Hypothalamic CRF neurons facilitate brain reward function.

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.

Factors influencing JUUL e-cigarette nicotine vapour-induced reward, withdrawal, pharmacokinetics and brain connectivity in rats: sex matters.

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.

Meta-analysis of the efficacy of acupuncture in the treatment of the vascular cognitive impairment associated with cerebral small vessel disease.

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.

Association between remnant cholesterol and arterial stiffness in a Chinese community-based population: A cross-sectional study.

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.

Comparison of carotid-femoral and brachial-ankle pulse wave velocity in association with carotid plaque in a Chinese community-based population.

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.

Metanephrine and normetanephrine associated with subclinical myocardial injuries in pheochromocytoma and paraganglioma.

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.

Predictive value of 10-year atherosclerotic cardiovascular disease risk equations from the China-PAR for new-onset lower extremity peripheral artery disease.

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.

Association of remnant cholesterol and lipid parameters with new-onset carotid plaque in Chinese population.

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.

Effects of Acupuncture in Ischemic Stroke Rehabilitation: A Randomized Controlled Trial.

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.

Pervasive translation of circular RNAs driven by short IRES-like elements.

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.

Left atrial phasic function remodeling during its enlargement: a two-dimensional speckle-tracking echocardiography study.

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.

Prevalence and characteristics of cannabis-induced toxicoses in pets: Results from a survey of veterinarians in North America.

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.

Effects of Acupuncture Combined with Rehabilitation on Chronic Pelvic Pain Syndrome in Females: A Meta-Analysis Running Head-Acupuncture Combined with Rehabilitation on Chronic Pelvic Pain.

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.

Associations between remnant lipoprotein cholesterol and central systolic blood pressure in a Chinese community-based population: a cross-sectional study.

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.

Study of circular RNA translation using reporter systems in living cells.

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.

Prognostic value of tumor length and diameter for esophageal squamous cell cancer patients treated with definitive (chemo)radiotherapy: Potential indicators for nonsurgical T staging.

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.

Analysis of definitive chemo-radiotherapy for esophageal cancer with supra-clavicular node metastasis based on CT in a single institutional retrospective study: a propensity score matching analysis.

BACKGROUND: The prognostic value of supra-clavicular lymph node (SCLN) metastases in esophageal cancer (EC) is still not clear. METHOD: From January 2009 to December 2015, a survival analysis was performed to retrospectively identify the prognostic value of SCLN metastasis on survival on 751 patients with EC treated with definitive chemo-radiotherapy (dCRT). RESULTS: The median follow-up duration for living patients was 56.6 months. The median overall survival (OS) for all patients was 16.6 months. Patients with SCLN metastasis had a much poorer prognosis for OS (χ2 = 17.342, P < 0.001), distant metastasis-free survival (DMFS) (χ2 = 24.793, P < 0.001) and progression-free survival (PFS) (χ2 = 25.802, P < 0.001) than those without SCLN metastasis. The same results were found after propensity score matching. Nonetheless, the prognosis of patients with cervical or upper thoracic EC metastasis in SCLN was better than those of patients with middle or lower thoracic EC metastasis in SCLN for OS (χ2 = 4.516, P = 0.038), DMFS (χ2 = 8.326, P = 0.004) and PFS (χ2 = 6.255, P = 0.012). Univariate analysis showed that gender, middle or lower thoracic EC with SCLN metastasis, tumor length, tumor diameter, concurrent chemo-radiotherapy (CCR) and number of lymph nodes were prognostic factors for PFS. Gender, age, middle or lower thoracic EC with SCLN metastasis, tumor diameter, tumor length, and number of lymph nodes were prognostic factors for DMFS. According to the multivariate analysis, only middle or lower thoracic EC with SCLN metastasis and number of lymph nodes were independent prognostic factors for DMFS and PFS. CONCLUSION: For patients with cervical or upper thoracic EC, metastasis in SCLN should be considered to be regional lymph nodes and treated with curative intent if the total number of lymph nodes is limited. However, for patients with middle or lower thoracic EC, metastasis should be considered to be a higher level N stage or M1 stage, and it is thus necessary to provide consolidation chemotherapy after dCRT.

Glia maturation factor-ß: a potential therapeutic target in neurodegeneration and neuroinflammation.

Glia maturation factor-ß (GMFB) is considered to be a growth and differentiation factor for both glia and neurons. GMFB has been found to be upregulated in several neuroinflammation and neurodegeneration conditions. It may function by mediating apoptosis and by modulating the expression of superoxide dismutase, granulocyte-macrophage colony-stimulating factor, and neurotrophin. In this review, we mainly discussed the role of GMFB in several neuroinflammatory and neurodegenerative diseases. On review of the literature, we propose that GMFB may be a promising therapeutic target for neuroinflammatory and neurodegenerative diseases.

[The method and application to construct experience recommendation platform of acupuncture ancient books based on data mining technology].

OBJECTIVE: To construct a knowledge platform of acupuncture ancient books based on data mining technology, and to provide retrieval service for users. METHODS: The Oracle 10 g database was applied and JAVA was selected as development language; based on the standard library and ancient books database established by manual entry, a variety of data mining technologies, including word segmentation, speech tagging, dependency analysis, rule extraction, similarity calculation, ambiguity analysis, supervised classification technology were applied to achieve text automatic extraction of ancient books; in the last, through association mining and decision analysis, the comprehensive and intelligent analysis of disease and symptom, meridians, acupoints, rules of acupuncture and moxibustion in acupuncture ancient books were realized, and retrieval service was provided for users through structure of browser/server (B/S). RESULTS: The platform realized full-text retrieval, word frequency analysis and association analysis; when diseases or acupoints were searched, the frequencies of meridian, acupoints (diseases) and techniques were presented from high to low, meanwhile the support degree and confidence coefficient between disease and acupoints (special acupoint), acupoints and acupoints in prescription, disease or acupoints and technique were presented. CONCLUSIONS: The experience platform of acupuncture ancient books based on data mining technology could be used as a reference for selection of disease, meridian and acupoint in clinical treatment and education of acupuncture and moxibustion.

Assessment of reporting quality in randomised controlled trials of acupuncture for post-stroke rehabilitation using the CONSORT statement and STRICTA guidelines.

OBJECTIVES: To evaluate the completeness of reporting of randomised controlled trials (RCTs) of acupuncture for post-stroke rehabilitation in order to provide information to facilitate transparent and more complete reporting of acupuncture RCTs in this field. METHODS: Multiple databases were searched from their inception through September 2015. Quality of reporting for included papers was assessed against a subset of criteria adapted from the Consolidated Standards for Reporting Trials (CONSORT) 2010 statement and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines. Each item was scored 1 if it was reported, or 0 if it was not clearly stated. Descriptive statistical analysis was performed. Cohen's κ-statistics were calculated to assess agreement between the two reviewers. RESULTS: A total of 87 RCTs were included in the full text. Based on CONSORT, good reporting was evident for items ''Randomised' in the title or abstract', 'Participants', 'Statistical methods', 'Recruitment', 'Baseline data', and 'Outcomes and estimation', with positive rates >80%. However, the quality of reporting for the items 'Trial design', 'Outcomes', 'Sample size', 'Allocation concealment', 'Implementation', 'Blinding', 'Flow chart', 'Intent-to-treat analysis', and 'Ancillary analyses' was very poor with positive rates <10%. Based on STRICTA, the items 'Number of needle insertions per subject per session', 'Responses sought', and 'Needle type' had poor reporting with positive rates <50%. Substantial agreement was observed for most items and good agreement was observed for some items. CONCLUSIONS: The reporting quality of RCTs in acupuncture for post-stroke rehabilitation is unsatisfactory and needs improvement.