Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial.

BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Synergistic actions of three MYB transcription factors underpins the high accumulation of myricetin in Morella rubra.

Flavonols are health-promoting bioactive compounds important for human nutrition, health, and plant defense. The transcriptional regulation of kaempferol and quercetin biosynthesis has been studied extensively, while little is known about the regulatory mechanisms underlying myricetin biosynthesis, which has strong antioxidant, anticancer, antidiabetic, and anti-inflammatory activities. In this study, the flavonol-specific MrMYB12 in Morella rubra preferred activating the promoter of flavonol synthase 2 (MrFLS2) (6.4-fold) rather than MrFLS1 (1.4-fold) and upregulated quercetin biosynthesis. Furthermore, two SG44 R2R3-MYB members, MrMYB5 and MrMYB5L, were identified by yeast one-hybrid library screening using the promoter of flavonoid 3',5'-hydroxylase (MrF3'5'H), and transcript levels of these R2R3-MYBs were correlated with accumulation of myricetin derivatives during leaf development. Dual-luciferase and electrophoretic mobility shift assays demonstrated that both MrMYB5 and MrMYB5L could bind directly to MYB recognition sequence elements in promoters of MrF3'5'H or MrFLS1 and activate their expression. Protein-protein interactions of MrMYB5 or MrMYB5L with MrbHLH2 were confirmed by yeast two-hybrid and bimolecular fluorescence complementation assays. MrMYB5L-MrbHLH2 showed much higher synergistic activation of MrF3'5'H or MrFLS1 promoters than MrMYB5-MrbHLH2. Studies with Arabidopsis thaliana homologs AtMYB5 and AtTT8 indicated that similar synergistic regulatory effects occur with promoters of MrF3'5'H or MrFLS1. Transient overexpression of MrMYB5L-MrbHLH2 in Nicotiana benthamiana induced a higher accumulation of myricetin derivatives (57.70 µg g-1 FW) than MrMYB5-MrbHLH2 (7.43 µg g-1 FW) when MrMYB12 was coexpressed with them. This study reveals a novel transcriptional mechanism regulating myricetin biosynthesis with the potential use for future metabolic engineering of health-promoting flavonols.

Energy Gap of the Even-Denominator Fractional Quantum Hall State in Bilayer Graphene.

Bernal bilayer graphene hosts even-denominator fractional quantum Hall states thought to be described by a Pfaffian wave function with non-Abelian quasiparticle excitations. Here, we report the quantitative determination of fractional quantum Hall energy gaps in bilayer graphene using both thermally activated transport and by direct measurement of the chemical potential. We find a transport activation gap of 5.1 K at B=12 T for a half filled N=1 Landau level, consistent with density matrix renormalization group calculations for the Pfaffian state. However, the measured thermodynamic gap of 11.6 K is smaller than theoretical expectations for the clean limit by approximately a factor of 2. We analyze the chemical potential data near fractional filling within a simplified model of a Wigner crystal of fractional quasiparticles with long-wavelength disorder, explaining this discrepancy. Our results quantitatively establish bilayer graphene as a robust platform for probing the non-Abelian anyons expected to arise as the elementary excitations of the even-denominator state.

The percentage of circulating fibrocytes is associated with increased morbidity of pulmonary hypertension in patients on hemodialysis.

INTRODUCTION: Pulmonary hypertension (PH) is highly prevalent in patients receiving dialysis. The precise mechanisms underlying PH in hemodialysis (HD) patients have not been adequately addressed. Emerging experimental evidence indicates that circulating fibrocytes may contribute significantly to this process. METHODS: We measured the proportion of circulating fibrocytes using flow cytometry analysis and prospectively analyzed patients during HD from February 1, 2017, to February 1, 2022. Then we investigated correlations between circulating fibrocytes, inflammation cytokines, PH, and their affective factors that predict the prognosis of HD patients. RESULTS: The cohort included 192 patients. During a follow-up of 5 years, we registered 66 all-cause deaths, and 11 patients received kidney transplantation. The incidence of PH among HD patients was 30.9%. We found that the circulating fibrocyte level significantly correlated with pulmonary arterial systolic pressure (r = 0.412, p < 0.05). In the multiple logistic regression analysis, the percentage of circulating fibrocytes was an independent predictor of PH (odds ratio [OR]: 2.080, 95% confidence interval [CI]: 1.539-2.812, p < 0.001). Controlling for confounding covariates in the multivariate Cox regression models, the presence of PH conferred an increased risk of all-cause mortality in HD patients [hazard ratio (HR): 2.183, 95% CI:1.257-3.788, p = 0.006]. CONCLUSION: The prevalence of PH was high in HD patients and was associated with higher all-cause mortality. Higher circulating fibrocyte level was an independent predictor of the presence of PH; these fibrocytes may serve as early detection markers and novel therapeutic targets.

Randomized evaluation of 5-month Ticagrelor monotherapy after 1-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with drug-coated balloons: REC-CAGEFREE II trial rationale and design.

BACKGROUND: Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. METHODS: The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. DISCUSSION: The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04971356.

Drug-coated balloon angioplasty with provisional stenting versus primary stenting for the treatment of de novo coronary artery lesions: REC-CAGEFREE I trial rationale and design.

BACKGROUND: Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. STUDY DESIGN: The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. DISCUSSION: The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. TRIAL REGISTRATION: Registered on clinicaltrial.gov (NCT04561739).

Transcriptome profiling of Nephelium lappaceum: Sodium nitroprusside-induced delays of postharvest browning.

Sodium nitroprusside (SNP), as a nitric oxide donor, is widely used in postharvest fruit physiology and metabolism. Our previous study has indicated that SNP plays a crucial role in postharvest browning control of rambutan, but the molecular mechanism underlying this process is still unclear. In this research, we investigated the gene expression and function of postharvest rambutan in response to SNP during browning. We found 7336 differentially expressed genes (DEGs), among which 2206 were upregulated and 5130 were downregulated. Gene Ontology (GO) enrichment as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed, and the real-time quantitative PCR (qPCR) data were consistent with transcriptome data. The DEGs relevant to rambutan pericarp browning were mainly involved in anthocyanin biosynthesis, phenolic oxidation, reactive oxygen species (ROS) production, and energy supply. It was shown that SNP regulated the synthesis and degradation of anthocyanins, accumulation of phenols, level of ROS and energy metabolism to suppress the postharvest browning of rambutan. Also, one WRKY transcription factor involved in ROS metabolism was observed to be differentially regulated. These findings add to our insights into the molecular mechanisms of the SNP-induced browning delays of rambutan, which has implications for subsequent studies on molecular mechanisms of fruit browning.

Fragmented QRS complex on a 12-lead electrocardiogram predicts cardiovascular and all-cause mortality in dialysis patients.

BACKGROUND: Cardiovascular disease (CVD) is the most common cause of mortality in end-stage renal disease (ESRD) patients. Fragmented QRS complex (fQRS) has been reported as a helpful marker in evaluating various cardiovascular pathologies. We aimed to investigate the value of the fQRS complex clinical decision of ESRD patients receiving dialysis. METHODS: This prospective observational study included 411 patients receiving hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) between 2016-01-01 and 2020-12-31. The primary outcomes were all-cause and cardiovascular (CV) mortality. RESULTS: HD patients have elevated values of fQRS complex compared to CAPD patients (39.1% vs. 28.2%, P = 0.027). Significantly, fQRS complex in the anterior/lateral leads is associated with all-cause and CV mortality stronger than fQRS in the inferior leads (P = 0.008). In a multivariate Cox regression analysis, HD patients with fQRS complex had a higher incidence of all-cause mortality (hazard ratio [HR] = 1.860; 95% confidence interval [CI]: [1.032, 3.349]; p = 0.041) and CV mortality (HR = 2.989; 95% CI [1.357, 6.584]; p = 0.007). For CAPD patients, fQRS complex was also associated with increased risk of all-cause mortality (HR = 1.593; 95% CI [1.023, 2.580]; p = 0.049) and increased risk of CV mortality (HR = 2.392; 95% CI [1.348, 4.173]; p = 0.013). CONCLUSIONS: The presence of the fQRS complex was an independent predictor of all-cause and CV mortality in HD and CAPD patients. We suggested a potential role of the fQRS complex in CV risk strata for dialysis patients and the choice of dialysis modality.

Transcriptome analysis of oil palm pistil during pollination and fertilization to unravel the role of phytohormone biosynthesis and signaling genes.

Phytohormones play an important role in the pollination and fertilization of crops, but the regulatory mechanisms of oil palm pollination and fertilization are unclear. The purpose of this study is to explore the hormonal changes of oil palm pistils during flowering. We used RNA sequencing to evaluate differentially expressed genes (DEGs) in oil palm pistils at the pollination and non-pollination stages. In this study, we found that the hormone contents of oil palm pistil changed drastically after pollination. The transcriptome of the oil palm pistil without pollination and at 2 h, 4 h, 12 h, 24 h, and 48 h after pollination was comprehensively analyzed, and a large number of differential genes and metabolic pathways were explored. Based on the transcriptome data, it could be recognized that the changes of indoleacetic acid (IAA), zeatin riboside (ZR), and abscisic acid (ABA) during pollination were consistent with the changes in the corresponding gene transcripts. Differentially expressed genes during pollination and fertilization of oil palm were mainly related to energy metabolism and hormone signal transduction. It provides new insights to elucidate the interaction and regulation mechanisms of plant hormones before and after oil palm pollination, providing a theoretical basis and reference for the research on sexual reproduction of oil palm.

Substitution strategies for cooking energy: To use gas or electricity?

The Chinese government has called for clean and effective energy substitution for cooking in rural areas. This paper assesses the environmental and economic impacts of various types of cooking fuels and stoves. According to the assessment results, the environmental impacts are highly influenced by the types of fuels and the efficiency of stoves used for cooking. Using biogas, liquefied petroleum gas (LPG), and natural gas for cooking instead of solid fuels can significantly reduce environmental emissions. To provide 1 megajoule (MJ) of useful cooking heat, the environmental costs of lump coal, honeycomb briquettes, and straw are the largest, estimated to be 80.4 yuan/MJ, 73.1 yuan/MJ, and 71.4 yuan/MJ, respectively. In addition, the economic assessment results show that the most expensive source of cooking fuel is LPG, with an average annual cost of 1700 yuan, while the cost of straw and firewood is the cheapest, at less than 100 yuan. The average annual cost of electricity is higher than that of natural gas. Regarding the substitution effects, using natural gas for cooking is better than using electricity. The environmental benefit of electricity substitution is only 10%-20% of natural gas substitution, and the corresponding increasing cost for residents is 1.5 times that of natural gas substitution.

Metamaterial-based ultrashort multimode waveguide taper with low intermodal crosstalk.

We propose and theoretically demonstrate an ultrashort multimode waveguide taper based on the all-dielectric metamaterial. Attributed to the gradient index distribution of the metamaterial, the spot sizes of the four lowest-order transverse magnetic (TM) modes can be expanded in a short distance of 6 µm with negligible mode conversions. Numerical results prove that the insertion losses of the taper are lower than 1 dB, 1.12 dB, 1.26 dB and 1.66 dB for the TM0 - TM3 modes, respectively, and the intermodal crosstalk values are below -15 dB for the four modes, both in the wavelength range of 1.5 µm - 1.6 µm. To the best of our knowledge, this is the first multimode waveguide taper that has low intermodal crosstalk of < -15 dB over a 100-nm bandwidth.

Biological prevention and control of pitaya fruit canker disease using endophytic fungi isolated from papaya.

Pitaya fruit canker is an important disease in pitaya production. Facilitating resistance through the application of biological control principles is a promising alternative to traditional control strategies. This study evaluated the induced resistance of Penicillium rolfsii, numbered Y17 isolated from papaya leaves in pitaya fruit, and evaluated the activity of the defense enzymes, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content of the treated fruit. The results demonstrate that treatment with Y17 effectively induced resistance of pitaya fruit to canker disease caused by Neoscytalidium dimidiatum, with an inhibition rate of 70.87%. In addition, Y17 notably improved the activities of peroxidase, catalase, and polyphenol oxidase as well as the T-AOC of the treated samples. Y17 treatment reduced the MDA content in these fruits. Taken together, our results suggest that Y17 treatment could trigger pitaya fruit defense responses and effectively induce resistance to fruit canker disease.

AB2X6 Compounds and the Stabilization of Trirutile Oxides.

The properties of crystalline materials tend to be strongly correlated with their structures, and the prediction of crystal structure from only the composition is a coveted goal in the field of inorganic materials. However, even for the simplest compositions, such prediction relies on a complex network of interactions, including atomic or ionic radii, ionicity, electronegativity, position in the periodic table, and magnetism, to name only a few important parameters. We focus here on the AB2X6 (AB2O6 and AB2F6) composition space with the specific goal of finding new oxide compounds in the trirutile family, which is known for unusual one-dimensional (1D) antiferromagnetic behavior. Through machine learning methods, we develop an understanding of how geometric and bonding constraints determine the crystallization of compounds in the trirutile structure as opposed to other ternary structures in this space. In combination with density functional theory (DFT) calculations, we predict 16 previously unreported candidate trirutile oxides. We successfully prepare one of these and show it forms in the disordered rutile structure, under the preparation conditions adopted here.

Clinical outcomes in 2481 unselected real-world patients treated with a polymer-free sirolimus-eluting stent: 3 years results from the NANO multicenter Registry.

OBJECTIVES: To evaluate the 3-year clinical outcomes of a polymer-free sirolimus-eluting, Nano plus stent for the treatment of coronary artery disease in the NANO multicenter Registry. BACKGROUND: The long-term clinical data evaluating the safety and efficacy of the novel polymer-free sirolimus-eluting Nano plus stent (Lepu Medical, Beijing, China) is limited. METHODS: The NANO all-comers Registry trial was a prospective, multicenter clinical registry conducted in 26 centers in China between August 2016 and January 2017. A total of 2481 consecutive patients were exclusively treated with the Nano plus stent. The primary clinical endpoint, target lesion failure (TLF, defined as cardiac death, target vessel nonfatal myocardial infarction, and clinically driven target lesion revascularization [CD-TLR]), was analyzed at 3 years. RESULTS: At 3 years, 2295 patients (92.5%) were followed. The incidence of TLF was 6.8% (168/2481). The rate of cardiac death was 3.8% (94/2481), target vessel nonfatal myocardial infarction 0.7% (18/2481), and CD-TLR 2.9% (68/2481). The rate of definite/probable stent thrombosis was 0.5% (13/2481). The risk factors of diabetes mellitus, acute myocardial infarction, age, chronic renal failure, in-stent restenosis, chronic total occlusion, and left ventricular ejection fraction < 40% were the independent predictors of 3-year TLF. CONCLUSIONS: At three years, the rate of TLF was relatively low in patients treated with the polymer-free Nano plus stent. The polymer-free Nano plus stent showed a favorable safety and efficacy profile in real-world patients. Clinical trial registration URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02929030.

Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study.

AIMS: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20). CONCLUSION: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.

[Numerical study on the effect of middle ear malformations on energy absorbance].

In order to study the effect of middle ear malformations on energy absorbance, we constructed a mechanical model that can simulate the energy absorbance of the human ear based on our previous human ear finite element model. The validation of this model was confirmed by two sets of experimental data. Based on this model, three common types of middle ear malformations, i. e. incudostapedial joint defect, incus fixation and malleus fixation, and stapes fixation, were simulated by changing the structure and material properties of the corresponding tissue. Then, the effect of these three common types of middle ear malformations on energy absorbance was investigated by comparing the corresponding energy absorbance. The results showed that the incudostapedial joint defect significantly increased the energy absorbance near 1 000 Hz. The incus fixation and malleus fixation dramatically reduced the energy absorbance in the low frequency, which made the energy absorbance less than 10% at frequencies lower than 1 000 Hz. At the same time, the peak of energy absorbance shifted to the higher frequency. These two kinds of middle ear malformations had obvious characteristics in the wideband acoustic immittance test. In contrast, the stapes fixation only reduced the energy absorbance in the low frequency and increased energy absorbance in the middle frequency slightly, which had no obvious characteristic in the wideband acoustic immittance test. These results provide a theoretical reference for the wideband acoustic immittance diagnosis of middle ear malformations in clinic.

FOXO3a-mediated long non-coding RNA LINC00261 resists cardiomyocyte hypoxia/reoxygenation injury via targeting miR23b-3p/NRF2 axis.

Ischemia/reperfusion (I/R)-mediated acute myocardial infarction (AMI) is a major pathological factor implicated in the progression of ischemic heart disease (IHD). Long non-coding RNA plays an important role in regulating the occurrence and development of cardiovascular disease. The aim of this study was to investigate the regulating role of LINC00261 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis. The relative expression of LINC00261, miR-23b-3p and NRF2 were determined in rats I/R myocardial tissues and H/R-induced cardiomyocytes. The rat model and cell model of LINC00261 overexpression were established to investigate the biological function of LINC00261 on H9C2 cell. The interaction between LINC00261, miR-23b-3p, NRF2 and FOXO3a was identified using bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation (RIP) assay, chromatin immunoprecipitation (CHIP) assay and qRT-PCR. The expression of LINC00261 was significantly down-regulated in myocardial tissues and H9C2 cell. Overexpression of LINC00261 improves cardiac function and reduces myocardium apoptosis. Interestingly, transcription factor FOXO3a was found to promote LINC00261 transcription. Moreover, LINC00261 was confirmed as a spong of miR23b-3p and thereby positively regulates NRF2 expression in cardiomyocytes. Our findings reveal a novel role for LINC00261 in regulating H/R cardiomyocyte apoptosis and the potency of the LINC00261/miR-23b-3p/NRF2 axis as a therapeutic target for the treatment of MIRI.

One-year clinical results of the NANO registry: A multicenter, prospective all-comers registry study in patients receiving implantation of a polymer-free sirolimus-eluting stent.

OBJECTIVES: We aimed to evaluate the safety and efficacy of Nano+™ (Lepu Medical, Beijing, China) stent implantation in all-comer patients at the 1-year follow-up. BACKGROUND: The Nano+™ stent is a novel polymer-free sirolimus-eluting stent polymer that employs nanoporous stent surface technology to control drug-delivery. The Nano+™ stent is one of the most widely used drug-eluting stent (DES) in China. METHODS: A total of 2,481 consecutive patients were included in the multicenter and prospective NANO registry. In this study, the primary endpoint was target lesion failure (TLF) at 1-year follow-up, defined as a composite of cardiac death, target vessel nonfatal myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR). The safety endpoint was the occurrence of definite or probable stent thrombosis (ST). RESULTS: Up to 40.2% of patients presented with acute myocardial infarction (AMI). A total of 63.9% of the 2,904 lesions were American College of Cardiology/American Heart Association (ACC/AHA) type B2 or C lesions. One-year follow-up data were available for 98.4% of patients. The 1-year rate of TLF was 3.1% with rates of 1.3, 1.8, and 0.4% for clinically driven TLR, cardiac death, and TV-MI, respectively. ST occurred in 0.4% of patients. Diabetes mellitus, AMI, left ventricular ejection fraction <40% and long lesions (>40 mm) were independent predictors of 1-year TLF. CONCLUSIONS: The 1-year clinical outcomes were excellent for Nano+™ polymer-free SES implantation in an all-comer patient population. Follow-up will be extended up to 5 years, to further elucidate the potential long-term clinical benefits. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02929030.

The Prognostic Value of Soluble ST2 in Maintenance Hemodialysis Patients: A Meta-Analysis.

BACKGROUND: Much controversy remains in the literature with respect to whether soluble suppression of tumorigenicity 2 (sST2) can serve to predict all-cause death in patients undergoing maintenance hemodialysis (MHD). This meta-analysis therefore sought to analyze extant datasets exploring the association between these 2 variables in MHD patients in order to draw relevant conclusions. METHODS: Articles published through December 2018 in PubMed and Embase were independently reviewed by 2 authors to identify relevant articles, and STATA 12.0 was used for statistical analyses of relevant results and study parameters. RESULTS: In total, we identified 4 relevant studies that were incorporated into this meta-analysis. These studies included a total of 1,924 participants (60% male, mean follow-up 911 days). The combined study results suggested that increased levels of sST2 were significantly linked to a 2.23 fold rise in all-cause mortality (hazard ratio [HR] 2.23, 95% CI 1.81-2.75). Subgroup analyses confirmed that this same association was true in patients undergoing hemodialysis (HR 2.17, 95% CI 1.74-2.71), which indicated that the increased levels of sST2 were significantly linked to a 2.17 fold rise in all-cause mortality. CONCLUSIONS: This analysis suggests that there is a significant link between elevated levels of sST2 and death in patients undergoing MHD. Further large-scale trials, however, will be needed to fully validate these findings and their clinical relevance.

A deuterohemin peptide protects a transgenic Caenorhabditis elegans model of Alzheimer's disease by inhibiting Aß1-42 aggregation.

Alzheimer's disease (AD) is a progressive neurodegenerative brain disease and is the most common cause of dementia in the elderly. The main hallmark of AD is the deposition of insoluble amyloid (Aß) outside the neuron, leading to amyloid plaques and neurofibrillary tangles in the brain. Deuterohemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6), a novel porphyrin-peptide, has both microperoxidase activity and cell permeability. In the present study, DhHP-6 efficiently inhibited the aggregation of Aß and reduced the ß-sheet percentage of Aß from 89.1% to 78.3%. DhHP-6 has a stronger affinity (KD = 100 ±â€¯12 µM) for binding with Aß at Phe4, Arg5, Val18, Glu11 and Glu22. In addition, DhHP-6 (100 µM) significantly prolonged lifespan, alleviated paralysis and reduced Aß plaque formation in the Aß1-42 transgenic Caenorhabditis elegans CL4176 model of AD. Our results demonstrate that DhHP-6 is a potential drug candidate that efficiently protects a transgenic C. elegans model of Alzheimer's disease by inhibiting Aß aggregation.