Clinical Outcomes and Left Ventricular Functional Remodeling after Extracorporeal Membrane Oxygenation Assisted Percutaneous Coronary Intervention in Patients with Ischemic Cardiomyopathy: A Single-Center Retrospective Observational Study of 76 Cases.

Background: Ischemic cardiomyopathy (ICM) is a common condition that leads to left ventricular (LV) functional remodeling and poor prognosis. Extracorporeal membrane oxygenation (ECMO) can provide temporary circulatory support and facilitate percutaneous coronary intervention (PCI) in patients with ICM and hemodynamic instability. However, the impact of ECMO-assisted PCI on LV functional remodeling and clinical outcomes in ICM patients is unclear. Methods: We retrospectively analyzed 76 patients with ICM who underwent ECMO-assisted PCI at our institution between January 2013 and December 2022. We assessed the changes in LV functional remodeling using echocardiography at baseline and 12 months after the procedure. We also evaluated the incidence of major adverse cardiac and cerebrovascular events (MACCEs) and ECMO-related complications during hospitalization and at one-year follow-up. Results: The mean baseline left ventricular ejection fraction (LVEF) was 29.98 ± 2.65%. The rate of complete revascularization was 58%. The median duration of ECMO support was 38.99 hours. The most common ECMO-related complications were bleeding (8%) and lower extremity ischemia (5%). The one-year mortality rate was 30%. The overall freedom from MACCEs at 12 months was 59% (95% confidence interval (CI): 49-71%). LVEF increased significantly after the procedure from baseline to 6 months, yet decreased slightly at 12 months, although it was still higher than the baseline value. Wall motion score index (WMSI), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI) decreased significantly from baseline to 12 months, indicating an improvement in LV function and a reduction in LV size. Conclusions: In a high-volume tertiary center with extensive experience in advanced heart failure therapies and a dedicated ECMO team, ECMO-assisted PCI demonstrated feasibility and safety in patients with ischemic cardiomyopathy. However, the rate of complete revascularization was modest at 58%. Despite the high-risk profile of the patients, ECMO-assisted PCI was associated with a significant improvement in LV functional remodeling and a favorable 12-month survival rate. Further prospective studies are needed to confirm these findings and to identify the optimal patient and device selection criteria for ECMO-assisted PCI.

YTHDF1-regulated ALOX5 in retinal pigment epithelial cells under hypoxia enhances VEGF expression and promotes viability, migration, and angiogenesis of vascular endothelial cells.

Upregulation of vascular endothelial growth factor (VEGF) and enhanced angiogenesis have been implicated in the severe progression of age-related macular degeneration (AMD). Abnormal arachidonate 5-lipoxygenase (ALOX5) is associated with AMD pathogenesis. However, no reports have shown the causal role of ALOX5 in angiogenesis during AMD. In the present study, ARPE-19 cells were exposed to hypoxia, an inducer of VEGF expression. Potential proteins implicated in AMD progression were predicted using bioinformatics. RNA affinity antisense purification-mass spectrometry (RAP-MS) was applied to identify the binding proteins of ALOX5 3'UTR. Expression of ALOX5 and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1) was detected by qRT-PCR and western blotting. VEGF expression and secretion were assessed by immunofluorescence and ELISA, respectively. The chicken embryo chorioallantoic membrane (CAM) was used to analyze the effect of ALOX5 on angiogenesis. RNA stability was assayed using the Actinomycin D assay. The results show that hypoxia promoted cell growth and increased VEGF expression in ARPE-19 cells. ALOX5 was associated with AMD progression, and hypoxia upregulated ALOX5 expression in ARPE-19 cells. ALOX5 silencing reduced VEGF expression induced by hypoxia in ARPE-19 cells. Moreover, the conditioned medium of ALOX5-silenced ARPE-19 cells could suppress the viability and migration of HUVECs and diminish angiogenesis in the CAM. Furthermore, YTHDF1 was validated to bind to ALOX5 3'UTR, and YTHDF1 promoted ALOX5 expression by elevating the stability of ALOX5 mRNA. In conclusion, our findings demonstrate that YTHDF1-regulated ALOX5 increases VEGF expression in hypoxia-exposed ARPE-19 cells and enhances the viability, migration, and angiogenesis of vascular endothelial cells.

Aerobic exercise prevents and improves cognitive dysfunction caused by morphine withdrawal via regulating endogenous opioid peptides in the brain.

BACKGROUND: Morphine withdrawal leads to serious cognitive deficits in which dynorphins are directly involved. Recently, exercise has been shown to prevent and improve cognition dysfunction in a variety of ways. Meanwhile, exercise can regulate the endogenous opioid peptides including dynorphins. However, it remains unclear whether exercise influences cognitive dysfunction caused by morphine withdrawal via dynorphins. In the current study, we investigate the physiological mechanism of exercise prevention and improvement aganist cognition dysfunction caused by morphine withdrawal. METHODS: Male, adult C57BL/6 mice were randomly divided into 5 groups : Saline control (WT), exercise (EXE), morphine withdrawl (MW), exercise + morphine withdrawl (EMW), morphine withdrawl + exercise (MWE). We established aerobic exercise prevention/improvement models, and conducted behavioral tests including Open field test (OFT), Temporal order memory test (TOM) and Y-maze. Through Western Blotting and immunofluorescence staining, we detected endogenous opioid peptides in hippocampus and mPFC. RESULTS: Compared with MW group, EMW group and MWE group showed the same performance as WT group in TOM and Y-maze, with correct object recognition and memory ability. In Western Blotting and immunofluorescence staining experiments, it indicated that EMW group reduced the expression of PDYN and its fluorescence intensity in hippocampus; MWE group reduced the expression of OPRK1 and its fluorescence intensity in mPFC. CONCLUSION: Our data suggest that aerobic exercise can both prevent and improve cognitive dysfunction caused by acute morphine withdrawal via respectively down-regulating PDYN in the hippocampus and down-regulating OPRK1 in the mPFC. They may become new targets for drugs development in the future.

Ultrasound elastography: a brief clinical history of an evolving technique.

The history of the emerging elastographic technique is presented. Ultrasound imaging of elasticity and tissue strain has gained clinical acceptance as an established technique useful in routine daily clinical practice.

Impact of informal social support on the mental health of older adults.

Objective: The role of informal social support in fostering active aging within the context of the "silver wave" is significant. This study investigated how such support influenced the mental health of older adults, with the goal of affirming its indispensable contribution to enhancing their psychological well-being. Methods: Employing Principal Component Analysis (PCA) to construct the informal social support variable, this study rigorously analyzed the effects and underlying mechanisms of informal social support on mental health in older adults, utilizing data from the 2018 China Longitudinal Aging Social Survey (CLASS). Results: Informal social support exerted a substantial positive influence on the mental health of older adults, particularly among younger, non-agricultural older adult populations who preferred cohabitation with their children. This form of support significantly enhanced mental well-being by elevating life satisfaction, improving access to medical services, and fostering active social engagement. Conclusion: This study elucidates the role of informal social support in bolstering the mental health of older adults. Future efforts should focus on fostering a supportive environment that enhances older adult care experiences, reforming the healthcare system to better meet the needs of the aging population, and promoting avenues for social engagement, thereby achieving a balanced integration of their emotional and physical care.

Heat shock protein 22 alleviates doxorubicin-induced kidney injury by suppressing oxidative stress and apoptosis.

This study investigated the effects of heat shock protein 22 (HSP22) against doxorubicin (DOX)-induced kidney injury. Mice were randomly assigned to four groups: CON, ad-HSP22, DOX, and ad-HSP22 + DOX. Adeno-associated virus carrying the HSP22 gene (ad-HSP22) was administered via tail vein injection for four weeks, followed by intraperitoneal simulation with DOX (20 mg/kg) for another five days. Upon euthanasia, ELISA, histological staining (H&E, IHC, DHE, and TUNEL), and western blot analyses were employed to assess relevant markers. Serum biomarkers of kidney injury, SCr, and BUN, were upregulated after DOX administration but normalized with HSP22 overexpression. Pathological changes induced by DOX were also reversed by HSP22 overexpression in H&E, IHC, DHE, and TUNEL stains. DOX-induced upregulation of NOX-2 and NOX-4 and downregulation of SOD-1 and SOD-2 were reversed by HSP22 overexpression. Similarly, DOX-induced increases in Bax and decrease in Bcl-2 were attenuated by HSP22 overexpression. The study further demonstrated that the Nrf2/HO-1 signaling pathway was activated by HSP22 overexpression. In vitro experiments corroborated the findings from in vivo experiments. In conclusion, HSP22 alleviates DOX-induced kidney injury by suppressing oxidative stress and apoptosis, primarily through the activation of the Nrf2/HO-1 signaling pathway. These results suggest HSP22 as a potential therapeutic target for DOX-induced kidney injury.

Novel heterozygous mutation of CACNA2D1 gene in a Chinese family with arrhythmia.

BACKGROUND: Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. METHODS: We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. RESULTS: A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband's parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. CONCLUSIONS: WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.

CRISPR-Cas12a detection of DNA glycosylases via DNA modification switching.

A programmable CRISPR-Cas12a system for selective detection of various DNA glycosylases is described. By temporarily inactivating Cas12a through the introduction of specific DNA modifications in the complementary DNA strand of Cas12a's crRNA, the system is able to detect the target DNA glycosylases. This approach addresses critical gaps in current CRISPR-Cas12a diagnostics for non-nucleic acid detection beyond the limitations of aptamers.

An [illustrative] update on pediatric emergency ultrasound: part 3 - cerebral, musculoskeletal and other applications.

Point-of-care ultrasound (POCUS) plays an essential role in pediatric emergency medicine by improving diagnostics and procedural safety. The role of POCUS in the care of pediatric patients in the emergency department has expanded considerably in recent years. Cranial and musculoskeletal imaging has significant potential, yet POCUS has also become a vital tool for common procedures, such as central and difficult peripheral intravenous access. The purpose of this article is to provide an overview of pediatric POCUS applications for cranial, small parts (head, eyes, nose, throat, and soft tissue), musculoskeletal, and common procedural applications, forming the third part of the series.

Ultrasound of the spleen - an update on measurements, reference values, and influencing factors. A systematic review.

Reliable and reproducible measurement methods have been established, and reference values are used in almost all scientific disciplines. The knowledge of reference values is crucial to distinguish physiological from pathological processes and, therefore, subsequently, for the clinical management of patients. The image storage and documentation of measurements and normal findings should be part of quality assurance in imaging. This paper aims to review published literature and provide current knowledge of sonographic measurements of the spleen, examination techniques, and knowledge of normal values with their possible clinical implications. Moreover, the role of clinical influencing factors such as age, gender, or ethnicity is also analyzed.

Pancreatic ultrasound: An update of measurements, reference values, and variations of the pancreas.

Reliable and reproducible measurement methods have been established, and reference values are used in almost all scientific disciplines. Knowledge of reference values is crucial to distinguish physiological from pathological processes and, therefore, subsequently, for the clinical management of patients. Image storage and documentation of measurements and normal findings should be part of quality assurance in imaging. This paper aims to review the published literature and provide current knowledge of sonographic measurements and reference values of the pancreas. Moreover, the role of clinical influencing factors such as age, gender, constitution, and ethnicity is also analyzed.

Perfluorobutane-Enhanced CEUS in Intrahepatic Cholangiocarcinoma: Correlating Imaging Features With Liver Backgrounds and Tumor Sizes.

OBJECTIVE: To investigate Sonazoid contrast-enhanced ultrasound (CEUS) features of intrahepatic cholangiocarcinoma (ICC) based on liver backgrounds and tumor sizes. METHODS: A retrospective analysis was conducted on patients with histopathologically diagnosed ICC at two centers. Patients underwent Sonazoid CEUS examination at a dose of 0.0165 mL/kg before surgery or biopsy. Continuous imaging was recorded for the first 70 s, followed by intermittent scanning every 15-20 s for 5 min, with a Kupffer phase captured after an 8-min delay. Patients were categorized by liver backgrounds and tumor sizes. Two ultrasound experts evaluated the enhancement patterns of ICCAs during the arterial, portal, delayed, and Kupffer phases according to current guidelines. RESULTS: From February 2019 to July 2022, a total of 85 ICC lesions were included. ICCs were categorized into normal liver (n = 24), chronic liver disease with fibrosis (n = 40), and cirrhosis (n = 21) groups based on different liver backgrounds, and into groups measuring ≤30 mm (n = 22), 31-50 mm (n = 32), and >50 mm (n = 31) based on tumor sizes. Most ICCs in liver fibrosis or liver cirrhosis tended to show non-rim enhancement in arterial phase (p = 0.022) and relatively later washout (39.9 ± 8.5 s vs. 39.7 ± 13.0 s) compared with those on a normal liver background (28.1 ± 5.6 s) (p < 0.001). Based on CEUS Liver Imaging Reporting and Data System, the diagnostic performance of LR-M criteria showed an accuracy of 100% in our high-risk populations. ICCs of ≤30 mm more commonly showed non-rim enhancement in arterial phase (p = 0.003) and relatively later washout (41.3 ± 12.5 s) compared with larger ICCs (p = 0.046). In the Kupffer phase, all ICCs showed marked washout with sharp margin delineation on Sonazoid CEUS, regardless of liver backgrounds and tumor sizes. CONCLUSION: Sonazoid CEUS features of ICCs differ according to different liver backgrounds and tumor sizes. Arterial phase non-rim enhancement and relatively later washout were more commonly observed in ICCs on liver fibrosis or cirrhosis background or smaller ICCs (≤30 mm).

Triglyceride-glucose index is associated with all-cause mortality in critically ill patients with alcohol use disorder: a retrospective cohort study.

BACKGROUND: The relationship between Triglyceride-glucose (TyG) index and clinical outcomes in patients with alcohol use disorder (AUD) is unclear. The aim of this study was to evaluate the association between TyG index and all-cause mortality in critically ill patients with AUD. METHODS: We used data from the multi-parameter intelligent monitoring in intensive care IV (MIMIC-IV) database. The patients were equally divided into quartiles. Kaplan-Meier curves were used for survival analysis. The primary endpoint of the study was 28-day mortality, followed by 1-year mortality. We used Cox proportional hazard models to assess the relationship between TyG index and all-cause mortality at different endpoints. RESULTS: A total of 537 AUD patients were included. Using TyG value as a continuous variable (HR 1.460, 95% CI 1.121-1.903, p = 0.005) and categorical variable (HR 1.447-3.477 from Q2 to Q4, with Q1 as reference), elevated TyG value was significantly associated with increased 28-day mortality. TyG was positively associated with 1-year mortality in AUD patients with an HR of 1.295 (95% CI 1.011-1.659, p = 0.041). CONCLUSION: TyG index is positively associated with different clinical outcomes of critically ill AUD patients.

Cardiac power output associated with hospitalization and mortality in coronary artery disease patients at stage B heart failure.

Background: Cardiac power output (CPO) predicts outcomes in advanced heart failure (HF) and cardiogenic shock, but its role in early HF stages is unclear. This study assessed the prognostic value of CPO in coronary artery disease patients with asymptomatic left ventricular systolic dysfunction (ALVSD) at stage B HF. Methods: We conducted a retrospective analysis of coronary artery disease patients who underwent coronary and pulmonary artery catheterization between 2006 and 2016. Stage B HF with ALVSD was defined as left ventricular ejection fraction < 50 %, without HF symptoms, signs, or prior HF hospitalization. CPO was derived from invasive hemodynamic parameters. Endpoints included HF hospitalization, cardiovascular mortality, and all-cause mortality over a 5-year follow-up. Results: A total of 783 coronary artery disease patients with ALVSD at stage B HF were enrolled. Incidence rates (per 1000 person-years) were 13.9 for HF hospitalization, 14.5 for cardiovascular mortality, and 23.7 for all-cause mortality.Multivariate analysis adjusting for covariates demonstrated that CPO was independent associated with all endpoints. Patients with a low CPO (<0.97 Watts) were at significantly higher risk for HF hospitalization (adjusted hazard ratio [HR]: 4.04; 95 % CI: 1.53 - 10.6; p = 0.005), cardiovascular mortality (adjusted HR: 2.73; 95 % CI: 1.19 - 6.27; p = 0.018), and all-cause mortality (adjusted HR: 1.86; 95 % CI: 1.05 - 3.30; p = 0.035) compared to those with higher CPO, regardless of subgroup classification. Conclusion: Resting CPO in patients with ALVSD is significantly associated with adverse events, including HF hospitalization and mortality, highlighting its value in early-stage HF management.

Genotype-phenotype correlation and founder effect analysis in southeast Chinese patients with sialidosis type I.

BACKGROUND: Sialidosis type 1 (ST-1) is a rare autosomal recessive disorder caused by mutation in the NEU1 gene. However, limited reports on ST-1 patients in the Chinese mainland are available. METHODS: This study reported the genetic and clinical characteristics of 10 ST-1 patients from southeastern China. A haplotype analysis was performed using 21 single nucleotide polymorphism (SNP) markers of 500 kb flanking the recurrent c.544 A > G in 8 families harboring the mutation. Furthermore, this study summarized and compared previously reported ST-1 patients from Taiwan and mainland China. RESULTS: Five mutations within NEU1 were found, including two novel ones c.557 A > G and c.799 C > T. The c.544 A > G mutation was most frequent and identified in 9 patients, 6 patients were homozygous for c.544 A > G. Haplotype analysis revealed a shared haplotype surrounding c.544 A > G was identified, suggesting a founder effect presenting in southeast Chinese population. Through detailed assessment, 52 ST-1 patients from 45 families from Taiwan and mainland China were included. Homozygous c.544 A > G was the most common genotype and found in 42.2% of the families, followed by the c.544 A > G/c.239 C > T compound genotype, which was observed in 22.2% of the families. ST-1 patients with the homozygous c.544 A > G mutation developed the disease at a later age and had a lower incidence of cherry-red spots significantly. CONCLUSION: The results contribute to gaps in the clinical and genetic features of ST-1 patients in southeastern mainland China and provide a deeper understanding of this disease to reduce misdiagnosis.

Comments and illustrations of the European Federation of Societies for Ultrasound in Medicine contrast-enhanced ultrasound guidelines: Multiparametric imaging and EUS-guided sampling in rare pancreatic tumors. Benign mesenchymal pancreatic tumors.

The focus of the review is on primary benign mesenchymal pancreatic tumors and their imaging appearance. These tumors are extremely rare. Usually, they are not diagnosed until postoperative histology is available, and so even benign tumors have undergone extensive pancreatic resection. The very limited data on abdominal and EUS findings including contrast-enhanced techniques of these pancreatic lesions are summarized here. Case reports will be presented for some of these rare tumors with application of modern ultrasound and endosonographic techniques.

Earlier intrathecal dexamethasone effectively alleviate immune effector cell-associated neurotoxicity syndrome.

Chimeric antigen receptor T cell (CAR-T) therapy is effective in treating relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, the side effects of immune effector cell-associated neurotoxicity syndrome (ICANS) remain a problem. The current frontline therapies for ICANS include steroids and supportive care. For the steroid-refractory and severe ICANS, several studies have reported excellent efficacy of intrathecal (IT) corticosteroids alone or in combination with chemotherapy. However, whether patients can benefit from IT dexamethasone (dex) before grade 3 or refractory ICANS remains unclear. In this study, the patients with ICANS (≥1) after CAR-T cell therapy were assigned to the IT group and non-IT group. Clinical information, laboratory parameters, and serum cytokine levels were analyzed. A significant and rapid reduction in inflammatory cytokines and biomarkers was observed after 24 h of IT dex treatment. With IT dex, 83.3 % (15/18) of patients recovered from neurotoxicity. Moreover, this option significantly shortens the recovery time of ICANS without affecting the efficacy of CAR-T cell therapy. Earlier initiation of IT dex is the optimal management of ICANS resulting from CAR-T cell therapy, but larger sample studies are needed to determine its efficacy in these settings.

The Association between the Severity of Distal Sensorimotor Polyneuropathy and Increased Carotid Atherosclerosis in Individuals with Type 2 Diabetes.

BACKGROUND: Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM). Method: Participants underwent comprehensive assessments including nerve conduction studies (NCS), Toronto Clinical Neuropathy Score (TCNS) evaluations, assessment of cardiometabolic risk factors, and carotid sonography studies covering dynamic and morphological parameters. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) in both the common carotid artery (CCA) and internal carotid artery (ICA), carotid intima-media thickness (IMT), and carotid plaque score (CPS) were also measured. Peripheral nerve function severity was assessed using composite amplitude scores (CAS) derived from NCS. RESULTS: Individuals with DSPN exhibited lower EDV in the CCA and ICA (p < 0.0001 and p = 0.002), higher PI and RI in both CCA and ICA (all p < 0.0001), and higher CPS (p = 0.002). They also demonstrated a higher prevalence of retinopathy as an underlying condition, higher index HbA1c, and reduced estimated glomerular filtration rate (eGFR) (all p < 0.0001). Multiple linear regression analysis revealed significant associations where eGFR, ICA-PI, index HbA1c, waist circumference, and age were correlated with CAS. Meanwhile, diabetes duration, waist circumference, age, and index HbA1c showed significant associations with TCNS. CONCLUSIONS: Our study suggests that individuals with T2DM who exhibit more severe carotid atherosclerosis may not only be at increased risk of developing DSPN but also may experience greater severity of DSPN. PI in both the CCA and ICA, along with the CPS, serve as surrogate biomarkers for DSPN severity.

Enhancing Perovskite Solar Cell Performance through Propylamine Hydroiodide Passivation.

In recent years, the power conversion efficiency of perovskite solar cells has increased rapidly. Perovskites can be prepared using simple and cost-effective solution methods. However, the perovskite films obtained are usually polycrystalline and contain numerous defects. Passivation of these defects is crucial for enhancing the performance of solar cells. Here, we report the use of propylamine hydroiodide (PAI) for defect passivation. We found that PAI can result in higher-efficiency cells by reducing the defects and suppressing non-radiative recombination. Consequently, n-i-p perovskite solar cells with a certificated efficiency of 21% were obtained. In addition, PAI exhibited excellent performance in p-i-n devices by serving as a buried interface layer, leading to an improved efficiency of 23%.