolic syndrome is a medical condition characterized by several metabolic disorders in the body. Long-term metabolic disorders raise the risk of cardiovascular disease (CVD) and type 2 diabetes ...mellitus (T2DM). Therefore, it is essential to actively explore the aetiology of metabolic syndrome (MetS) and its comorbidities to provide effective treatment options. Ferroptosis is a new form of cell death that is characterized by iron overload, lipid peroxide accumulation, and decreased glutathione peroxidase 4(GPX4) activity, and it involves the pathological processes of a variety of diseases. Lipid deposition caused by lipid diseases and iron overload is significant in metabolic syndrome, providing the theoretical conditions for developing ferroptosis. Recent studies have found that the major molecules of ferroptosis are linked to common metabolic syndrome consequences, such as T2DM and atherosclerosis. In this review, we first discussed the mechanics of ferroptosis, the regulatory function of inducers and inhibitors of ferroptosis, and the significance of iron loading in MetS. Next, we summarized the role of ferroptosis in the pathogenesis of MetS, such as obesity, type 2 diabetes, and atherosclerosis. Finally, we discussed relevant ferroptosis-targeted therapies and raised some crucial issues of concern to provide directions for future Mets-related treatments and research.
The authors sought to better understand the stent geometry of the Lotus valve after transcatheter aortic valve replacement (TAVR) and its potential implications for valve size selection.
The authors ...hypothesized that the greatest interference between the frame and aortic valvar complex occurs across the aortic valve leaflets.
The authors retrospectively analyzed the multidetector computed tomography (MDCT) scans of 32 consecutive patients undergoing Lotus valve (Boston Scientific, Natick, Massachusetts) implantation. The prosthesis cross section was analyzed at 3-mm increments along its length. The plane where the frame had the smallest area was defined as the waist. The corresponding plane of the waist on pre-procedural MDCT was identified by surrounding structures such as calcium deposits, commissural fusion, and commissural gaps, and was referred to as the supra-annulus. The spline of the supra-annulus was circumscribed with reference to the post-implant stent geometry at the waist.
The waist was 5.8 ± 1.7 mm higher than the native annulus on post-procedural MDCT. The waist had a nearly 2-fold larger compression rate than the stent at the native annulus level (36.3 ± 10.4% vs. 18.9 ± 9.6%; p < 0.01), irrespective of valve morphologies. The supra-annulus was 5.9 ± 1.6 mm higher than the annulus on pre-procedural MDCT. Patients had an approximately 17% decrease in area from the annulus to the supra-annulus (18.3 ± 4.4% for bicuspid morphology and 16.0 ± 3.5% for tricuspid morphology).
Major interference between the implanted prosthesis and anatomy occurred at a level above the annulus. The decrease in area from the annulus to supra-annulus may explain the feasibility of implanting a smaller valve than that suggested by traditional annular measurements.
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BACKGROUNDIt is unknown whether the sex difference whereby female transcatheter aortic valve replacement (TAVR) candidates had a lower risk profile, a higher incidence of in-hospital complications, ...but more favorable short- and long-term survival observed in tricuspid cohorts undergoing TAVR would persist in patients with bicuspid aortic valves (BAVs). OBJECTIVESThe aim of this study was to reexamine the impact of sex on outcomes following TAVR in patients with BAVs. METHODSIn this single-center study, patients with BAVs undergoing TAVR for severe aortic stenosis from 2012 to 2021 were retrospectively included. Baseline characteristics, aortic root anatomy, and in-hospital and 1-year valve hemodynamic status and survival were compared between sexes. RESULTSA total of 510 patients with BAVs were included. At baseline, women presented with fewer comorbidities. Men had a greater proportion of Sievers type 1 BAV, higher calcium volumes (549.2 ± 408.4 mm3 vs 920.8 ± 654.3 mm3; P < 0.001), and larger aortic root structures. Women experienced more vascular complications (12.9% vs 4.9%; P = 0.002) and bleeding (11.1% vs 5.3%; P = 0.019) and higher residual gradients (16.9 ± 7.7 mm Hg vs 13.2 ± 6.4 mm Hg; P < 0.001), while men were more likely to undergo second valve implantations during index TAVR (6.3% vs 15.9%; P = 0.001). Death at 1 year was not significantly different between sexes (HR: 1.15; 95% CI: 0.56-2.35; P = 0.70). Bleeding (adjusted HR: 4.62; 95% CI: 1.51-14.12; P = 0.007) was the single independent predictor of 1-year death for women. CONCLUSIONSIn patients with BAVs undergoing TAVR, women presented with fewer comorbidities, while men had a greater proportion of type 1 BAV, more calcification, and larger aortic roots. In-hospital outcomes favored men, with fewer complications except for the need for second valve implantation, but 1-year survival was comparable between sexes.
The chemical composition discrepancies of five sweet potato leaves (SPLs) and their phenolic profile variations during in vitro digestion were investigated. The results indicated that Ecaishu No. 10 ...(EC10) provided better retention capacity for phenolic compounds after drying. Furthermore, polyphenols were progressively released from the matrix as the digestion process proceeded. The highest bioaccessibility of polyphenols was found in EC10 intestinal chyme at 48.47%. For its phenolic profile, 3-, 4-, and 5-monosubstituted caffeoyl quinic acids were 9.75%, 57.39%, and 79.37%, respectively, while 3,4-, 3,5-, and 4,5-disubstituted caffeoyl quinic acids were 6.55, 0.27 and 13.18%, respectively. In contrast, the 3,4-, 3,5-, 4,5-disubstituted caffeoylquinic acid in the intestinal fluid after dialysis bag treatment was 62.12%, 79.12%, and 62.98%, respectively, which resulted in relatively enhanced bioactivities (DPPH, 10.51 μmol Trolox/g; FRAP, 8.89 μmol Trolox/g; ORAC, 7.32 μmol Trolox/g; IC50 for α-amylase, 19.36 mg/g; IC50 for α-glucosidase, 25.21 mg/g). In summary, desirable phenolic acid release characteristics and bioactivity of EC10 were observed in this study, indicating that it has potential as a functional food ingredient, which is conducive to the exploitation of the sweet potato processing industry from a long-term perspective.
Theoretically, lactic acid bacteria (LABs) could degrade polyphenols into small molecular compounds. In this study, the biotransformation of lotus seedpod and litchi pericarp procyanidins by ...Lactobacillus plantarum 90 (Lp90), Streptococcus thermophilus 81 (ST81), Lactobacillus rhamnosus HN001 (HN001), and Pediococcus pentosus 06 (PP06) were analysed. The growth curve results indicated that procyanidins did not significantly inhibit the proliferation of LABs. Ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC–HRMS) revealed that procyanidin B2 and procyanidin B3 in lotus seedpod decreased by 62.85% and 25.45%, respectively, with ST81 metabolised, while kaempferol and syringetin 3-O-glucoside content increased. Although bioconversion did not increase the inhibitory function of procyanidins against glycosylation end-products in vitro, the 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) free radical scavenging capacity and ferric reducing antioxidant power of litchi pericarp procyanidins increased by 157.34% and 6.8%, respectively, after ST81 biotransformation. These findings may inspire further studies of biological metabolism of other polyphenols and their effects on biological activity.
To compare reverse left ventricular (LV) remodeling after transcatheter aortic valve replacement (TAVR) between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). We ...retrospectively reviewed data of patients with at least two serial echocardiographic follow-ups (1, 3, 6 months and 1 year) post-TAVR. A total of 116 patients were identified. BAV morphology was documented in 67 patients. LV mass index (LVMi) at baseline was not significantly different between the TAV and BAV group (178.0 ± 6.9 vs. 166.3 ± 6.4 g/m
2
, P = 0.14). Reverse LV remodeling was observed in both BAV and TAV patients, but the reduction of LVMi from baseline was significantly more pronounced in TAV patients compared with BAV patients from 6 months post-TAVR (− 56.3 ± 8.1 vs. − 30.0 ± 4.7 g/m
2
, P < 0.01 at 6-month follow-up; − 60.6 ± 7.6 vs. − 37.9 ± 6.2 g/m
2
, P = 0.02 at 1-year follow-up). EDV value changes during follow-up were similar between patient with TAV and BAV. There were no significant differences in the proportions of patients with more than mild PVL or new permanent pacemaker between TAV and BAV morphology throughout the follow-up. Patients with bicuspid morphology might experience less pronounced reverse LV remodeling post-TAVR than patients with tricuspid morphology.
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