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DNA quality is of paramount importance for molecular biology research. This study aimed to assess the DNA extracted from residual blood clots after serological testing, focusing on the impact of blood clot segments, extraction kits, temporary storage durations (TSDs), and thawing methods on DNA quality. We divided the residual blood clot column (BCC) from healthy donors into three segments and utilized two different extraction kits. The BCCs were subjected to four TSDs at 4°C (7 days, 10 days, 1 month, and 2 months) and three thawing methods (4°C, room temperature, and 37°C). We found that the TIANamp Blood Clot DNA Kit yielded consistently high-quality DNA from each segment with stable A260/280 and A260/230 ratios. The DNA yield showed a strong positive correlation with leukocyte concentration, and a satisfactory median DNA yield of 28.79 µg/g BCC was obtained across all segments. DNA integrity, as measured by the DNA integrity number and DNA fragment peak size, decreased with increasing TSD at 4°C, with a notable decrease after 10 days of storage. Thawing at 37°C resulted in the lowest DNA fragment peak size. In conclusion, BCC could be an ideal DNA source with satisfactory yield and purity. A prolonged TSD at 4°C leads to an obvious decrease in DNA integrity, and thawing the frozen BCC at 37°C decreases DNA fragment sizes. To maintain DNA integrity, BCCs should be cryopreserved as soon as possible after short TSDs at 4°C and thawed at 4°C.
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ADN , Humanos , ADN/aislamiento & purificación , ADN/análisis , Pruebas Serológicas , Coagulación SanguíneaRESUMEN
BACKGROUND: Extensive metastatic and refractory cancer pain is common, and exhibits a dissatisfactory response to the conventional intrathecal infusion of opioid analgesics. CASE PRESENTATION: The present study reports a case of an extensive metastatic esophageal cancer patient with severe intractable pain, who underwent translumbar subarachnoid puncture with intrathecal catheterization to the prepontine cistern. After continuous infusion of low-dose morphine, the pain was well-controlled with a decrease in the numeric rating scale (NRS) of pain score from 9 to 0, and the few adverse reactions to the treatment disappeared at a low dose of morphine. CONCLUSIONS: The patient achieved a good quality of life during the one-month follow-up period.
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Dolor en Cáncer , Neoplasias , Dolor Intratable , Humanos , Morfina , Dolor Intratable/etiología , Dolor Intratable/inducido químicamente , Dolor en Cáncer/tratamiento farmacológico , Calidad de Vida , Analgésicos Opioides , Inyecciones Espinales/efectos adversosRESUMEN
Topological vacua are a family of degenerate ground states of Yang-Mills fields with zero field strength but nontrivial topological structures. They play a fundamental role in particle physics and quantum field theory, but have not yet been experimentally observed. Here we report the first theoretical proposal and experimental realization of synthetic topological vacua with a cloud of atomic Bose-Einstein condensates. Our setup provides a promising platform to demonstrate the fundamental concept that a vacuum, rather than being empty, has rich spatial structures. The Hamiltonian for the vacuum of topological number n=1 is synthesized and the related Hopf index is measured. The vacuum of topological number n=2 is also realized, and we find that vacua with different topological numbers have distinctive spin textures and Hopf links. Our Letter opens up opportunities for exploring topological vacua and related long-sought-after instantons in tabletop experiments.
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Teoría CuánticaRESUMEN
Underwater wireless optical communication (UWOC) has great potential to provide higher data rates and lower time delay communication compared to radio frequency and acoustic counterparts. However, UWOC systems with wide bandwidths are subject to photon absorption and scattering, which result in severe energy loss for optical beams and inter-symbol interference. To overcome these issues, this Letter interprets the UWOC system as an autoencoder (AE), named UWOC-AE, which takes advantage of the double Gamma function approximating channel impulse response of underwater optical links to learn the channel characteristics. Thus, within the AE framework, the encoder and decoder can be optimized jointly. Experiments indicate that the proposed UWOC-AE can achieve superior performance with high data rates compared to existing techniques.
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BACKGROUND: Hearing loss is becoming more and more general. It may occur at all age and affect the language learning ability of children and trigger serious social problems. METHODS: The hearing loss differentially expressed genes (HL-DEGs) were recognized through a comparison with healthy subjects. The Gene Ontology (GO) analysis was executed by DAVID. The reactome analysis of HL-DEGs was performed by Clue-GO. Next, we used STRING, an online website, to identify crucial protein-protein interactions among HL-DEGs. Cytoscape software was employed to construct a protein-protein interaction network. MCODE, a plug-in of the Cytoscape software, was used for module analysis. Finally, we used DGIdb database to ascertain the targeted drugs for MCODE genes. RESULTS: Four hundred four HL-DEGs were identified, among which the most up-regulated 10 genes were AL008707.1, SDR42E1P5, BX005040.1, AL671883.2, MT1XP1, AC016957.1, U2AF1L5, XIST, DAAM2, and ADAMTS2, and the most down-regulated 10 genes were ALOX15, PRSS33, IL5RA, SMPD3, IGHV1-2, IGLV3-9, RHOXF1P1, CACNG6, MYOM2, and RSAD2. Through STRING database and MCODE analysis, we finally got 16 MCODE genes. These genes can be regarded as hearing loss related genes. Through biological analysis, it is found that these genes are enriched in pathways related to apoptosis such as tumor necrosis factor. Among them, MMP8, LTF, ORM2, FOLR3, and TCN1 have corresponding targeted drugs. Foremost, MCODE genes should be investigated for its usefulness as a new biomarker for diagnosis and treatment. CONCLUSION: In summary, our study produced a sixteen-gene signature and associated drugs that could be diagnosis and treatment of hearing loss patients.
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Biología Computacional/métodos , Bases de Datos Farmacéuticas , Pérdida Auditiva/genética , Mapas de Interacción de Proteínas/genética , Transcriptoma , Perfilación de la Expresión Génica , Ontología de Genes , Humanos , Neutrófilos/fisiologíaRESUMEN
BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872.
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Várices Esofágicas y Gástricas , Trombosis de la Vena , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/epidemiología , Várices Esofágicas y Gástricas/patología , Hemorragia Gastrointestinal/patología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Vena Porta/patología , Prevalencia , Estudios Retrospectivos , Trombosis de la Vena/complicaciones , Trombosis de la Vena/epidemiología , Trombosis de la Vena/patologíaRESUMEN
In this study, we describe the genome sequence of a novel double-stranded RNA (dsRNA) mycovirus, designated as "Rhizoctonia solani partitivirus 15" (RsPV15), from the phytopathogenic fungus Rhizoctonia solani. RsPV15 consists of two genomic double-stranded RNA segments, dsRNA-1 and dsRNA-2, which are 2433 bp and 2350 bp long, respectively. Each of the dsRNA segments contains a single open reading frame, encoding the putative RNA-dependent RNA polymerase and coat protein, respectively. Homology searches and phylogenetic analysis suggested that RsPV15 is a new member of the genus Betapartitivirus within the family Partitiviridae.
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Virus Fúngicos/aislamiento & purificación , Enfermedades de las Plantas/microbiología , Virus ARN/aislamiento & purificación , Rhizoctonia/virología , Virus Fúngicos/clasificación , Virus Fúngicos/genética , Genoma Viral , Filogenia , Virus ARN/clasificación , Virus ARN/genética , ARN Bicatenario/genética , ARN Viral/genéticaRESUMEN
BACKGROUND: Retinoic acid (RA), an active metabolite of vitamin A, possesses enormous protective effects on vascular systems. It may also be positively related to good functional outcome after ischemic stroke. However, whether circulating RA concentration is associated with poststroke cognitive impairment (PSCI) remains unclear. This study aimed to detect the association between RA level and PSCI among patients with first-ever acute ischemic stroke. METHODS: Two hundred and 61 consecutive patients were prospectively recruited during March 2018 and March 2019. Serum RA concentration was measured at admission for all patients. We also performed cognitive function examination using the Montreal Cognitive Assessment (MoCA) at admission and at every follow-up visit. Patients with MoCA score less than 26 were identified as developing PSCI. RESULTS: The median serum RA level was 2.0 ng/mL (interquartile range, 1.1-3.2 ng/mL) after admission. Patients diagnosed as PSCI at admission, 1-month and 3-month were 53 (20.3%), 91 (34.6%), and 141 (54.0%), respectively. Univariate analysis showed that reduced RA level was correlated with PSCI at 3-month (Pâ¯=â¯.003), but not at admission (Pâ¯=â¯.416) and 1-month poststroke (P = .117). After adjusting for all potential confounders, the odds ratio for the lowest tertile of RA, compared with the highest tertile, was 1.97 (95% confidence interval, 1.01-3.83, Pâ¯=â¯.046) for PSCI at 3 months. Furthermore, multiple-adjusted spline regression model further confirmed the dose-response relationships between RA level and 3-month PSCI (P < .001). CONCLUSIONS: Decreasing serum RA level might be associated with 3-month PSCI in ischemic stroke patients.
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Isquemia Encefálica/sangre , Cognición , Disfunción Cognitiva/etiología , Accidente Cerebrovascular/sangre , Tretinoina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Factores de TiempoRESUMEN
Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus with high mortality. Immune suppression is thought to be crucial in disease progression. However, data on immune responses during SFTS are scarce. This study aimed to evaluate the changes in CD4 T-cell subsets throughout the entirety of infection and analyse their relationships with disease severity in SFTS patients. In parallel with CD4 T-cell depletion, decreased Th1, Th2 and Treg numbers, but comparable Th17-cell numbers, were observed in deceased patients compared with those in surviving patients. Additionally, increased Th2 and Th17-cell percentages in the residual CD4 T-cell population led to aberrant Th2/Th1 and Th17/Treg ratios, which were positively correlated with disease severity. Collectively, our data indicated that CD4 T-cell deficiency, Th2 and Th17 bias were closely correlated with the severity of SFTS, indicating therapeutic potential of early immune interventions to ameliorate disease severity.
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Infecciones por Bunyaviridae/inmunología , Phlebovirus/inmunología , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Células Th17/inmunología , Células Th2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD4/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Terapia de Inmunosupresión , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Balance Th1 - Th2 , Adulto JovenRESUMEN
Hypothalamic inflammation and apoptosis cause neural injury, playing an important role in metabolic syndrome development. Nuclear Factors of Activated T cells (NFATc3) show many physiological and pathological effects. However, the function of NFATc3 in high fat diet (HFD)-induced hypothalamus injury remains unknown. The wild type (WT) and NFATc3-knockout (KO) mice were subjected to HFD feeding for 16 weeks to examine NFATc3 function in vivo. Astrocytes isolated from WT or KO mice were cultured and exposed to fructose (Fru) in vitro. The liver damage, hypothalamus injury, pro-inflammatory markers, NF-κB (p65), Caspase-3 and mitogen-activated protein kinases (MAPKs) pathways were evaluated. NFATc3 was significantly up-regulated in hypothalamus from mice challenged with HFD, and in astrocytes incubated with Fru. Both in vivo and in vitro studies indicated that NFATc3-deletion attenuated metabolism syndrome, reduced inflammatory regulators expression, inactivated NF-κB (p65), Caspase-3 and p38/JNK signaling pathway. Of note, we identified that promoting p38 or JNK activation could rescue inflammatory response and apoptosis in NFATc3-KO astrocytes stimulated by Fru. Together, these findings revealed an important role of NFATc3 NFATc3 for HFD-induced metabolic syndrome and particularly hypothalamus injury, and understanding of the regulatory molecular mechanism might provide new and effective therapeutic strategies for prevention and treatment of hypothalamic damage associated with dietary obesity-associated neuroinflammation and apoptosis.
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Apoptosis , Hipotálamo/patología , Inflamación/patología , Sistema de Señalización de MAP Quinasas , Factores de Transcripción NFATC/deficiencia , Fármacos Neuroprotectores/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Astrocitos/efectos de los fármacos , Astrocitos/enzimología , Dieta Alta en Grasa , Fructosa/farmacología , Eliminación de Gen , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Síndrome Metabólico/metabolismo , Síndrome Metabólico/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Factores de Transcripción NFATC/metabolismoRESUMEN
BACKGROUND: MicroRNAs (miR) have come into focus as powerful regulators of gene expression and potential diagnostic tools during renal ischemia reperfusion injury (IRI). The aim of this study was to investigate the molecular regulation and function of miR-21, and to analyze the relationship between caspases and miR-21 expression levels in an experimental model of renal IRI. METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. The male BALB/c mice were randomly assigned to the following groups: pre-miR-21 + IRI group, antagomiR-21 + IRI group, PBS + IRI group, pre-miR-21 + sham operation group, antagomiR-21 + sham operation group, PBS + sham operation group. The pre-miR-21 or antagomiR-21 was administered intraperitoneally (200 ng/kg weight) 24 and 6 h before induction of ischemia. Renal function, histological damage, renal cell apoptosis proteins were evaluated at 24 h after reperfusion. RESULTS: Mice upregulated miR-21 had lower plasma levels of blood urea nitrogen (BUN) and creatinine, lower histopathological scores and a decrease in programmed cell death 4 (PDCD4) mRNA and active caspase-3, caspase-8 proteins expressions. CONCLUSIONS: miR-21 is endowed with anti-apoptotic properties by suppressing the expression of PDCD4 gene and active caspase 3/8 fragments in the condition of renal IRI. miR-21 exerts significant functional protection in our renal murine model of IRI.
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Caspasas/metabolismo , Isquemia/metabolismo , Riñón/patología , MicroARNs/genética , MicroARNs/metabolismo , Daño por Reperfusión/patología , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Nitrógeno de la Urea Sanguínea , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Interleucina-18/sangre , Riñón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas de Unión al ARN/metabolismo , Distribución Aleatoria , Transducción de Señal , Regulación hacia ArribaRESUMEN
The commonly used titanium alloy dental implants currently apply solid structures. However, issues such as stress shielding and stress concentration may arise due to the significant difference in elastic modulus between the implant and host. In order to address these problems, this paper proposes five porous structures based on the Gibson-Ashby theoretical model. We utilized selective laser melting technology to shape a porous structure using Ti-6Al-4V material precisely. The mechanical properties of the porous structure were verified through simulation and compression experiments. The optimal porous structure, which best matched the human bone, was a circular ring structure with a pillar diameter of 0.6 mm and a layer height of 2 mm. The stress and strain of the porous implant on the surrounding cortical and cancellous bone under different biting conditions were studied to verify the effectiveness of the optimal circular ring porous structure in alleviating stress shielding in both standard and osteoporotic bone conditions. The results confirm that the circular ring porous structure meets implant requirements and provides a theoretical basis for clinical dental implantation.
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BACKGROUND: Caloric restriction (CR) might be effective for alleviating/preventing Alzheimer's disease (AD), but the biological mechanisms remain unclear. In the current study, we explored whether CR caused an alteration of gut microbiome and resulted in the attenuation of cognitive impairment of AD animal model. METHODS: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks. RESULTS: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aß40, Aß42, IL-1ß, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet. CONCLUSIONS: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy.
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Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Restricción Calórica , Microbioma Gastrointestinal , Ratones Transgénicos , Animales , Microbioma Gastrointestinal/fisiología , Restricción Calórica/métodos , Enfermedad de Alzheimer/microbiología , Enfermedad de Alzheimer/dietoterapia , Enfermedad de Alzheimer/prevención & control , Masculino , Ratones , Precursor de Proteína beta-Amiloide/genética , Presenilina-1/genética , Péptidos beta-Amiloides/metabolismo , Modelos Animales de Enfermedad , Aprendizaje por Laberinto/fisiología , Encéfalo/metabolismo , Ratones Endogámicos C57BLRESUMEN
Photoreduction of carbon dioxide (CO2) into fuels presents a promising approach to mitigate global warming and energy crises. Halide perovskite nanocrystals (NCs) with prominent optoelectronic properties have triggered substantial attention as photocatalysts but are limited by the charge recombination and instability. Here, we develop stable CsPbBr3/titania microspheres (TMs) by in situ growth of CsPbBr3 NCs inside mesoporous TMs through solid-state sintering, which significantly improves the stability of perovskite NCs, making them applicable in water with efficient CO2 photoreduction performance. Notably, the CsPbBr3/TMs demonstrates a 6.73- and 9.23-fold increase in the rate of CH4 production compared to TMs and CsPbBr3, respectively. The internal electric field facilitates S-scheme charge transfer, enhancing the separation of electron-hole pairs, as evidenced by X-ray photoelectron spectroscopy and electron paramagnetic resonance analysis, which is pivotal for the selective photoreduction of CO2. These insights pave the way for the design of CsPbBr3-based photocatalysts with superior efficiency and stability.
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BACKGROUND: Primary trigeminal neuralgia (PTN) is a type of chronic neuropathic pain disorder caused by neurovascular compression. Percutaneous balloon compression (PBC) is a widely used method for the treatment of PTN. OBJECTIVES: To examine the correlation of balloon pressure (BP) during percutaneous microballoon compression (PBC) with postoperative pain relief and complications in the treatment of primary trigeminal neuralgia (PTN). STUDY DESIGN: Forty-five patients diagnosed with PTN and treated with PBC were recruited. The BP was recorded at 2 time points: when the balloon achieved the ideal pear shape (initial BP [IBP]) and when the pressure was maintained for 2 min (final BP [FBP]). SETTING: This study was conducted at the Department of Pain and Rehabilitation of the Second Affiliated Hospital at the University of South China in Hunan, China. METHODS: The patients' Barrow Neurological Institute (BNI) pain intensity score, BNI facial numbness score, masticatory muscle weakness score, and recurrence were recorded before and after surgery. The receiver operating characteristic (ROC) curves were generated for the IBP to predict treatment effectiveness, severe facial numbness, and severe masticatory muscle weakness. RESULTS: The BNI pain intensity score, BNI facial numbness score, and masticatory muscle weakness score were significantly decreased after surgery (all P < 0.001). IBP was positively correlated with the difference between IBP and FBP (P < 0.01). Both IBP and the difference between IBP and FBP were negatively correlated with the BNI pain intensity score and positively correlated with the BNI facial numbness score and masticatory muscle weakness score (P < 0.01). The IBP and the difference between the IBP and FBP were significantly lower in patients experiencing recurrence than in the nonrecurrent group (P < 0.05). The areas under the ROC curves of the IBP for predicting effective pain relief, severe facial numbness, and severe masticatory muscle weakness were 0.875, 0.980, and 0.988, respectively. LIMITATIONS: The sample size was relatively small, and the follow-up time was short. The correlations between the BP and other factors, such as filling amount, Meckel's cavity, and the size of the foramen ovale, were not investigated. The impact of the BP on long-term postoperative outcomes was not explored. CONCLUSIONS: An intraoperative BP of 138.65-153.90 KPa can be maintained for effective PBC treatment without causing serious complications.
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Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/cirugía , Hipoestesia , Resultado del Tratamiento , Dolor , Manejo del DolorRESUMEN
BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.
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BACKGROUND: In our previous study, we showed that pioglitazone exerts protective effects on renal ischemia-reperfusion injury (IRI) in mice by abrogating renal cell apoptosis. Oxidative stress due to excessive production of reactive oxygen species and subsequent lipid peroxidation plays a critical role in renal IRI. The purpose of the current study is to demonstrate the effect of pioglitazone on renal IRI by modulation of oxidative stress. MATERIALS AND METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. Thirty healthy male Balb/c mice were randomly assigned to one of the following groups: phosphate buffer solution (PBS) + IRI, pioglitazone + IRI, PBS + sham IRI, pioglitazone + sham IRI. Kidney function tests and kidney antioxidant activities were determined 24 h after reperfusion. RESULTS: Pretreatment with pioglitazone produced reduction in serum levels of blood urea nitrogen and creatinine caused by IRI. Pretreatment with pioglitazone before IRI resulted in a higher level of kidney enzymatic activities of superoxide dismutase, glutathione, catalase, and total antioxidant capacity than in the PBS-pretreated IRI group. CONCLUSIONS: Our results indicate that pioglitazone can provide protection for kidneys against IRI by enhancing antioxidant capacity. Therefore, pioglitazone could be a potential therapeutic approach to prevent renal IRI relevant to various clinical conditions.
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Antioxidantes/uso terapéutico , Riñón/irrigación sanguínea , Riñón/patología , Daño por Reperfusión/prevención & control , Tiazolidinedionas/uso terapéutico , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Riñón/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Pioglitazona , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Tiazolidinedionas/farmacologíaRESUMEN
Background: RNA extracted from human blood has been widely applied to biological, medical, and clinical research of numerous diseases. Previous studies have demonstrated that high-quality RNA is indispensable to guarantee the reliability of downstream assays. In this study, we investigated the effects of freezing procedures, rewarming methods, and blood components on RNA quality of blood samples. Methods: Rabbit blood samples were divided into two groups: (1) whole blood (WB) and (2) blood cell components (BCC) with plasma removed. Samples were frozen using four representative freezing procedures (snap freezing in liquid nitrogen, snap freezing at -80°C, traditional slow freezing, and programmable controlled rate freezing) and rewarmed by placing at 4°C or by vortexing. RNA was extracted using the phenol-chloroform RNA extraction method and measured by an Agilent bioanalyzer. Then, human blood was used to verify the best protocol obtained from the rabbit blood experiment. Results: For the four freezing procedures, there were no differences in RNA integrity. For different rewarming methods, RNA integrity number (RIN) values of RNA extracted from frozen WB and BCC samples in the vortex group were above 9, while RNA obtained from WB showed worse quality compared with BCC in the 4°C group. For verification using human blood, RIN values of frozen human WB rewarmed by vortexing ranged from 8.0 to 9.1. Conclusions: Blood components and rewarming methods could affect the RNA quality of blood samples. For scenarios where WB samples have already been cryopreserved, the vortex rewarming method is optimal for high-quality RNA. Otherwise, we would recommend centrifuging fresh WB and cryopreserving it in the form of BCC, which showed a tendency to obtain high-quality RNA by either of the two rewarming methods.
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ARN , Recalentamiento , Animales , Humanos , Conejos , Congelación , Reproducibilidad de los Resultados , Criopreservación/métodosRESUMEN
BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a complex pathophysiologic process involving cell apoptosis and oxidant damages that leads to acute renal failure in both native kidneys and renal allografts. Pioglitazone is a novel class of oral antidiabetic agents currently used to treat type 2 diabetes mellitus. Pioglitazone exerts protective effects on acute myocardial ischemia and acute cerebral ischemia. The aim of this study was to investigate the possible beneficial effects of pioglitazone on renal IRI in mice. METHODS: IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion. Fifty-five healthy male Balb/c mice were randomly assigned to one of the following groups: PBS + IRI, pioglitazone + IRI, PBS + sham IRI, pioglitazone + sham IRI. Kidney function tests, histopathologic examination, renal cell Bcl-2, and Bax expression were determined 24 h after reperfusion. Animals' survival was examined 7 days after operation. RESULTS: Animals pretreated with pioglitazone had lower plasma levels of blood urea nitrogen and creatinine caused by IRI, lower histopathologic scores, and improved survival rates following IRI. Renal cell apoptosis induced by IRI was abrogated in kidneys of mice pretreated by pioglitazone, with an increase in Bcl-2 expression and a decrease in Bax expression. Furthermore, pioglitazone pretreatment protected against lethal renal IRI. CONCLUSIONS: Peroxisome proliferator-activated receptor activation by pioglitazone exerts protective effects on renal IRI in mice by abrogating renal cell apoptosis. Thus, pioglitazone could be a novel therapeutic tool in renal IRI.
Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Tiazolidinedionas/farmacología , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Modelos Animales de Enfermedad , Hipoglucemiantes/farmacología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Pioglitazona , Distribución Aleatoria , Daño por Reperfusión/patologíaRESUMEN
Renal ischemia-reperfusion injury (RIRI) is a common pathological process that causes kidney injury. Previous studies have indicated that both peroxisome proliferator-activated receptor γ (PPARγ) and microRNA-21 (miR-21) exert protective effects against RIRI. However, their relationship is not well understood. In the present study, we investigated the role of the PPARγ/miR-21/programmed cell death 4 (PDCD4) axis in IRI, both in vivo and in vitro. In vitro cell hypoxia/reoxygenation (H/R) and in vivo RIRI models were established, and cell viability, cell apoptosis, and key molecule expression profiles were analyzed. Our results showed that both PPARγ and miR-21 had protective effects against RIRI to varying degrees, and there was an interaction between PPARγ and miR-21. PPARγ could promote the expression of miR-21 and partially protect against RIRI by reducing the level of the miR-21 target protein (PDCD4). Our findings underscore the potential utility of future clinical investigations of PPARγ activation and targeting of the underlying miR-21/PDCD4/caspase-3 pathway, which may participate in the pathogenesis of human IRI.