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The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease. Furthermore, following N-methyl-D-aspartate (NMDA)-induced excitotoxicity damage of RGCs, Lhx2 mitigates the loss of visual signal transduction. Mechanistic analysis revealed that overexpression of Lhx2 supports axon regeneration by systematically regulating the transcription of regeneration-related genes and inhibiting transcription of Semaphorin 3C (Sema3C). Collectively, our studies identify a critical role of Lhx2 in promoting RGC survival and axon regeneration, providing a promising neural repair strategy for glaucomatous neurodegeneration.
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Axones , Modelos Animales de Enfermedad , Glaucoma , Proteínas con Homeodominio LIM , Regeneración Nerviosa , Células Ganglionares de la Retina , Factores de Transcripción , Animales , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patología , Proteínas con Homeodominio LIM/metabolismo , Proteínas con Homeodominio LIM/genética , Glaucoma/genética , Glaucoma/patología , Glaucoma/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Axones/metabolismo , Axones/patología , Ratones , Regeneración Nerviosa/genética , Regeneración Nerviosa/fisiología , Ratones Endogámicos C57BL , Supervivencia Celular/genética , Semaforinas/metabolismo , Semaforinas/genética , N-Metilaspartato/metabolismoRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer (GC), the Wnt/ß-Catenin signaling pathway is closely linked to tumourigenesis. GC has a high mortality rate and treatment cost, and there are no drugs to prevent the progression of gastric precancerous lesions to GC. Therefore, it is necessary to find a novel drug that is inexpensive and preventive to against GC. AIM: To explore the effects of H. pylori and Moluodan on the Wnt/ß-Catenin signaling pathway and precancerous lesions of GC (PLGC). METHODS: Mice were divided into the control, N-methyl-N-nitrosourea (MNU), H. pylori + MNU, and Moluodan groups. We first created an H. pylori infection model in the H. pylori + MNU and Moluodan groups. A PLGC model was created in the remaining three groups except for the control group. Moluodan was fed to mice in the Moloudan group ad libitum. The general condition of mice were observed during the whole experiment period. Gastric tissues of mice were grossly and microscopically examined. Through quantitative real-time PCR (qRT-PCR) and Western blotting analysis, the expression of relevant genes were detected. RESULTS: Mice in the H. pylori + MNU group showed the worst performance in general condition, gastric tissue visual and microscopic observation, followed by the MNU group, Moluodan group and the control group. QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes, the results showed that the H. pylori + MNU group had the highest expression, followed by the MNU group, Moluodan group and the control group. CONCLUSION: H. pylori can activate the Wnt/ß-catenin signaling pathway, thereby facilitating the development and progression of PLGC. Moluodan suppressed the activation of the Wnt/ß-catenin signaling pathway, thereby decreasing the progression of PLGC.
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Light yellowish-white colonies of a bacterial strain, designated LNNU 24178T, were isolated from the rhizosphere soil of halophyte Suaeda aralocaspica (Bunge) Freitag and Schütze grown at Shihezi district, Xinjiang, PR China. Cells were Gram-stain-negative, non-flagellum-forming, rod-shaped and non-motile. The results of phylogenetic analysis based on the 16S rRNA gene sequence indicated that LNNU 24178T represented a member of the genus Luteimonas and shared the highest sequence similarity with Luteimonas yindakuii CGMCC 1.13927T (97.1â%) and lower sequence similarity (< 97.0â%) to other known species. The genomic DNA G+C content of LNNU 24178T was 68.8â%. The average nucleotide identity (ANI) values between LNNU 24178T and Luteimonas yindakuii CGMCC 1.13927T, Luteimonas mephitis DSM 12574T, Luteimonas arsenica 26-35T and Luteimonas huabeiensis HB2T were 78.7, 78.6, 78.4 and 80.0â%, respectively. The digital DNA-DNA hybridisation (dDDH) values between LNNU 24178T and L. yindakuii CGMCC 1.13927T, L. mephitis DSM 12574T, L. arsenica 26-35T and L. huabeiensis HB2T were 22.0, 22.3, 22.2 and 23.5â%, respectively. The respiratory quinone detected in LNNU 24178T was ubiquinone-8 (Q-8). The major fatty acids (> 5.0â%) of LNNU 24178T were identified as iso-C15â:â0 (33.9â%), iso-C17â:â0 (8.7â%), iso-C11â:â0 (6.2â%), iso-C16â:â0 (5.7â%), C16â:â0 (5.3â%) and summed feature 9 (iso-C17â:â1ω9c/10-methyl C16â:â0) (21.1â%). The major polar lipids of LNNU 24178T were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), one unidentified phospholipid (PL), one unidentified glycolipid (GL) and three unidentified lipids. According to the data obtained from phenotypic, chemotaxonomic and phylogenetic analyses, strain LNNU 24178T represents a novel species of the genus Luteimonas, for which the name Luteimonas suaedae sp. nov. is proposed, with LNNU 24178T (= CGMCC 1.17331T= KCTC 62251T) as the type strain.
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Ácidos Grasos , Rizosfera , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Análisis de Secuencia de ADN , FosfolípidosRESUMEN
Neurons in the mammalian central nervous system (CNS) gradually lose their intrinsic regeneration capacity during maturation mainly because of altered transcription profile. Recent studies have made great progress by identifying genes that can be manipulated to enhance CNS regeneration. However, as a complex process involving many genes and signaling networks, it is of great importance to deciphering the underlying neuronal chromatin and transcriptomic landscape coordinating CNS regeneration. Here we identify UTX, an X-chromosome associated gene encoding a histone demethylase, as a novel regulator of mammalian neural regeneration. We demonstrate that UTX acts as a repressor of spontaneous axon regeneration in the peripheral nerve system (PNS). In the CNS, either knocking out or pharmacological inhibiting UTX in retinal ganglion cells (RGCs) leads to significantly enhanced neuronal survival and optic nerve regeneration. RNA-seq profiling revealed that deleting UTX switches the RGC transcriptomics into a developmental-like state. Moreover, microRNA-124, one of the most abundant microRNAs in mature neurons, is identified as a downstream target of UTX and blocking endogenous microRNA124-5p results in robust optic nerve regeneration. These findings revealed a novel histone modification-microRNA epigenetic signaling network orchestrating transcriptomic landscape supporting CNS neural regeneration.
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Objective To build a prostate cancer (PCa) risk prediction model based on common clinical indicators to provide a theoretical basis for the diagnosis and treatment of PCa and to evaluate the value of artificial intelligence (AI) technology under healthcare data platforms. Methods After preprocessing of the data from Population Health Data Archive, smuothly clipped absolute deviation (SCAD) was used to select features. Random forest (RF), support vector machine (SVM), back propagation neural network (BP), and convolutional neural network (CNN) were used to predict the risk of PCa, among which BP and CNN were used on the enhanced data by SMOTE. The performances of models were compared using area under the curve (AUC) of the receiving operating characteristic curve. After the optimal model was selected, we used the Shiny to develop an online calculator for PCa risk prediction based on predictive indicators. Results Inorganic phosphorus, triglycerides, and calcium were closely related to PCa in addition to the volume of fragmented tissue and free prostate-specific antigen (PSA). Among the four models, RF had the best performance in predicting PCa (accuracy: 96.80%; AUC: 0.975, 95% CI: 0.964-0.986). Followed by BP (accuracy: 85.36%; AUC: 0.892, 95% CI: 0.849-0.934) and SVM (accuracy: 82.67%; AUC: 0.824, 95% CI: 0.805-0.844). CNN performed worse (accuracy: 72.37%; AUC: 0.724, 95% CI: 0.670-0.779). An online platform for PCa risk prediction was developed based on the RF model and the predictive indicators. Conclusions This study revealed the application value of traditional machine learning and deep learning models in disease risk prediction under healthcare data platform, proposed new ideas for PCa risk prediction in patients suspected for PCa and had undergone core needle biopsy. Besides, the online calculation may enhance the practicability of AI prediction technology and facilitate medical diagnosis.
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Inteligencia Artificial , Neoplasias de la Próstata , Masculino , Humanos , Antígeno Prostático Específico , Aprendizaje Automático , AlgoritmosRESUMEN
BACKGROUND: COVID-19 affects healthcare resource allocation, which could lead to treatment delay and poor outcomes in patients with acute myocardial infarction (AMI). We assessed the impact of the COVID-19 pandemic on AMI outcomes. METHODS: We compared outcomes of patients admitted for acute ST-elevation MI (STEMI) and non-STEMI (NSTEMI) during a non-COVID-19 pandemic period (January-February 2019; Group 1, n = 254) and a COVID-19 pandemic period (January-February 2020; Group 2, n = 124). RESULTS: For STEMI patients, the median of first medical contact (FMC) time, door-to-balloon time, and total myocardial ischemia time were significantly longer in Group 2 patients (all p < 0.05). Primary percutaneous intervention was performed significantly more often in Group 1 patients than in Group 2 patients, whereas thrombolytic therapy was used significantly more often in Group 2 patients than in Group 1 patients (all p < 0.05). However, the rates of and all-cause 30-day mortality and major adverse cardiac event (MACE) were not significantly different in the two periods (all p > 0.05). For NSTEMI patients, Group 2 patients had a higher rate of conservative therapy, a lower rate of reperfusion therapy, and longer FMC times (all p < 0.05). All-cause 30-day mortality and MACE were only higher in NSTEMI patients during the COVID-19 pandemic period (p < 0.001). CONCLUSIONS: COVID-19 pandemic causes treatment delay in AMI patients and potentially leads to poor clinical outcome in NSTEMI patients. Thrombolytic therapy should be initiated without delay for STEMI when coronary intervention is not readily available; for NSTEMI patients, outcomes of invasive reperfusion were better than medical treatment.
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COVID-19 , Infarto del Miocardio , Infarto del Miocardio sin Elevación del ST , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/terapia , Infarto del Miocardio sin Elevación del ST/diagnóstico , Infarto del Miocardio sin Elevación del ST/terapia , Pandemias , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Background: Several studies have demonstrated that using a higher dose of statin can easily induce liver injury and myopathy. Low-density lipoprotein cholesterol (LDL-C) is a well-established modifiable risk factor for cardiovascular disease; however, the large majority of Chinese patients cannot meet the target level of LDL-C recommended by the Chinese expert consensus. Evolocumab has been demonstrated to reduce LDL-C by approximately 60% in many studies. Nevertheless, whether combined evolocumab and moderate-intensity statin is as effective in lowering LDL-C and decreasing incidence of MACE in Chinese patients presenting with the acute phase of acute coronary syndrome (ACS) remains unknown. Therefore, the "Evolocumab added to Moderate-Intensity Statin therapy on LDL-C lowering and cardiovascular adverse events in patients with Acute Coronary Syndrome" (EMSIACS) is conducted. Methods: The EMSIACS is a prospective, randomized, open-label, parallel-group, multicenter study involving analyzing the feasibility and efficacy of evolocumab added to moderate-intensity statin therapy on lowering LDL-C levels in adult Chinese patients hospitalized for acute phase ACS. The sample size calculation is based on the primary outcome, and 500 patients will be planned to recruit. Patients are randomized in evolocumab arm (evolocumab 140mg every 2weeks plus rosuvastatin 10mg/day or atorvastatin 20mg/day) and statin-only arm (rosuvastatin 10mg/day or atorvastatin 20mg/day). The primary outcome is the percentage change in LDL-C in weeks 4 and week 12 after treatment. The secondary outcome is the occurrence of MACE after 12weeks and 1year of treatment. Discussion: If the EMSIACS trial endpoints prove statistically significant, the evolocumab added to moderate-intensity statin therapy will have the potential to effectively lower subjects' LDL-C levels, especially for the Chinese patients with acute phase ACS. However, if the risk of MACE is not significantly different between the two groups, we may extend follow-up time for secondary outcome when the clinical trial is over. Clinical trial registration: The study is registered to ClinicalTrials.gov (NCT04100434), which retrospectively registered on November 24, 2020.
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BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (Pcsk9) correlated with incidence and prognosis of coronary heart disease. However, it is unclear whether Pcsk9 contributed to coronary artery lesion severity in patients with premature myocardial infarction (PMI). The present study investigated associations between Pcsk9 and coronary artery lesion severity in PMI patients who underwent coronary angiography (CAG). METHODS: This prospective cohort study included young men (age ≤ 45 years, n = 332) with acute MI who underwent CAG between January 2017 and July 2019. Serum Pcsk9 levels and clinical characteristics were evaluated. SYNTAX scores (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) were calculated to quantify coronary artery lesions. RESULTS: Serum Pcsk9 levels were positively associated with SYNTAX scores (r = 0.173, P < 0.05). The diagnostic cutoff value of PSCK9 level was 122.9 ng/mL, yielding an area under the curve (AUC) of 0.63, sensitivity 81%, and specificity 40%. Serum Pcsk9, LDL-C, Apob, NT-proBnp, CK level, and diabetes history were independent predictors of high SYNTAX scores (P < 0.05). After stratifying by serum LDL-C level (cutoff = 2.6 mmol/L), medium-high Pcsk9 levels had increased risk of high SYNTAX scores in patients with high LDL-C (P < 0.05), and higher serum Pcsk9 levels had increased risk of major adverse cardiac events (MACE) after adjusting for confounding factors (P < 0.05). CONCLUSION: Serum Pcsk9 levels correlates with severity of coronary artery lesion in PMI patients and may serve as a biomarker for severity of coronary artery stenosis in this patient population, which may contribute to risk stratification.
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Enfermedad de la Arteria Coronaria/sangre , Estenosis Coronaria/sangre , Infarto del Miocardio/sangre , Proproteína Convertasa 9/sangre , Adulto , Apolipoproteína B-100/sangre , Área Bajo la Curva , Biomarcadores/sangre , LDL-Colesterol/sangre , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/cirugía , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/patología , Estenosis Coronaria/cirugía , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/patología , Infarto del Miocardio/cirugía , Péptido Natriurético Encefálico/sangre , Gravedad del Paciente , Fragmentos de Péptidos/sangre , Intervención Coronaria Percutánea , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
Whether the clinical outcomes of stent thrombosis (ST) are different when stratified by time of occurrence remains unclear. The objective of this study was to compare the short- and long-term clinical outcomes after percutaneous coronary intervention (PCI) for early stent thrombosis (EST) versus late stent thrombosis (LST) and very late stent thrombosis (VLST). We enrolled eligible studies searched from the main electronic databases (EMBASE, PubMed, Cochrane). The primary endpoints were in-hospital, 30-day, 1-year and long-term mortality. The secondary endpoints included recurrent stent thrombosis (RST) and target vessel/lesion revascularization (TVR/TLR) during hospitalization, at 30 days, at 1 year and at long-term follow-up. A total of 23 studies with 17,592 patients were included. Compared with mortality rates of the late and very late thrombosis (LST/VLST) group, in-hospital (P = 0.004), 30-day (P < 0.00001), 1-year (P < 0.00001) and long-term mortality rates (P = 0.04) were significantly higher in the EST group. The in-hospital TVR/TLR rates were similar between the EST group and the LST/VLST group. However, a higher trend in TVR/TLR rate at 30 days and a significantly higher TVR/TLR rate at 1 year (P = 0.002) as well as at long-term follow up (P = 0.009) were found in the EST group. EST patients also trended toward higher risk of RST in both short- and long-term follow-up than LST/VLST patients, although differences were not statistically significant. After PCI treatment, patients with EST have worse clinical outcomes in both short- and long-term follow-up than patients with LST/VLST. Further studies are warranted to determine the optimal treatment strategies for EST.
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Reestenosis Coronaria , Intervención Coronaria Percutánea/efectos adversos , Stents/efectos adversos , Trombosis , Reestenosis Coronaria/diagnóstico , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/cirugía , Humanos , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/epidemiología , Efectos Adversos a Largo Plazo/prevención & control , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/métodos , Reoperación/estadística & datos numéricos , Trombosis/diagnóstico , Trombosis/epidemiología , Trombosis/etiología , Trombosis/cirugíaRESUMEN
BACKGROUND: Although drug-eluting stents (DES) have reduced the rates of in-stent restenosis (ISR) compared with bare-metal stents (BMS), DES related ISR (DES-ISR) still occurs and outcomes of DES-ISR remain unclear. The objective of this meta-analysis was to investigate the long-term clinical outcomes of patients with DES-ISR compared with patients with BMS related ISR (BMS-ISR) after the treatment of DES or drug-eluting balloon (DEB). Methods and results. We searched the literature in the main electronic databases including PUBMED, EMBASE, Cochrane Library, and Web of Science. The primary endpoints were target lesion revascularization (TLR) and target vessel revascularization (TVR). The secondary endpoints included all cause death (ACD), cardiac death (CD), myocardial infarction (MI), stent thrombosis or re-in-stent restenosis (ST/RE-ISR), and major adverse cardiovascular events (MACEs). A total of 19 studies with 6256 participants were finally included in this meta-analysis. Results showed that the rates of TLR (P < 0.00001), TVR (P < 0.00001), CD (P=0.02), ST/RE-ISR (P < 0.00001), and MACEs (P < 0.00001) were significantly higher in the DES-ISR group than in the BMS-ISR group. No significant differences were found between the two groups in the rates of MI (P=0.05) and ACD (P=0.21). CONCLUSIONS: Our study demonstrated that patients with DES-ISR had worse clinical outcomes at the long-term follow-up than patients with BMS-ISR after the treatment of DES or DEB, suggesting that DES and DEB may be more effective for BMS-ISR than that for DES-ISR. Positive prevention of DES-ISR is indispensable and further studies concentrating on detecting the predictors of outcomes of DES-ISR are required.
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Reestenosis Coronaria/cirugía , Stents Liberadores de Fármacos/efectos adversos , Isquemia Miocárdica , Revascularización Miocárdica , Stents , Investigación sobre la Eficacia Comparativa , Humanos , Isquemia Miocárdica/mortalidad , Isquemia Miocárdica/cirugía , Revascularización Miocárdica/efectos adversos , Revascularización Miocárdica/instrumentación , Revascularización Miocárdica/métodos , Stents/efectos adversos , Stents/clasificaciónRESUMEN
Trauma or neurodegenerative diseases trigger the retrograde death of retinal ganglion cells (RGCs), causing an irreversible functional loss. AT-rich interaction domain 1A (ARID1A), a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, has been shown to play crucial roles in cell homeostasis and tissue regeneration. However, its function in adult RGC regeneration remains elusive. Here, we show that optic nerve injury induces dynamic changes of Arid1a expression. Importantly, deleting Arid1a in mice dramatically promotes RGC survival, but insignificantly impacts axon regeneration after optic nerve injury. Next, joint profiling of transcripts and accessible chromatin in mature RGCs reveals that Arid1a regulates several genes involved in apoptosis and JAK/STAT signaling pathway. Thus, our findings suggest modulation of Arid1a as a potential therapeutic strategy to promote RGC neuroprotection after damage.
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Mammalian retinal ganglion cells (RGCs) in the central nervous system (CNS) often die after optic nerve injury and surviving RGCs fail to regenerate their axons, eventually resulting in irreversible vision loss. Manipulation of a diverse group of genes can significantly boost optic nerve regeneration of mature RGCs by reactivating developmental-like growth programs or suppressing growth inhibitory pathways. By injury of the vision pathway near their brain targets, a few studies have shown that regenerated RGC axons could form functional synapses with targeted neurons but exhibited poor neural conduction or partial functional recovery. Therefore, the functional restoration of eye-to-brain pathways remains a greatly challenging issue. Here, we review recent advances in long-distance optic nerve regeneration and the subsequent reconnecting to central targets. By summarizing our current strategies for promoting functional recovery, we hope to provide potential insights into future exploration in vision reformation after neural injuries.
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BACKGROUND: Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control. METHODS: Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models. RESULTS: The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively). CONCLUSIONS: More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/metabolismo , Insulina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , China , Femenino , Humanos , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
There is little evidence to recommend the optimal invasive mechanical ventilation (IMV) modes and ideal positive end-expiratory pressure stress levels for acute myocardial infarction-cardiogenic shock (AMI-CS) patients. The aim of this study was to compare the mortality outcome in patients with AMI-CS who were treated with percutaneous coronary intervention (PCI) assisted by intra-aortic balloon pump (IABP) + IMV with historical controls. From January 1, 2016 to June 1, 2017, 60 patients were retrospectively enrolled at Tianjin Chest Hospital. Out of these, 88.3% of patients achieved thrombolysis in myocardial infarction (TIMI) flow 3 after PCI. The all-cause mortality rate in-hospital and at 1 year was 25% (95% CI: 0.14-0.36) and 33.9% (0.22-0.46), respectively. A systematic review followed by meta-analysis was performed with four historical studies of patients treated by PCI + IMV with partial IABP, which found an in-hospital mortality rate of 66.0% (95% CI: 0.62-0.71). Recently, a meta-analysis of patients receiving PCI + IABP with partial IMV showed that the 1 year mortality rate was 52.2% (95% CI: 0.47-0.58). In Cox regression analysis of patient data from the current study, lactic acid level ≥4.5 mmol/L, hyperuricemia, and TIMI flow <3 were independent predictors of death at 1 year. All-cause mortality, in-hospital and at 1 year, in patients with AMI-CS treated with PCI + IABP and IMV was lower than in those treated with PCI + partial IABP or IMV. Larger, longer-term direct comparisons are warranted.
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Angioplastia Coronaria con Balón/métodos , Aorta/efectos de los fármacos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/métodos , Respiración Artificial/métodos , Choque Cardiogénico/complicaciones , Choque Cardiogénico/terapia , Enfermedad Aguda , Anciano , Femenino , Mortalidad Hospitalaria , Humanos , Hipoxia/terapia , Investigación Interdisciplinaria , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Respiración con Presión Positiva , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Saphenous vein grafts disease (SVGD) is a common complication after coronary artery bypass graft (CABG) and usually treated by percutaneous coronary intervention (PCI). In this prospective cohort study, we performed virtual histology-intravascular ultrasound to investigate whether plaque composition and morphological characteristics were associated with post-PCI major adverse cardiac events (MACEs) and slow/no-reflow in patients with SVGD. Patients (n = 90) were studied (76.7% men, mean age 64.9 ± 8.2 years and mean duration of SVG 8.0 ± 3.6 years). There were 77.8% lesions with a plaque burden of at least 70%; 18 MACE incidences accumulated in 14 patients over 12 months post-PCI and slow/no-reflow was observed in 12 patients. On adjusted multivariate analysis, lesion length (hazard ratio [HR] = 1.05; 95% confidence interval [CI]: 1.01-1.08]); age of CABG (HR = 1.51 [95% CI: 1.11-2.05], and absolute necrotic core (NC) area (HR = 8.04 [95% CI: 1.86-34.73]) were independently associated with MACEs. Factors independently associated with slow/no-reflow post-PCI were preprocedure systolic blood pressure (odds ratio [OR] = 0.98; 95% CI: 0.96-0.99) and absolute NC area (OR = 2.47 (95% CI: 1.14-5.36). A cutoff value of absolute NC area at ≥1.1 mm2 may serve as a significant risk predictor for no-reflow after SVG-PCI. Factors associated with MACEs and the slow/no-reflow phenomenon following PCI of the SVG can be used in risk assessment of SVG.
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Puente de Arteria Coronaria/efectos adversos , Oclusión de Injerto Vascular/cirugía , Intervención Coronaria Percutánea , Vena Safena/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Sistema Cardiovascular/fisiopatología , Femenino , Oclusión de Injerto Vascular/etiología , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/cirugía , Medición de Riesgo , Factores de Riesgo , Vena Safena/fisiopatología , Stents/efectos adversos , Ultrasonografía Intervencional/efectos adversos , Adulto JovenRESUMEN
The aim of the present study was to investigate the role of microRNA21 (miR21) in regulating the classical WNT/ßcatenin signaling pathway by targeting lowdensity lipoproteinrelated receptor 6 (LRP6) in nonalcoholic fatty liver disease (NAFLD). For this purpose, we established a NAFLD model by feeding C57BL/6J mice a methioninecholineâdeficient diet. Antagomir21 was then injected via the tail vein, and the expression levels of WNT/ßcatenin signaling pathwayrelated proteins, such as LRP6, glycogen synthase kinase3ß (GSK3ß), pßcatenin, ßcatenin and the downstream protein, peroxisome proliferatoractivated receptor γ (PPARγ), and lipid metabolismrelated genes, including sterol regulatory elementbinding transcription factor 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyl transferase 1α (CPT1α) and adenosine 5monophosphate (AMP)activated protein kinase α (AMPKα), were detected. The results revealed that in the NAFLD model, LRP6 expression was negatively associated with miR21 expression. After antagonizing the expression of miR21, the protein level of LRP6 was increased. In addition, the WNT/ßcatenin signaling pathway was activated, and lipid accumulation and inflammation were alleviated in the liver. However, the expression of PPARγ was not inhibited following the upregulation of the WNT signaling pathway. Taken together, the results of this study demonstrate that the inhibition of miR21 expression can alleviate NAFLD by targeting LRP6 to activate the WNT/ßcatenin signaling pathway.
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Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad/genética , MicroARNs/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Vía de Señalización Wnt/genética , Animales , Antagomirs/genética , Antagomirs/farmacología , Colina/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/genética , Glucógeno Sintasa Quinasa 3 beta/genética , Humanos , Metionina/metabolismo , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , beta Catenina/genéticaRESUMEN
The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing in recent years. Previous studies have suggested that micro (mi)RNAs may be involved in the pathogenesis of NAFLD. To investigate the role of miRNAs in rat NAFLD, a total of 16 male Sprague Dawley rats were randomly divided into a control group and a model group. Rats in the control group were fed a normal diet for 12 weeks, whereas the rats in the model group were fed a highfat and highsugar diet for 12 weeks. Following this, the animals were sacrificed and liver tissues were rapidly removed to investigate the severity of NAFLD. Blood samples were collected to investigate liver function, in addition to total cholesterol, total triglyceride and fasting plasma glucose levels. Total RNA from three fresh liver samples per experimental group was extracted for subsequent miRNA gene chip analysis using GeneChip miRNA 4.0 to investigate differentially expressed miRNAs, and miRNA expression was further verified via reverse transcriptionquantitative polymerase chain reaction (RTqPCR). Compared with the control group, the results revealed that there were 10 differentially expressed miRNAs in the model group, five of which were overexpressed and five of which were underexpressed compared with the control group. The results of the RTqPCR analysis revealed that miR182, miR29b3p and miR7413p were significantly overexpressed in the model group compared with the control group, which was largely consistent with the results of the microarray analysis. The results suggested that the differentially expressed microRNAs demonstrated in the present study may be involved in the pathogenesis of NAFLD; however, the mechanism underlying the differential expression of miRNAs in NAFLD requires further investigation.
Asunto(s)
Hígado/metabolismo , MicroARNs/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Animales , Colesterol/sangre , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Masculino , MicroARNs/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ratas , Ratas Sprague-Dawley , Transcriptoma , Triglicéridos/sangreRESUMEN
OBJECTIVES: The two-child policy took effect in China on 1 January 2016, thus officially ending the one-child policy. The resultant growth in the population will create a considerable demand for public services such as paediatric healthcare, even while there are limited paediatric resources. We estimated the relationship between paediatric health resources and services and child mortality to determine the degree of the deficiency of such resources in China. Projecting the quantity of paediatric health resource allocation and service supply through 2030 will help provide data reference for future policy decision making. DESIGN: Time-series study. SETTING: The People's Republic of China. PARTICIPANTS: Paediatric patients whose data were recorded between 2003 and 2012 from the National Health and Family Planning Commission of the People's Republic of China. PRIMARY AND SECONDARY OUTCOME MEASURES: Child mortality and paediatric health resources and services data were entered into a cubic polynomial regression model to project paediatric health resources and services to 2030. RESULTS: Child mortality decreased throughout the past decade. Furthermore, the number of paediatric beds, paediatricians and nurses increased between 2003 and 2012, although the proportions increased rather slowly. Both the number and proportion of paediatric outpatients and inpatients increased rapidly. The observed and model-predicted values matched well (adjusted R2=93.8% for paediatric beds; adjusted R2=96.6% for paediatric outpatient visits). Overall, the projection indicated that paediatric beds, paediatricians and nurses will reach 460 148, 233 884 and 184 059 by 2030, respectively. Regarding paediatric services, the number of paediatric outpatient visits and inpatients is expected to reach upwards of 449.95 million and 21.83 million by 2030, respectively. CONCLUSIONS: Despite implementation of the two-child policy, resource allocation in paediatrics has many deficiencies. Proper measures should be taken to actively respond to the demand for paediatric health services.
Asunto(s)
Mortalidad del Niño/tendencias , Recursos en Salud/tendencias , Servicios de Salud/tendencias , Pediatría/tendencias , Niño , China/epidemiología , Servicios de Planificación Familiar/legislación & jurisprudencia , Humanos , Dinámica Poblacional , Política Pública , Análisis de Regresión , Asignación de Recursos , Estudios Retrospectivos , Recursos HumanosRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is a chronic disorder characterized by hepatic fat accumulation and abnormal lipid metabolism. Although miR-21 has been implicated in nonalcoholic fatty liver disease, it is unknown whether miR-21 could function as a therapeutic target. Here, we perform transfection analysis of miR-21 mimic or control mimic to evaluate the effects of miR-21 expression levels on human HepG2 nonalcoholic fatty liver cells. We used siRNA techniques to knock down miR-21 in HepG2 and control 293T cell lines, and then monitored lipid production and the expression levels of genes involved in lipid metabolism. The effects of miR-21 expression levels on LDL receptor-related protein 6 (LRP6) expression were evaluated using qRT-PCR and western blot analyses. Luciferase reporter assays were conducted to confirm the effects of miR-21 expression levels on LRP6. The results indicated that transfection of miR-21 mimic induced changes in the expression levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), stearoyl CoA desaturase (1SCD1), sterol regulatory element-binding protein 1 (SREBP1), and liver X receptor alpha (LXRα). Transfection of miR-21 mimic suppressed the transcription and translation of LRP6 at the mRNA and protein levels, whereas miR-21 knockdown increased the expression levels of LRP6. Transfection of miR-21 mimic in HepG2 cells also induced lipid production and triggered the expression of critical lipid metabolic enzymes. These data suggest that mutation of miR-21 may be a new therapeutic strategy to treat nonalcoholic fatty liver diseases by targeting endogenous LRP6.
RESUMEN
OBJECTIVE: To investigate the correlation between Adiponectin gene polymorphisms and the genetic susceptibility of nonalcoholic fatty liver disease (NAFLD). METHODS: 357 NAFLD patients from January 2005 to December 2013 and 357 cases of healthy controls among the Han population were collected; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect three tagSNPs (Rs2241767, rsl501299 and rs3774261) of Adiponectin. Risk factors were analyzed by multivariate logistic regression and haplotype analysis was performed using SHEsis software. RESULTS: Rs2241767, rsl501299 and rs3774261 polymorphisms were associated with the risk of NAFLD. Haplotype analysis showed that, A-T-A haplotype was a protective factor of NAFLD (OR: 0.154, 95% CI: 0.011-0.576, P = 0.004) and G-G-A (OR: 4.012, 95% CI: 2.118-10.324, P < 0.001) and G-T-G (OR: 5.219, 95% CI: 2.751-12.651, P < 0.001) haplotype was risk factors of NAFLD. CONCLUSION: There was an association between Adiponectin gene polymorphisms and the genetic susceptibility of NAFLD.