Variations in TOR1A were thought to be associated with early-onset isolated dystonia. The variant S287Y (NM_000113.2: c.860C > A, p. Ser287Tyr, rs766483672) was found in our late-onset isolated dystonia patient. This missense variant is adjacent to R288Q (c.863G > A, p. Arg288Gln), which was reported to be associated with isolated dystonia. The potentially pathogenic role of S287Y is not conclusively known.

The mechanism through which death-associated protein kinase 1 (DAPK1) causes hepatocellular carcinoma (HCC) progression remains unclear. In this study, we aimed to identify key proteins that were altered after DAPK1 knockout.

The aim of this study was to investigate the neural plasticity in contralesional cortex and the effects of tongxinluo (TXL) in cerebral ischemic rats.

BACKGROUND Cerebral hemorrhage has been increasingly reported in patients with nephrotic syndrome (NS). However, the clinical features and pathogenesis of NS patients with cerebral hemorrhage remain unclear. MATERIAL AND METHODS From January 2007 to August 2017, continuous NS patients with cerebral hemorrhage at the First Affiliated Hospital of Guangxi Medical University were selected. The clinical manifestations, laboratory measurements, and neurological images of these patients were collected and analyzed. RESULTS Acute cerebral hemorrhage was recorded in 15 of 10 461 NS patients. The average age of these 15 patients (9 males and 6 females) was 50.87±23.27 years old. Among these 15 patients, conventional vascular risk factors were identified in 8 patients, hypoalbuminemia and proteinuria were recorded in all 15 patients, coagulopathy was observed in 9 patients, increased D-dimer level was recorded in 13 patients, hyperlipidemia was recorded in 11 patients, and impaired renal function was recorded in 9 patients. The hemorrhage developed in the lobe (n=9), basal ganglia (n=3), cerebellum (n=2), and cerebral hemisphere (n=1). Eight patients were in a coma on the day the cerebral hemorrhage occurred, while 12 patients had a poor prognosis after 30 days of hemorrhage onset. CONCLUSIONS Poor prognosis was recorded in NS patients with cerebral hemorrhage. Although conventional vascular risk factors have only been identified in 8 patients, biochemical abnormalities (hypoalbuminemia, proteinuria, elevated D-dimer, and hyperlipidemia) were recorded in the majority of these 15 patients. Furthermore, most of the hemorrhages developed in the lobes. Coagulopathy might be the potential pathogenesis of cerebral hemorrhage in NS patients.

To investigate the feasibility and safety of remote ischemic postconditioning (RIPC) in acute ischemic stroke patients after intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis (IVT).

TOR1A plays a very important role in early-onset isolated dystonia. Studying the association between the common variants of this gene and dystonia can help us understand the connection between TOR1A mutations and this disease.

Transcription factor FOXM1 plays a critical role in maintenance of stem cell pluripotency through stimulating the transcription of pluripotency-related genes in mouse pluripotent stem cells. In this study, we have found that the repression of FOXM1 expression is mediated by FOXM1 3'UTR during retinoic acid-induced differentiation of human pluripotent NT2/D1 embryonal carcinoma cells. FOXM1 3'UTR contains a microRNA response element (MRE) for miR-134, which has been shown to attenuate the expression of pluripotency-related genes post-transcriptionally during mouse embryonic stem cell differentiation. We have determined that miR-134 is induced during RA-induced differentiation of NT2/D1 cells and the overexpression of miR-134 represses the expression of FOXM1 protein but not FOXM1 mRNA. Furthermore, the expression of OCT4 is diminished by FOXM1 knockdown and the OCT4 promoter is regulated directly by FOXM1, suggesting that FOXM1 is required for maintaining the expression of OCT4 in NT2/D1 cells. Together, our results suggest that FOXM1 is essential for human pluripotent stem cells and miR-134 attenuates its expression during differentiation.

Butyrylcholinesterase (BChE) has been an important protein used for development of anti-cocaine medication. Through computational design, BChE mutants with ∼2000-fold improved catalytic efficiency against cocaine have been discovered in our lab. To study drug-enzyme interaction it is important to build mathematical model to predict molecular inhibitory activity against BChE. This report presents a neural network (NN) QSAR study, compared with multi-linear regression (MLR) and molecular docking, on a set of 93 small molecules that act as inhibitors of BChE by use of the inhibitory activities (pIC₅₀ values) of the molecules as target values. The statistical results for the linear model built from docking generated energy descriptors were: r(2)=0.67, rmsd=0.87, q(2)=0.65 and loormsd=0.90; the statistical results for the ligand-based MLR model were: r(2)=0.89, rmsd=0.51, q(2)=0.85 and loormsd=0.58; the statistical results for the ligand-based NN model were the best: r(2)=0.95, rmsd=0.33, q(2)=0.90 and loormsd=0.48, demonstrating that the NN is powerful in analysis of a set of complicated data. As BChE is also an established drug target to develop new treatment for Alzheimer's disease (AD). The developed QSAR models provide tools for rationalizing identification of potential BChE inhibitors or selection of compounds for synthesis in the discovery of novel effective inhibitors of BChE in the future.

With the development of medical technique, many medical challenges have been solved. This cross-sectional study was aimed to assess the reliability and validity of a new developed scale for assessing the professionalism of young health care workers.This cross-sectional population-based study was conducted based on cluster sampling method in 2015. The participants were from 2 medical centers of Nantong city of Jiangsu province in China. The internal consistency reliability was assessed using Cronbach's alpha and split-half reliability coefficients. Construct validity was analyzed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Content, convergent, and discriminant validities were also assessed in this study.Total 749 individuals aged 29.09 ± 3.91 years old participated in this investigation. There were 745 valid questionnaires and 730 were complete. Cronbach's alpha value (0.944) and the split-half reliability coefficient (0.873) reflected satisfactory internal consistency reliability of this new professionalism assessment scale. EFA extracted a 7-factor model. About 63.4% of the total variance was explained by these factors. However, CFA showed a good model fit after excluding the items with factor loading lower than 0.5. Good discriminant validity of this new developed professionalism assessment scale was also shown (P < .05). However, the evidences for content and convergent validity were not enough in this study.The results showed the satisfactory reliability of this new developed professionalism assessment scale. However, this scale should be modified to improve the validity in further studies.

The management of blood pressure (BP) for acute ischemic stroke (AIS) patients undergoing thrombolysis is still under debate. The purpose of this study was (1) to explore the association between post-thrombolysis BP and functional outcome and (2) to examine whether post-thrombolysis BP can predict functional outcome in Chinese AIS patients undergoing thrombolysis therapy.

Background. Under septic conditions, LPS induced lung vascular endothelial cell (EC) injury, and the release of inflammatory mediator launches and aggravates acute lung injury (ALI). There are no effective therapeutic options for ALI. Genistein-3'-sodium sulfonate (GSS) is a derivative of native soy isoflavone, which exhibits neuroprotective effects via its antiapoptosis property. However, whether GSS protect against sepsis-induced EC injury and release of inflammatory mediators has not been determined. In this study, we found that GSS not only downregulated the levels of TNF-α and IL-6 in the lung and serum of mice in vivo but also inhibited the expression and secretion of TNF-α and IL-6 in ECs. Importantly, we also found that GSS blocked LPS-induced TNF-α and IL-6 expression in ECs via the Myd88/NF-κB signaling pathway. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on inflammatory response in lung ECs.

Under septic conditions, Lipopolysaccharide (LPS)-induced apoptosis of lung vascular endothelial cells (ECs) triggers and aggravates acute lung injury (ALI), which so far has no effective therapeutic options. Genistein-3'-sodium sulphonate (GSS) is a derivative of native soy isoflavone, which has neuro-protective effects through its anti-apoptotic property. However, whether GSS protects against sepsis-induced lung vascular endothelial cell apoptosis and ALI has not been determined. In this study, we found that LPS-induced Myd88/NF-κB/BCL-2 signalling pathway activation and subsequent EC apoptosis were effectively down-regulated by GSS in vitro. Furthermore, GSS not only reversed the sepsis-induced BCL-2 changes in expression in mouse lungs but also blocked sepsis-associated lung vascular barrier disruption and ALI in vivo. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on Myd88/NF-κB/BCL-2 signalling in lung ECs.

To develop a deep learning model for objective evaluation of experimental autoimmune uveitis (EAU), the animal model of posterior uveitis that reveals its essential pathological features via fundus photographs.

Sensorineural hearing loss (SNHL) has been reported rarely in patients with meningeal carcinomatosis (MC). We summarized the clinical data of eight MC patients with SNHL and 35 patients reported from publications. In the eight patients with SNHL, the medium onset age was 48 (range from 37 to 66) years and six (75%) were male. Seven (87.5%) suffered from headaches as the initial symptom, and they experienced SNHL during the first two months after the occurrence of headaches (0.5 to 2 months, average 1.5 months). The audiogram configuration was flat in three patients (37.5%) and showed total deafness in five patients (62.5%). The damage of cranial nerves VI (abducens) was observed in six patients (75%), and four patients (50%) had cranial nerves VII (facial) injury during the disease course. The percentage of damage of cranial nerves was higher than the patients without SNHL (VIth, 75.0% vs. 13.3%, p = 0.002 and VIIth 50.0% vs. 6.7%, p = 0.012). Four (50%) patients suffered from lung adenocarcinoma as primary tumor, two (25%) experienced stomach adenocarcinoma, one had colon cancer, and one patient was unknown. The symptom of SNHL improved after individualized therapy in four patients (focal radiotherapy and chemotherapy for three patients and whole brain radiotherapy for one patient), but all passed away from 2 to 11 months after diagnosis. Total deafness and flat hearing loss in audiogram were the common types of SNHL resulting from MC. MC patients with SNHL were more likely to suffer from the damage of other cranial nerves, especially to cranial nerves VI and VII. Treatment might improve SNHL, but not improve the case fatality rate.

Tai people are widely distributed in Thailand, Laos and southwestern China and are a large population of Southeast Asia. Although most anthropologists and historians agree that modern Tai people are from southwestern China and northern Thailand, the place from which they historically migrated remains controversial. Three popular hypotheses have been proposed: northern origin hypothesis, southern origin hypothesis or an indigenous origin. We compared the genetic relationships between the Tai in China and their "siblings" to test different hypotheses by analyzing 10 autosomal microsatellites. The genetic data of 916 samples from 19 populations were analyzed in this survey. The autosomal STR data from 15 of the 19 populations came from our previous study (Lin et al., 2010). 194 samples from four additional populations were genotyped in this study: Han (Yunnan), Dai (Dehong), Dai (Yuxi) and Mongolian. The results of genetic distance comparisons, genetic structure analyses and admixture analyses all indicate that populations from northern origin hypothesis have large genetic distances and are clearly differentiated from the Tai. The simulation-based ABC analysis also indicates this. The posterior probability of the northern origin hypothesis is just 0.04 [95%CI: (0.01-0.06)]. Conversely, genetic relationships were very close between the Tai and populations from southern origin or an indigenous origin hypothesis. Simulation-based ABC analyses were also used to distinguish the southern origin hypothesis from the indigenous origin hypothesis. The results indicate that the posterior probability of the southern origin hypothesis [0.640, 95%CI: (0.524-0.757)] is greater than that of the indigenous origin hypothesis [0.324, 95%CI: (0.211-0.438)]. Therefore, we propose that the genetic evidence does not support the hypothesis of northern origin. Our genetic data indicate that the southern origin hypothesis has higher probability than the other two hypotheses statistically, suggesting that the Tai people most likely originated from southern China.

Echovirus 6 (E6) infections are associated with aseptic meningitis and acute flaccid paralysis (AFP). But some infections, sometimes most of them, are asymptomatic. The mechanism of E6 virulence is unknown. Analyses of the molecular evolution of asymptomatic E6 may help understand why the infections show different manifestations.

Correlation of triglyceride (TG)-to-high density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) and the survival of gastric cancer (GC) remain unclear. The purpose of this study was to explore the precise effect of preoperative TG/HDL-C on clinical outcomes in GC patients. Patients with GC were enrolled from 2006 to 2014. A total of 957 individuals from a single center were divided into prospective training and retrospective test cohorts. The optimal cutoff value of TG/HDL-C was determined using X-tile software to separate the training cohort into low and high survival groups according to TG/HDL-C levels. Survival analyses were performed using Kaplan-Meier curves and a Cox proportional hazards regression model. Preoperative TG/HDL-C and clinical outcomes were obtained to determine the prognostic significance of serum lipids in the training and test cohorts. We observed that high TG and TG/HDL-C were significantly correlated with poor outcome in GC patients, and high TG/HDL-C harbored the highest area under curve to independently predict 5-year overall survival in two cohorts. Furthermore, c-index of the prognostic nomogram including TG/HDL-C was significantly higher than that without it. In summary, TG/HDL-C was an efficient and independent prognostic factor to predict 5-year case fatality of GC patients and to improve the efficacy of its prognostic nomogram.

Abnormal calcium homeostasis related to the development of hypertension. As the key regulator of intracellular calcium concentration, voltage-dependent calcium channels (VDCCs), the variations in these genes may have important effects on the development of hypertension. Here we evaluate VDCCs variability with respect to hypertension in the Dai ethnic group of China.

Transcription factor FOXM1 is a potential target for anti-cancer drug development. An interfering peptide M1-21, targeting FOXM1 and FOXM1-interacting proteins, is developed and its anti-cancer efficacy is evaluated.

Artificial intelligence (AI) has shown excellent diagnostic performance in detecting various complex problems related to many areas of healthcare including ophthalmology. AI diagnostic systems developed from fundus images have become state-of-the-art tools in diagnosing retinal conditions and glaucoma as well as other ocular diseases. However, designing and implementing AI models using large imaging data is challenging. In this study, we review different machine learning (ML) and deep learning (DL) techniques applied to multiple modalities of retinal data, such as fundus images and visual fields for glaucoma detection, progression assessment, staging and so on. We summarize findings and provide several taxonomies to help the reader understand the evolution of conventional and emerging AI models in glaucoma. We discuss opportunities and challenges facing AI application in glaucoma and highlight some key themes from the existing literature that may help to explore future studies. Our goal in this systematic review is to help readers and researchers to understand critical aspects of AI related to glaucoma as well as determine the necessary steps and requirements for the successful development of AI models in glaucoma.