Stop Ischemic Event to the Brain: Screening Risk Factors of Cerebrovascular Stenosis in Coronary Artery Disease Patients.

OBJECTIVES: In this study, we investigated the difference in risk factors between the 2 diseases, aiming to further clarify who needs to do ischemic cerebrovascular disease (ICVD)-related screening among coronary artery disease (CAD) patients. METHODS: Clinical data of 326 patients with first-episode CAD from June 1, 2017, to July 31, 2020, in the Chinese PLA General Hospital were retrospectively reviewed. Outcomes, including clinical features and laboratory examination, were taken. Features related to ICVD including the extension of intracranial arterial (internal carotid artery intracranial segment, middle cerebral artery M1 segment, anterior cerebral A1 segment, vertebrobasilar artery intracranial segment, posterior cerebral artery P1 segment) and carotid arterial (internal carotid artery extracranial segment, common carotid artery, subclavian artery) stenosis were detected. Risk factors for the occurrence of ICVD in patients with CAD were analyzed. RESULTS: Among patients with the onset of CAD, in comparison of the nonstenosis and stenosis of intracranial artery subgroups, there were statistical differences in the onset age, hypertension, and duration of hypertension as well as the biochemical indicators, including high-density lipoprotein and glycosylated hemoglobin. In addition, statistical differences were detected in the onset age as well as the biochemical indicators, including glycosylated hemoglobin and blood glucose serum protein, along with the difference in the degree of cardiovascular stenosis. CONCLUSIONS: The onset age of CAD was shown to serve as a vital risk factor for ICVD. The primary prevention of ICVD in patients with CAD should lay more emphasis on the management of hypertension and diabetes.

A review of big data technology and its application in cancer care.

The development of modern medical devices and information technology has led to a rapid growth in the amount of data available for health protection information, with the concept of medical big data emerging globally, along with significant advances in cancer care relying on data-driven approaches. However, outstanding issues such as fragmented data governance, low-quality data specification, and data lock-in still make sharing challenging. Big data technology provides solutions for managing massive heterogeneous data while combining artificial intelligence (AI) techniques such as machine learning (ML) and deep learning (DL) to better mine the intrinsic connections between data. This paper surveys and organizes recent articles on big data technology and its applications in cancer, dividing them into three different types to outline their primary content and summarize their critical role in assisting cancer care. It then examines the latest research directions in big data technology in cancer and evaluates the current state of development of each type of application. Finally, current challenges and opportunities are discussed, and recommendations are made for the further integration of big data technology into the medical industry in the future.

Metal-Free Catalytic Formation of a Donor-Acceptor-Donor Molecule and Its Lewis Acid-Adduct Singlet Diradical with High-Efficient NIR-II Photothermal Conversion.

We have synthesized a quinone-incorporated bistriarylamine donor-acceptor-donor (D-A-D) semiconductor 1 by B(C6F5)3 (BCF) catalyzed C-H/C-H cross coupling via radical ion pair intermediates. Coordination of Lewis acids BCF and Al(ORF)3 (RF=C(CF3)3) to the semiconductor 1 afforded diradical zwitterions 2 and 3 by integer electron transfer. Upon binding to Lewis acids, the LUMO energy of 1 is significantly lowered and the band gap of the semiconductor is significantly narrowed from 1.93 eV (1) to 1.01 eV (2) and 1.06 eV (3). 2 and 3 are rare near-infrared (NIR) diradical dyes with broad absorption both centered around 1500 nm. By introducing a photo BCF generator, 2 can be generated by light-dependent control. Furthermore, the integer electron transfer process can also be reversibly regulated via the addition of CH3CN. In addition, the temperature of 2 sharply increased and reached as high as 110 °C in 10 s upon the irradiation of near-infrared-II (NIR-II) laser (1064 nm, 0.7 W cm-2), exhibiting a fast response to laser. It displays excellent photothermal stability with a photothermal (PT) conversion efficiency of 62.26 % and high-quality PT imaging.

A Review about C-TIRADS, ACR-TIRADS, and K-TIRADS Combined with Real-Time Tissue Elastography to Diagnose Thyroid Nodules.

PURPOSE: This study aimed to evaluate the diagnostic efficiency of the Chinese version of thyroid imaging reporting and data system (C-TIRADS), American College of Radiology (ACR)-TIRADS, and Korean (K)-TIRADS combined with real-time tissue elastography to diagnose thyroid nodules. METHODS: A total of 574 thyroid nodule ultrasonographic images were retrospectively analyzed and classified based on the three TIRADS methods. The MedCale statistical software was used to construct the receiver operating characteristic (ROC) curve based on the pathological results of surgery. The diagnostic efficiency before and after assessing elastographies from the three TIRADS was compared between C-TIRADS, ACR-TIRADS, and K-TIRADS groups and within before and after TIRADS combined with elastic imaging. Furthermore, the unnecessary biopsy rates were also compared. Comparing area under ROC curve (AUC) with MEDCALC software (20.0.15, MedCalc Software Ltd., Ostend, Belgium), Delong test was used. The sensitivity and specificity were compared by STATA software (15.1, StataCorp LP, College Station, TX, USA) and Chi-square test. The rate of unnecessary biopsy was compared by SPSS software (23.0, IBM, Armonk, NY, USA) and Chi-square test. RESULTS: C-TIRADS, ACR-TIRADS, K-TIRADS cut-off values, and real-time tissue elastography (RTE) were 4b, 5, 5, and 3, respectively, and the areas under the ROC curve were 0.932, 0.914, 0.904, and 0.883, respectively. C-TIRADS had the highest AUC (p < 0.05) and sensitivity (p < 0.001), while ACR-TIRADS had the highest specificity (p < 0.001). After conducting a combined elastography with the three TIRADS, AUC showed increases of different degrees. Comparing TIRADS with TIRADS+RTE, the difference of C-TIRADS had statistical significance (p < 0.001), but the difference of ACR-TIRADS and K-TIRADS had no statistical significance (p > 0.05). The unnecessary biopsy rate showed decreases of different degrees. Differences between C-TIRADS and K-TIRADS were significant (p < 0.05), but in the case of ACR-TIRADS were not significant (p > 0.05). CONCLUSIONS: C-TIRADS, ACR-TIRADS, K-TIRA and RTE showed high diagnostic efficiency, with C-TIRADS having the highest. Real-time tissue elastography can improve TIRADS diagnostic efficiency and reduce its unnecessary biopsy rate. In this case C-TIRADS showed again the highest efficiency.

Selection and quantification of volatile indicators for quality deterioration of reheated pork based on simultaneously extracting volatiles and reheating precooked pork.

This study was to screen and quantify characteristic volatiles tied to the quality deterioration of reheated pork via simultaneously reheating (75 °C, 30 min) and collecting headspace volatiles of precooked pork (100 °C, 10 min; stored: 0 °C, 0-14 d) for GC-MS analysis. The concentrations of hexanal (6.05 ± 0.86-12.05 ± 0.44 mg/kg), (E)-2-octenal (1.54 ± 0.16-3.07 ± 0.08 mg/kg), (E,E)-2,4-heptadienal (1.52 ± 0.44-2.58 ± 0.31 mg/kg) and 8 other selected volatiles in reheated pork increased as the storage time of the precooked counterparts increased. The increase rate of hexanal was 2.9-199 times faster than that of other volatiles based on zero-order reaction fitting (R2 = 0.876-0.997). Results from clustering analysis of these volatiles were consistent with their formation pathways tied to lipid autooxidation. This simple approach, reheating and collecting volatiles of precooked meat concurrently, introduces a new possibility for standardizing volatile analysis of precooked meats required being reheated before consumption.

AlphaFold accelerates artificial intelligence powered drug discovery: efficient discovery of a novel CDK20 small molecule inhibitor.

The application of artificial intelligence (AI) has been considered a revolutionary change in drug discovery and development. In 2020, the AlphaFold computer program predicted protein structures for the whole human genome, which has been considered a remarkable breakthrough in both AI applications and structural biology. Despite the varying confidence levels, these predicted structures could still significantly contribute to structure-based drug design of novel targets, especially the ones with no or limited structural information. In this work, we successfully applied AlphaFold to our end-to-end AI-powered drug discovery engines, including a biocomputational platform PandaOmics and a generative chemistry platform Chemistry42. A novel hit molecule against a novel target without an experimental structure was identified, starting from target selection towards hit identification, in a cost- and time-efficient manner. PandaOmics provided the protein of interest for the treatment of hepatocellular carcinoma (HCC) and Chemistry42 generated the molecules based on the structure predicted by AlphaFold, and the selected molecules were synthesized and tested in biological assays. Through this approach, we identified a small molecule hit compound for cyclin-dependent kinase 20 (CDK20) with a binding constant Kd value of 9.2 ± 0.5 µM (n = 3) within 30 days from target selection and after only synthesizing 7 compounds. Based on the available data, a second round of AI-powered compound generation was conducted and through this, a more potent hit molecule, ISM042-2-048, was discovered with an average Kd value of 566.7 ± 256.2 nM (n = 3). Compound ISM042-2-048 also showed good CDK20 inhibitory activity with an IC50 value of 33.4 ± 22.6 nM (n = 3). In addition, ISM042-2-048 demonstrated selective anti-proliferation activity in an HCC cell line with CDK20 overexpression, Huh7, with an IC50 of 208.7 ± 3.3 nM, compared to a counter screen cell line HEK293 (IC50 = 1706.7 ± 670.0 nM). This work is the first demonstration of applying AlphaFold to the hit identification process in drug discovery.

Investigation of Advanced Glycation End-Products, α-Dicarbonyl Compounds, and Their Correlations with Chemical Composition and Salt Levels in Commercial Fish Products.

The contents of free and protein-bound advanced glycation end-products (AGEs) including Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL), along with glyoxal (GO), methylglyoxal (MGO), chemical components, and salt in commercially prepared and prefabricated fish products were analyzed. Snack food classified as commercially prepared products exhibited higher levels of GO (25.00 ± 3.34-137.12 ± 25.87 mg/kg of dry matter) and MGO (11.47 ± 1.39-43.23 ± 7.91 mg/kg of dry matter). Variations in the contents of free CML and CEL increased 29.9- and 73.0-fold, respectively. Protein-bound CML and CEL in commercially prepared samples were higher than those in raw prefabricated ones due to the impact of heat treatment. Levels of GO and MGO demonstrated negative correlations with fat (R = -0.720 and -0.751, p < 0.05) in commercially prepared samples, whereas positive correlations were observed (R = 0.526 and 0.521, p < 0.05) in raw prefabricated ones. The heat-induced formation of protein-bound CML and CEL showed a negative correlation with the variations of GO and MGO but was positively related to protein levels in prefabricated products, suggesting that GO and MGO may interact with proteins to generate AGEs during heating. The influence of NaCl on the formation of GO and MGO exhibited variations across different fish products, necessitating further investigation.

Application of random forest based on semi-automatic parameter adjustment for optimization of anti-breast cancer drugs.

The optimization of drug properties in the process of cancer drug development is very important to save research and development time and cost. In order to make the anti-breast cancer drug candidates with good biological activity, this paper collected 1974 compounds, firstly, the top 20 molecular descriptors that have the most influence on biological activity were screened by using XGBoost-based data feature selection; secondly, on this basis, take pIC50 values as feature data and use a variety of machine learning algorithms to compare, soas to select a most suitable algorithm to predict the IC50 and pIC50 values. It is preliminarily found that the effects of Random Forest, XGBoost and Gradient-enhanced algorithms are good and have little difference, and the Support vector machine is the worst. Then, using the Semi-automatic parameter adjustment method to adjust the parameters of Random Forest, XGBoost and Gradient-enhanced algorithms to find the optimal parameters. It is found that the Random Forest algorithm has high accuracy and excellent anti over fitting, and the algorithm is stable. Its prediction accuracy is 0.745. Finally, the accuracy of the results is verified by training the model with the preliminarily selected data, which provides an innovative solution for the optimization of the properties of anti- breast cancer drugs, and can provide better support for the early research and development of anti-breast cancer drugs.

Plasma lncRNA LOC338963 and mRNA AP3B2 are upregulated in paraneoplastic Lambert-Eaton myasthenic syndrome.

INTRODUCTION/AIMS: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular junction disorder. Long noncoding RNA (lncRNA) can regulate the expression of mRNA and is involved in the development of autoimmune diseases, but few genetic studies are available. In this study we aimed to explore the lncRNA and mRNA changes of LEMS. METHODS: Plasma lncRNA and mRNA expression profiles of three LEMS patients with small cell lung cancer (SCLC) and three matched healthy controls were analyzed by microarray. Differentially expressed lncRNAs and adjacent mRNAs were jointly analyzed, and candidates were verified by quantitative real-time polymerase chain reaction (qRT-PCR). The identified genes were subsequently evaluated in 9, 8, and 4 patients with paraneoplastic LEMS, nontumor LEMS, and SCLC, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine possible functions. RESULTS: A total of 320 lncRNA and 168 mRNAs were differentially expressed in the three LEMS with SCLC and compared with healthy controls. Among these, lncRNA LOC338963 and its neighboring mRNA AP3B2 were upregulated jointly, which was confirmed by qRT-PCR. qRT-PCR revealed significant upregulation of the two genes in patients with paraneoplastic LEMS compared with nontumor LEMS or SCLC. GO analysis of AP3B2 identified the enrichment terms anterograde synaptic vesicle transport and establishment of synaptic vesicle localization. KEEG analysis showed that AP3B2 was enriched in lysosomal pathways. DISCUSSION: LOC338963 and AP3B2 were upregulated in patients with paraneoplastic LEMS, suggesting their involvement in pathogenesis. These genes could be targets for exploring the pathomechanism of paraneoplastic LEMS.

The gut microbiome modulates nitroglycerin-induced migraine-related hyperalgesia in mice.

BACKGROUND: Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. METHODS: Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. RESULTS: In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. CONCLUSION: Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.

Development and validation of a risk prediction scale for hypothermia during cesarean section: A prospective study.

Background: Evidence shows that active insulation can reduce the incidence of hypothermia during cesarean section; however, compliance is lower than recommended. Moreover, several aspects of temperature management via active heat preservation remain unclear, including patient indications, timing, methods, and duration. Therefore, promptly identifying parturients at a high risk for hypothermia during cesarean section is crucial. Objective: To develop and validate a scale for predicting hypothermia in parturients during cesarean section. Design: Prospective study. Setting: Three grade A hospitals in Hunan Province, China. Participants: The prediction scale was developed based on data from 369 parturients who underwent cesarean section from July 2018 to January 2019. Inclusion criteria were as follows: cesarean section under lumbar anesthesia, epidural anesthesia, or combined lumbar and epidural anesthesia; voluntary participation in the study and completion of the informed consent form; age >18 years. Methods: Univariate and multivariate analyses were used to determine factors influencing hypothermia and establish the predictive model for hypothermia risk during cesarean section. The Hosmer-Lemeshow test was used to determine the goodness of fit of the prediction tool, and the area under the receiver operating characteristic curve was used to determine the predictive ability of the proposed scale. The cutoff value of the prediction scale was determined according to the Youden index. Results: In the logistic regression prediction model, the Hosmer-Lemeshow goodness-of-fit test yielded a p-value of 0.425. The area under the receiver operating characteristic curve was 0.888. The model exhibited a good fitting effect and discriminant validity. Total risk scores for hypothermia ranged from 0 to 11. A score of 7 was used as the diagnostic cutoff value. Parturients during the operation who had total scores of ≥7 and <7 were considered the high-risk and low-risk groups, respectively. The area under the receiver operating characteristic curve for the scale was 0.891. The authenticity evaluation indicated that the incidence of hypothermia was significantly higher in the high-risk group than in the low-risk group. Conclusions: The risk prediction scale developed in this study exhibits moderately predictive efficiency, sensitivity, and specificity for identifying parturients at high risk of hypothermia during cesarean section. Implementing this scale in clinical practice may help to decrease the incidence of hypothermia in such patients. Tweetable:  . abstract: This new predictive model can identify women who are at a high risk of hypothermia during cesarean section.

Functional correlation of ATP1A2 mutations with phenotypic spectrum: from pure hemiplegic migraine to its variant forms.

BACKGROUND: Mutations in ATP1A2, the gene encoding the α2 subunit of Na+/K+-ATPase, are the main cause of familial hemiplegic migraine type 2 (FHM2). The clinical presentation of FHM2 with mutations in the same gene varies from pure FHM to severe forms with epilepsy and intellectual disability, but the correlation of these symptoms with different ATP1A2 mutations is still unclear. METHODS: Ten ATP1A2 missense mutations were selected according to different phenotypes of FHM patients. They caused pure FHM (FHM: R65W, R202Q, R593W, G762S), FHM with epilepsy (FHME: R548C, E825K, R938P), or FHM with epilepsy and intellectual disability (FHMEI: T378N, G615R, D718N). After ouabain resistance and fluorescence modification, plasmids carrying those mutations were transiently transfected into HEK293T and HeLa cells. The biochemical functions were studied including cell survival assays, membrane protein extraction, western blotting, and Na+/K+-ATPase activity tests. The electrophysiological functions of G762S, R938P, and G615R mutations were investigated in HEK293T cells using whole-cell patch-clamp. Homology modeling was performed to determine the locational distribution of ATP1A2 mutations. RESULTS: Compared with wild-type pumps, all mutations showed a similar level of protein expression and decreased cell viability in the presence of 1 µM ouabain, and there was no significant difference among the mutant groups. The changes in Na+/K+-ATPase activity were correlated with the severity of FHM phenotypes. In the presence of 100 µM ouabain, the Na+/K+-ATPase activity was FHM > FHME > FHMEI. The ouabain-sensitive Na+/K+-ATPase activity of each mutant was significantly lower than that of the wild-type protein, and there was no significant difference among all mutant groups. Whole-cell voltage-clamp recordings in HEK293T cells showed that the ouabain-sensitive pump currents of G615R were significantly reduced, while those of G762S and R938P were comparable to those of the wild-type strain. CONCLUSIONS: ATP1A2 mutations cause phenotypes ranging from pure FHM to FHM with epilepsy and intellectual disability due to varying degrees of deficits in biochemical and electrophysiological properties of Na+/K+-ATPase. Mutations associated with intellectual disability presented with severe impairment of Na+/K+-ATPase. Whether epilepsy is accompanied, or the type of epilepsy did not seem to affect the degree of impairment of pump function.

miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts.

BACKGROUND: Radiation exposure of the thorax is associated with a greatly increased risk of cardiac morbidity and mortality even after several decades of advancement in the field. Although many studies have demonstrated the damaging influence of ionizing radiation on cardiac fibroblast (CF) structure and function, myocardial fibrosis, the molecular mechanism behind this damage is not well understood. miR-21, a small microRNA, promotes the activation of CFs, leading to cardiac fibrosis. miR-21 is overexpressed after irradiation; however, the relationship between increased miR-21 and myocardial fibrosis after irradiation is unclear. This study was conducted to investigate gene expression after radiation-induced CF damage and the role of miR-21 in this process in rats. METHODS: We sequenced irradiated rat CFs and performed weighted correlation network analysis (WGCNA) combined with differentially expressed gene (DEG) analysis to observe the effect on the expression profile of CF genes after radiation. RESULTS: DEG analysis showed that the degree of gene changes increased with the radiation dose. WGCNA revealed three module eigengenes (MEs) associated with 8.5-Gy-radiation-the Yellow, Brown, Blue modules. The three module eigengenes were related to apoptosis, G2/M phase, and cell death and S phase, respectively. By blocking with the cardiac fibrosis miRNA miR-21, we found that miR-21 was associated with G2/M blockade in the cell cycle and was mainly involved in regulating extracellular matrix-related genes, including Grem1, Clu, Gdf15, Ccl7, and Cxcl1. Stem-loop quantitative real-time PCR was performed to verify the expression of these genes. Five genes showed higher expression after 8.5 Gy-radiation in CFs. The target genes of miR-21 predicted online were Gdf15 and Rsad2, which showed much higher expression after treatment with antagomir-miR-21 in 8.5-Gy-irradiated CFs. Thus, miR-21 may play the role of fibrosis and G2/M blockade in regulating Grem1, Clu, Gdf15, Ccl7, Cxcl1, and Rsad2 post-irradiation.

The Protective Effect of Safinamide in Ischemic Stroke Mice and a Brain Endothelial Cell Line.

Stroke is one of the leading causes of mortality in cardiovascular diseases. The disruption of the brain-blood barrier is the common feature of stroke-related complications. Safinamide is a newly approved add-on drug to treat Parkinson's disease, and previously studies suggest safinamide could have a potential role on neuroprotection. In this study, we investigated its preventive effect in both acutely induced stroke animals and brain endothelial cells. By the induction of middle cerebral artery occlusion (MCAO) in mice, we established a transit stroke model. Mice were administered 90 mg/kg/day safinamide prior to MCAO and during ischemia and reperfusion. Results indicate that the administration of safinamide significantly ameliorated MCAO-caused cerebral infarction volume, neurological deficit, disruption of the brain-blood barrier (BBB), and impaired expression of tight junction protein occludin and ZO-1. In cultured brain endothelial cell line bEND.3, pre-treatment with safinamide alleviated oxygen and glucose deprivation/reperfusion (OGD/R) caused cytotoxicity and favored cell survival. Transwell assay showed safinamide prevented OGD/R-induced hyperpermeability and the reduction of occludin and ZO-1. Moreover, safinamide treatment suppressed OGD/R-caused induction of metalloproteinase 2 (MMP-2) and 9 (MMP-9). Collectively, our data conclude safinamide has a preventive neuroprotection in acute stroke animals. The protective effect of safinamide on brain endothelial cells suggests the drug may ameliorate BBB disruption and improve vascular integrity in ischemia stroke.

Incivility in nursing practice education in the operating room.

BACKGROUND: Incivility toward nursing students has been identified as a contributor to negative experiences in clinical education and may cause a weakened learning environment, anxiety, depression and workplace violence. However, few data with regard to uncivilized behavior toward nursing students in the operating room are available. The operation room is a special place where the tempo is fast and the risk is high. Nursing students may have to face pressure from different people, such as anesthesiologists, surgeons, clinical instructors, and staff nurses. OBJECTIVES: To explore uncivilized behavior toward nursing students in the operating room and to discuss the source of uncivilized behavior and the attitude of clinical instructors when it occurs. METHOD: A total of 215 nursing students in the operating room of the Second XiangYa Hospital from January to December 2018 were investigated. The uncivilized behavior in clinical nursing education tool and self-designed questionnaire were used. RESULTS: The incivility mean score was (4.6 ± 6.7). In all, 122 (56.7%) participants had experienced various degrees of uncivilized behavior in the operating room. There were significant differences in incivility toward students according to degree of education and age. The most frequent uncivilized behavior toward students was raising of the voice when speaking to students (41.9%), followed by inappropriate tone (36.7%), being embarrassed in front of others (36.3%), and snide remarks (34.4%). Surgeons (59%) were considered as the most important source of uncivil behaviors, followed by staff nurses (46.7%). When students experienced uncivilized behavior, 61.5% clinical instructors defended and comforted them, 23% comforted them privately, 13.1% ignored them, and 2.5% even criticized them together with the uncivil behavior actor. CONCLUSION: Nursing managers and instructors should pay more attention to the incivility toward students and take actions to foster a healthy, civilized and respectful work environment in the operating room for students.

A Chinese family with familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2.

BACKGROUND: ATP1A2 has been identified as the genetic cause of familial hemiplegic migraine type 2. Over 80 ATP1A2 mutations have been reported, but no data from Chinese family studies has been included. Here, we report the first familial hemiplegic migraine type 2 Chinese family with a novel missense mutation. METHODS: Clinical manifestations in the family were recorded. Blood samples from patients and the unaffected members were collected for whole-exome sequencing to identify the pathogenic mutation. Seven online softwares (SIFT, PolyPhen-2, PROVEAN, PANTHER, MutationTaster2, MutationAssessor and PMut) were used for predicting the pathogenic potential of the mutation. PredictProtein, Jpred 4 and PyMOL were used to analyze structural changes of the protein. The mutation function was further tested by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. RESULTS: All patients in the family had typical hemiplegic migraine attacks. Co-segregation of the mutation with the migraine phenotype in four generations, with 10 patients, was completed. The identified novel mutation, G762S in ATP1A2, exhibited the disease-causing feature by all the predictive softwares. The mutation impaired the local structure of the protein and decreased cell viability. CONCLUSION: G762S in ATP1A2 is a novel pathogenic mutation identified in a Chinese family with familial hemiplegic migraine, which causes loss of function by changing the protein structure of the Na+/K+-ATPase α2 subunit.

Aminophylline promotes mitochondrial biogenesis in human pulmonary bronchial epithelial cells.

Recently, mitochondrial dysfunction has been linked to the development of common airway disorders, such as chronic obstructive pulmonary disease (COPD) and asthma. Phosphodiesterase inhibitors are therapeutic agents for various diseases. Aminophylline is a nonselective phosphodiesterase inhibitor used to treat common lung diseases. In this study, we show that aminophylline promotes mitochondrial biogenesis in cultured human pulmonary bronchial epithelial cells (HPBECs). Aminophylline treatment induces the expression of transcriptional coactivator PGC-1α and transcriptional factors NRF1 and TFAM. The effect of aminophylline on mitochondrial biogenesis can be revealed by its promotion of the ratio of mitochondrial DNA to nuclear DNA (mtDNA/nDNA), mitochondrial protein cytochrome B and mitochondrial mass. At the cellular level, aminophylline increases the mitochondrial respiration rate and ATP production but reduces oxygen content. Consistently, we show that aminophylline activates the CREB-PGC-1α signaling pathway to promote mitochondrial biogenesis. The inhibition of CREB activation by its specific inhibitor H89 obscures the induction of PGC-1α, NRF1, and TFAM by aminophylline, and also abolishes the action of aminophylline on the mtDNA/nDNA ratio and respiration rate, suggesting that the activation of CREB is required for the action of aminophylline. Collectively, our study supports that aminophylline is a potent metabolic inducer of mitochondrial biogenesis in epithelial cells. Aminophylline could have a therapeutic effect on epithelial mitochondrial function in lung diseases.

Regulation of Intestinal Epithelial Cells Properties and Functions by Amino Acids.

Intestinal epithelial cells (IECs) line the surface of intestinal epithelium, where they play important roles in the digestion of food, absorption of nutrients, and protection of the human body from microbial infections, and others. Dysfunction of IECs can cause diseases. The development, maintenance, and functions of IECs are strongly influenced by external nutrition, such as amino acids. Amino acids play important roles in regulating the properties and functions of IECs. In this article, we briefly reviewed the current understanding of the roles of amino acids in the regulation of IECs' properties and functions in physiological state, including in IECs homeostasis (differentiation, proliferation, and renewal), in intestinal epithelial barrier structure and functions, and in immune responses. We also summarized some important findings on the effects of amino acids supplementation (e.g., glutamine and arginine) in restoring IECs' and intestine functions in some diseased states. These findings will further our understanding of the important roles of amino acids in the homeostasis of IECs and could potentially help identify novel targets and reagents for the therapeutic interventions of diseases associated with dysfunctional IECs.

Role of piwi-interacting RNA-651 in the carcinogenesis of non-small cell lung cancer.

Piwi-interacting RNAs (piRNAs/piRs) are small non-coding RNAs that can serve important roles in genome stability by silencing transposable genetic elements. piR651, one of these novel piRNAs, regulates a number of biological functions, as well as carcinogenesis. Previous studies have reported that piR651 is overexpressed in human gastric cancer tissues and in several cancer cell lines, including non-small cell lung cancer (NSCLC) cell lines. However, the role of piRNAs in carcinogenesis has not been clearly defined. In the present study, a small interfering RNA inhibitor of piR651 was transfected into the NSCLC A549 and HCC827 cell lines to evaluate the effect of piR651 on cell growth. The association between piR651 expression and apoptosis was evaluated by flow cytometry and western blot analysis. Wound-healing and Transwell migration and invasion assays were used to determine the effect of piR651 on the migration and invasion of NSCLC cell lines. The results revealed that inhibition of piR651 inhibited cell proliferation and significantly increased the apoptotic rate compared with the negative control (NC), as well as altering the expression of apoptosis-associated proteins. There were fewer migrating and invading cells in the piR651-inhibited group than in the NC group in the Transwell assays. Furthermore, in the wound-healing assay, the wound remained wider in the piR651 inhibitor group, suggesting decreased cell migration compared with that in the NC group. The results of the present study demonstrate that piR651 potentially regulates NSCLC tumorigenic behavior by inhibiting cell proliferation, migration and invasion and by inducing apoptosis. Therefore, piR651 is a potential cancer diagnosis marker.

Deletion of ADP Ribosylation Factor-Like GTPase 13B Leads to Kidney Cysts.

The gene for ADP ribosylation factor-like GTPase 13B (Arl13b) encodes a small GTPase essential for cilia biogenesis in multiple model organisms. Inactivation of arl13b in zebrafish leads to a number of phenotypes indicative of defective cilia, including cystic kidneys. In mouse, null mutation in Arl13b results in severe patterning defects in the neural tube and defective Hedgehog signaling. Human mutations of ARL13B lead to Joubert syndrome, a ciliopathy. However, patients with mutated ARL13B do not develop kidney cysts. To investigate whether Arl13b has a role in ciliogenesis in mammalian kidney and whether loss of function of Arl13b leads to cystic kidneys in mammals, we generated a mouse model with kidney-specific conditional knockout of Arl13b Deletion of Arl13b in the distal nephron at the perinatal stage led to a cilia biogenesis defect and rapid kidney cyst formation. Additionally, we detected misregulation of multiple pathways in the cystic kidneys of this model. Moreover, valproic acid, a histone deacetylase inhibitor that we previously showed slows cyst progression in a mouse cystic kidney model with neonatal inactivation of Pkd1, inhibited the early rise of Wnt7a expression, ameliorated fibrosis, slowed cyst progression, and improved kidney function in the Arl13b mutant mouse. Finally, in rescue experiments in zebrafish, all ARL13B allele combinations identified in patients with Joubert syndrome provided residual Arl13b function, supporting the idea that the lack of cystic kidney phenotype in human patients with ARL13B mutations is explained by the hypomorphic nature of the mutations.