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1-Nitropyrene (1-NP) is a neurodevelopmental toxicant. This study was to evaluate the impact of exposure to 1-NP after weaning on anxiety-like behavior. Five-week-old mice were administered with 1-NP (0.1 or 1 mg/kg) daily for 4 weeks. Anxiety-like behaviour was measured using elevated-plus maze (EPM) and open field test (OFT). In EPM test, time spending in open arm and times entering open arm were reduced in 1-NP-treated mice. In OFT test, time spent in the center region and times entering the center region were diminished in 1-NP-treated mice. Prefrontal dendritic length and number of dendrite branches were decreased in 1-NP-treated mice. Prefrontal PSD95, an excitatory postsynaptic membrane protein, and gephyrin, an inhibitory postsynaptic membrane protein, were downregulated in 1-NP-treated mice. Further analysis showed that peripheral steroid hormones, including serum testosterone (T) and estradiol (E 2), testicular T, and ovarian E 2 , were decreased in 1-NP-treated mice. Interestingly, T and E 2 were diminished in 1-NP-treated prefrontal cortex. Prefrontal T and E 2 synthases were diminished in 1-NP-treated mice. Mechanistically, GCN2-eIF2α, a critical pathway that regulates ribosomal protein translation, was activated in 1-NP-treated prefrontal cortex. These results indicate that exposure to 1-NP after weaning induces anxiety-like behaviour partially by inhibiting steroid hormone synthesis in prefrontal cortex. [Display omitted] • Adolescent exposure to 1-nitropyrene (1-NP) induces anxiety-like behavior. • 1-NP reduces dendritic length and synaptic proteins in prefrontal cortex. • 1-NP reduces steroid hormone synthases and steroid hormones in prefrontal cortex. • GCN2-eIF2α signal mediates 1-NP-evoked reduction of steroid hormone synthases. • Prefrontal steroid hormone reduction mediates 1-NP-evoked anxiety-like behavior. [ABSTRACT FROM AUTHOR]

Purpose: One-year mortality is vital for elderly oncologic patients undergoing surgery. Recent studies have demonstrated that sarcopenia can predict outcomes after major abdominal surgeries, but the association of sarcopenia and 1-year mortality has never been investigated in a prospective study. Methods: We conducted a prospective study of elderly patients (≥65 years) who underwent curative gastrectomy for gastric cancer from July 2014 to July 2015. Sarcopenia was determined by the measurements of muscle mass, handgrip strength, and gait speed. Univariate and multivariate analyses were used to identify the risk factors associated with 1-year mortality. Results: A total of 173 patients were included, in which 52 (30.1 %) patients were identified as having sarcopenia. Twenty-four (13.9 %) patients died within 1 year of surgery. Multivariate analysis showed that sarcopenia was an independent risk factor for 1-year mortality. Area under the receiver operating characteristic curve demonstrated an increased predictive power for 1-year mortality with the inclusion of sarcopenia, from 0.835 to 0.868. Solely low muscle mass was not predictive of 1-year mortality in the multivariate analysis. Conclusions: Sarcopenia is predictive of 1-year mortality in elderly patients undergoing gastric cancer surgery. The measurement of muscle function is important for sarcopenia as a preoperative assessment tool. [ABSTRACT FROM AUTHOR]

Right heart thrombus (RHT) is a rare but life‐threatening condition in acute pulmonary embolism (APE) without clear management guidelines. This study aimed to address the clinical characteristics and outcomes of RHT‐APE in Chinese patients. In this study, 17 RHT‐APE and 329 non‐RHT‐APE patients, who were diagnosed between September 2015 and August 2019, were retrospectively recruited with the median follow‐up was 360 days. The overall prevalence of RHT was 4.91% in APE. Its prevalence increased along the increase of APE risk stratifications. Comparisons showed that with higher proportion of male gender and younger age, RHT‐APE patients also had worse hemodynamic instability and heart function, and higher risk stratification levels than non‐RHT‐APE patients. After adjusting by age and gender, multivariate logistic regression analysis found high/intermediate‐high risk stratification, decreased right ventricular (RV) motion, NT‐proBNP >600 pg/mL, and RV dysfunction were risk factors for RHT. Kaplan−Meier analysis showed non‐RHT had better prognosis than RHT patients (30‐day survival: log‐rank: p < 0.001; 90‐day survival: log‐rank: p = 0.002). The multivariate logistic regression analysis showed RHT was an independent risk factor for 30‐day mortality in APE. The subgroup analysis showed RHT would result in worse outcomes in patients who already had higher APE early mortality risk. RHT would increase the risk of 30‐ and 90‐day mortality in APE. More attention should be paid to young male APE patients with decreased RV motion, NT‐proBNP >600 pg/mL, RV dysfunction, or high level of risk stratification, to exclude the coexistence of RHT. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1‐nitropyrene (1‐NP), a key component of motor vehicle exhaust, on autism‐like behaviors in a mouse model. Three‐chamber test finds that prenatal 1‐NP exposure causes autism‐like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1‐NP‐exposed weaning pups. Immunofluorescence finds that prenatal 1‐NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1‐NP exposure retards tangential migration of GAD67‐positive interneurons and downregulates interneuron migration‐related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1‐NP exposure reduces hydroxymethylation of interneuron migration‐related genes through inhibiting ten‐eleven translocation (TET) activity in fetal forebrain. Supplement with alpha‐ketoglutarate (α‐KG), a cofactor of TET enzyme, reverses 1‐NP‐induced hypohydroxymethylation at specific sites of interneuron migration‐related genes. Moreover, α‐KG supplement alleviates 1‐NP‐induced migration retardation of interneurons in fetal forebrain. Finally, maternal α‐KG supplement improves 1‐NP‐induced autism‐like behaviors in weaning offspring. In conclusion, prenatal 1‐NP exposure causes autism‐like behavior partially by altering DNA hydroxymethylation of interneuron migration‐related genes in developing brain. [ABSTRACT FROM AUTHOR]

The inhaled sevoflurane (sevo) is known to protect against myocardial ischemia/reperfusion (I/R) injury (MIRI), in which the functions of microRNAs (miRNAs) have been uncovered. However, the effect of sevo regulating miR-204 on this disease remains unknown. This research aims to explore the roles of sevo and miR-204 in the progression of MIRI. The MIRI mice models induced by coronary artery ligation were treated by sevo, miR-204 mimics or silenced coactosin-like protein-1 (Cotl1). The pathology of mice myocardial tissues, apoptosis and ultrastructure of cardiomyocytes were observed. The expression of miR-204, Cotl1, Bax and Bcl-2 was determined. The contents of oxidative stress-related factors and inflammatory factors in mouse myocardial tissues were assessed, and the serum levels of indicators that correlated with myocardial infarction were determined as well. The target relation between miR-204 and Cotl1 was confirmed. MiR-204 was down-regulated, and Cotl1 was up-regulated in myocardial tissues of MIRI mice, and Cotl1 was targeted by miR-204. Sevo, elevated miR-204 and inhibited Cotl1 could promote cardiac function of MIRI mice, and protect myocardial tissue against MIRI by repressing the cardiomyocyte apoptosis, oxidative stress and inflammation reaction in MIRI mice. We found that sevo could up-regulate miR-204 to ameliorate MIRI in mice by inhibiting Cotl1 expression, which may provide candidates for the MIRI treatment. [ABSTRACT FROM AUTHOR]

• Multiple arteries can be involved simultaneously or successively over the course of BD. • Aneurysm/dilation is more common in the aorta but stenosis/occlusion is more prevalent in aortic branches. • The 5- and 10-year survival rates of BD patients with arterial involvement were 87.4 % and 84.1 %, respectively. • Cardiac involvement and pulmonary artery aneurysm/dilation were independent prognostic factors of BD patients with arterial involvement. To investigate the imaging characteristics and prognostic factors for the long-term survival of Behcet's disease (BD) with arterial involvement. In this retrospective study, BD patients with arterial involvement were identified from January 2003 to January 2020. Arterial lesions were detected by ultrasonography, traditional arteriography, and/or computed tomography angiography (CTA). Cox proportional hazards regression analyses were performed to identify the prognostic factors. Totally, 84 BD patients with arterial involvement were identified (73.8 % males). The mean age at BD diagnosis was 39.1 ± 13.1 years. Arterial involvement was the initial manifestation in 33.3 % of the patients, and the median time from BD diagnosis to arterial involvement was 6 (IQR 1–15.5) years for the rest of patients. Systemic artery involvement and pulmonary artery involvement (PAI) were found in 64 and 27 patients, respectively. Approximately 94.0 % (79/84) of the patients had more than one artery involved concurrently or successively during the course of BD. Aneurysm/dilation was the most prevalent lesion in the aorta (76.0 %), while stenosis/occlusion was the main lesion of the coronary artery (90.9 %) and other aortic branches (74.5 %). Pulmonary hypertension was found in 70.4 % (19/27) of patients with PAI. The 5- and 10-year survival rates of BD patients with arterial involvement were 87.4 % and 84.1 %, respectively. Cardiac involvement (HR: 4.34) and pulmonary artery aneurysm/dilation (HR: 4.89) were independently associated with mortality. Arterial lesions associated with BD usually involve multiple arteries and manifest differently in different types of arteries. Cardiac involvement and pulmonary artery aneurysm/dilation are independent prognostic factors of BD patients with arterial involvement. [ABSTRACT FROM AUTHOR]

1-Nitropyrene (1-NP), a typical nitro-polycyclic aromatic hydrocarbon, is a developmental toxicant. This study was to evaluate gestational 1-NP-induced anxiety-like behavior in male adult offspring. Pregnant mice were orally administered to 1-NP daily throughout pregnancy. Anxiety-like behaviors, as determined by Elevated Plus-Maze (EPM) and Open-Field Test (OFT), were showed in male adult offspring whose mothers were exposed to 1-NP. Gestational 1-NP exposure reduced dendritic arborization, dendritic length and dendritic spine density in ventral hippocampus of male adult offspring. Additional experiments showed that gephyrin, an inhibitory synaptic marker, was reduced in fetal forebrain and hippocampus in male adult offspring. Nrg1 and Erbb4, two gephyrin-related genes, were reduced in 1-NP-exposed fetuses. Accordingly, 5hmC contents in two CpG sites (32008909 and 32009239) of Nrg1 gene and three CpG sites (69107743, 69107866 and 69107899) of Erbb4 gene were decreased in 1-NP-exposed fetuses. Mechanistically, ten-eleven translocation (TET) activity and alpha-ketoglutarate (α-KG) content were decreased in 1-NP-exposed fetal forebrain. Supplementation with α-KG alleviated 1-NP-induced downregulation of gephyrin-related genes, prevented hippocampal synaptic damage, and improved anxiety-like behavior in male adult offspring. These results indicate that early-life 1-NP exposure causes anxiety-like behavior in male adulthood partially by altering hippocampal epigenetic reprogramming of synaptic plasticity. [Display omitted] • Gestational 1-NP exposure induces anxiety-like behavior in male adult offspring. • 1-NP impairs hippocampal synaptic plasticity. • 1-NP reduces 5hmC of inhibitory synaptic related genes by inhibiting TET activity. • α-KG reverses epigenetic reprogramming of hippocampal synaptic plasticity. • α-KG alleviates 1-NP-induced anxiety-like behavior in male adult offspring. [ABSTRACT FROM AUTHOR]

Objective This meta-analysis aimed to compare the diagnostic accuracy of diffusion-weighted magnetic resonance imaging ( DW-MRI) and fluorodeoxyglucose-positron emission tomography ( FDG-PET) or FDG-PET/computed tomography ( CT) in evaluating and predicting pathological response to preoperative neoadjuvant chemoradiotherapy ( NCRT) in patients with rectal cancer. Methods A comprehensive literature research was conducted to identify the relevant studies for this meta-analysis. Combined sensitivity, specificity, positive ( PPV) and negative predictive values ( NPV) were calculated. Results A total of 33 studies including 1564 patients met the inclusion criteria. The pooled sensitivity (81% [95% CI 74-86%] vs 85% [95% CI 75-91%]) and NPV (80% [95% CI 68-89%] vs 91% [95% CI 80-95%]) for FDG-PET or FDG-PET/CT were significantly lower than those for DW-MRI ( P < 0.05). No differences were observed in pooled specificity and PPV between DW-MRI and FDG-PET or FDG-PET/CT. Further subgroup analyses showed that DW-MRI had higher sensitivity on adenocarcinomas alone than on those including mucinous-type adenocarcinomas (92% [95% CI 83-99%] vs 76% [95% CI 63-90%], P = 0.00). Conclusions DW-MRI is superior to FDG-PET or FDG-PET/CT in predicting and evaluating pathological responses to preoperative NCRT in patients with rectal cancer. However, its relatively low specificity and PPV limit its application in clinic, making it currently inappropriate to monitor such patients, especially those with mucinous-type rectal adenocarcinomas. [ABSTRACT FROM AUTHOR]

Objectives: Right ventricular (RV) function is considered the major determinant of prognosis in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this meta-analysis was to evaluate RV remodelling and function following balloon pulmonary angioplasty (BPA) in patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension (PH) after pulmonary endarterectomy (PEA).Methods: We reviewed all studies evaluating RV function by cardiac magnetic resonance (CMR) and/or echocardiography pre- and post-BPA from PubMed/Medline prior to 15 December 2019. Ten (299 patients) of the 29 studies retrieved met the inclusion criteria: 5 CMR and 5 echocardiography studies. The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines.Results: Pooled data from CMR studies revealed BPA resulted in a significantly decreased RV end-diastolic volume index (weighted mean difference (WMD) - 28.33 ml/m2, p < 0.00001) and RV end-systolic volume index (WMD - 29.06 ml/m2, p < 0.00001) accompanied by an increased RV ejection fraction (RVEF, WMD 8.97%, p < 0.00001). Data from the echocardiography studies showed BPA resulted in decreased RV basal diameter (WMD - 0.37 cm, p = 0.0009) and an increase of RV fractional area change (WMD 5.97 %, p = 0.003), but improvements of tricuspid annular plane systolic excursion (TAPSE) and S' were not significant.Conclusions: BPA improves RVEF and decreases RV volumes in patients with inoperable CTEPH or persistent/recurrent PH after PEA.Key Points: • Balloon pulmonary angioplasty improves RVEF and decreases RV volumes in patients with inoperable CTEPH or persistent/recurrent PH after PEA. [ABSTRACT FROM AUTHOR]

Reportedly, nestin was re-expressed in proliferative synthetic-type pulmonary artery smooth muscle cells (PASMCs) and obligatory for PASMC proliferation in pulmonary arterial hypertension (PAH). Accordingly, nestin is increased in pulmonary vascular lesions of congenital heart disease (CHD)-associated PAH patients. We tested the hypothesis whether nestin was re-expressed in proliferative synthetic-type PASMCs and associated with pulmonary vascular remodeling in CHD-PAH. Nestin expression was tested using lung tissues from CHD-PAH patients and monocrotaline (MCT) plus aortocaval (AV) shunt-induced PAH rats, human PASMCs (HPASMCs), and pulmonary artery endothelial cells (PAECs) and PASMCs from MCT-AV-induced PAH rats. The role and possible mechanism of nestin on HPASMC proliferation, apoptosis, cell cycle and migration were investigated by assays of CCK-8, EdU, TUNEL, flow cytometry, transwell chamber and immunoblotting assays. Nestin was solely expressed in proliferative synthetic-type PASMCs, but rarely detected in PAECs. Nestin was barely detected in normal pulmonary arterioles and occlusive pulmonary vascular lesions. Its expression was robustly increased in developing pulmonary vasculature, but returned to normal levels at the late stage of pulmonary vascular remodeling in lung tissues from CHD-PAH patients and MCT-AV-induced PAH rats. Besides, nestin peaks were consistent with the histological features in lung tissues of MCT-AV-induced PAH rats. Moreover, nestin overexpression effectively promoted HPASMC phenotypic transformation, proliferation, apoptosis resistance and migration via enhancing Wnt/β-catenin activation. These data indicated that nestin was re-expressed in proliferative synthetic-type PASMCs and might represent a potential marker of pulmonary vascular remodeling in CHD-PAH. Nestin overexpression effectively promoted HPASMC phenotypic transformation, proliferation, apoptosis resistance and migration via enhancing Wnt/β-catenin activation, which contributes to the progression of pulmonary vascular remodeling in CHD-PAH. Unlabelled Image • Nestin was re-expressed in proliferative synthetic-type PASMCs. • Nestin promoted HPASMC phenotypic transformation. • Nestin modulated Wnt/β-catenin signaling pathway. • Wnt/β-catenin signaling pathway mediated HPASMC phenotypic transformation. [ABSTRACT FROM AUTHOR]

Background: With the increased prevalence of obesity and sarcopenia, those patients with both visceral obesity and sarcopenia were at higher risk of adverse outcomes.Aim: The aim of this study was to ascertain the combined impact of visceral obesity and sarcopenia on short-term outcomes in patients undergoing colorectal cancer surgery.Methods: We conducted a prospective study from July 2014 to February 2017. Patients' demographic, clinical characteristics, physical performance, and postoperative short-term outcomes were collected. Patients were classified into four groups according to the presence of sarcopenia or visceral obesity. Clinical variables were compared. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed.Results: A total of 376 patients were included; 50.8 and 24.5% of the patients were identified as having "visceral obesity" and "sarcopenia," respectively. Patients with sarcopenia and visceral obesity had the highest incidence of total, surgical, and medical complications. Patients with sarcopenia or/and visceral obesity all had longer hospital stays and higher hospitalization costs. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Rectal cancer and visceral obesity were independent risk factors for surgical complications. Age ≥ 65 years and sarcopenia were independent risk factors for medical complications. Laparoscopy-assisted operation was a protective factor for total and medical complications.Conclusion: Patients with both visceral obesity and sarcopenia had a higher complication rate after colorectal cancer surgery. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Laparoscopy-assisted operation was a protective factor. [ABSTRACT FROM AUTHOR]

Background A geriatric assessment is needed to identify high-risk elderly patients with gastric cancer. However, the current geriatric assessment has been considered to be either time-consuming or subjective. The present study aimed to investigate the predictive effect of sarcopenia on the postoperative complications for elderly patients who underwent radical gastrectomy. Materials and methods We conducted a prospective study of patients who underwent radical gastrectomy from August 2014 to December 2015. Computed tomography–assessed lumbar skeletal muscle, handgrip strength, and gait speed were measured to define sarcopenia. Results Sarcopenia was present in 69 of 240 patients (28.8%) and was associated with lower body mass index, lower serum albumin, lower hemoglobin, and higher nutritional risk screening 2002 scores. Postoperative complications significantly increased in the sarcopenic patients (49.3% versus 24.6%, P < 0.001), compared with nonsarcopenic patients. The multivariate analysis demonstrated that sarcopenia (odds ratio: 2.959, 95% CI: 1.629-5.373, P < 0.001) and the Charlson comorbidity index ≥2 (odds ratio: 3.357, 95% CI: 1.144-9.848, P = 0.027) were independent risk factors for postoperative complications. Conclusions Sarcopenia, presented as a new geriatric assessment factor, was a strong and independent risk factor for postoperative complications of elderly patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: T2* relaxation is a primary determinant of image contrast with Gradient echo (GRE) sequences, and it has been widely used across body regions. Purpose: To compare the diagnostic performance of T2* mapping in combination with T2-weighted (T2W) imaging to T2W imaging alone for prostate cancer (PCa) detection. Material and Methods: The study included 31 patients (mean age, 62 ± 3 years; age range, 45-78 years) who underwent magnetic resonance imaging (MRI) at 3.0T and histological examination. Three observers with varying experience levels reviewed T2W imaging alone, T2* mapping alone, and T2W imaging combined with T2* mapping. A five-point scale was used to assess the probability of PCa in each segment on MR images. Statistical analysis was performed using Z tests after adjusting for data clustering. Results: The area under the curve (AUC) of T2W imaging and T2* mapping data (observer 1, 0.93; observer 2, 0.90; observer 3, 0.77) was higher than T2W imaging (observer 1, 0.84; observer 2, 0.79; observer 3, 0.69) for all observers (P < 0.01 in all comparisons). The AUC of T2W imaging and T2* mapping data was higher for observers 1 and 2 than for observer 3 (P < 0.01). The sensitivity and specificity of T2W imaging and T2* mapping data (observer 1, 95%, 85%; observer 2, 90%, 83%; and observer 3, 82%, 63%, respectively) was higher than T2W imaging (observer 1, 78%, 79%; observer 2, 76%, 72%; observer 3, 74%, 51%, respectively) for all observers (P < 0.01 for observer 1; P < 0.01 for observers 2 and 3). Conclusion: The addition of T2* mapping to T2W imaging improved the diagnostic performance of MRI in PCa detection. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the clinical efficacy of using conventional magnetic resonance imaging (MRI) alone and in combination diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting upper urinary tract cancer. Conventional MRI and DW-MRI were performed in 70 patients with suspected UUT cancer and ureteroscopic and histopathologic as well as imaign findings were compared. Results showed that diagnostic accuracy and sensitivity were increased using DW-MRI.

Abstract: Purpose: To evaluate the performance of computed tomographic urography (CTU), static-fluid magnetic resonance urography (static-fluid MRU) and combinations of CTU, static-fluid MRU and diffusion weighted imaging (DWI) in the diagnosis of upper urinary tract cancer. Material and Methods: Between January 2010 and June 2011, patients with suspected UUT cancer underwent CTU, static-fluid MRU and DWI (b =1000s/mm2) within a 1-week period. The diagnostic performances of CTU, static-fluid MRU and combinations of CTU, static-fluid MRU and DWI for upper urinary tract cancer were prospectively evaluated. The ureteroscopic and histopathologic findings were compared with the imaging findings. Results: Compared to static-fluid MRU alone (sensitivity: 76/75%, reader 1/reader 2), combining DWI with MRI can increase the sensitivity (sensitivity: 84/84%, p =0.031/p =0.016) of upper urinary tract cancer diagnosis. CTU had greater sensitivity (95/94%) and accuracy (92/91%) than both static-fluid MRU (sensitivity: p <0.001/p <0.001 and accuracy: 83/81%, p =0.001/p <0.001) and static-fluid MRU with DWI (sensitivity: p =0.023/p =0.039 and accuracy: 87/85%, p =0.042/p =0.049) for the diagnosis of upper urinary tract cancers. Compared with CTU alone, CTU with DWI did not significantly increase sensitivity, specificity or accuracy. However, the diagnostic confidence was improved when the combined technique was used (p =0.031/p =0.024). Moreover, there was no significant change in sensitivity, specificity, accuracy or diagnostic confidence when static-fluid MRU was used in combination with CTU and DWI. Conclusion: Although there is a potential role for static-fluid MRU and static-fluid MRU with DWI in urinary tract imaging, CTU is still the better choice for the diagnosis of upper urinary tract cancer. Combining DWI with CTU can help improve confidence in upper urinary tract cancer diagnoses. [Copyright &y& Elsevier]