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OBJECTIVES: To explore the efficacy of electroacupuncture (EA) based on the "ascending lucidity and descending turbidity" theory in patients with diabetic gastrointestinal dysfunction and its regulatory effect on gut microbiota. METHODS: A total of 48 patients with diabetic gastrointestinal dysfunction were randomly divided into the EA group (24 cases, 3 cases dropped-off) and the control group (24 cases, no dropped off). Both groups received blood glucose control and basic symptomatic treatment. EA (15 Hz/100 Hz) was applied to Zhongwan (CV12), Tianshu (ST25), Zhongfu (LU1), bilateral Zhangmen (LR13), bilateral Taibai (SP3), bilateral Taiyuan (LU9), bilateral Zusanli (ST36), and bilateral Shangjuxu (ST37) in the EA group. Sham EA was applied to corresponding non-acupoints without electric stimulation in the control group. Both groups received treatment for 30 min per time, once daily, for a total of 5 treatments followed by a 2-day break, over a consecutive period of 2 weeks. Symptoms were evaluated by gastrointestinal symptom rating scale (GSRS) and gastroparesis cardinal symptom index (GCSI) before and after treatment, and 4 weeks after treatment. During the treatment period, fasting blood glucose levels were monitored daily. Stool samples were collected before and after treatment for 16S rDNA sequencing analysis to examine changes in gut microbiota. RESULTS: Compared with the control group, GSRS and GCSI scores in the EA group were significantly decreased (P<0.001) after treatment and at follow-up at the same time point, and compared with those before treatment, GSRS and GCSI scores in the EA group were significantly decreased after treatment and at follow-up (P<0.001). After treatment, the 16S rDNA sequencing showed that at the phylum level, the ratio of Proteobacteria in the EA group was higher than that in the control group (FDR<0.05). At the genus level, a total of 18 different gut microbiota were identified between the two groups. Compared to the control group, patients in the EA group showed a significant decrease in the abundance of Pseudomonas and Alkalibacter (FDR<0.05), while the abundance of the remaining 16 gut microbiota was significantly increased (FDR<0.05). Compared to the baseline, the EA group showed a significant up-regulation of Olsenella (FDR<0.05) and a significant down-regulation of Pseudomonas (FDR<0.05) after treatment. CONCLUSIONS: EA based on the "ascending lucidity and descending turbidity" theory can effectively improve the symptoms of patients with diabetic gastrointestinal dysfunction. EA can also affect the distribution of gut microbiota by up-regulating the levels of certain beneficial bacteria and suppressing pathogenic bacteria .
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Electroacupuntura , Microbioma Gastrointestinal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Puntos de Acupuntura , Resultado del Tratamiento , Enfermedades Gastrointestinales/terapia , Enfermedades Gastrointestinales/microbiología , Complicaciones de la Diabetes/terapia , Complicaciones de la Diabetes/microbiología , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificaciónRESUMEN
Recognizing expressions from dynamic facial videos can find more natural affect states of humans, and it becomes a more challenging task in real-world scenes due to pose variations of face, partial occlusions and subtle dynamic changes of emotion sequences. Existing transformer-based methods often focus on self-attention to model the global relations among spatial features or temporal features, which cannot well focus on important expression-related locality structures from both spatial and temporal features for the in-the-wild expression videos. To this end, we incorporate diverse graph structures into transformers and propose a CDGT method to construct diverse graph transformers for efficient emotion recognition from in-the-wild videos. Specifically, our method contains a spatial dual-graphs transformer and a temporal hyperbolic-graph transformer. The former deploys a dual-graph constrained attention to capture latent emotion-related graph geometry structures among local spatial tokens for efficient feature representation, especially for the video frames with pose variations and partial occlusions. The latter adopts a hyperbolic-graph constrained self-attention that explores important temporal graph structure information under hyperbolic space to model more subtle changes of dynamic emotion. Extensive experimental results on in-the-wild video-based facial expression databases show that our proposed CDGT outperforms other state-of-the-art methods.
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Emociones , Expresión Facial , Grabación en Video , Humanos , Emociones/fisiología , Algoritmos , Redes Neurales de la Computación , Reconocimiento Facial/fisiología , Reconocimiento de Normas Patrones Automatizadas/métodos , Reconocimiento Facial Automatizado/métodosRESUMEN
Accurate annotation of coding regions in RNAs is essential for understanding gene translation. We developed a deep neural network to directly predict and analyze translation initiation and termination sites from RNA sequences. Trained with human transcripts, our model learned hidden rules of translation control and achieved a near perfect prediction of canonical translation sites across entire human transcriptome. Surprisingly, this model revealed a new role of codon usage in regulating translation termination, which was experimentally validated. We also identified thousands of new open reading frames in mRNAs or lncRNAs, some of which were confirmed experimentally. The model trained with human mRNAs achieved high prediction accuracy of canonical translation sites in all eukaryotes and good prediction in polycistronic transcripts from prokaryotes or RNA viruses, suggesting a high degree of conservation in translation control. Collectively, we present a general and efficient deep learning model for RNA translation, generating new insights into the complexity of translation regulation.
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BACKGROUND: Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of these tumors have been described, there have been no large-scale investigations of the profile of HT and changes in cardiac structure and function that occur in patients with pheochromocytomas and paragangliomas (PPGL). MATERIALS AND METHODS: In this study, we investigated the prevalence of HT and left ventricular remodeling (LVR) in a cohort of 598 patients who underwent surgery for PPGL at our center between January 2001 and April 2022. Information on demographics, reason for hospitalization, medical history, biochemical parameters, findings on echocardiography, and tumor characteristics were recorded. The LVR index was compared according to whether or not there was a history of HT. RESULTS: The average age was 47.07 ± 15.07 years, and 277 (46.32%) of the patients were male. A history of HT was found in 423 (70.74%) of the 598 patients. Paraganglioma was significantly more common in the group with HT (26.00% vs. 17.71%, P = 0.030) and significantly less likely to be found incidentally during a health check-up in this group (22.93% vs. 59.43%, P < 0.001). Among 365 patients with complete echocardiography data, left ventricular mass index (86.58 ± 26.70 vs. 75.80 ± 17.26, P < 0.001) and relative wall thickness (0.43 ± 0. 08 vs. 0.41 ± 0.06, P = 0.012) were significantly higher in patients with PPGL and a history of HT. The proportions with left ventricular hypertrophy (LVH) (19.40% vs. 8.25%, P = 0.011) and LVR (53.73% vs. 39.18%, P = 0.014) were also higher when there was a history of HT. After adjusting for age, gender, body mass index, alcohol consumption, smoking status, diabetes, stroke, creatinine level, tumor location, and tumor size, a history of HT was significantly correlated with LVH (odds ratio 2.71, 95% confidence interval 1.18-6.19; P = 0.018) and LVR (odds ratio 1.83, 95% confidence interval 1.11-3.03; P = 0.018). CONCLUSION: HT is common in patients with PPGL (70.74% in this cohort). PPGL without a history of HT is more likely to be found incidentally (59.43% in our cohort). HT is associated with LVR in PPGL patients with complete echocardiography data. These patients should be observed carefully for cardiac damage, especially those with a history of HT.
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Neoplasias de las Glándulas Suprarrenales , Hipertensión , Paraganglioma , Feocromocitoma , Función Ventricular Izquierda , Remodelación Ventricular , Humanos , Feocromocitoma/complicaciones , Feocromocitoma/epidemiología , Feocromocitoma/diagnóstico por imagen , Feocromocitoma/cirugía , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de las Glándulas Suprarrenales/epidemiología , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Adulto , Paraganglioma/epidemiología , Paraganglioma/complicaciones , Paraganglioma/diagnóstico por imagen , Hipertensión/epidemiología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Medición de Riesgo , Anciano , Presión SanguíneaRESUMEN
Aversive stimuli activate corticotropin-releasing factor (CRF)-expressing neurons in the paraventricular nucleus of hypothalamus (PVNCRF neurons) and other brain stress systems to facilitate avoidance behaviors. Appetitive stimuli also engage the brain stress systems, but their contributions to reward-related behaviors are less well understood. Here, we show that mice work vigorously to optically activate PVNCRF neurons in an operant chamber, indicating a reinforcing nature of these neurons. The reinforcing property of these neurons is not mediated by activation of the hypothalamic-pituitary-adrenal (HPA) axis. We found that PVNCRF neurons send direct projections to the ventral tegmental area (VTA), and selective activation of these projections induced robust self-stimulation behaviors, without activation of the HPA axis. Similar to the PVNCRF cell bodies, self-stimulation of PVNCRF-VTA projection was dramatically attenuated by systemic pretreatment of CRF receptor 1 or dopamine D1 receptor (D1R) antagonist and augmented by corticosterone synthesis inhibitor metyrapone, but not altered by dopamine D2 receptor (D2R) antagonist. Furthermore, we found that activation of PVNCRF-VTA projections increased c-Fos expression in the VTA dopamine neurons and rapidly triggered dopamine release in the nucleus accumbens (NAc), and microinfusion of D1R or D2R antagonist into the NAc decreased the self-stimulation of these projections. Together, our findings reveal an unappreciated role of PVNCRF neurons and their VTA projections in driving reward-related behaviors, independent of their core neuroendocrine functions. As activation of PVNCRF neurons is the final common path for many stress systems, our study suggests a novel mechanism underlying the positive reinforcing effect of stressful stimuli.
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Hormona Liberadora de Corticotropina , Hormonas Liberadoras de Hormona Hipofisaria , Ratones , Animales , Hormona Liberadora de Corticotropina/metabolismo , Hormonas Liberadoras de Hormona Hipofisaria/metabolismo , Hormonas Liberadoras de Hormona Hipofisaria/farmacología , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Hipotálamo/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Neuronas Dopaminérgicas/metabolismoRESUMEN
Though vaping likely represents a safer alternative to smoking, it is not without risks, many of which are not well understood, especially for vulnerable populations. Here we evaluate the sex- and age-dependent effects of JUUL nicotine vapour in rats. Following passive nicotine vapour exposures (from 59 mg/ml JUUL nicotine pods), rats were evaluated for reward-like behaviour, locomotion, and precipitated withdrawal. Pharmacokinetics of nicotine and its metabolites in brain and plasma and the long-term impact of nicotine vapour exposure on functional magnetic resonance imaging-based brain connectivity were assessed. Adult female rats acquired conditioned place preference (CPP) at a high dose (600 s of exposure) of nicotine vapour while female adolescents, as well as male adults and adolescents did not. Adult and adolescent male rats displayed nicotine vapour-induced precipitated withdrawal and hyperlocomotion, while both adult and adolescent female rats did not. Adult females showed higher venous and arterial plasma and brain nicotine and nicotine metabolite concentrations compared to adult males and adolescent females. Adolescent females showed higher brain nicotine concentration compared to adolescent males. Both network-based statistics and between-component group connectivity analyses uncovered reduced connectivity in nicotine-exposed rats, with a significant group by sex interaction observed in both analyses. The short- and long-term effects of nicotine vapour are affected by sex and age, with distinct behavioural, pharmacokinetic, and altered network connectivity outcomes dependent on these variables.
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Sistemas Electrónicos de Liberación de Nicotina , Nicotina , Ratas , Masculino , Femenino , Animales , Nicotina/farmacología , Fumar , Encéfalo/metabolismo , RecompensaRESUMEN
OBJECTIVE: To systematically evaluate the efficacy and safety of acupuncture in the treatment of the vascular cognitive impairment (VCI) associated with cerebral small vessel disease (CSVD-VCI) and to provide a theoretical basis for clinical acupuncture treatment for CSVD-VCI. METHOD: Various databases, including China National Knowledge Infrastructure, Wanfang Data, Chinese Science and Technology Journal Database, Chinese BioMedical Literature Service System, PubMed, the Cochrane Library, and EBSCOhost, were searched for randomized controlled trials (RCTs) related to acupuncture treatment for CSVD-VCI. The quality of the included trials was evaluated, and a meta-analysis was conducted using the Review Manager 5.4 software. RESULTS: Ten articles on RCTs were included, involving 761 patients, i.e., 381 in the acupuncture group and 380 in the control group. The meta-analysis results indicated that the use of acupuncture alone and acupuncture alongside other therapies for CSVD-VCI could improve the overall clinical response rate [odds ratio = 3.51, 95% confidence interval (CI) = (2.05, 6.00), P < 0.00001], increase the patients' Montreal Cognitive Assessment scores [mean difference (MD) = 3.33, 95%CI (2.98, 3.68), P < 0.00001], Mini-Mental State Examination scores [MD = 2.78, 95%CI (2.51, 3.06), P < 0.00001], and activities of daily living scores [MD = 6.30, 95%CI (4.22, 8.37), P < 0.00001], and shorten the latency of auditory evoked potential P300 [MD = -14.67, 95%CI (-19.54, -9.80), P < 0.00001]. CONCLUSION: Acupuncture alone and acupuncture alongside other therapies are superior to non-acupuncture-based therapies in the treatment of CSVD-VCI. However, due to the small number of relevant available articles and their general low quality, this conclusion may be biased. More clinical RCTs with a larger sample size and higher quality are needed to support this theory.
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Terapia por Acupuntura , Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Humanos , Terapia por Acupuntura/métodos , Disfunción Cognitiva/terapia , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/terapia , ChinaRESUMEN
Objectives: As a surrogate of arterial stiffness, the brachial-ankle pulse wave velocity (baPWV) is a good predictor of incident cardiovascular disease. Remnant cholesterol (RC) is a proven independent risk factor for cardiovascular disease. However, the relationship between RC and baPWV is unknown. The present study was performed to explore this relationship. Design: Cross-sectional study. Setting and participants: This study involved 8,028 participants of a community-based atherosclerosis cohort from China. Community residents aged ≥40 years were enrolled by responding to detailed research recruitment posters or by phone invitation. The participants comprised 2,938 (36.60%) men, and their mean age was 56.57 ± 9.04 years. Methods and results: The baPWV was measured with a standard protocol using the Omron Colin BP-203RPE III device (Omron Healthcare, Kyoto, Japan). RC was calculated as follows: RC = TC - LDL-C - HDL-C. The mean baPWV was 1,646.85 ± 374.11 cm/s. The median RC concentration was 0.56 (0.41-0.74) mmol/L. In the multivariate logistic regression analyses, the concentrations of RC, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) were all positively and independently associated with baPWV. The baPWV was higher in the fourth than first lipid profile quartile. The HDL-C concentration was inversely associated with baPWV. When RC was forced into the model with other lipid profile indices simultaneously, only the RC and TG concentrations remained significantly associated with baPWV. Conclusion: Lipids are independently associated with baPWV. The RC and TG concentrations have stronger associations with arterial stiffness than other lipid indices in the Chinese community-based population.
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Pulse wave velocity (PWV) is the most widely used measurement of arterial stiffness in clinical practice. This study aimed to evaluate and compare the relationships between carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle PWV (baPWV) and the presence of carotid plaque. This study was designed cross-sectionally and included 6027 participants from a community-based cohort in Beijing. Logistic regression analyses were performed to evaluate and compare the associations of cfPWV and baPWV with the presence of carotid plaque. The mean (SD) cfPWV and baPWV were 8.55 ± 1.83 and 16.79 ± 3.36, respectively. The prevalence of carotid plaque was 45.26% (n = 2728). Both cfPWV (per 1 m/s increase: OR = 1.11, 95% CI: 1.07-1.16) and baPWV (OR = 1.04, 95% CI: 1.02-1.06) were independently associated with carotid plaque after adjusting for various confounders. Compared with bottom quartile (cfPWV ≤7.31 m/s and baPWV ≤14.44 m/s), the top quartile of cfPWV and baPWV had a significantly higher prevalence of carotid plaque (for cfPWV: OR = 1.59, 95% CI: 1.32-1.92; for baPWV: OR = 1.53, 95% CI: 1.26-1.86). However, the relationship of baPWV and carotid plaque was nonlinear, with a positive trend only when baPWV < 16.85 m/s. When comparing relationships between PWV indices and carotid plaque in one model, both cfPWV and baPWV were significantly associated with carotid plaque in participants with baPWV < 16.85 m/s; however, only cfPWV was independently associated with carotid plaque in participants with baPWV ≥16.85 m/s. Both cfPWV and baPWV were significantly associated with carotid plaque in the Chinese community-based population. Furthermore, cfPWV was more strongly correlated with carotid plaque than baPWV in participants with baseline baPWV ≥16.85 m/s.
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Hipertensión , Análisis de la Onda del Pulso , Humanos , Índice Tobillo Braquial , Pueblos del Este de Asia , BeijingRESUMEN
Objective: To analyze the correlation between metanephrine and normetanephrines (MNs) and subclinical myocardial injuries (SMI) diagnosed by low left ventricular global longitudinal strain (LV GLS) in patients with pheochromocytoma and paraganglioma (PPGL). Methods: Seventy-six patients who underwent surgery for pheochromocytoma or paraganglioma from September 2017 to April 2022 were examined. All the patients enrolled had normal left ventricular ejection fraction (LVEF) and myocardial injury biomarkers including cardiac troponin I and B-natriuretic peptide. Univariate analysis and multivariate analysis were performed to evaluate the association of MNs and subclinical myocardial injury (SMI)(defined as LV GLS<18). Results: LV GLS of 13(17.11%) PPGL patients was less than 18. The percentage of patients with elevation of single hormone (metanephrine, normetanephrine, 3-methoxytyramine) or any one of MNs was not significantly correlated with SMI (P=0.987, 0.666, 0.128 and 0.918, respectively). All MNs elevation was associated with SMI (OR: 11.27; 95% CI, 0.94-135.24; P= 0.056). After adjusting for age, All MNs elevation was significantly correlated with SMI (OR: 16.54; 95% CI, 1.22-223.62; P= 0.035). Conclusion: MNs might be an important factor influencing myocardial function. All MNs elevation might indicate SMI. If all MNs elevated, LV GLS measurement was recommended for PPGL patients to detect SMI in the absence of decrease LVEF or other heart disease in clinical practice.
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Lower extremity peripheral artery disease (LEPAD) is a common and serious health-threatening disease. The aim of this study was to evaluate the predictive value of 10-year atherosclerotic cardiovascular disease (ASCVD) risk equations from the Prediction for ASCVD Risk in China (China-PAR) project for incident LEPAD after 6.75 ± 0.13 years of follow-up. A total of 3,595 Chinese participants without baseline ASCVD or LEPAD from a community-based cohort were enrolled in our study. The mean (interquartile range) baseline 10-year China-PAR ASCVD risk was 4.35% (2.24-8.44%), and the incidence of new-onset LEPAD during 6.75 ± 0.13 years was 4.23%. In univariable logistic regression analysis, 10-year China-PAR ASCVD risk was significantly associated with LEPAD incidence (odds ratio [OR] for each 1% increase in the risk score = 1.06, 95% confidence interval [CI]: 1.03-1.08, P < 0.001). After adjusting confounders, the relationship remained significant (OR: 1.09, 95% CI: 1.05-1.1. P < 0.001). Participants with the highest risk (≥10%) had significantly increased risk compared to those with the lowest risk (<5%) (OR = 2.65, 95% CI: 1.15-6.07, P = 0.022). Further interaction analyses showed no evidence of heterogeneity according to sex, age, body mass index (BMI), smoking, drinking, hypertension, diabetes mellitus, dyslipidemia, renal function, waist circumference, and family history. In conclusion, 10-year China-PAR ASCVD risk independently predicted the risk of new-onset LEPAD in a Chinese community-based population, indicating the importance of polyvascular diseases (PVDs) and the intrinsic interactions of its components.
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Background: Remnant lipoprotein cholesterol (RC) is an independent risk factor for cardiovascular disease (CVD). However, the relationships of remnant cholesterol and other conventional lipid parameters with new-onset carotid plaque are not fully understood in the Chinese community-based population. Materials and methods: A total of 872 plaque-free participants (51.39 ± 4.96 years old) with no history of CVD were included in this study. The plasma concentrations of RC were calculated by subtracting low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC). Multivariate regression models were used to evaluate and compare the associations between RC and other lipid parameters and new-onset carotid plaque. Results: After a mean 6.77-year follow-up, the incidence of new-onset carotid plaque was 188 (21.56%). RC was significantly associated with new-onset carotid plaque [Odd ratio (OR) = 1.57 per 1 mmol/L increase, 95% confidence interval (CI): 1.03-2.41, p = 0.038]. The highest tertile of RC (T3 group) had the highest risk of new-onset carotid plaque (OR = 2.53, 95% CI: 1.63-3.95). Similar results were seen for increased other lipid parameters, but decreased HDL-C levels. When adding another lipid parameter into the adjusted model with RC simultaneously, only RC remained significantly associated with new-onset carotid plaque after adjusting for other lipid parameters (all p value < 0.005). Furthermore, RC was strongly associated with new-onset carotid plaque in participants with lower baseline LDL-C levels. Conclusion: Increased RC levels were superior to other conventional lipid parameters to be associated with new-onset carotid plaque in the Chinese community-based population. Furthermore, RC should be considered in participants with lower LDL-C levels for the purpose of early atherosclerosis prevention.
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Background: Acupuncture is a well-known treatment option for ischemic stroke recovery, but evidence of its effectiveness remains limited. This is a randomized controlled trial to evaluate the effectiveness of acupuncture treatment for ischemic stroke rehabilitation. Methods: Rehabilitation training was provided to the control group. In acupuncture arm 1, these acupoints were derived from the ancient books, including GV20 (baihui), GV26 (shuigou), PC9 (zhongchong), ST6 (jiache), ST4 (dicang), LI15 (jianyu), LI11 (quchi), LI4 (hegu), GB30 (huantiao), GB31 (fengshi), GB34 (yanglingquan), and GB39 (xuanzhong). In acupuncture arm 2, the acupoints used were GV20 (baihui), PC6 (neiguan), LI11 (quchi), LI10 (shousanli), SJ5 (waiguan), LI4 (hegu), GB30 (huantiao), ST36 (zusanli), GB34 (yanglingquan), SP6 (sanyinjiao), ST41 (jiexi), and LR3 (taichong), which were extracted from Acupuncture and Moxibustion Science. After acupuncture, the needles were left in for 30 min and manually manipulated every 10 min. The three groups received treatment once a day, 5 times a week for 2 weeks. The primary outcome was the National Institutes of Health Stroke Scale (NIHSS), and the secondary outcomes were the Barthel Index (BI) and the Modified Ashworth Scale (MAS). Outcomes were measured in patients both before and after treatment. Results: A total of 497 patients with ischemic stroke were randomized into either arm 1 (159 cases), arm 2 (173 cases), or the control group (165 cases). After 2 weeks of treatment, the NIHSS scores for arm 1 were lower than those of the control group (P = 0.017); the BI scores were higher in arm two than that in the control group at T2 (P = 0.016) and follow-up (P = 0.020). Additionally, there was no significant difference between arm one and the control group for either the BI scores or the MAS scores (P > 0.05) and no significant difference between arm two and the control group for the MAS scores or the NIHSS scores (P > 0.05). Conclusion: The clinical efficacy of arm 1 and arm 2 (acupuncture groups) was superior to that of the control group, but there was no difference between the effects of the two acupuncture groups. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR-IOR-16008627.
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Some circular RNAs (circRNAs) were found to be translated through IRES-driven mechanism, however the scope and functions of circRNA translation are unclear because endogenous IRESs are rare. To determine the prevalence and mechanism of circRNA translation, we develop a cell-based system to screen random sequences and identify 97 overrepresented hexamers that drive cap-independent circRNA translation. These IRES-like short elements are significantly enriched in endogenous circRNAs and sufficient to drive circRNA translation. We further identify multiple trans-acting factors that bind these IRES-like elements to initiate translation. Using mass-spectrometry data, hundreds of circRNA-coded peptides are identified, most of which have low abundance due to rapid degradation. As judged by mass-spectrometry, 50% of translatable endogenous circRNAs undergo rolling circle translation, several of which are experimentally validated. Consistently, mutations of the IRES-like element in one circRNA reduce its translation. Collectively, our findings suggest a pervasive translation of circRNAs, providing profound implications in translation control.
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Biosíntesis de Proteínas , ARN Circular , Sitios Internos de Entrada al Ribosoma/genética , Biosíntesis de Proteínas/genética , ARN Circular/genéticaRESUMEN
BACKGROUND: Left atrial (LA) size is often used as a surrogate marker of LA function in clinical practice, with larger atrial thought to represent a "dysfunctioning" atrium, since there is no accepted 'gold' standard to evaluate LA function. The exact relationship between LA size and phasic function, and whether LA dysfunction occur before LA enlargement (LAE) may be of clinical interest while have not been fully studied. Two-dimensional speckle-tracking echocardiography (2D STE) was showed a promising method in measuring LA physical deformation. MATERIALS AND METHODS: A community cohort of 715 subjects at cardiovascular disease high risk accepted comprehensive echocardiography. LA longitudinal phasic strain Sa (absolute peak strain during atrial contraction), Se (peak strain at early diastole) and Stot (total atrial strain = Sa + Se), representing contractile, conduit, and reservoir function respectively, were measured using off-line 2D STE software in apical 4 chamber view, and data were compared among groups at different LA size and between subgroups in normal LA size with and without hypertension (HT). RESULTS: With LAE (from normal size, mild, moderate to severe LAE), the Stot (21.74 ± 5.97, 20.75 ± 4.99, 20.49 ± 5.27, 17.75 ± 4.71, respectively, ANOVA P = 0.003) and Sa (11.84 ± 3.92, 11.00 ± 3.29, 10.11 ± 2.57, 8.55 ± 2.88, respectively, ANOVA P < 0.001) reduced while Se had no change. Stot of Severe LAE group was significantly lower than that of Normal LA size group (P = 0.002). Sa of the three LAE groups were all significantly lower than that of Normal LA size group (P = 0.024, P = 0.002, P < 0.001, respectively). In normal sized LA subgroups, Stot (21.35 ± 5.91 vs. 23.01 ± 6.02, P = 0.008) and Se (9.51 ± 4.41 vs. 11.17 ± 4.89, P < 0.001) reduced in subjects with HT comparing with those without. CONCLUSION: LA phasic function remodeling occurs before LAE and continues with LAE, with reservoir, conduit and contractile function being affected unparalleled.
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Remodelación Atrial , Hipertensión , Función del Atrio Izquierdo , Ecocardiografía/métodos , Atrios Cardíacos/diagnóstico por imagen , HumanosRESUMEN
Cannabis legalization in North America has coincided with an increase in reports of cannabis-induced toxicosis in pets, but the magnitude of this problem, as well as outcomes of these incidents remain unknown. Therefore, we examined the frequency, diagnostic criteria, clinical signs, and prognoses of cannabis toxicoses in pets in North America. We conducted an online survey between January, 2021 and April, 2021 targeting veterinarians practicing in Canada and the United States (US). Out of the 251 study participants, 191 practiced in Canada. Cannabis toxicosis was most commonly reported in dogs (n = 226 veterinarians), and the number of toxicosis cases increased significantly in Canada (p<0.0001) and the US (p = 0.002) after October, 2018. Frequently reported clinical signs of cannabis toxicosis included: urinary incontinence (n = 195), disorientation (n = 182), ataxia (n = 178), lethargy (n = 150), hyperesthesia (n = 134), and bradycardia (n = 112). Edibles were most commonly suspected to be the cause of toxicosis (n = 116). The most common route of exposure was ingestion (n = 135), while the most cited reason was ingestion while unattended (n = 135). Cannabis toxicosis was mostly diagnosed using supportive clinical signs (n = 229), the most common treatment was outpatient monitoring (n = 182), and pets were most often treated as out-patients (n = 103). The legalization of cannabis use in Canada and the US is likely an important factor associated with the increased cannabis toxicosis cases in pets; however, the legal status may also increase reporting. The medicinal use of cannabis by pet-owners for pets may also contribute to a portion of the reported toxicoses. Most pets that experienced cannabis toxicosis recovered completely, suggesting that most cannabis toxicoses do not result in long-term ill effects. Even though some deaths (n = 16) were reported in association with cannabis toxicosis, the presence of confounders such as toxins, and underlying conditions cannot be ruled out, emphasizing the need for rigorous controlled laboratory studies to investigate this important issue.
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Cannabis , Alucinógenos , Veterinarios , Animales , Cannabis/efectos adversos , Perros , Humanos , América del Norte/epidemiología , Mascotas , Prevalencia , Estados Unidos/epidemiologíaRESUMEN
Objective: To investigate the clinical efficacy of this combined treatment for chronic pelvic pain syndrome (CPPS) by meta-analysis. Methods: Relevant articles were retrieved from PubMed, CNKI, Wanfang Data, Web of Science, and Embase, including randomized controlled trials on acupuncture combined with rehabilitation for CPPS in females. Results: A total of 224 articles were retrieved in this study, and 14 studies were finally identified for inclusion. Among them, the treatment group was treated with acupuncture combined with pelvic floor rehabilitation therapy, while the control group was treated with acupuncture or pelvic floor rehabilitation therapy. Meta-analysis showed that the treatment effective rate in the treatment group was significantly higher than that in the control group (OR = 6.54; 95% CI: 4.20, 10.21; P < 0.05). After treatment, compared with the control group, the treatment group showed lower incidences of adverse reactions (OR = 0.16; 95% CI: 0.09, 0.27; P < 0.05), bladder prolapse (OR = 0.36; 95% CI: 0.18, 0.73; P < 0.05), cervical prolapse (OR = 0.22; 95% CI: 0.10, 0.49; P < 0.05), and pelvic peritoneal hernia (OR = 0.14; 95% CI: 0.05, 0.38; P < 0.05); in addition, the treatment group was also associated with lower pain score (SMD = -4.05; 95% CI: -6.75, -1.34; P < 0.05) and pelvic dysfunction score (SMD = -4.35; 95% CI: -5.37, -3.34; P < 0.05). Conclusion: Acupuncture combined with rehabilitation is effective for CPPS in females, which can significantly reduce the pain intensity and improve pelvic dysfunction of patients.
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Terapia por Acupuntura , Dolor Crónico , Prostatitis , Carrera , Terapia por Acupuntura/efectos adversos , Dolor Crónico/complicaciones , Dolor Crónico/terapia , Femenino , Humanos , Masculino , Dolor Pélvico/complicaciones , Dolor Pélvico/terapia , Prolapso , Prostatitis/complicaciones , Prostatitis/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: The lipid profile is reportedly related to peripheral blood pressure or pulse wave velocity. However, no studies have investigated the associations between lipid parameters, especially remnant lipoprotein cholesterol (RLP-C), and central systolic blood pressure (cSBP). METHODS: This study used baseline data of a community-based cohort in Beijing, China. Participants who had been treated with anti-hypertensive or lipid-lowering agents were excluded. RLP-C is equal to total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). An Omron HEM-9000AI device was used to measure non-invasive cSBP. The associations between blood lipid profile and non-invasive cSBP were evaluated using multivariable regression models. RESULTS: The 5173 included participants were 55.0 ± 8.5 years old; 35.7% (1845) of participants were men. Increased cSBP was significantly associated with increased TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), and RLP-C but with decreased HDL-C, even after adjusting for possible covariates. When simultaneously entering individual pairs of RLP-C and other blood lipid parameters into the multivariable regression model, RLP-C remained significantly associated with cSBP, even after adjusting for other lipids. Compared with participants who had RLP-C levels in the first quartile (Q1), cSBP for those with RLP-C in Q4 was increased to 4.57 (95% confidence interval [CI]: 3.08-6.06) mmHg after adjusting for LDL-C, 4.50 (95%CI: 2.98-6.02) mmHg after adjusting for TC, 3.91 (95%CI: 1.92-5.89) mmHg after adjusting for TG, 5.15 (95%CI: 3.67-6.63) mmHg after adjusting for HDL-C, and 4.10 (95%CI: 2.36-5.84) mmHg after adjusting for non-HDL-C. CONCLUSIONS: Increased blood RLP-C level was significantly associated with higher cSBP in a Chinese population, independently of other lipids, which indicates its importance in individual cardiovascular risk assessment.
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Presión Sanguínea/fisiología , Colesterol/sangre , Lipoproteínas/sangre , Triglicéridos/sangre , China , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Hipertensión/sangre , Masculino , Persona de Mediana EdadRESUMEN
Recently, a large number of circular RNAs (circRNAs) were discovered in eukaryotes, some of which were reported to be translated through a cap-independent fashion. However, study of circRNA translation is still not trivial. Here we describe two distinct systems to generate the translatable circRNAs containing validated open reading frames (ORF) to analyze their translation in living cells. The first system is a plasmid reporter containing a single exon with split GFP fragments in reverse order, which can be efficiently back-spliced to generate a circRNA encoding intact GFP. The second system is a self-splicing reporter containing an intact Renilla luciferase (Rluc) ORF and the flanking split group I introns in reverse order, which can produce circRNAs through in vitro self-splicing of the precursor RNAs. Both circRNA systems can serve as the platforms for mechanistic studies of circRNA translation, and also serve as the reliable systems to measure the activity of IRES-mediated translation.
Asunto(s)
Biosíntesis de Proteínas , ARN Circular , Regulación de la Expresión Génica , Sistemas de Lectura Abierta , Biosíntesis de Proteínas/genética , ARN/genética , ARN/metabolismo , Empalme del ARN , ARN Circular/genéticaRESUMEN
PURPOSE: The aim of this work was to evaluate the prognostic value of tumor length and diameter for patients with esophageal squamous cell cancer (ESCC) treated with definitive (chemo)radiotherapy to identify potential indicators for separate nonsurgical T staging, which are needed in clinical practice. MATERIALS AND METHODS: A total of 682 patients with ESCC who underwent definitive (chemo)radiotherapy between 2009 and 2015 were reviewed. Esophageal tumor length and diameter were determined by barium esophagography and computed tomography before treatment. Univariate and multivariate analyses were used to assess the impact of tumor length and diameter on long-term overall survival (OS) and progression-free survival (PFS). Propensity score matching (PSM) analysis was also used to control intergroup heterogeneity. RESULTS: The median OS and PFS were 22.2 months and 15.4 months, respectively, in the tumor length ≤ 6 cm group, which were significantly longer than those in the tumor length > 6 cm group (13.4 and 8.5 months, respectively). The median OS and PFS were 23.3 months and 15.9 months, respectively, in the tumor diameter ≤ 3.5 cm group, which were also significantly longer than those in the tumor diameter > 3.5 cm group (13.3 and 8.8 months, respectively). Similar results were found after PSM. Univariate and multivariate analyses showed that tumor length and diameter were both independent predictors of long-term survival. CONCLUSION: Tumor length and diameter are both independent prognostic factors for ESCC patients treated with definitive (chemo)radiotherapy. These two imaging parameters have the potential for development and use in nonsurgical T staging.