Processing neutral tone under the non-attentional condition: a mismatch negativity study.

The neutral tone is a unique tone form in Mandarin as it distinguishes from four canonical tones or full tones on the one hand and integrates phonetic, morphological, syntactical and prosodic information on the other hand. Research to date has been focusing on its unique and variant acoustic features. However, little is known about how native Mandarin speakers process such a unique tone. In the present study, the mismatch negativity was used to explore the comparison-based pre-attentive change detection of Mandarin neutral tone. The mismatch negativity at the time window of 400-800 ms post-first-tone onset was obtained by subtracting event-related potentials to standard neutral tone from event-related potentials to a deviant natural tone. The source analysis of mismatch negativity showed the cortex generator was located at the left temporal lobe. The data suggest that Chinese native speakers process neutral tone automatically under non-attentional conditions, as revealed by the mismatch negativity data aligned with a neutral tone, and that neutral tone does exist as an automatically recognizable one in native Mandarin speakers' tone system.

[Comparison of early clinical outcomes between SuperCap and direct anterior approaches for total hip arthroplasty].

OBJECTIVE: To compare the short-term clinical efficacy of SuperCap approach and direct anterior approach in total hip arthroplasty. METHODS: Clinical data of 70 patients who underwent minimally invasive SuperCap approach and DAA THA in January 2016 to June 2017 were retrospective analyzed. These patients were divided into two groups:SuperCap approach group(SuperCap group) and direct anterior approach group(DAA group). There were 15 males and 15 females in SuperCap group, aged from 45 to 71 years old, and the follow-up time ranged from 24 to 30 months. There were 24 males and 16 females in Group B, aged from 51 to 76 years and the follow-up time ranged from 24 to 36 months. Hemoglobin level of the 3rd day after operation, transfusion rate, acetabular abduction angle, anteversion angle and creatine kinase level of the 3rd day after operation, Harris score of 3 months and the last time, VAS score of 1 week and the last time were recorded and compared. Complications were recorded at the final follow-up. RESULTS: All patients were followed up, the follow-up time of SuperCap group ranged from 24 to 30 months, that of DAA group ranged from 24 to 36 months. No significant differences were found in hemoglobin level on the 3rd day after operation, transfusion rate, Harris score or VAS score between two group (P>0.05). There was no significant difference in Harris score between 3 months after operation and the final follow-up in both groups (P>0.05). There were no significant difference in VAS scores of 6 weeks after operation and on the final follow-up neither(P>0.05). The level of creatine kinase in SuperCap group was significant lower than that in DAA group(P<0.05). Until the final follow-up, there was no significant difference in the incidence of complications between the two groups(P>0.05). CONCLUSION: The clinical effect of minimally invasive SuperCap approach after total hip arthroplasty is comparable to that of DAA approach with less soft tissue injury. Patients can recover rapidly after operation and it is a safe and effective surgical approach for surgeons with short learning curve.

Negative feedback of SNRK to circ-SNRK regulates cardiac function post-myocardial infarction.

A limited delivery of oxygen and metabolic substrate to the heart caused by myocardial infarction (MI) impairs the cardiac function, and often results in heart failure. Here, we identified a circRNA (circ-SNRK) from SNRK (sucrose nonfermenting 1-related kinase, which can increase the cardiac mitochondrial efficiency) in cardiomyocytes (CMs). Circ-SNRK can sponge the miR-33 and in turn improved the ATP synthesis via SNRK, proving the existence of circ-SNRK - miR-33 - SNRK axis. Furthermore, we found that protein NOVA1 (NOVA alternative splicing regulator 1) could accelerate the circ-SNRK formation; a cleaved peptide (~55 kDa) from SNRK enters the nucleus and blocks the cyclization of circ-SNRK via binding to NOVA1. The aforementioned negative feedback of SNRK to circ-SNRK limited the SNRK at a proper level, and inhibited the protective role of circ-SNRK in ischemic heart. In addition, our in vivo experiment indicated that the overexpression of exogenic circ-SNRK could break this loop and improves the cardiac function post-MI in rats. Together, our results demonstrated that the negative loop of circ-SNRK with SNRK regulates the energy metabolism in CMs, thus might be a potential therapeutic target for heart failure.

Pseudobullous pilomatricoma: A rare variant of pilomatricoma.

Pilomatricoma (PM; calcifying epithelioma of Malherbe) is an uncommon adnexal tumour originating from the matrix of the hair follicles. Bullous appearance is a rare variant of PM, and its pathogenesis remains unclear. Here, we present a case of a 17-year-old girl with a pseudobullous PM on the right shoulder. Lymphatic dilatation and collagen disorder were histopathologically observed in this case, which may provide clues to elucidate the pathogenesis of pseudobullous PM.

Preoperative Heart Rate Variability During Sleep Predicts Vagus Nerve Stimulation Outcome Better in Patients With Drug-Resistant Epilepsy.

Objective: Vagus nerve stimulation (VNS) is an adjunctive and well-established treatment for patients with drug-resistant epilepsy (DRE). However, it is still difficult to identify patients who may benefit from VNS surgery. Our study aims to propose a VNS outcome prediction model based on machine learning with multidimensional preoperative heart rate variability (HRV) indices. Methods: The preoperative electrocardiography (ECG) of 59 patients with DRE and of 50 healthy controls were analyzed. Responders were defined as having at least 50% average monthly seizure frequency reduction at 1-year follow-up. Time domain, frequency domain, and non-linear indices of HRV were compared between 30 responders and 29 non-responders in awake and sleep states, respectively. For feature selection, univariate filter and recursive feature elimination (RFE) algorithms were performed to assess the importance of different HRV indices to VNS outcome prediction and improve the classification performance. Random forest (RF) was used to train the classifier, and leave-one-out (LOO) cross-validation was performed to evaluate the prediction model. Results: Among 52 HRV indices, 49 showed significant differences between DRE patients and healthy controls. In sleep state, 35 HRV indices of responders were significantly higher than those of non-responders, while 16 of them showed the same differences in awake state. Low-frequency power (LF) ranked first in the importance ranking results by univariate filter and RFE methods, respectively. With HRV indices in sleep state, our model achieved 74.6% accuracy, 80% precision, 70.6% recall, and 75% F1 for VNS outcome prediction, which was better than the optimal performance in awake state (65.3% accuracy, 66.4% precision, 70.5% recall, and 68.4% F1). Significance: With the ECG during sleep state and machine learning techniques, the statistical model based on preoperative HRV could achieve a better performance of VNS outcome prediction and, therefore, help patients who are not suitable for VNS to avoid the high cost of surgery and possible risks of long-term stimulation.

A three-microRNA panel in serum as novel biomarker for papillary thyroid carcinoma diagnosis.

BACKGROUND: Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC). METHODS: The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature. RESULTS: Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease. CONCLUSION: We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.

MicroRNA-26a reduces synovial inflammation and cartilage injury in osteoarthritis of knee joints through impairing the NF-κB signaling pathway.

Objective: Inflammation is closely implicated in the process of osteoarthritis (OA) and affects disease progression and pain. Herein, the present study explored the effect of microRNA-26a (miR-26a) on the synovial inflammation and cartilage injury in OA, with the involvement with the NF-κB signaling pathway.Methods: Rat models of OA were established by anterior cruciate ligament transection, which were then treated with miR-26a mimics/inhibitors or BMS-345541 (inhibitor of NF-κB pathway). The expression of miR-26a and activator proteins of NF-κB pathway (P-IκBα and P-P65) in synovial tissues was determined. Hematoxylin-eosin (HE) staining was adopted to observe pathological changes of knee joints, synovial tissues, and cartilage of femoral condyle. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the apoptosis of synoviocytes and chondrocytes.Results: Poorly expressed miR-26a and increased protein levels of P-IκBα and P-P65 were identified in synovial tissues of OA rats. Besides, OA rats showed obvious synovial tissue hyperplasia, inflammation and cartilage injury of femoral condyle, as well as increased inflammation and cartilage injury scores, and apoptosis of synoviocytes and chondrocytes. In response to miR-26a mimics, protein levels of P-IκBα and P-P65 were reduced; meanwhile, synovial tissue hyperplasia, inflammation and cartilage injury of femoral condyle were ameliorated, with decreased inflammation and cartilage injury scores, and apoptosis of synoviocytes and chondrocytes.Conclusion: MiR-26a suppressed the activation of the NF-κB signaling pathway, by which mechanism the synovial inflammation and cartilage injury in OA rats were alleviated.

Values of aortic dissection detection risk score combined with ascending aorta diameter >40 mm for the early identification of type A acute aortic dissection.

BACKGROUND: Type A acute aortic dissection (A-AAD), involving the ascending aorta, is a life-threatening disease. To detect A-AAD early and rapidly in patients with acute chest pain, especially in patients with acute myocardial infarction (AMI) secondary to A-AAD, we investigated values of combined use of the risk score and the ascending aorta diameter >40 mm for the early identification of A-AAD. METHODS: Our study retrospectively encompassed 239 patients with acute chest pain on admission to our hospital between July 2010 and December 2016. The risk score was calculated according to the aortic dissection detection (ADD) risk score system, and the ascending aorta diameter was accurately obtained from the transthoracic echocardiography (TTE). RESULTS: A risk score ≥1 had an excellent sensitivity of 94.9% and a fair negative predictive value (NPV) of 77.8%, with a poor specificity of 8.7% and a positive predictive value (PPV) of 33.5% for the diagnosis of A-AAD. A risk score ≥2 had an excellent specificity of 91.3% and a fair NPV of 73.1%, whereas it had a lower sensitivity of 30.8% and a PPV of 63.2%. A risk score ≥1, combined with an ascending aorta diameter >40 mm, had a sensitivity, a specificity, a PPV, and an NPV of 84.6%, 87.6%, 76.7%, and 92.2% for the diagnosis of A-AAD, respectively. The combined use of a risk score ≥2 and an ascending aorta diameter >40 mm had an excellent specificity of 98.1% and a PPV of 86.4%, a fair NPV of 72.8%, and a poor sensitivity of 24.4% for the detection of A-AAD. Moreover, the omission diagnostic rate for A-AAD was significantly decreased from 33.3% to 7.4% using a risk score ≥1 combined with an ascending aorta diameter >40 mm in patients with AMI secondary to A-AAD. CONCLUSIONS: The combined use of an ADD risk score ≥1 and an ascending aorta diameter >40 mm was highly indicative of A-AAD in patients presenting with acute chest pain, especially in patients with AMI secondary to A-AAD, which urgently needed computed tomography angiography (CTA) or magnetic resonance imaging (MRI) to confirm the diagnosis of A-AAD.

Inhibition of hepatocellular carcinoma growth by antisense oligonucleotides to type I insulin-like growth factor receptor in vitro and in an orthotopic model.

AIM: The type I insulin-like growth factor receptor (IGF-IR) is overexpressed in many tumors including human hepatocellular carcinoma (HCC). It is a critical signaling molecule for tumor cell proliferation and survival. In the present study, IGF-IR expression was down-regulated by phosphorothioate antisense oligonucleotides (AS[S]ODN) to evaluate their specific effects on growth of hepatoma cells in vitro and in vivo. METHODS: HepG2 cells were transfected with different doses of AS[S]ODN, sense [S]ODN, mismatch [S]ODN, or Lipofectin for 72 h, and cell proliferation was analyzed by MTS assay. In vivo, an orthotopic transplant model of HCC was established in nude mice, which were then injected with AS[S]ODN, sense [S]ODN, 5-fluorouracil or saline. At the endpoint of treatment, the tumors were excised and evaluated. RESULTS: Compared to sense and mismatched oligonucleotides, AS[S]ODN targeting to IGF-IR mRNA significantly inhibited hepatoma cell lines HepG2 proliferation and IGF-IR expression at both mRNA and protein levels. The in vivo results showed that systemic treatment also resulted in significant inhibition in tumor growth. Tumor growth in mice treated with AS[S]ODN (50 and 75 mg/kg per day) was significantly inhibited (71.81% and 61.74%, respectively) compared to the saline-treated group (P < 0.01) in a dose-dependent manner. The antitumor effect of IGF-IR AS[S]ODN was associated with down-regulation of IGF-IR in tumor xenografts. Furthermore, IGF-IR AS[S]ODN prevented liver recurrence tumor growth and metastasis in the lung, showing a dose-dependent response. The level of serum alpha-fetoprotein in AS[S]ODN-treated groups was also decreased in a dose-dependent manner, and a good correlation was observed between tumor volume and serum alpha-fetoprotein concentration. CONCLUSIONS: These data suggest that IGF-IR AS[S]ODN can effectively and specifically inhibit HCC growth in vitro and in vivo. Blockage of IGF-IR expression could be a promising therapeutic approach for the management of patients with HCC.

The missed diagnosis of aortic dissection in patients with acute myocardial infarction: a disastrous event.

We present a case of aortic dissection (AD) accompanied by acute myocardial infarction (AMI). For patients with AMI, the missed diagnosis of AD could be catastrophic. Therefore, we strongly recommend that portable echocardiography should be routinely available in the ambulance. Moreover, multicenter studies concerning the cost-benefit ratio of portable echocardiography routinely available in the ambulance should urgently be considered.

Pathogenicity of a currently circulating Chinese variant pseudorabies virus in pigs.

AIM: To test the pathogenicity of pseudorabies virus (PRV) variant HN1201 and compare its pathogenicity with a classical PRV Fa strain. METHODS: The pathogenicity of the newly-emerging PRV variant HN1201 was evaluated by different inoculating routes, virus loads, and ages of pigs. The classical PRV Fa strain was then used to compare with HN1201 to determine pathogenicity. Clinical symptoms after virus infection were recorded daily and average daily body weight was used to measure the growth performance of pigs. At necropsy, gross pathology and histopathology were used to evaluate the severity of tissue damage caused by virus infection. RESULTS: The results showed that the efficient infection method of RPV HN1201 was via intranasal inoculation at 10(7) TCID50, and that the virus has high pathogenicity to 35- to 127-d old pigs. Compared with Fa strain, pigs infected with HN1201 showed more severe clinical symptoms and pathological lesions. Immunochemistry results revealed HN1201 had more abundant antigen distribution in extensive organs. CONCLUSION: All of the above results suggest that PRV variant HN1201 was more pathogenic to pigs than the classical Fa strain.

SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity.

The tumor suppressor p53-related p73 shares significant amino-acid sequence identity with p53. Like p53, p73 recognizes canonical p53 DNA-binding sites and activates p53-responsive target genes and induces apoptosis. Moreover, SIRT1 binds to p53 while repressing the expression of their target genes. Here, we report that SIRT1 also binds to p73 and suppresses p73-dependent transcriptional activity. SIRT1 in human cells reduces the transcriptional activity of p73, and partly inhibits apoptosis induced by p73. Furthermore, SIRT1 can deacetylate p73 protein acetylation both in vivo and in vitro. Collectively, these data suggest that SIRT1 can modulate p73 activity via deacetylation.