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Shortening analgesic onset has been researched and it has been documented that prewarming epidural medications to body temperature (37°C) prior to administration increases medication efficacy. Our double-blind randomized controlled trial was designed to investigate if a lower degree of prewarming in providers' pockets could achieve similar results without the need of a bedside incubator. A total of 136 parturients were randomized into either the pocket-warmed group or the room temperature group to receive 10 mL of 0.125% bupivacaine with 2 µg/mL fentanyl epidural bolus at either the 27.8 ±1.7°C or 22.1 ±1.0°C temperatures, respectively. Primary outcome, time to analgesic onset (verbal rating scale pain score ≤ 3) was recorded in 0-, 5-, 10-, 15-, 20-, 30-, and 60-minutes intervals. It was observed that the pocket-warming group (n = 64) and room temperature group (n = 72) had no significant difference of analgesic onset time (median 8 vs. 6.2 minutes; p = 0.322). The incidence of adverse events such as hypotension, fever (≥ 38°C), nausea, vomiting, and number of top-off epidural boluses, as well as patient satisfaction rates and mode of delivery, were not significantly different between the groups as well. Further research is warranted to confirm these findings and explore the impact of different temperatures on analgesic onset time as well as the logistical issues associated with their clinical implementations.
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Analgesia Epidural , Bupivacaína , Fentanilo , Humanos , Femenino , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Analgesia Epidural/métodos , Bupivacaína/administración & dosificación , Adulto , Método Doble Ciego , Embarazo , Analgesia Obstétrica/métodos , Analgesia Obstétrica/efectos adversos , Anestésicos Locales/administración & dosificación , Adulto JovenRESUMEN
Postoperative sore throat (POST) is one of the most reported complications after general anesthesia with an incidence of as high as 60% which may impact patient satisfaction and increase the cost of treatment. The aim of this review is to summarize the currently accepted approaches and new trends intended to reduce the risk and increase the treatment efficacy of POST. Difficult intubation, traumatic intubation, and several other factors contribute to the development of POST. Endotracheal intubation using a stylet-loaded tube exerts excessive pressure on the anterior tracheal wall predisposing to mucosal trauma and contributing to development of POST. Pharmacological interventions are aimed at prevention, amelioration of symptoms, and treatment of POST. Medications suggested for this purpose include corticosteroids, topical sprays and creams, non-steroidal anti-inflammatory drugs (NSAID), and N-methyl-D-aspartate (NMDA) receptor antagonists. The use of video-laryngoscopes (VL) for endotracheal intubation improves the glottic view and increases the success rates with less force required to ensure adequate laryngoscopic view. Nevertheless, despite advances in laryngoscopic devices, the incidence of POST remains high. A novel intubation technique with endotracheal tube (ETT) rotation 180 degrees (ETT 180°) has been suggested to overcome stylet related injury and, possibly, decrease the POST. To date, no clinical trials have been conducted to test the efficacy of ETT 180° in reducing the incidence of POST. Undoubtedly, the suggested method deserves further investigation to determine its role in patient care.
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BACKGROUND: The use of labor neuraxial analgesia (NA) in China has increased significantly in the past decade, and the current rate of use is unknown. This study aimed to describe the epidemiology of NA based on a large multicenter cross-sectional survey, the China Labor and Delivery Survey (CLDS) (2015-2016), and to evaluate the association between NA and intrapartum caesarean delivery (CD) and maternal and neonatal outcomes. METHODS: The CLDS was a facility-based cross-sectional investigation with a cluster random sampling scheme conducted from 2015 to 2016. A specific weight was assigned to each individual based on the sampling frame. Logistic regression was adopted to analyze the factors associated with the use of NA. A propensity score matching scheme was used to analyze the associations between NA and intrapartum CD and perinatal outcomes. RESULTS: A total of 51,488 vaginal deliveries or intrapartum CD were included in our study, excluding prelabor CDs. The weighted NA rate was 17.3% (95% confidence interval [CI], 16.6-18.0) in this survey population. Nulliparous, previous CD, hypertensive disorders, and labor augmentation were associated with higher use of NA. In the propensity score-matched analysis, NA was associated with reduced risks of intrapartum CD, especially intrapartum CD by maternal request (adjusted odds ratio [aOR], 0.68; 95% CI, 0.60-0.78 and aOR, 0.48; 95% CI, 0.30-0.76, respectively), 3rd or 4th degree perineal laceration (aOR, 0.36; 95% CI, 0.15-0.89), and 5-minute Apgar score ≤3 (aOR, 0.15; 95% CI, 0.03-0.66). CONCLUSIONS: The use of NA may be associated with improved obstetric outcomes, including fewer intrapartum CD, less birth canal trauma, and better neonatal outcomes in China.
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Analgesia Epidural , Trabajo de Parto , Embarazo , Femenino , Humanos , Puntaje de Propensión , Estudios Transversales , Parto , Parto Obstétrico , Analgesia Epidural/efectos adversosRESUMEN
The evolutionary and functional features of RNA editing are well studied in mammals, cephalopods, and insects, but not in birds. Here, we integrated transcriptomic and whole-genomic analyses to exhaustively characterize the expansive repertoire of adenosine-to-inosine (A-to-I) RNA editing sites (RESs) in the chicken. In addition, we investigated the evolutionary status of the chicken editome as a potential mechanism of domestication. We detected the lowest editing level in the liver of chickens, compared to muscles in humans, and found higher editing activity and specificity in the brain than in non-neural tissues, consistent with the brain's functional complexity. To a certain extent, specific editing activity may account for the specific functions of tissues. Our results also revealed that sequences critical to RES secondary structures remained conserved within avian evolution. Furthermore, the RNA editome was shaped by purifying selection during chicken domestication and most RESs may have served as a selection pool for a few functional RESs involved in chicken domestication, including evolution of nervous and immune systems. Regulation of RNA editing in chickens by adenosine deaminase acting on RNA (ADAR) enzymes may be affected by non-ADAR factors whose expression levels changed widely after ADAR knockdown. Collectively, we provide comprehensive lists of candidate RESs and non-ADAR-editing regulators in the chicken, thus contributing to our current understanding of the functions and evolution of RNA editing in animals.
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Adenosina Desaminasa , Pollos , Edición de ARN , Animales , Humanos , Adenosina/genética , Adenosina Desaminasa/genética , Adenosina Desaminasa/metabolismo , Pollos/genética , Genómica , Inosina/genética , ARN/genética , TranscriptomaRESUMEN
Phellinus igniarius is a valuable medicinal fungus. P. igniarius is rich in a variety of chemical compounds with medicinal value, among which are flavonoids. Therefore, increasing the content of flavonoids in P. igniarius is beneficial for its potential use in medicinal applications. This study demonstrated that exogenous treatment with citric acid (CA) could significantly increase flavonoid accumulation in P. igniarius. Additionally, we found that CA induced the biosynthesis of flavonoids in a concentration- and time-dependent manner. The flavonoid content could be increased up to 60.96 mg/g when using the treatment with 2.77 mM citric acid for 69.74 h, which was determined by using the response surface method. The changes in the fingerprint profiles of P. igniarius flavonoids with the treatment of CA as an exogenous inducer were also analyzed. In this study, the effect of citric acid as the exogenous inducer on the flavonoid content of P. igniarius was studied, and the processing conditions were optimized through the surface response curve. This approach provides novel insights and a theoretical basis for the production of high-quality P. igniarius.
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Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5-50 µM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 µM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs.
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Anticolesterolemiantes/farmacología , Atorvastatina/farmacología , Células Endoteliales/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Anticolesterolemiantes/química , Atorvastatina/química , Diferenciación Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
BACKGROUND: Splenic hamartoma (SH) is a rare, benign vascular proliferation that is often found incidentally. It may be misdiagnosed as a splenic aneurysm or splenic malignancy. CASE SUMMARY: A 21-year-old male patient was admitted to our hospital with a complaint of an incidentally discovered asymptomatic splenic space-occupying lesion for 2 wk. Abdominal computed tomography (CT) scan showed a circular low-density shadow in the hilum of the spleen. Contrast-enhanced CT revealed an aneurysm located in the hilum of the spleen before operation. Laparoscopic splenectomy was performed and postoperative pathology revealed the presence of SH. CONCLUSION: Imaging studies are insufficient for the differential diagnosis of SH from other diseases, and laparoscopic splenectomy is a less invasive procedure and useful for the diagnostic purpose as well.
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OBJECTIVE: China has a high cesarean delivery (CD) and low labor epidural analgesia (LEA) rate. This online survey was conducted to explore the reasons behind this phenomenon and potential solutions. METHODS: A voluntary, anonymous survey was distributed via both WeChat and professional websites for 4 months amongst groups of Chinese perinatal professionals. Data was collected and analyzed using a Chi-square test and presented as percentages of respondents. RESULTS: 1412 respondents were recorded (43% anesthesiologists, 35% obstetricians, 15.5% midwives or labor and delivery nurses, and 6.5% others), and 1320 respondents were care providers. It was found that 82.7% (1092/1320) of the provider respondents used CD per patient request in fear of lawsuits or yinao/yibao and 63.4% (837/1320) used CD for respecting superstitious culture. The number one reason (noted by 60.2% (795/1320) of all the three specialties) for low LEA use was lack of anesthesia manpower without statistical difference among specialties. The most recommended solution was increasing the anesthesia workforce, proposed by 79.8% (1053/1320) of the three specialties. However, the top solution provided by the two non-anesthesia specialties is different from the one proposed by anesthesiologists. The later (83%, 504/606) suggested increasing the incentive to provide the service is more effective. The answers to questions related to medical knowledge about CD and LEA, and unwillingness of anesthesiologists, parturients and their family members to LEA were similar for the most part, while the opinions regarding low LEA use related to poor experiences and unwillingness of obstetricians and hospital administrators were significantly divided among the three specialties. In the providers' point of view, the unwillingness to LEA from parturient's family members was the most salient (26.1%, 345/1320), which is more than all care providers, hospital administrators, and parturients themselves (16.8%, 222/1320). CONCLUSION: The reasons for high CD rate and low LEA use are multifactorial. The sociological issues (fear of yinao/yibao and superstitious culture) were the top two contributing factors for the high CD rate in China, while lack of anesthesia manpower was the top response for the low LEA use, which contributes to its being the most recommended solution overall from the three specialties. An incentive approach to providers is a short-term solution while training more perinatal care providers (especially among anesthesiologists and midwives), improving billing systems, and reforming legal systems are 3 systemic approaches to tackling this problem in the long-term.
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Analgesia Epidural/estadística & datos numéricos , Anestesia Epidural/estadística & datos numéricos , Cesárea/estadística & datos numéricos , Atención Perinatal/estadística & datos numéricos , Analgesia Obstétrica/estadística & datos numéricos , Pueblo Asiatico , Femenino , Humanos , Trabajo de Parto/efectos de los fármacos , Partería/estadística & datos numéricos , Motivación , Embarazo , Encuestas y CuestionariosRESUMEN
BACKGROUND: The proportion of live births by cesarean delivery (CD) in China is significant, with some, particularly rural, provinces reporting up to 62.5%. The No Pain Labor & Delivery-Global Health Initiative (NPLD-GHI) was established to improve obstetric and neonatal outcomes in China, including through a reduction of CD through educational efforts. The purpose of this study was to determine whether a reduction in CD at a rural Chinese hospital occurred after NPLD-GHI. We hypothesized that a reduction in CD trend would be observed. METHODS: The NPLD-GHI program visited the Weixian Renmin Hospital, Hebei Province, China, from June 15 to 21, 2014. The educational intervention included problem-based learning, bedside teaching, simulation drill training, and multidisciplinary debriefings. An interrupted time-series analysis using segmented logistic regression models was performed on data collected between June 1, 2013 and May 31, 2015 to assess whether the level and/or trend over time in the proportion of CD births would decline after the program intervention. The primary outcome was monthly proportion of CD births. Secondary outcomes included neonatal intensive care unit (NICU) admissions and extended NICU length of stay, neonatal antibiotic and intubation use, and labor epidural analgesia use. RESULTS: Following NPLD-GHI, there was a level decrease in CD with an estimated odds ratio (95% confidence interval [CI]) of 0.87 (0.78-0.98), P = .017, with odds (95% CI) of monthly CD reduction an estimated 3% (1-5; P < .001), more in the post- versus preintervention periods. For labor epidural analgesia, there was a level increase (estimated odds ratio [95% CI] of 1.76 [1.48-2.09]; P < .001) and a slope decrease (estimated odds ratio [95% CI] of 0.94 [0.92-0.97]; P < .001). NICU admissions did not have a level change (estimated odds ratio [95% CI] of 0.99 [0.87-1.12]; P = .835), but the odds (95% CI) of monthly reduction in NICU admission was estimated 9% (7-11; P < .001), greater in post- versus preintervention. Neonatal intubation level and slope changes were not statistically significant. For neonatal antibiotic administration, while the level change was not statistically significant, there was a decrease in the slope with an odds (95% CI) of monthly reduction estimated 6% (3-9; P < .001), greater post- versus preintervention. CONCLUSIONS: In a large, rural Chinese hospital, live births by CD were lower following NPLD-GHI and associated with increased use of labor epidural analgesia. We also found decreasing NICU admissions. International-based educational programs can significantly alter practices associated with maternal and neonatal outcomes.
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Analgesia Epidural/tendencias , Analgesia Obstétrica/tendencias , Cesárea/tendencias , Capacitación en Servicio , Dolor de Parto/tratamiento farmacológico , Manejo del Dolor/tendencias , Adulto , Analgesia Epidural/efectos adversos , Analgesia Obstétrica/efectos adversos , Cesárea/efectos adversos , China , Femenino , Conocimientos, Actitudes y Práctica en Salud , Hospitales Rurales/tendencias , Humanos , Recién Nacido , Cuidado Intensivo Neonatal/tendencias , Análisis de Series de Tiempo Interrumpido , Dolor de Parto/etiología , Nacimiento Vivo , Manejo del Dolor/efectos adversos , Grupo de Atención al Paciente , Embarazo , Evaluación de Programas y Proyectos de Salud , Resultado del Tratamiento , Adulto JovenAsunto(s)
Betacoronavirus , COVID-19/prevención & control , Infecciones por Coronavirus/prevención & control , Infección Hospitalaria/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Personal de Salud , Humanos , Equipo de Protección Personal , Distanciamiento Físico , SARS-CoV-2RESUMEN
Dr Guang-Bo Zhang was the first anesthesiologist to administer and study the effects of labor epidural analgesia in China. Between September 1963 and March 1964, she conducted an observational study evaluating the effects of neuraxial analgesia for laboring women. She presented her research and prepared an article; however, due to the Great Proletarian Cultural Revolution (Cultural Revolution), which began in 1966, her work went unpublished. She successfully preserved her unpublished article, notes, and slides throughout the Cultural Revolution by hiding them in a countryside location near Beijing. These 54-year-old, previously unpublished documents represent the first known clinical trial of neuraxial labor analgesia conducted in China.
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Analgesia Epidural/historia , Analgesia Obstétrica/historia , Investigación Biomédica/historia , Dolor de Parto/historia , Médicos Mujeres/historia , China , Femenino , Historia del Siglo XX , Humanos , Dolor de Parto/terapia , EmbarazoRESUMEN
Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) is a well-known marker of endothelial cells and a key factor for adhesion and accumulation of platelets. CD31 plays roles in cell proliferation, apoptosis, migration, and cellular immunity. CD31 is also expressed on tumor cells, such as breast cancer cells and non-Hodgkin's lymphomas, and contributes to tumor cell invasion. Here, our experiments show that CD31 promotes metastasis by inducing the epithelial-mesenchymal transition in hepatocellular carcinoma by up-regulating integrin ß1 via the FAK/Akt signaling pathway.
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Carcinoma Hepatocelular/tratamiento farmacológico , Cicloheximida/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Proteínas Adaptadoras Transductoras de Señales , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Quinasa 1 de Adhesión Focal/metabolismo , Células Hep G2 , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Inhibidores de la Síntesis de la Proteína/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Autologous transfusion of intraoperative cell salvage blood may be a potential method to decrease the need for allogeneic packed red blood cell transfusions after cesarean delivery, although there are limited data on the benefits of this method. This study evaluated the implementation of targeted intraoperative cell salvage during cesarean delivery in women at increased risk for hemorrhage at the Women's and Children's Hospital in Ningbo, China. METHODS: All women who underwent cesarean delivery >28 weeks of gestation were included in the study. The period before intraoperative cell collection (October 1, 2010, to August 31, 2012, n = 11,322) was compared with the postimplementation period (September 1, 2012, to June 30, 2015, n = 17,456) using an interrupted time series analysis. In the postimplementation period, women suspected to be at increased risk of the need for a blood transfusion (1604, 9.2%) underwent intraoperative cell salvage collection. The primary outcomes were the monthly rate of allogeneic packed red blood cell use and the incidence of clinical manifestation of acute blood transfusion reactions. RESULTS: The mean (standard deviation) estimated monthly allogeneic packed blood cell transfusion rate at the end of the 57-month study was 2.2% ± 0.7% with the implementation compared with 2.7% ± 0.9% without, difference -0.5%, 95% CI, -1.4% to 0.3%; P = .22. The mean number of allogeneic units transfused per patient was 4.1 ± 0.4 units with implementation and 3.9 ± 0.9 units without, difference 0.2, 95% CI, -1.7 to 1.1 units; P = .69. Intraoperative cell salvage blood was reinfused in 757 (47%) and wasted in 847 (53%) cases. The monthly intraoperative allogeneic packed red blood cells use rate was lower after implementation (difference -0.7%, 95% CI, -0.1% to -1.4%; P = .03); however, the monthly postpartum allogeneic packed red blood cell use rate was unchanged (difference -0.2%, 95% CI, -0.4% to 0.7%; P = .56). The clinical manifestation of acute blood transfusion reactions rate was unchanged (difference -2%, 99% CI, -9% to 5%; P = .55) between the periods. CONCLUSIONS: Our findings suggest that targeted intraoperative cell salvage in women undergoing cesarean delivery was associated with less allogeneic blood exposure in the operating room, but not in the postoperative period. Intraoperative cell salvage in targeted cesarean deliveries was not associated with a lesser allogeneic red blood cell exposure over the hospital admission period. The lack of adverse events associated with intraoperative cell salvage supports the safety of intraoperative cell salvage in cesarean delivery.
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Transfusión de Sangre Autóloga/métodos , Cesárea/métodos , Transfusión de Eritrocitos/métodos , Maternidades , Recuperación de Sangre Operatoria/métodos , Adulto , Cesárea/efectos adversos , China/epidemiología , Estudios de Cohortes , Femenino , Humanos , Recién Nacido , Complicaciones Intraoperatorias/diagnóstico , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/prevención & control , EmbarazoRESUMEN
There is an urgent need in China to better predict vaginal birth after cesarean (VBAC) to face the challenge of the second child policy. We aimed to validate a widely used VBAC prediction model (Grobman's model) and a modified version of this model in a Chinese population. In this retrospective cohort study, 444 women with one cesarean delivery and at least one subsequent attempt for a trial of labor in Nanjing, China were included. The considered potential VBAC predictors included Grobman's background variables and five new variables. Overall, a total of 370 women had VBAC, with a success rate of 83.3%. The new background variables "maternal height" and "estimated fetal weight" were considered as two additional predictors for VBAC. The AUC of Grobman's model was 0.831 (95%CI = 0.775-0.886) while the AUC of our modified model with two new variables added was 0.857 (sensitivity = 72.2%, specificity = 83.8%). However, the difference between the AUC of the two models was not significant (Z = -1.69, P = 0.091). We confirmed that Grobman's model was accepted in the Chinese population. A modified model that is supplemented with maternal height and estimated fetal weight needs to be further studied in the Chinese population.
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Parto Vaginal Después de Cesárea/estadística & datos numéricos , Adulto , Pueblo Asiatico/genética , Cesárea/estadística & datos numéricos , China , Femenino , Peso Fetal , Predicción , Humanos , Modelos Logísticos , Edad Materna , Parto/genética , Parto/fisiología , Embarazo , Atención Prenatal , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Esfuerzo de Parto , Parto Vaginal Después de Cesárea/tendenciasRESUMEN
BACKGROUND: Numerous biological functions of long intergenic non-coding RNAs (lincRNAs) have been identified. However, the contribution of lincRNAs to the domestication process has remained elusive. Following domestication from their wild ancestors, animals display substantial changes in many phenotypic traits. Therefore, it is possible that diverse molecular drivers play important roles in this process. RESULTS: We analyzed 821 transcriptomes in this study and annotated 4754 lincRNA genes in the chicken genome. Our population genomic analysis indicates that 419 lincRNAs potentially evolved during artificial selection related to the domestication of chicken, while a comparative transcriptomic analysis identified 68 lincRNAs that were differentially expressed under different conditions. We also found 47 lincRNAs linked to special phenotypes. CONCLUSIONS: Our study provides a comprehensive view of the genome-wide landscape of lincRNAs in chicken. This will promote a better understanding of the roles of lincRNAs in domestication, and the genetic mechanisms associated with the artificial selection of domestic animals.
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Pollos/genética , Domesticación , ARN Largo no Codificante/genética , Animales , Animales Domésticos/genética , Cromosomas/genética , Perfilación de la Expresión Génica , Genética de Población , Genoma , Anotación de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Aves de Corral/genética , Transcriptoma/genéticaRESUMEN
Ampelopsin (AMP) is isolated from the Chinese medicinal herb Ampelopsis grossedentata (Hand-Mazz) and has been associated with numerous biological and pharmacological activities. However, it is not clear whether AMP has a direct protective effect on cerebral ischemia reperfusion injury. Therefore, the present study investigated its role in acute brain injury following focal cerebral ischemia in rats. The current study induced transient focal cerebral ischemia by performing middle cerebral artery occlusion (MCAO) for 60 min, followed by 24 h of reperfusion. Rats were exposed to 40, 80 and 160 mg/kg AMP by oral administration 30 min prior to MCAO and the cysteinyl leukotriene receptor 1-antagonist, pranlukast (0.1 mg/kg, i.p.) was used as a positive control. Neurological deficit scores were observed and an inclined board test was used to assess behavioral dysfunction. The coronal slices were stained with 3,5-triphenyltetrazolium chloride to determine the infarct volume and brain edema. Neuronal morphology was assessed in brain sections stained with cresyl violet and degenerating neurons were identified using Fluoro-Jade B staining. Blood-brain barrier permeability was determined with immunoglobulin (Ig)G immunohistochemistry. Interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α) in serum and cerebrospinal fluid were measured using ELISA kits. AMP at 80 and 160 mg/kg attenuated neurological deficits, reduced infarct volume, brain edema, IgG exudation and neuron degeneration and loss. Similar to pranlukast, AMP also inhibited the MCAO-induced IL-1ß and TNF-α release. Thus, AMP has a neuroprotective effect on acute brain injury following focal cerebral ischemia in rats at an effective oral dose of 80-160 mg/kg. The results of the current study indicate a therapeutic role for AMP in the treatment of ischemic stroke.
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Colony-stimulating factor-1 (CSF-1) and its receptor, CSF-1R, regulate the differentiation and function of macrophages and play an important role in macrophage infiltration in the context of hepatocellular carcinoma. The therapeutic effects of CSF-1R blockade in hepatocellular carcinoma remain unclear. In this study, we found that CSF-1R blockade by PLX3397, a competitive inhibitor with high specificity for CSF-1R tyrosine kinase, significantly delayed tumor growth in mouse models. PLX3397 inhibited the proliferation of macrophages in vitro, but intratumoral macrophage infiltration was not decreased by PLX3397 in vivo Gene expression profiling of tumor-associated macrophages (TAM) showed that TAMs from the PLX3397-treated tumors were polarized toward an M1-like phenotype compared with those from vehicle-treated tumors. In addition, PLX3397 treatment increased CD8+ T-cell infiltration, whereas CD4+ T-cell infiltration was decreased. Further study revealed that tumor cell-derived CSF-2 protected TAMs from being depleted by PLX3397. In conclusion, CSF-1R blockade delayed tumor growth by shifting the polarization rather than the depletion of TAMs. CSF-1R blockade warrants further investigation in the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1544-54. ©2017 AACR.
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Carcinoma Hepatocelular/patología , Polaridad Celular , Neoplasias Hepáticas/patología , Macrófagos/patología , Receptor de Factor Estimulante de Colonias de Macrófagos/antagonistas & inhibidores , Aminopiridinas/química , Aminopiridinas/farmacología , Aminopiridinas/uso terapéutico , Animales , Biomarcadores de Tumor/metabolismo , Células de la Médula Ósea/patología , Línea Celular Tumoral , Polaridad Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Factor Estimulante de Colonias de Macrófagos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Modelos Biológicos , Monocitos/patología , Fenotipo , Pirroles/química , Pirroles/farmacología , Pirroles/uso terapéutico , Receptor de Factor Estimulante de Colonias de Macrófagos/metabolismo , Microambiente Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: Postoperative pharyngolaryngeal complications are commonly reported following laryngeal mask airway (LMA) insertion. After induction of anaesthesia, the airway structures fall backwards under the influence of gravity, and this may contribute to difficulty in placement of a LMA. External airway alignment by lifting the larynx during insertion of an airway may avoid collision of the airway with laryngeal structures. OBJECTIVE(S): To compare pharyngolaryngeal complications after either conventional airway insertion with or without cuff semi-inflation and a method, including an external larynx lift. DESIGN: Randomised controlled, double-blind, clinical trial. SETTING: Ambulatory surgical operating rooms of a university hospital. PATIENTS: American Society of Anaesthesiologists class 1 to 3 patients undergoing ambulatory surgery scheduled to receive general anaesthesia for which a LMA was not contraindicated. INTERVENTIONS: Patients were randomised into three groups for LMA placement: G1, deflated airway; G2, pre-inflated cuff; G3, pre-inflated cuff with external lifting of the larynx. Assessment of pharyngolaryngeal complications (blinded assessor) was made at the time of LMA removal and again at 1, 2 and 24âh. MAIN OUTCOME MEASURES: A pharyngolaryngeal complication, defined as a composite of one or more of sore throat, dysphonia or dysphagia at any time point, or blood on the airway at removal. RESULTS: Of the 450 consecutive patients, 441 were studied. There were no differences in insertion times or number of insertion attempts among the groups. There was no difference in pharyngolaryngeal complications among the groups: G1, 57%; G2, 55%; G3, 52%, (Pâ=â0.77). Blood on the airway was observed less frequently in G3 (9%) compared with G1 and G2 combined (17%): difference -8% (95% confidence interval of the difference -0.8 to -16%, Pâ=â0.01). CONCLUSION: The external larynx lift technique was associated with a lower incidence of blood on the airway at removal, suggesting that the method may decrease trauma to the tissues of the upper airway during insertion. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01749033.
Asunto(s)
Máscaras Laríngeas/efectos adversos , Laringe/patología , Posicionamiento del Paciente/métodos , Faringe/patología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Adulto , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Método Doble Ciego , Femenino , Ronquera/diagnóstico , Ronquera/etiología , Humanos , Masculino , Persona de Mediana Edad , Faringitis/diagnóstico , Faringitis/etiologíaRESUMEN
RNA editing was first discovered in mitochondrial RNA molecular. However, whether adenosine-to-inosine (A-to-I) RNA editing has functions in nuclear genes involved in mitochondria remains elusive. Here, we retrieved 707,246 A-to-I RNA editing sites in Macaca mulatta leveraging massive transcriptomes of 30 different tissues and genomes of nine tissues, together with the reported data, and found that A-to-I RNA editing occurred frequently in nuclear genes that have functions in mitochondria. The mitochondrial structure, the level of ATP production, and the expression of some key genes involved in mitochondrial function were dysregulated after knocking down the expression of ADAR1 and ADAR2, the key genes encoding the enzyme responsible for RNA editing. When investigating dynamic changes of RNA editing during brain development, an amino-acid-changing RNA editing site (I234/V) in MFN1, a mediator of mitochondrial fusion, was identified to be significantly correlated with age, and could influence the function of MFN1. When studying transcriptomes of brain disorder, we found that dysregulated RNA editing sites in autism were also enriched within genes having mitochondrial functions. These data indicated that RNA editing had a significant function in mitochondria via their influence on nuclear genes.