ABSTRACT
Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.
Subject(s)
HLA Antigens , Hematopoietic Stem Cell Transplantation , Isoantibodies , Humans , Hematopoietic Stem Cell Transplantation/methods , Male , Female , Adult , Retrospective Studies , Middle Aged , HLA Antigens/immunology , Isoantibodies/blood , Isoantibodies/immunology , Tissue Donors , Graft Rejection/immunology , Plasma Exchange/methods , Adolescent , Transplantation, Haploidentical/methods , Young Adult , Biomarkers/blood , Desensitization, Immunologic/methodsABSTRACT
BACKGROUND: Sleeping late has been a common phenomenon and brought harmful effects to our health. The purpose of this study was to investigate the association between sleep timing and major adverse cardiovascular events (MACEs) in patients with percutaneous coronary intervention (PCI). METHODS: Sleep onset time which was acquired by the way of sleep factors questionnaire in 426 inpatients was divided into before 22:00, 22:00 to 22:59, 23:00 to 23:59 and 24:00 and after. The median follow-up time was 35 months. The endpoints included angina pectoris (AP), new myocardial infarction (MI) or unplanned repeat revascularization, hospitalization for heart failure, cardiac death, nonfatal stroke, all-cause death and the composite endpoint of all events mentioned above. Cox proportional hazards regression was applied to analyze the relationship between sleep timing and endpoint events. RESULTS: A total of 64 composite endpoint events (CEEs) were reported, including 36 AP, 15 new MI or unplanned repeat revascularization, 6 hospitalization for heart failure, 2 nonfatal stroke and 5 all-cause death. Compared with sleeping time at 22:00-22:59, there was a higher incidence of AP in the bedtime ≥ 24:00 group (adjusted HR: 5.089; 95% CI: 1.278-20.260; P = 0.021). In addition, bedtime ≥ 24:00 was also associated with an increased risk of CEEs in univariate Cox regression (unadjusted HR: 2.893; 95% CI: 1.452-5.767; P = 0.003). After multivariable adjustments, bedtime ≥ 24:00 increased the risk of CEEs (adjusted HR: 3.156; 95% CI: 1.164-8.557; P = 0.024). CONCLUSION: Late sleeping increased the risk of MACEs and indicated a poor prognosis. It is imperative to instruct patients with PCI to form early bedtime habits.
Subject(s)
Percutaneous Coronary Intervention , Sleep , Humans , Male , Percutaneous Coronary Intervention/adverse effects , Female , Middle Aged , Aged , Time Factors , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Risk Factors , Proportional Hazards Models , Follow-Up Studies , Surveys and QuestionnairesABSTRACT
Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources. Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing. Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/µl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%. Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Milk, Human , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Sensitivity and Specificity , Humans , Cytomegalovirus/genetics , Cytomegalovirus/isolation & purification , Milk, Human/virology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/virology , Nucleic Acid Amplification Techniques/methods , Molecular Diagnostic Techniques/methods , Female , Infant, Newborn , Time FactorsABSTRACT
Background: Skeletal malocclusion is common among populations. Its severity often increases during adolescence, yet it is frequently overlooked. The introduction of deep learning in stomatology has opened a new avenue for self-health management. Methods: In this study, networks were trained using lateral photographs of 2109 newly diagnosed patients. The performance of the models was thoroughly evaluated using various metrics, such as sensitivity, specificity, accuracy, confusion matrix analysis, the receiver operating characteristic curve, and the area under the curve value. Heat maps were generated to further interpret the models' decisions. A comparative analysis was performed to assess the proposed models against the expert judgment of orthodontic specialists. Results: The modified models reached an impressive average accuracy of 84.50% (78.73%-88.87%), with both sex and developmental stage information contributing to the AI system's enhanced performance. The heat maps effectively highlighted the distinct characteristics of skeletal class II and III malocclusion in specific regions. In contrast, the specialist achieved a mean accuracy of 71.89% (65.25%-77.64%). Conclusions: Deep learning appears to be a promising tool for assisting in the screening of skeletal malocclusion. It provides valuable insights for expanding the use of AI in self-monitoring and early detection within a family environment.
Subject(s)
Malocclusion , Humans , Female , Malocclusion/diagnosis , Male , Adolescent , Deep Learning , Artificial Intelligence/trends , ROC Curve , ChildABSTRACT
Traditional diagnostic methods, such as blood tests, are invasive and time-consuming, while sweat biomarkers offer a rapid physiological assessment. Surface-enhanced Raman spectroscopy (SERS) has garnered significant attention in sweat analysis because of its high sensitivity, label-free nature, and nondestructive properties. However, challenges related to substrate reproducibility and interference from the biological matrix persist with SERS. This study developed a novel ratio-based 3D hydrogel SERS chip, providing a noninvasive solution for real-time monitoring of pH and glucose levels in sweat. Encapsulating the probe molecule (4-MBN) in nanoscale gaps to form gold nanoflower-like nanotags with internal standards and integrating them into an agarose hydrogel to create a 3D flexible SERS substrate significantly enhances the reproducibility and stability of sweat analysis. Gap-Au nanopetals modified with probe molecules are uniformly dispersed throughout the porous hydrogel structure, facilitating the effective detection of the pH and glucose in sweat. The 3D hydrogel SERS chip demonstrates a strong linear relationship in pH and glucose detection, with a pH response range of 5.5-8.0 and a glucose detection range of 0.01-5 mM, with R2 values of 0.9973 and 0.9923, respectively. In actual sweat samples, the maximum error in pH detection accuracy is only 1.13%, with a lower glucose detection limit of 0.25 mM. This study suggests that the ratio-based 3D hydrogel SERS chip provides convenient, reliable, and rapid detection capabilities with substantial application potential for analyzing body fluid pH and glucose.
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Plant parasitic nematodes (PPNs) pose a significant threat to global crop productivity, causing an estimated annual loss of US $157 billion in the agriculture industry. While synthetic chemical nematicides can effectively control PPNs, their overuse has detrimental effects on human health and the environment. Biocontrol agents (BCAs), such as bacteria and fungi in the rhizosphere, are safe and promising alternatives for PPNs control. These BCAs interact with plant roots and produce extracellular enzymes, secondary metabolites, toxins, and volatile organic compounds (VOCs) to suppress nematodes. Plant root exudates also play a crucial role in attracting beneficial microbes toward infested roots. The complex interaction between plants and microbes in the rhizosphere against PPNs is mostly untapped which opens new avenues for discovering novel nematicides through multi-omics techniques. Advanced omics approaches, including metagenomics, transcriptomics, proteomics, and metabolomics, have led to the discovery of nematicidal compounds. This review summarizes the status of bacterial and fungal biocontrol strategies and their mechanisms for PPNs control. The importance of omics-based approaches for the exploration of novel nematicides and future directions in the biocontrol of PPNs are also addressed. The review highlighted the potential significance of multi-omics techniques in biocontrol of PPNs to ensure sustainable agriculture.
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Cardiovascular diseases (CVDs) tend to affect the young population and are associated with a significant economic burden and psychological distress to the society and families. The physiological and pathological processes underlying CVDs are complex. Ca2+/calmodulin-dependent kinase II (CaMK II), a protein kinase, has multiple biological functions. It participates in multiple pathological processes and plays a central role in the development of CVDs. Based on this, this paper analyzes the structural characteristics and distribution of CaMK II, the mechanism of action of CaMK II, and the relationship between CaMK II and CVDs, including ion channels, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy, cardiotoxicity, hypertension, and dilated cardiomyopathy. Given the different regulatory mechanisms of different isoforms of CaMK II, the clinical use of specific targeted inhibitors or novel compounds should be evaluated in future research to provide new directions.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Cardiovascular Diseases , Humans , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors , Animals , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistrySubject(s)
Bridged Bicyclo Compounds, Heterocyclic , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Propensity Score , Sulfonamides , Humans , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/diagnosis , Sulfonamides/therapeutic use , Sulfonamides/administration & dosage , Male , Aged , Female , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Aged, 80 and overABSTRACT
Cardiomyopathy is particularly common in septic patients. Our previous studies have shown that activation of the alpha 1 adrenergic receptor (α1-AR) on cardiomyocytes inhibits sepsis-induced myocardial dysfunction. However, the role of cardiac endothelial α1-AR in septic cardiomyopathy has not been determined. Here, we identified α1-AR expression in mouse and human endothelial cells and showed that activation of α1-AR with phenylephrine (PE) improved cardiac function and survival by preventing cardiac endothelial injury in septic mice. Mechanistically, activating α1-AR with PE decreased the expression of ICAM-1, VCAM-1, iNOS, E-selectin, and p-p38MAPK, while promoting PKC and ERK1/2 phosphorylation in LPS-treated endothelial cells. These effects were abolished by a PKC inhibitor or α1-AR antagonist. PE also reduced p65 nuclear translocation, but this suppression is not blocked by PKC inhibition. Treatment with U0126 (a specific ERK1/2 inhibitor) reversed the effects of PE on p38MAPK phosphorylation. Our results demonstrate that cardiac endothelial α1-AR activation prevents sepsis-induced myocardial dysfunction in mice by inhibiting the endothelial injury via PKC-ERK/p38MAPK signaling pathway and a PKC-independent inhibition of p65 nuclear translocation. These findings offer a new perspective for septic patients with cardiac dysfunction by inhibiting cardiac endothelial cell injury through α1-AR activation.
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Accurately assessing the changes in soil organic carbon storage ï¼SOCSï¼ before and after the Grain for Green Project ï¼GFGï¼ in the Loess Plateau ï¼LPï¼ and exploring the relationship between its spatial and temporal distribution and the influencing factors were important references for the development of regional recycling as well as the formulation of ecological protection policies. Based on the data of climate, human activities, and SOCD in the surface ï¼0-20 cmï¼ and deep ï¼0-100 cmï¼ soil before and after GFG in the LP from 2001 to 2020, we investigated the changes in SOCD at different spatial and temporal scales by using the methods of trend analysis, the kriging method, and variance partitioning analysis. The results showed thatï¼ â Before and after the GFG, the surface SOCS of the whole region increased by 8 338.7×104 tï¼ the deep SOCS increased by 1 160.02×104 t. â¡ In each bioclimatic subregion, the whole-region average SOCD of â ï¼Semi-Humid Forest Regionï¼, â ¡ ï¼Semi-Humid Semi-Arid Forest and Grassland Regionï¼, and â ¢ ï¼Semi-Arid Typical Grassland Regionï¼ showed a significant increasing trend, with a decreasing trend in â £ ï¼arid semi-arid desert grassland areaï¼ and â ¤ ï¼arid desert areaï¼. ⢠The average surface SOCS increase in different ecosystems was ranked as followsï¼ cropland > grassland > woodland > shrubs > bare land and sparse vegetation. The deep soil increase was ranked as followsï¼ grassland > cropland > woodland > shrubs > bare land and sparse vegetation. ⣠Climate factors were the most important driving factors for changes in SOCDï¼ the annual average temperature and precipitation were significantly positively correlated with changes in SOCD. The results of the study could provide data support for regional ecological management and land use policy formulation to promote high quality development of the ecological environment in the LP.
Subject(s)
Carbon , Climate Change , Soil , Soil/chemistry , China , Carbon/analysis , Organic Chemicals/analysis , Conservation of Natural Resources , Human Activities , Forests , Ecosystem , Environmental Monitoring/methods , Altitude , Grassland , Carbon Sequestration , Humans , Crops, Agricultural/growth & developmentABSTRACT
Acute myeloid leukemia (AML) arises from leukemia stem cells (LSCs) and is maintained by cells which have acquired features of stemness. We compared transcription profiles of AML cells with/without stem cell features defined as in vitro clonogenicity and serial engraftment in immune-deficient mice xenograft model. We used multi-parameter flow cytometry (MPFC) to separate CD34+ bone marrow-derived leukemia cells into sphingosine-1 phosphate receptor 1 (S1PR1)+ and S1PR1- fractions. Cells in the S1PR1+ fraction demonstrated significantly higher clonogenicity and higher engraftment potential compared with those in the S1PR1- fraction. In contrast, CD34+ bone marrow cells from normal samples showed reduced clonogenicity in the S1PR1+ fraction compared with the S1PR1- fraction. Inhibition of S1PR1 expression in an AML cell line reduced the colony-forming potential of KG1 cells. Transcriptomic analyses and rescue experiments indicated PI3K/AKT pathway and MYBL2 are downstream mediators of S1PR1-associated stemness. These findings implicate S1PR1 as a functional biomarker of LSCs and suggest its potential as a therapeutic target in AML treatment.
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OBJECTIVE: This study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats. METHODS: A total of 40 male Sprague Dawley rats were divided into three groups: normal control, chronic unpredictable mild stress (CUMS), and EA (CUMS + EA). The rats in CUMS and EA groups underwent chronic stress for 10 weeks, and EA group rats received EA treatment for 4 weeks starting from week 7. Body weight and behavioral tests, including the sucrose preference test (SPT), the forced swimming test (FST), and the open field test (OFT) were monitored. Gut microbiota composition was assessed via 16S rDNA sequencing, and lipid metabolism was analyzed by using UPLC-Q-TOF/MS technology. RESULTS: In comparison to CUMS group, EA could improve the behavior including bodyweight, immovability time, sucrose preference index, crossing piece index and rearing times index. After 4 weeks of EA treatment, 5-HT in hippocampus, serum and colon of depressive rats were simultaneously increased, indicating a potential alleviation of depression-like behaviors. In future studies revealed that EA could regulate the distribution and functions of gut microbiota, and improve the intestinal barrier function of CUMS rats. The regulation of intestinal microbial homeostasis by EA may further affect lipid metabolism in CUMS rats, and thus play an antidepressant role. CONCLUSION: This study suggested that EA has potential antidepressant effects by regulating gut microbiota composition and abundance, subsequently affecting lipid metabolism.
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BACKGROUND: The triglyceride glucose (TyG) index is a cutting-edge and highly effective marker of insulin resistance, a crucial factor in the development and exacerbation of diabetic kidney disease (DKD). To date, there has been limited research on how the triglyceride-glucose (TyG) index affects the outlook for patients suffering from DKD. METHODS: In this multicenter retrospective cohort study, the analysis recruited 2,203 DKD patients from the National Health and Nutrition Examination Survey (NHANES) dataset, which covers the US from 2001 to 2018. The research applied a Cox proportional hazards model with multiple variables to investigate the association of the TyG index with mortality outcomes. Restricted cubic splines (RCS) and methods for analyzing threshold effects were employed to identify possible non-linear relationships. RESULTS: Over nearly 19 years of follow-up, this study captured data on 753 all-cause and 231 cardiovascular disease-specific fatalities. Sophisticated statistical methods, including RCS and smoothing curve adjustments via penalized splines, helped identify distinctive patterns: The baseline TyG index was observed to have a U-shaped pattern related to overall mortality and an L-shape with cardiovascular diseases(CVD) mortality among individuals with DKD. Notably, TyG index below 9.15 for overall mortality and 9.27 for CVD mortality were linked to reduced death rates (HR = 0.65, 95% CI = 0.52-0.82 for all-cause; HR = 0.58, 95% CI = 0.43-0.83 for CVD). On the other hand, TyG index exceeding these benchmarks (greater than 9.15 for all-cause and 9.27 for CVD) correlated with increased all-cause mortality risks (HR = 1.21, 95% CI = 1.02-1.43) and showed a non-significant change in CVD mortality risks (HR = 1.07, 95% CI = 0.83-1.38). CONCLUSIONS: This study emphasizes the non-linear linkage involving the TyG index and death rates due to CVD and other factors in patients with DKD, demonstrating its effectiveness in estimating potential adverse events within this demographic.
Subject(s)
Blood Glucose , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Nutrition Surveys , Triglycerides , Humans , Triglycerides/blood , Diabetic Nephropathies/mortality , Diabetic Nephropathies/blood , Male , Female , Middle Aged , Retrospective Studies , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Blood Glucose/analysis , Aged , Proportional Hazards Models , Adult , Risk FactorsABSTRACT
In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S-catalyzing enzymes, such as cystathionine-ß-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia-reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.
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Background: Outside of pregnancy, intuitive eating (IE) is associated with lower body weight, blood glucose, and higher positive mood. However, little was known about the relationship between IE and anxiety-depression in the GDM population. Thus, this study aimed to investigate the association of IE with anxiety and depression, pregnancy weight and pregnancy blood glucose in the first and second GDM visit. Methods: Data from 310 pregnant women with GDM from the Fujian Maternal and Child Health Hospital Trial (Approval Number: 2020Y9133) were analyzed. IE was assessed using the Intuitive Eating Scale-2 subscales of Eating for Physiological Reasons rather than Emotional Reasons (EPR), Relying on Hunger and Satiety Cues (RHSC) and Body-Food Choice Consistency (B-FCC). Observations included weight, body mass index (BMI), fasting plasma glucose (FPG) and 2-h postprandial blood glucose; the Hospital Anxiety and Depression Scale (HADS) was used to assess the level of anxiety and depression in pregnant women with GDM. Linear regression analysis was used to assess the correlation between IE and anxiety, depression, pregnancy blood glucose and weight. Results: The cross-sectional analysis showed that the EPR eating behavior was negatively correlated with anxiety and depression, and the B-FCC eating behavior was negatively correlated with depression at both the first and second GDM visit; in addition, the B-FCC eating behavior was associated with lower BMI in the third trimester (all p < 0.05). In longitudinal analyses, the EPR eating behavior in the first visit for GDM predicted lower levels of anxiety and depression in the second GDM visit, whereas the RHSC eating behavior in the first visit for GDM was associated with lower FPG in the second GDM visit (all p < 0.01). Conclusion: These results suggest that practicing intuitive eating may be beneficial and that higher intuitive eating adherence can lead to lower levels of anxiety and depression and more ideal gestational weight and blood glucose values.
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Phase control over cation exchange (CE) reactions has emerged as an important approach for the synthesis of nanomaterials (NMs). Although factors such as crystal structure and morphology have been studied for the phase engineering of CE reactions in NMs, there remains a lack of systematic investigation to reveal the impact factors in heterogeneous materials. Herein, we report a molybdenum disulfide induced phase control method for synthesizing multidimensional Co3S4-MoS2 heteronanostructures (HNs) via cation exchange. MoS2 in parent Cu1.94S-MoS2 HNs are proved to affect the thermodynamics and kinetics of CE reactions, and facilitate the formation of Co3S4-MoS2 HNs with controlled phase. This MoS2 induced phase control method can be extended to other parent HNs with multiple dimensions, which shows its universality. Further, theoretical calculations demonstrate that Co3S4 (111)/MoS2 (001) exhibits a higher adhesion work, providing further evidence that MoS2 enables phase control in the HNs CE reactions, inducing the generation of novel Co3S4-MoS2 HNs. As a proof-of-concept application, the obtained Co3S4-MoS2 heteronanoplates (HNPls) show remarkable performance in hydrogen evolution reactions (HER) under alkaline media. This synthetic methodology provides a unique way to control the crystal structure and fills the gap in the study of heterogeneous materials on CE reaction over phase engineering.
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AIMS: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD. METHODS: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression. RESULTS: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3. CONCLUSIONS: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.
Subject(s)
Delirium , MicroRNAs , Neurons , Postoperative Complications , RNA, Circular , Sirtuin 3 , Animals , Sirtuin 3/metabolism , Sirtuin 3/genetics , Delirium/metabolism , Mice , MicroRNAs/metabolism , MicroRNAs/genetics , RNA, Circular/metabolism , Neurons/metabolism , Neurons/drug effects , Male , Postoperative Complications/metabolism , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/drug effects , Mice, Inbred C57BL , Tibial Fractures/surgery , Membrane Potential, Mitochondrial/drug effects , Membrane Potential, Mitochondrial/physiologyABSTRACT
A base promoted oxidative [4+2] annulation of pyrrole-2-carbaldehyde derivatives with o-hydroxyphenyl propargylamines for the synthesis of highly substituted indolizines has been developed. Using DBN as base, a broad range of 5,6,7-trisubstituted indolizines have been prepared in good to excellent yields under mild conditions, and many useful functional groups can be tolerated.
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BACKGROUND: The number of cesarean sections performed is increasing every year, and obstetric anesthesia is of great interest to physicians and research scholars because of its specificity, high risk, and high complication rate. OBJECTIVE: To investigate the effects of combined spinal epidural anesthesia (CSEA) with different intervertebral spaces during cesarean section on anesthesia effect, anesthesia onset time, anesthesia recovery time, maternal adverse reactions, and neonates. METHODS: Ninety-two women who underwent cesarean section in our hospital from September 2022 to February 2023 were selected as the study subjects and randomly divided them into two groups (group A and group B), 46 women in each group. Group A underwent CSEA via an L2-3 gap and group B underwent CSEA via an L3-4 gap puncture. The anesthesia effect, anesthesia onset time, sensory recovery time, adverse effects, and neonatal Apgar score were compared between the two groups. RESULTS: When CSEA was performed from L2-3, the anesthesia efficiency was higher, but the difference was not statistically significant. When anesthesia was performed by puncture from L2-3, the onset of anesthesia and recovery time was shorter, and the incidence of intraoperative maternal nausea and vomiting, hypotension, respiratory depression, and other adverse reactions was low with a statistically significant difference. However, the Apgar scores of the neonates in the two groups have no difference. CONCLUSIONS: When CSEA is induced via L2-3 interspace, anesthesia has a rapid onset of action, shorter recovery time, and few maternal adverse effects, without affecting the final anesthetic outcome.