Clinical characteristics of delirium in older patients with first-ever acute myocardial infarction who underwent percutaneous coronary intervention : A retrospective study.

OBJECTIVES: Delirium is a serious complication of cardiac surgery and a common clinical problem. The study aimed to identify the incidence, risk factors, and outcomes of delirium in older patients (≥ 65 years) with first-ever acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI). METHODS: A retrospective cohort study was performed in a hospital in northern China. A total of 1033 older patients with first-ever AMI who underwent PCI between January 2018 and April 2021 were screened for delirium using the CAM-ICU method. Clinical and laboratory data were collected. RESULTS: A total of 134 (12.97%) patients were diagnosed with delirium. Patients with delirium were older. The most common concomitant diseases were cardiac arrest, chronic renal failure, and a history of coronary artery bypass graft (CABG). Delirious patients experienced more times of mechanical ventilation, more intra-aortic balloon pump (IABP) support, high postoperative immediate pain score (VAS), more non-bedside cardiac rehabilitation, and longer total length of stay and cardiac care unit (CCU) time. Multivariable logistic regression showed that age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently associated with delirium. Delirium was an independent predictor of prolonged CCU stay, total length of stay, and 1­year mortality. CONCLUSION: Age, mechanical ventilation, postoperative immediate pain score, and non-bedside cardiac rehabilitation were independently closely related to delirium in older patients with first-ever AMI who underwent PCI. Delirium was associated with a higher 1­year all-cause mortality.

Differential expression of diacylglycerol kinase ζ is involved in inferior parietal lobule-related dysfunction in schizophrenia with cognitive impairments.

BACKGROUND: Cognitive impairment is the main factor in the poor prognosis of schizophrenia, but its mechanism remains unclear. The inferior parietal lobule (IPL) is related to various clinical symptoms and cognitive impairment in schizophrenia. We aimed to explore the relationship between IPL-related functions and cognitive impairment in schizophrenia. METHODS: 136 schizophrenia patients and 146 demographically matched healthy controls were enrolled for a cross-sectional study. High-spatial-resolution structural and resting-state functional images were acquired to demonstrate the alternations of brain structure and function. At the same time, the digit span and digit symbol coding tasks of the Chinese Wechsler Adult Intelligence Test Revised (WAIS-RC) were utilized in assessing the subjects' cognitive function. Patients were divided into cognitive impairment and normal cognitive groups according to their cognitive score and then compared whether there were differences between the three groups in fractional amplitude of low-frequency fluctuation (fALFF). In addition, we did a correlation analysis between cognitive function and the fALFF for the left IPL of patients and healthy controls. Based on the Allen Human Brain Atlas, we obtained genes expressed in the left IPL, which were then intersected with the transcriptome-wide association study results and differentially expressed genes in schizophrenia. RESULTS: Grouping of patients by the backward digit span task and the digit symbol coding task showed differences in fALFF values between healthy controls and cognitive impairment patients (P < 0.05). We found a negative correlation between the backward digit span task score and fALFF of the left IPL in healthy controls (r = - 0.388, P = 0.003), which was not seen in patients (r = 0.203, P = 0.020). In addition, none of the other analyses were statistically significant (P > 0.017). In addition, we found that diacylglycerol kinase ζ (DGKζ) is differentially expressed in the left IPL and associated with schizophrenia. CONCLUSION: Our study demonstrates that the left IPL plays a vital role in cognitive impairment in schizophrenia. DGKζ may act as an essential regulator in the left IPL of schizophrenia patients with cognitive impairment.

Affected cortico-striatal-cerebellar network in schizophrenia with catatonia revealed by magnetic resonance imaging: indications for electroconvulsive therapy and repetitive transcranial magnetic stimulation.

Catatonia is a psychomotor syndrome that can occur in a broad spectrum of brain disorders, including schizophrenia. Current findings suggest that the neurobiological process underlying catatonia symptoms in schizophrenia is poorly understood. However, emerging neuroimaging studies in catatonia patients have indicated that a disruption in anatomical connectivity of the cortico-striatal-cerebellar system is part of the neurobiology of catatonia, which could serve as a target of neurostimulation such as electroconvulsive therapy and repetitive transcranial magnetic stimulation.

Prebiotic-like cyclodextrin assisted silybin on NAFLD through restoring liver and gut homeostasis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with no currently approved treatment. The natural compound silybin (SLN) has versatile hepatoprotective efficacy with negligible adverse effects; however, poor absorption limits its clinical applications. Gut microbiota has been proposed to play a crucial role in the pathophysiology of NAFLD and targeted for disease control. Cyclodextrins, the cyclic oligosaccharides, were documented to have various health benefits with potential prebiotic properties. This study aimed to develop a silybin-2-hydroxypropyl-ß-cyclodextrin inclusion (SHßCD) to improve the therapeutic efficacy of SLN and elucidate the mechanisms of improvement. The results showed that SLN formed a 1:1 stoichiometric inclusion complex with HP-ß-CD. The solubility of SLN was increased by generating SHßCD, resulting in improved drug permeability and bioavailability. In high-fat diet (HFD)-fed hamsters, SHßCD modulated gut health by restoring the gut microbiota and intestinal integrity. SHßCD showed superior anti-lipid accumulation, antioxidant, and anti-inflammatory effects compared with SLN alone. Transcriptome analysis in the liver tissue implied that the improved inflammation and/or energy homeostasis was the potential mechanism. Therefore, SHßCD may be a promising alternative for the treatment of NAFLD, attributing to the dual functions of HßCD on drug absorption and gut microbial homeostasis.

Bicyclol Alleviates Atherosclerosis by Manipulating Gut Microbiota.

Atherosclerosis (AS) is associated with high morbidity and mortality, thus imposing a growing burden on modern society. Herb-derived bicyclol (BIC) is a versatile bioactive compound that can be used to treat AS. However, its efficacy in AS is not yet described. Here, it is shown that BIC normalizes gut microflora dysbiosis induced by a high fat diet in Apoe(-/-) mice. Metagenome-wide association study analysis verifies that the modulation on carbohydrate-active enzymes and short-chain fatty acid generating genes in gut flora is among the mechanisms. The gut healthiness, especially the gut immunity and integrity, is restored by BIC intervention, leading to improved systemic immune cell dynamic and liver functions. Accordingly, the endothelial activation, macrophage infiltration, and cholesterol ester accumulation in the aortic arch are alleviated by BIC to lessen the plaque onset. Moreover, it is proved that the therapeutic effect of BIC on AS is transmissible by fecal microbiota transplantation. The current study, for the first time, demonstrates the antiatherosclerotic effects of BIC and shows that its therapeutic value can at least partially be attributed to its manipulation of gut microbiota.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

Mesenchymal Stromal Cells from Patients with Cyanotic Congenital Heart Disease are Optimal Candidate for Cardiac Tissue Engineering.

Engineered heart tissues (EHTs) are regarded as being the most promising alternative to synthetic materials, and autologous mesenchymal stem cells (MSCs) are widely used as seeding cells. However, few studies have evaluated the feasibility of using MSCs from patients with cyanotic congenital heart disease (C-CHD) as seeding cells for EHTs, in comparison with cells from patients of acyanotic congenital heart disease (A-CHD). In the present study, we cultured MSCs from A-CHD and C-CHD patients in normoxia or hypoxia conditions, and compared their pro-angiogenic, anti-apoptotic and inflammation-modulatory potentials. In vivo, we seeded the cells into collagen patches conjugated with, or without, proangiogenic cytokines, which were used to repair the right ventricular outflow tract (RVOT) of rats. The in vitro results showed that C-CHD MSCs expressed higher levels of VEGFA and VEGFR2, and secreted more pro-angiogenic and anti-inflammatory cytokines under hypoxic conditions. On the other hand, apoptosis-related genes from C-CHD MSCs were modulated adaptably, converting these cells into an anti-apoptotic phenotype. In vivo studies demonstrated that in 4 weeks after RVOT reconstruction, cytokine-immobilized patches seeded with C-CHD MSCs exhibited preserved morphology, prolonged cell survival and enhanced angiogenesis compared to A-CHD MSCs. C-CHD MSCs that undergo "naturally hypoxic precondition" present a better cell source for EHTs, which would provide a promising individualized biomaterial for C-CHD patients.

A novel swine model for evaluation of dyslipidemia and atherosclerosis induced by human CETP overexpression.

BACKGROUND: The mechanism of cholesteryl ester transfer protein (CETP) in lipid metabolism is still unclear. Furthermore, the relationship of CETP and atherosclerosis (AS) has been controversial. As pigs are a good model for both lipid and AS research, we investigated the lipid metabolism of human CETP (hCETP) transgenic pigs and explored the mechanism of CETP in lipid modulation. METHODS: Plasmids expressing the hCETP gene were designed, successfully constructed, and transfected into porcine fetal fibroblasts by liposomes. Using somatic cell nuclear transfer technology and embryonic transfer, hCETP transgenic pigs were generated. After the DNA, RNA, and protein levels were identified, positive hCETP transgenic pigs were selected. Blood samples were collected at different ages to evaluate the phenotypes of biochemical markers, and the metabolomes of plasma samples were analyzed by liquid mass spectrometry. RESULTS: Eight positive hCETP transgenic pigs and five negative cloned pigs were generated by transgenic technology. Finally, five hCETP transgenic and five cloned pigs were grown healthily. After feeding with a normal diet, hCETP transgenic pigs compared with unmodified pigs had no significant differences in body weight, liver function, kidney function, or plasma ions, while total cholesterol and low-density lipoprotein were higher than in unmodified pigs, and high-density lipoprotein was significantly decreased. Metabolomics analysis showed that there were differences in metabolic components between hCETP transgenic pigs, cloned pigs, and unmodified pigs. CONCLUSIONS: In this study, we created hCETP transgenic pigs that could serve as an excellent model for lipid disorders and atherosclerosis.

A novel model of intimal hyperplasia with graded hypoosmotic damage.

BACKGROUND: The purpose was to develop a rabbit model of intimal hyperplasia with controllable lesion. METHODS: Following 1 week of a 2% cholesterol diet, 32 New Zealand White male rabbits underwent right femoral arteries surgical perfusion with distilled water for 1, 3, 5, or 7 min (n=8/group). After a further 4 weeks of the same diet, serum total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were measured in all rabbits. Intimal hyperplasia in histological sections of arteries were assessed by intimal proliferation ratio. Macrophage numbers and levels of proteins matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 2, and alpha smooth muscle actin in lesions were analyzed by immunohistochemistry. RESULTS: Serum lipids levels showed no statistical difference between experimental groups. Intimal proliferation ratio increased gradually with perfusion time, and a positive linear correlation was calculated between intimal proliferation ratio and duration of distilled water perfusion. Similarly, number of macrophages and levels of matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 2, and alpha smooth muscle actin in lesions increased with perfusion time. CONCLUSIONS: A novel model of intimal hyperplasia was established by intravascular distilled water perfusion in high-cholesterol-fed rabbits. Importantly, this model exhibits time-dependent neointimal proliferation lesions that can be readily controlled in terms of extent, thus providing an avenue for further studies.