[Effect of prenatal glucocorticoid therapy on hearing screening in premature infants].

Objective:To explore the effect of prenatal glucocorticoids therapy on hearing screening in premature infants Methods:Data of 693 preterm infants with gestational age of 24-34+6weeks admitted to theJiangxi Maternal and Child Health Hospital within 24 h after birth from June 2022 to June 2023 were retrospectively analyzed. The infants were divided into the DXM group （544 cases） and the non-DXM group （149 cases） based on whether dexamethasone （DXM） was administered prenatally. General data of preterm infants and parturients in two groups were compared, and the effects of different doses and timing of DXM on hearing screening were analyzed. Results:In the terms of preliminary hearing screening. the pass rate of initial hearing screening in DXM group was significantly higher than that in non-DXM group（53.9% vs 35.6%）, with statistical significance（P<0.05）. Further subgroup analysis showed that the passing rate of preliminary hearing screening in adequate prenatal dose（=4 doses） DXM group（58.1%） was significantly higher than that in insufficient group（48.0%） and excessive group（42.4%）, with statistical significance（P<0.05）. Administering DXM 48 hours to 7 days before birth resulted in a higher pass rate for initial hearing screening compared to administration <48 hours or >7 days before birth （56.4% vs. 48.6%）, with a statistically significant difference （P < 0.05）. In terms of re-hearing screening, the pass rate of secondary hearing screening was not significantly correlated with DXM treatment（P>0.05）, but was significantly correlated with gestational age, birth weight, hospital stays, invasive mechanical ventilation, and common neonatal diseases（bronchopulmonary dysplasia, respiratory distress syndrome）（P<0.05）. Among them, bronchopulmonary dysplasia was an independent risk factor forsecondary hearing screening referral（P<0.05）. Conclusion:A single course of adequate dexamethasone use within 48 h-7 d of prenatal has a positive effect on the preliminary hearing screening of preterm infants.

Identification of the Beta Subunit Fas1p of Fatty Acid Synthetase as an Interacting Partner of Yeast Calcium/Calmodulin-Dependent Protein Kinase Cmk2p Through Mass Spectrometry Analysis.

The calcium/calmodulin-dependent protein kinase II (CaMKII) is a mediator of calcium signals and regulates fatty acid metabolism in mammalian cells. Cmk2p is a yeast homolog of CaMKII and functions as a negative regulator of calcium signaling. However, its substrates remain to be identified. Combination of immunoprecipitation (IP) and mass spectrometry has been proven to be very useful for identification of interacting partner proteins and interactome. In this study, through these approaches, we have identified 65 and 110 potential Cmk2p-interacting proteins in yeast cells in the absence or presence of calcium stress, respectively. In yeast cells expressing both CMK2-HA and FAS1-GFP fusion proteins, in the absence or presence of calcium stress, less amounts of FAS1-GFP proteins are present in cell lysates after IP with anti-HA antibody than cell lysates before IP, while FAS1-GFP proteins are detected on both types of IP beads. However, as an internal control, similar amounts of Pgk1p proteins were detected in both after-IP and before-IP cell lysates but not on the IP beads. Therefore, our biochemical analysis demonstrates that the ß subunit Fas1p of fatty acid synthetase interacts with Cmk2p in yeast cells independent of calcium stress. It is also interesting to note that, in addition to the expected 52-kDa CMK2-HA band, a faster-moving 48-kDa CMK2-HA band is present in the calcium-stressed cell lysate but not in the cell lysate without calcium stress. Our data would provide important clues for understanding the functions of CaMKII in the regulation of fatty acid metabolism as well as related diseases such as cancers, diabetes, and obesity.

Amino acid metabolism and MAP kinase signaling pathway play opposite roles in the regulation of ethanol production during fermentation of sugarcane molasses in budding yeast.

Sugarcane molasses is one of the main raw materials for bioethanol production, and Saccharomyces cerevisiae is the major biofuel-producing organism. In this study, a batch fermentation model has been used to examine ethanol titers of deletion mutants for all yeast nonessential genes in this yeast genome. A total of 42 genes are identified to be involved in ethanol production during fermentation of sugarcane molasses. Deletion mutants of seventeen genes show increased ethanol titers, while deletion mutants for twenty-five genes exhibit reduced ethanol titers. Two MAP kinases Hog1 and Kss1 controlling the high osmolarity and glycerol (HOG) signaling and the filamentous growth, respectively, are negatively involved in the regulation of ethanol production. In addition, twelve genes involved in amino acid metabolism are crucial for ethanol production during fermentation. Our findings provide novel targets and strategies for genetically engineering industrial yeast strains to improve ethanol titer during fermentation of sugarcane molasses.

Transcriptional expression of PHR2 is positively controlled by the calcium signaling transcription factor Crz1 through its binding motif in the promoter.

IMPORTANCE: The fungal cell wall consists of glucans, mannoproteins, and chitin and is essential for cell viability, morphogenesis, and pathogenesis. The enzymes of the GH72 family are responsible for ß-(1,3)-glucan elongation and branching, which is crucial for the formation of the glucan-chitin polymer at the bud neck of yeast cells. In the human fungal pathogen Candida albicans, there are five GH72 enzyme-encoding genes: PHR1, PHR2, PHR3, PGA4, and PGA5. It is known that expression of PHR1 and PHR2 is controlled by the pH-responsive Rim101 pathway through the transcription factor Rim101. In this study, we have demonstrated that the transcription expression of PHR2 is also controlled by the transcription factor Crz1 through its binding motif in the promoter. Therefore, we have uncovered a dual-control mechanism by which PHR2 expression is negatively regulated via CaRim101 through the pH-responsive pathway and positively modulated by CaCrz1 through the calcium/calcineurin signaling pathway.

Comparison between Amplatzer and Watchman Left Atrial Appendage Closure Devices for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Meta-Analysis.

INTRODUCTION: The Amplatzer and Watchman left atrial appendage closure (LAAC) devices are the two most frequently used devices for LAAC devices worldwide. This meta-analysis aimed to compare the safety and efficacy of the two devices. METHODS: We searched the PubMed, EMBASE, and the Cochrane Library for studies up to February 6, 2022 that compared the safety and efficacy of the Amplatzer and Watchman devices. RESULTS: Fifteen studies including 2,150 patients in randomized controlled trials and 2,526 patients in observational studies were included in the meta-analysis. Amplatzer device was associated with higher rates of major procedure-related complications (odds ratio [OR]: 1.99, 95% confidence interval [CI]: 1.45-2.74, p < 0.0001) and device embolization (OR: 1.99, 95% CI: 1.09-3.64, p = 0.03). However, Amplatzer device had lower rates of total peridevice leak (PDL) (OR: 0.48, 95% CI: 0.27-0.83, p = 0.009), significant PDL (OR: 0.27, 95% CI: 0.12-0.57, p = 0.0007) and device-related thrombus (DRT) (OR: 0.67, 95% CI: 0.48-0.95, p = 0.02). No statistical differences were observed between the two devices in other safety and efficacy endpoints, such as pericardial effusion, cardiac tamponade, air embolism, vascular complications, ischemic stroke/transient ischemic attack (TIA), hemorrhagic stroke, all-cause death, cardiovascular death, and bleeding. CONCLUSIONS: Amplatzer LAAC device was associated with higher rates of major procedure-related complications, especially in device embolization. Watchman LAAC device was associated with higher rates of PDL and DRT. There were no significant differences between two devices in ischemic stroke/TIA, hemorrhagic stroke, all-cause death, cardiovascular death, and bleeding.

Deferred Versus Immediate Stenting in Patients With ST-Segment Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis.

BACKGROUND: A number of studies have evaluated the efficacy of deferred stenting vs immediate stenting in patients with ST-segment elevation myocardial infarction, but the findings were not consistent across these studies. This meta-analysis aims to assess optimal treatment strategies in patient with ST-segment elevation myocardial infarction. METHODS AND RESULTS: We searched the PubMed, EMBASE, and the Cochrane Library for studies that assessed deferred vs immediate stenting in patients with ST-segment elevation myocardial infarction. Nine studies including 1456 patients in randomized controlled trials and 719 patients in observational studies were included in the meta-analysis. No significant differences were observed in the incidence of no- or slow-reflow between deferred stenting and immediate stenting in randomized controlled trials (odds ratio [OR] 0.51, 95%CI 0.17-1.53, P=0.23, I2=70%) but not in observational studies (OR 0.13, 95%CI 0.06-0.31, P<0.0001, I2=0%). Deferred stenting was associated with an increase in long-term left ventricular ejection fraction (weighted mean difference 1.90%, 95%CI 0.77-3.03, P=0.001, I2=0%). No significant differences were observed in the rates of major adverse cardiovascular events (OR 0.53, 95%CI 0.27-1.01, P=0.06 [randomized OR 0.98, 95%CI 0.73-1.30, P=0.87, I2=0%; nonrandomized OR 0.30, 95%CI 0.15-0.58, P=0.0004, I2=0%]), major bleeding (OR=0.1.61, 95%CI 0.70-3.69, P=0.26, I2=0%), death (OR=0.78, 95%CI 0.53-1.15, P=0.22, I2=0%), MI (OR=0.97, 95%CI 0.34-2.78, P=0.96, I2=35%) and target vessel revascularization (OR 0.97, 95%CI 0.40-2.37, P=0.95, I2=24%), between deferred and immediate stenting. CONCLUSIONS: Compared with immediate stenting, a deferred-stenting strategy did not reduce the occurrence of no- or slow-reflow, death, myocardial infarction, or repeat revascularization compared with immediate stenting in patients with ST-segment elevation myocardial infarction, but showed an improved left ventricular function in the long term.

Sphingomyelin in erythrocyte membranes increases the total cholesterol content of erythrocyte membranes in patients with acute coronary syndrome.

OBJECTIVES: To investigate whether the sphingomyelin content of erythrocyte membranes (SEM) is changed in patients with acute coronary syndrome (ACS) and determine the correlation between SEM and the total cholesterol content of erythrocyte membranes (CEM). METHODS: The SEM and CEM levels were measured in 354 patients undergoing coronary artery angiography in three different groups: ACS patients (n=199), patients with stable angina pectoris (SAP) (n=82), and controls (n=73). RESULTS: The SEM levels in the ACS group were significantly higher than those of the SAP group. The SEM levels were correlated positively with the CEM levels in patients with coronary artery disease. Multivariable logistic regression analysis showed that patients with higher levels of both SEM and CEM had an 8.569-fold greater risk of developing ACS than other patients, after adjusting for all potential confounding variables. CONCLUSION: Elevated SEM and CEM levels showed both independent and combined correlations with the occurrence of ACS and were positively correlated with each other in patients with coronary artery disease. These data suggest that the increased levels of SEM may play a role in the progression to plaque instability in ACS and may be the mechanisms underlying elevated levels of CEM in patients with ACS.

Total cholesterol content of erythrocyte membranes in acute coronary syndrome: correlation with apolipoprotein A-I and lipoprotein (a).

OBJECTIVES: Recent studies reported that total cholesterol erythrocyte membrane (CEM) levels were associated with the presence of acute coronary syndrome (ACS). However, little is known about the mechanisms of CEM elevation in these patients. The aim of this study was to investigate the association between CEM and the circulating lipid profile to delineate the possible mechanisms of CEM elevation in patients with ACS. METHODS: CEM levels, serum concentrations of triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein (a), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and high-sensitive C-reactive protein levels were measured in 418 Chinese patients undergoing coronary artery angiography, including ACS (n=311) and stable angina pectoris (n=107). RESULTS: CEM levels in the ACS group were significantly higher (median, 129.82; interquartile range, 110.99-156.54 µg/mg, P<0.001) compared with the stable angina pectoris group (median, 80.88; interquartile range, 66.69-98.57 µg/mg). Multivariable logistic regression analyses showed a significantly independent relationship between CEM levels and the presence of ACS (odds ratio, 10.257; 95% confidence interval, 5.380-19.556, P<0.001). CEM levels were positively correlated with plasma lipoprotein (a) levels (r=0.175; P<0.001) and negatively correlated with serum Apo A-I levels (r=-0.149; P=0.002). CONCLUSION: CEM levels are closely associated with the occurrence of ACS as an independent determinant. The correlation of CEM with lipoprotein (a) and Apo A-I suggests that changes to these lipid proteins could be one possible mechanism for CEM increase in patients with ACS.

Effect of simvastatin on collagen I deposition in non-infarcted myocardium: role of NF-κB and osteopontin.

The novel biological effect of statins in alleviating myocardium fibrosis following infarction has been increasingly recognized, yet the underlying mechanisms are not fully understood. The purpose of this study was to characterize the effect of simvastatin on myocardial fibrosis and collagen I deposition in the non-infarcted region after myocardial infarction (MI) and to identify the role of NF-κB and osteopontin in simvastatin-mediated inhibition of post-MI collagen over-expression. A rat model of MI was generated by ligating the left anterior descending coronary artery. The rats surviving the MI operation were randomly divided into the following 3 groups: myocardial infarction (MI, vehicle), simvastatin (Sim, 30 mg·kg-1·day-1), and pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB, 100 mg·kg-1·day-1). Four weeks after MI, cardiac function, mRNAs, and protein expression in non-infarcted myocardium were analyzed. Myocardial fibrosis and collagen I over-expression were observed following MI, accompanied by an increase of NF-κB and osteopontin. Simvastatin improved post-MI left ventricular dysfunction and ameliorated post-MI associated changes to several cardiac parameters, including the left ventricular end diastolic pressure (LVEDP), the maximal rate of pressure development (+dP/dtmax), and the maximal rate of pressure decline (-dP/dtmax). Concurrently, simvastatin significantly suppressed the over-expression of NF-κB, osteopontin, and collagen I in the non-infarcted region following MI. Inhibition of NF-κB by PDTC also reduced osteopontin over-expression and excessive collagen I production and improved the above functional myocardial parameters. These results show that post-MI myocardial fibrosis and collagen I over-expression in the non-infarcted region is associated with activation of NF-κB and osteopontin up-regulation. The anti-fibrotic effect of simvastatin following MI is associated with the attenuation of the expression of osteopontin and NF-κB. The inhibition of NF-κB activation could be the process upstream of osteopontin suppression in the simvastatin-mediated effect.