RESUMO
BACKGROUND: Chinese chest pain centers (CPCs) have been expanding and maturing for the past decade, but patient wait times for pre-hospital care remain long. OBJECTIVE: To demonstrate that the remote electrocardiogram (ECG) monitoring system can ensure more efficient treatment for patients with ST-elevation myocardial infarction (STEMI) in CPCs, we compared patients with high-risk chest pain who used remote ECG monitoring systems to those who used conventional ECGs in retrospective cohort study. METHODS: Based on the inclusion and exclusion criteria, 290 patients who visited our CPC between June 2019 and March 2022 with acute chest pain and a diagnosis of STEMI as well as patients who had undergone an emergency primary percutaneous coronary intervention were selected. Among them, 73 patients with STEMI had employed remote real-time dynamic 12-lead ECG monitoring devices, while 217 patients with STEMI (i.e., the controls) had used conventional ECG monitoring. The effectiveness of treatment procedures for the two groups was investigated. As statistical measures, the symptom onset-to-wire times, first medical contact (FMC)-to-wire times, door-to-wire times, major adverse cardiac events in hospital, and the troponin T levels were analyzed. RESULTS: Compared with the control group, the patients with remote real-time dynamic 12-lead ECG monitoring devices showed shorter times for both symptom onset-to-wire (234.8 ± 95.8 min vs. 317.6 ± 129.6 min, P= 0.0321) and from symptom onset-to-FMC (170.5 ± 86.3 min vs. 245.3 ± 115.6 min, P= 0.0287); this group also had a lower 30-day mortality rate (2.73% vs. 4.14%, P= 0.003). The differences between the two groups were statistically significant (P< 0.05). CONCLUSION: With remote real-time dynamic 12-lead ECG monitoring equipment, myocardial ischemia can be treated more quickly, leading to fewer possible cardiac events and a better prognosis.
Assuntos
Serviços Médicos de Emergência , Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Estudos Retrospectivos , Clínicas de Dor , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Eletrocardiografia/métodosRESUMO
Th22 cells are a newly identified subpopulation of CD4+ T lymphocytes distinct from Th1, Th2, and Th17 cells, which secretes mainly interleukin-22 (IL-22), in addition to a variety of other cytokines. The function of Th22 cells in tumors is mainly realized through IL-22, which can activate JAK/STAT and MAPK cell signaling pathways, thereby regulating the anti-tumor immune response of the body. The main function of Th22 cells is to participate in mucosal defense, tissue repair, and wound healing. However, controversial data have shown that overexpression of IL-22 can lead to pathological changes under inflammatory conditions and tumor progression. In this review, we searched the PubMed and Web of Science databases for articles and reviews published before May 6, 2022, using the keywords "Th22 cells, T helper 22 cells, cancer, tumor", and conducted a comprehensive review of the relevant literature. In addition, this article offers an overview of the relevant findings on the function of Th22 cells in tumors published in recent years, along with a more comprehensive analysis of the functions and mechanisms of Th22 cells in tumors. This article will hopefully inspire new future directions in the research on cancer therapy.
RESUMO
The impact of the immune response on the therapeutical efficacy of neoadjuvant chemotherapy for breast cancer remains largely unknown. To characterize the role of regulatory T cells (CD4+CD25+CD127lowTreg), T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+) and NK cells in neoadjuvant chemotherapy, we investigated the correlation patterns of these immune cell subsets with the progression of breast cancer. A total of 120 breast cancer patients receiving neoadjuvant chemotherapy in Nanjing Maternal and Child Health Hospital from May 2019 to November 2021 were retrospectively collected as the breast cancer group, and 46 healthy women were selected as the control group. The number of regulatory T cells, T lymphocyte subsets and NK cells in the peripheral blood were analyzed by flow cytometry. Compared with the control group, CD3+, CD4+, CD4+/CD8+ ratio and NK cells were significantly decreased in patients with breast cancer (P < 0.05), while the levels of Treg and CD8+ cells were significantly increased (P < 0.05). In addition, the status of the immune response among breast cancer patients at different clinical stages was obviously different. In higher tumor stages, the level of CD3+, CD4+, CD4+/CD8+ ratio and NK cell were reduced, while the level of Treg and CD8+ T cells gradually increased. Furthermore, we found a lower percentage of CD3+, CD4+, CD4+/CD8+ and NK cells in association with lymph node metastasis, accompanied by a higher number of CD8+ T cells. Interestingly, after treatment with neoadjuvant chemotherapy, the levels of Tregs, CD3+, CD4+ and CD4+/CD8+ ratio of patients were all upregulated compared with the levels before treatment, indicating the recovery of cytotoxic lymphocytes and a consolidation of the immunosuppressive microenvironment at the same time (P < 0.05). Immune dysfunction is commonly observed in breast cancer patients, which is closely associated with tumor progression and lymph node metastasis. Neoadjuvant chemotherapy was found to highly influence the number of T lymphocytes and improve the immune function of T lymphocyte subsets in breast cancer patients. At the same time, as immunosuppressive cells, the proportion of Tregs (CD4+CD25+CD127lowTreg) also increased after treatment with neoadjuvant chemotherapy. Our results provide guidance for the development of new combination strategies during neoadjuvant chemotherapy to reverse the immunosuppressive microenvironment and achieve better clinical outcomes.
RESUMO
Methamphetamine (METH) abuse is known to cause executive dysfunction. However, the molecular mechanism underlying METH induced executive dysfunction remains unclear. Go/NoGo experiment was performed in mice to evaluate METH-induced executive dysfunction. Immunoblot analysis of Nuclear factor-E2-related factor 2 (Nrf2), phosphorylated Nrf2 (p-Nrf2), heme-oxygenase-1 (HO-1), Glucose Regulated Protein 78(GRP78), C/EBP homologous protein (CHOP), Bcl-2, Bax and Caspase3 was performed to evaluate the levels of oxidative stress, endoplasmic reticulum (ER) stress and apoptosis in the dorsal striatum (Dstr). Malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activity was conducted to evaluate the level of oxidative stress. TUNEL staining was conducted to detect apoptotic neurons. The animal Go/NoGo testing confirmed that METH abuse impaired the inhibitory control ability of executive function. Meanwhile, METH down-regulated the expression of p-Nrf2, HO-1 and GSH-Px and activated ER stress and apoptosis in the Dstr. Microinjection of Tert-butylhydroxyquinone (TBHQ), an Nrf2 agonist, into the Dstr increased the expression of p-Nrf2, HO-1, and GSH-Px, ameliorated ER stress, apoptosis and executive dysfunction caused by METH. Our results indicated that the p-Nrf2/HO-1 pathway was potentially involved in mediating methamphetamine-induced executive dysfunction by inducing endoplasmic reticulum stress and apoptosis in the dorsal striatum.
Assuntos
Metanfetamina , Camundongos , Animais , Metanfetamina/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse do Retículo Endoplasmático , Estresse Oxidativo , Antioxidantes/metabolismo , Apoptose , Heme Oxigenase-1/metabolismoRESUMO
Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the lethal ventricular arrhythmias. Thus, it is necessary for exploring whether LRP6 and its upstream genes circRNA1615 mediate the phosphorylation of Cx43 in VT of AMI. Here, we showed that circRNA1615 regulated the expression of LRP6 mRNA through sponge adsorption of miR-152-3p. Importantly, LRP6 interference fragments aggravated hypoxia injury of Cx43, while overexpression of LRP6 improved the phosphorylation of Cx43. Subsequently, interference with G-protein alpha subunit (Gαs) downstream of LRP6 further inhibited the phosphorylation of Cx43, along with increasing VT. Our results demonstrated that LRP6 upstream genes circRNA1615 controlled the damage effect and VT in AMI, and LRP6 mediated the phosphorylation of Cx43 via Gαs which played a role in VT of AMI.
RESUMO
Coronary artery ectasia (CAE) is a rare finding that is associated with poor clinical outcomes (Kawsara et al. 2018), and disorders in lipid metabolism have been reported in CAE. Lipids constitute one of the three metabolite types that regulate bodily functions and are also powerful signaling molecules (Han 2016; Zhu et al. 2021) that affect immunoregulation and inflammatory responses via a series of transcription factors and signaling pathways (Barrera et al. 2013). Although abnormal lipid metabolism and immunoinflammatory responses have been reported in CAE, their roles in the pathogenic mechanisms underlying CAE are currently unclear.
RESUMO
BACKGROUND: Since the discovery of the Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) gene has been involved in regulating low-density lipoprotein metabolism and cardiovascular disease (CVD), many therapeutic strategies directly targeting PCSK9 have been introduced. PCSK9 gain of function (GoF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis. In contrast, PCSK9 loss of function (LOF) mutations have cardioprotective effects and can lead to familial hypo cholesterol in some instances. However, its potential impacts beyond the typical effects on lipid metabolism have not been elucidated. Therefore the study aimed to identify and verify PCSK9's possible effects beyond its traditional role in lipid metabolism. METHODS: The S127R is a PCSK9 gain of function mutation. Firstly, We used the data of the gene expression Omnibus(GEO) database to identify the differentially expressed genes between S127R mutation carriers and ordinary people. Secondly, the identification and analysis of significant genes were performed with various bioinformatics programs. Thirdly, to verify the possible effect and the potential pathways of PCSK9 on angiogenesis, we constructed PCSK9 low and high expression models by transfecting PCSK9-siRNA (small interfering RNA) and PCSK9-plasmid complex into human umbilical vein endothelial cells (HUVECs), respectively. Furthermore, Wound-Healing Assay and Capillary tube formation assay were applied to measure the effect of PCSK9 on angiogenesis. Fourthly, the expression level of VEGFR2 and the significant genes between PCSK9 low and high expression models were verified by quantitative real-time PCR. All data were analysed by GraphPad Prism 8 software. RESULTS: 88 DEGs were identified, including 45 up-regulated and 43 down-regulated DEGs. Furthermore, we identified the six genes (MMP9, CASP3, EGR1, NGFR, LEFTY1 and NODAL) as significantly different genes between PCSK9-S127R and Control hiPSC. Further, we found that these significant difference genes were mainly associated with angiogenesis after enrichment analysis. To verify the possible effect of PCSK9 on angiogenesis, we constructed low and high-expression PCSK9 models by transfecting siRNA and PCSK9-plasmid complex into human umbilical vein endothelial cells (HUVECs), respectively. The tubule formation test and Wound healing assays showed that overexpression of PCSK9 had an inhibitory effect on angiogenesis, which could be reversed by decreasing the expression of PCSK9. Moreover, bioinformatics analysis indicated that the six hub genes (MMP9, CASP3, EGR1, NGFR, LEFTY1 and NODAL) might play a vital role in the biological function of PCSK9 in angiogenesis. Real-time quantitative PCR was applied to clarify the expression profiles of these critical genes in overexpression/knockdown PCSK9. Finally, the expression levels of MMP9, Caspase3, LEFTY1, and NODAL were suppressed by overexpression of PCSK9 and could be alleviated by PCSK9 knockdown. Otherwise, EGR1 had the opposite expression trend, and there was no specific trend of NGFR after repeated experiments. CONCLUSION: PCSK9 might play an essential role in angiogenesis, unlike its typical role in lipid metabolism, and MMP9, Caspase3, LEFTY1, NODAL, and EGR1 may be involved in the regulation of angiogenesis as critical genes.
Assuntos
Pró-Proteína Convertase 9 , Serina Endopeptidases , Humanos , Pró-Proteína Convertase 9/genética , Serina Endopeptidases/genética , Pró-Proteína Convertases/genética , Pró-Proteína Convertases/metabolismo , Caspase 3/genética , Metaloproteinase 9 da Matriz/genética , Células Endoteliais/metabolismo , Mutação , RNA Interferente Pequeno , Receptores de LDL/genética , Receptores de LDL/metabolismoRESUMO
BACKGROUND: Current guidelines recommend a standard ticagrelor loading dose (LD) in ST-segment elevation myocardial infarction (STEMI) patients. However, antiplatelet therapy in STEMI patients at high risk of thrombotic events is suboptimal. The study was conducted to validate whether vasodilatorstimulated phosphoprotein (VASP)-guided ticagrelor dosing individual therapy may result in more effective platelet inhibition and better clinical outcomes. METHODS: This trial included 374 STEMI patients with a low platelet response after ticagrelor LD. The patients were randomized into a control group and a VASP-guided group, where the ticagrelor pretreatment was individually adjusted before and after percutaneous coronary intervention (PCI) to obtain a VASP index < 50%. Up to 2 additional boluses of ticagrelor (every additional dosing was 90 mg) were prescribed after the first LD, and the VASP index was assessed 2 hours after each administration until a VASP index < 50% was obtained or up to 3 dosages (360 mg). The primary endpoint was major adverse cardiovascular events (MACEs) at 30 days. The secondary endpoints were thrombolysis in myocardial infarction (TIMI) major and minor bleeding. RESULTS: The characteristics were similar in the two groups. After the ticagrelor doses increased, the platelet reactivity index (PRI) decreased, and 98.4% of patients reached PRI < 50% in the VASP-guided group. The adenosine concentration increased, and the rate of MACE was significantly lower in the VASP-guided group (10 [5.3%] vs. 20 [10.8%], hazard ratio 2.38, 95% confidence interval 1.21-3.28, p = 0.007). There were no major hemorrhagic complications (0 vs. 0, p = 1.0). The rate of minor bleeding in the VASP-guided group was higher than that in the control group, but the difference was not significant (24 [12.8%] vs. 16 [8.6%], p = 0.068). CONCLUSIONS: The incremental ticagrelor dosing strategy decreases the rate of MACE after PCI without increasing major and minor bleeding.
Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Ticagrelor , Inibidores da Agregação Plaquetária/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Fosforilação , Fosfoproteínas , Infarto do Miocárdio/etiologia , Hemorragia/induzido quimicamente , Resultado do TratamentoRESUMO
Nowadays, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose infectivity is awfully strong, has been a major global threat to the public health. Since lung is the major target of SARS-CoV-2, the infection can lead to respiratory distress syndrome (RDS), multiple organ failure (MOF), and even death. The studies on viral structure and infection mechanism have found that angiotensin-converting enzyme 2 (ACE2), a pivotal enzyme affecting the organ-targeting in the RAS system, is the receptor of the SARS-CoV-2 virus. Currently, the detection of SARSCoV-2 is mainly achieved using open plate real-time reverse-transcription polymerase chain reaction (RT-PCR). While open plate method has some limitations, such as a high false-negative rate, cumbersome manual operation, aerosol pollution and leakage risks. Therefore, a convenient method to rapidly detect SARS-CoV-2 virus is urgently and extremely required for timely epidemic control with the limited resources. In this review, the current real-time methods and principles for novel coronavirus detection are summarized, with the aim to provide a reference for real-time screening of coronavirus in areas with insufficient detection capacity and inadequate medical resources. The development and establishment of a rapid, simple, sensitive and specific system to detect SARS-CoV-2 is of vital importance for distinct diagnosis and effective treatment of the virus, especially in the flu season.
RESUMO
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder prevalent in school-age children. At present, however, its etiologies and risk factors are unknown. Transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor regulatory protein γ-8 (TARP γ-8, also known as calcium voltage-gated channel auxiliary subunit gamma 8 (CACNG8)) is an auxiliary AMPA receptor (AMPAR) subunit. Here, we report an association between TARP γ-8 and ADHD, whereby adolescent TARP γ-8 knockout (KO) mice exhibited ADHD-like behaviors, including hyperactivity, impulsivity, anxiety, impaired cognition, and memory deficits. Human single-nucleotide polymorphism (SNP) analysis also revealed strong associations between intronic alleles in CACNG8 genes and ADHD susceptibility. In addition, synaptosomal proteomic analysis revealed dysfunction of the AMPA glutamate receptor complex in the hippocampi of TARP γ-8 KO mice. Proteomic analysis also revealed dysregulation of dopaminergic and glutamatergic transmissions in the prefrontal cortices of TARP γ-8 KO mice. Methylphenidate (MPH), which is commonly used to treat ADHD, significantly rescued the major behavioral deficits and abnormal synaptosomal proteins in TARP γ-8 KO mice. Notably, MPH significantly reversed the up-regulation of Grik2 and Slc6a3 in the prefrontal cortex. MPH also significantly improved synaptic AMPAR complex function by up-regulating other AMPAR auxiliary proteins in hippocampal synaptosomes. Taken together, our results suggest that TARP γ-8 is involved in the development of ADHD in humans. This study provides a useful alternative animal model with ADHD-like phenotypes related to TARP γ-8 deficiency, which has great potential for the development of new therapies.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Canais de Cálcio , Animais , Transtorno do Deficit de Atenção com Hiperatividade/genética , Canais de Cálcio/genética , Humanos , Camundongos , Camundongos Knockout , ProteômicaRESUMO
More and more studies have proved that there are a small number of cells with self-renewal and differentiation ability in breast tumors, namely breast cancer stem cells. Such cells play a key role in the initiation, development and migration of breast tumors. The properties of breast tumor stem cells are regulated by a range of intracellular and extracellular factors, including important signaling pathways, transcription factors, non-coding RNAs, and cytokines such as Hedgehog, Wnt, Notch, microRNA93, microRNA100, and IL-6. Tumor microenvironment (such as mesenchymal stem cells, macrophages and cytokines) plays an important role in the regulation of breast tumor stem cells. Using the keywords including "breast cancer stem cells", "signal pathway", "chemotherapy tolerance", and "non-coding RNA", "triple negative breast cancer", "inhibitors", this study retrieved the original articles and reviews published before October 3, 2021, from PubMed and WEB OF SCI database and this study performed a comprehensive review of them. After treatment, there is a correlation between the metastasis-prone nature and recurrence with breast cancer stem cells. The signaling pathway of breast cancer stem cells plays a significant role in activating the function of breast cancer cells, regulating the differentiation of breast cancer cells and controlling the division of breast cancer cells. This imbalance leads to the uncontrolled growth and development of breast cancer cells. Targeted therapy that blocks the corresponding pathway may become a new perspective for breast cancer treatment. In addition, corresponding therapeutic strategies can be used according to the expression characteristics of different molecular types of breast cancer stem cells. For ER-positive breast cancer, simultaneous endocrine therapy and targeted therapy of tumor stem cells may improve the efficacy of endocrine therapy. Trastuzumab therapy significantly reduces the risk of recurrence of HER2-positive breast cancer. For drug-resistant patients, combination therapy is required due to the different phenotypes of epithelial-mesenchymal transforming tumor stem cells. This study briefly reviews the research progress of breast cancer stem cell-related signaling pathways and their inhibitors, in order to provide a reference for breast cancer patients to obtain more effective clinical treatment.
RESUMO
AbstractObjective: To explore the distribution characteristics and clinical significance of peripheral blood monocyte subgroups in patients with diffuse large Bîcell lymphoma(DLBCL). METHODS: The percentage of peripheral blood monocyte subsets of 82 DLBCL patients (including 32 newly diagnosis, 29 remission and 21 relapse) and 30 healthy controls were detected by flow cytometry, and the correlation with the clinical characteristics and its diagnostic value of DLBCL were analyzed. RESULTS: The proportion of intermediate monocytes in patients with newly diagnosed DLBCL group was higher than that in healthy controls (t=5.888, P<0.01). The proportion in relapsed group was higher than those in newly diagnosed DLBCL groupï¼t=2.106ï¼P=0.04ï¼ and remission group ï¼t=6.882ï¼ Pï¼0.01ï¼, and the proportion of intermediate monocytes in newly diagnosed DLBCL group was higher than that in Remission group (t=3.969, P<0.01). With the increase of International Prognostic Index (IPI) score, the percentage of intermediate monocytes in patients with DLBCL increased (r=0.37). Furthermore, when the proportion of intermediate monocytes was 10.91% as the cutîoff value, the sensitivity and specificity of the whole sample were 90.60% and 91î00%, respectively. CONCLUSION: The disease progression is related to the increased intermediate monocytes, which can be used as a potential diagnostic index for DLBCL.
Assuntos
Linfoma Difuso de Grandes Células B , Monócitos , Protocolos de Quimioterapia Combinada Antineoplásica , Progressão da Doença , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Monócitos/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: The CHA2DS2-VASc score has been associated with the prognosis of cardiovascular diseases. This study aimed to explore the association between the CHA2DS2-VASc score and all-cause mortality in coronary care unit (CCU) patients. METHODS: The study was based on the Medical Information Mart for Intensive Care (MIMIC) III database. CCU patients were divided into two groups according to CHA2DS2-VASc score: 0-3 (low risk)ï¼4-9 (intermediate and high risk). The primary outcome was 30-day mortality, and the secondary endpoints included in-hospital, 1-year, and 5-year mortality. Propensity score matching (PSM) and sensitivity analyzes for the confounders were also performed. The restricted cubic splines flexibility model was used to demonstrate the relation between red blood cell volume distribution width (RDW), blood urea nitrogen (BUN), platelet, white blood cell (WBC), hemoglobin, phosphorus, glucose, potassium, sodium and 30-day mortality in the 0-3 score versus the 4-9 score groups after PSM. RESULTS: Among 4491 eligible patients, 988 patients with low CHA2DS2-VASc scores and 988 patients with intermediate and high CHA2DS2-VASc scores had similar propensity scores and were included in the analyzes. In the survival analysis, the patients with intermediate and high CHA2DS2-VASc scores were associated with higher 30-day mortality [hazard ratio (HR): 1.11; 95% confidence interval (CI), 1.02-1.20, P = .014], 1-year mortality [HR: 1.13; 95%CI, 1.06-1.19, P < .001], and 5-year mortality [HR: 1.13; 95%CI, 1.07-1.18, P < .001]. The interaction for 30-day mortality among subgroups was not significant between the 0-3 score versus the 4-9 score groups. The restricted cubic splines for 30-day mortality demonstrated an L-shaped trajectory for platelets and hemoglobin, a J-shaped trajectory for WBC, glucose and potassium, and a U-shaped trajectory for sodium, respectively (all nonlinear P <.001). CONCLUSIONS: A high CHA2DS2-VASc score was an independent risk for 30-day, 1-year, and 5-year mortality for CCU patients.
Assuntos
Fibrilação Atrial , Unidades de Cuidados Coronarianos , Fibrilação Atrial/complicações , Glucose , Humanos , Potássio , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , SódioRESUMO
Objective: This study was designed to explore the effect of glimepiride combined with recombinant human insulin injection on serum insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), tartrate-resistant acid phosphatase 5b (TRACP-5b) and oxidative stress levels in patients with type 2 diabetes. Methods: A total of 217 patients with type 2 diabetes who were treated in our hospital from November 2018 to March 2020 were selected and divided into control group and treatment group. The control group was treated with glimepiride (n = 107). The study group was given glimepiride and recombinant human insulin injection) (n = 107). The levels of blood glucose, blood lipids, IGF-1, VEGF, TRACP-5b, and oxidative stress in the two groups were measured, respectively. We summarize the main results as follows. Insulin resistance index (HOMA-IR), fasting blood glucose (FPG), 2h postprandial blood glucose (2hBG), serum glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), serum malondialdehyde (MDA), reactive oxygen species (ROS), VEGF, and TRACP-5b levels were significantly lower than those before treatment, and the degree of reduction in the study group was greater than that in the control group (P < 0.05). The levels of insulin (INS), insulin beta cell function index (HOMA-beta), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and IGF-1 were significantly higher than those before treatment. Further, the study group demonstrated better results than the control group (P < 0.05). Conclusion: Glimepiride combined with recombinant human insulin injection can improve insulin sensitivity, reduce insulin resistance, significantly reduce glucose and lipids in patients, reduce the occurrence of oxidative stress, promote the secretion of oxidative resistance enzymes, lower the vascular endothelial growth factor (VEGF), reduced the formation of new blood vessels, and inhibit the growth and metastasis of cancer cells. Additionally, we found out that glimepiride combined with recombinant human insulin injection had a good prognosis for patients; it significantly reduced the bone resorption marker TRACP-5b and prevented the occurrence of complications such as osteoporosis. The combined use of the two is more effective than glimepiride alone. In conclusion, glimepiride combined with recombinant human insulin injection has higher application value in the treatment of patients with type 2 diabetes.
RESUMO
Diabetes mellitus is a common chronic disease. This study aimed to investigate the correlation between serum insulin-like growth factor 1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), endothelin (ET) levels, and bone mineral density (BMD) in type 2 diabetic mellitus (T2DM) patients treated with metformin plus α-glucosidase inhibitors and evaluate the predictive value of serum factors in the prognosis of osteoporosis in these patients. It was a prospective study that enrolled 142 patients with T2DM treated in Dinghu District People's Hospital from March 2019 to May 2020. All enrollments were randomized (1 : 1) to receive either metformin (control group) or metformin plus α-glucosidase inhibitors (study group). After 12 weeks of treatment, metformin plus α-glucosidase inhibitors were associated with significantly lower levels of 2 hPG, FPG, HbA1c, and HOMA-IR versus metformin alone (P < 0.05). After treatment, the BMD was positively correlated with IGF-1R and negatively correlated with VEGF and ET. Alpha-glucosidase inhibitors plus metformin for primary T2DM can effectively manage blood glucose and reduce insulin resistance in patients, but the prediction of osteoporosis development remains to be further explored in large sample studies.
RESUMO
AIM: To investigate the effect of nano-selenium loaded with different concentrations of lycium barbarum polysaccharide (LBP-SeNPs) on the proliferation of human lens epithelial cells (HLECs) from UV irradiation. METHODS: LBP-SeNPs were prepared and their particle size was detected. HLECs (SRA01/04) were irradiated with UVB for different time (0, 10, 20, 30, 40, 50, 60min) to construct a damaged model, the survival rate of cells was determined by methylthiazol tetrazolium (MTT) assay. The 4',6-Diamidine-2'-phenylindole dihydrochloride (DAPI) staining was used to observe the status of cell nucleus and drug entering cytoplasm through cell membrane in SRA01/04 cells after adding LBP-SENPS loaded with coumarin fluorescence agent 24h under fluorescence microscope. SRA01/04 normal and UVB-damaged cells were treated with different amounts of LBP-SeNPs at different concentrations, cells proliferation were observed. RESULTS: The particle size of LBP-SeNPs was stable in the range of 150-200 nm. The survival rate changes with time after UVB irradiation were statistically significant. The 10min of UVB exposure as the time was chosen to construct the cell damage model. With DAPI staining, LBP-SeNPs were observed to enter the cytoplasm through the cell membrane under fluorescence inverted microscope. Cytotoxicity of SRA01/04 at different concentrations of LBP-SeNPs were measured. Cell survival rate was statistically different compared with the control group. The higher the loading concentration of LBP in nano-Se drugs was, the higher the cell proliferation rate was (P<0.05). The lower the concentration of LBP-SeNPs, the higher the cell proliferation rate, showing a negative growth trend (P<0.05). The group with the highest average cell proliferation rate was 0.5 µmol/L 2.0 mg/mL LBP-SeNPs (128.80%). When the 2.0 mg/mL LBP-SeNPs group was selected for cell photography, the cell density was higher at 0.5 µmol/L. With the increase of concentration, SRA01/04 cells appeared more cytoplasm dehydration, cell shrinkage and apoptotic bodies, and cell density decreased. CONCLUSION: LBP-SeNPs has moderate particle size and good stability. LBP-SeNPs can protect HLECs (SRA01/04) from UVB-induced damage, and the cell proliferation rate is further increased with increasing the amount of loaded LBP and decreasing nano-selenium concentration.
RESUMO
BACKGROUND: This study was aimed at exploring the biological function and molecular mechanism of ferroptosis of LRP6 modulation in cardiomyocytes of myocardial infarction (MI). METHOD: We established the ferroptosis model of MI in vivo and in vitro and constructed the modulation network of circRNA-miRNA-LRP6 by bioinformatics analysis; then, we focused on exploring the regulatory relationship of LRP6 and its upstream genes circRNA1615 and miR-152-3p in the RIP experiments and the double luciferase reporter gene assay. Also, we tested the LRP6-mediated autophagy-related ferroptosis in MI. RESULTS: Ferroptosis was found in cardiomyocytes of MI, and ferroptosis inhibitor Ferrostatin-1 (Fer-1) could improve the pathological process of MI. LRP6 was involved in the process of ferroptosis in cardiomyocytes, and LRP6 deletion regulated ferroptosis in cardiomyocytes through autophagy. Screening and identification of the upstream gene circRNA1615 would target LRP6. circRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of MI. CONCLUSIONS: circRNA1615 inhibits ferroptosis via modulation of autophagy by the miRNA152-3p/LRP6 molecular axis in cardiomyocytes of myocardial infarction.
Assuntos
Ferroptose , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , RNA Circular/metabolismo , Animais , Autofagia , Linhagem Celular , Modelos Animais de Doenças , Regulação da Expressão Gênica , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologia , RNA Circular/genética , Transdução de SinaisRESUMO
Objective: The probability of late recurrent atrial fibrillation (AF) after radiofrequency ablation (RFA) has not yet been fully clarified. This study aims to study the association of left atrial appendage (LAA) morphology with AF recurrence after RFA. Methods: We retrospectively enrolled 84 patients (24 patients had persistent AF, 60 patients had paroxysmal AF) who underwent RFA in Shanghai East Hospital from June 2014 to May 2018. The mean follow-up of these patients was 618.6 days. According to preoperative transesophageal echocardiography (TEE), the morphology feature of LAA was classified and evaluated by two classification methods. The first method was divided into chicken-wing, windsock, cactus, and cauliflower, and the second method was divided into one lobe, two lobes, and multiple lobes. The correlation between morphological feature of LAA and the recurrence rate of AF after RFA was analyzed. Results: During follow-up, 12 patients (50%) and 10 patients (16.7%) had AF recurrence in persistent and paroxysmal AF, respectively. The LAA morphology was associated with the recurrence of AF after RFA with the chicken-wing highest recurrence risk (68.2%). The structure type of LAA was also related to the AF recurrence rate (p < 0.01). Compared with one lobe and multiple lobes, two lobes (recurrence, 47.6%) were more likely associated with the recurrence of AF (p < 0.02). Logistic regression analysis showed that the chicken-wing group had a higher risk of recurrence after RFA (OR = 8.13, p = 0.004), and the windsock group had a lower risk of recurrence (OR = 0.17, p = 0.002). Conclusion: The morphological feature of LAA is related to the recurrence risk of AF after RFA. LAA morphology assessment can predict the risk of AF recurrence.
RESUMO
OBJECTIVE: To compare the clinical efficacy of staged surgery on Sanders â £ calcaneal fractures with soft tissue â ¢ swelling. METHODS: The clinical data of 76 patients with Sanders type â £ closed calcaneal fracture with soft tissue three-degree swelling treated from June 2017 to May 2020 was retrospectively analyzed, including 54 males and 22 females, aged from 25 to 50 (38.16±10.24) years. The patients were divided into observation group and control group according to different treatment methods. Twenty-four patients in the observation group were treated by staged surgery stageâ closed prying traction reduction and Kirschner wire fixation, stageâ ¡open reduction and internal fixation with titanium plate, including 17 males and 7 females, aged from 25 to 50 (36.12±9.56) years. There were 52 patients in the control group, including 37 males and 15 females, aged from 25 to 50 (38.32±10.67) years, these patients were treated with open reduction and internal fixation with titanium plate after the dermatoglyphic signs appeared. The swelling subsidence time, the length of hospitalization days, and the incidence of postoperative incision complications were compared between two groups. The Bhler angle, Gissane angle, and calcaneal varus angle were measured by X-ray before and 6 months after operation. American Orthopedic Foot and Ankle Society (AOFAS) about the ankle hindfoot score was used to evaluate the clinical efficacy. RESULTS: All 76 patients were followed up for 8 to 12 (9.52±2.01) months. The swelling subsidence time and hospitalization days in observation group were (12.12± 3.24) d and (24.53±6.44) d, respectively, which in control group were (15.16±4.16) d and (29.46±9.61) d, with statistical difference between two groups (P<0.05). Postoperative 6 months, Bhler angle, Gissane angle and calcaneal varus angle were (31.33±10.15)°, (145.34±8.04) ° and (10.31±3.23) ° in observation group, while those in control group were (20.24±8.23) °, (165.28±10.29) °and (21.24±5.27) °, with statistical difference between two groups (P<0.05). And there was significant difference in all patients between before and 6 months after operation (P<0.05). The AOFAS score of the observation group and control group were 71.76±9.84 and 57.23±10.76 at 6 months after operation, with significant different between two groups (P< 0.05). The excellent rate of observation group was significantly higher than that of control group (P<0.05). CONCLUSION: Compared with open reduction and internal fixation with titanium plate after the appearance of dermatoglyphic signs, staged surgery for Sanders type â £ calcaneal fractures with soft tissue three-swelling does not increase the risk of soft tissue complications, and can significantly shorten the patient's swelling subsidence time and hospitalization days, improve the quality of fracture reduction and short term function, and relieve pain.