Stability evaluation of open-pit mine slope based on Bayesian optimization 1D-CNN.

As mechanized open-pit coal mining intensifies, assessing and predicting slope stability has become increasingly important. To address the limitations of traditional mechanical calculations, numerical simulations, and physical experiments, this paper identifies the key factors impacting slope stability in open-pit mines and develops a multi-parameter sample data set. The study employs hyperparameters optimized using a Bayesian algorithm, introduces additional convolutional layers, and combines the Adam optimizer with dropout techniques to enhance the feature extraction and performance of one-dimensional convolutional neural networks (1D-CNN). This leads to a Bayesian-optimized one-dimensional convolutional neural network (B-1D MCNN) model for predicting slope stability.The study evaluates the classification performance and accuracy of various models for slope stability, including BP neural networks, genetic algorithm-optimized convolutional neural networks, 1D-CNN, and B-1D MCNN, using accuracy, precision, and F1-score as metrics. The analysis also examines the influence of factor indicators and training set length on the model's output to assess its generalization capabilities.The research findings suggest that: (1) the B-1D MCNN model for evaluating slope stability demonstrates the capability to accurately depict the nonlinear correlation between influencing factors and slope stability. (2) Compared with other models, the B-1D MCNN model has shown enhancements of 10.96% to 27.85%, 10.26% to 28.55%, and 8.98% to 25.05% in terms of Accuracy, F1-Score, and Precision, respectively. (3) As the length of the training dataset increases, the performance of the model improves accordingly. (4) The B-1D MCNN model shows a generalization power of 87.5%.

Conditional reprogrammed human limbal epithelial cell model for anti-SARS-CoV-2 drug screening.

To minimize the global pandemic COVID-19 spread, understanding the possible transmission routes of SARS-CoV-2 and discovery of novel antiviral drugs are necessary. We describe here that the virus can infect ocular surface limbal epithelial, but not other regions. Limbal supports wild type and mutant SARS-CoV-2 entry and replication depending on ACE2, TMPRSS2 and possibly other receptors, resulting in slight CPE and arising IL-6 secretion, which symbolizes conjunctivitis in clinical symptoms. With this limbal model, we have screened two natural product libraries and discovered several unreported drugs. Our data reveal important commonalities between COVID-19 and ocular infection with SARS-CoV-2, and establish an ideal cell model for drug screening and mechanism research.

16S rRNA sequencing in chronic dacryocystitis.

CLINICAL RELEVANCE: The pathogenesis of chronic dacryocystitis (CDC) is associated with a variety of bacteria. Investigating microflora has the potential to provide a theoretical basis for preventing and treating CDC. BACKGROUND: 16S rRNA sequencing is a sequence-based bacterial analysis. The application of 16S rRNA sequencing in CDC is rarely reported. METHODS: A case-control study of infected and healthy eyes diagnosed as CDC patients was conducted. Seventy-eight patients were divided into A (conjunctival sac secretions from healthy eyes), B (conjunctival sac secretions from affected eyes), and C (lacrimal sac secretions from affected eyes) groups. The flora of samples was analysed with 16S rRNA sequencing, and the data was analysed using QIIME, R, LefSE and other software. The potential functions were analysed by PICRUSt. RESULTS: A total of 1440 operational taxonomic units (OTUs) were obtained, 139 specific to group A, 220 specific to group B, and 239 specific to group C. There was no significant difference in α index between the three groups. The beta diversity and grouping analysis data indicated that the three groups of flora were similar in species richness and diversity, but there were some differences in composition. In group A, the abundance of Pseudomonadaceae, Chlorobacteria, Moraceae, Staphylococcaceae, Bacillariophyceae, Immunobacterium spp. and Bacillus spp. was higher; in group B, the abundance of Burkholderiaceae, Sphingomonas, Rhizobia, Stalked Bacteria, Sphingomonadaceae, Enterobacteriaceae, Shortwaveomonas spp. was higher; in group C, the abundance of Streptococcus digestiveis, Propionibacterium, Enterobacteriaceae, Anaerobacteriaceae, Propionibacteriaceae, Bacillus spp. Neisseria spp. and Shortactomonas spp. was higher. Six pathways were identified to assess the potential microbial functions. CONCLUSION: Alterations in the microbiota of the conjunctiva and lacrimal sac are associated with the pathogenesis of CDC, which may provide certain guidance for antibiotic treatment of CDC.

Study on time-frequency features of induced charge signals during the damage and failure process of coal medium.

Monitoring and preventing coal-rock dynamic disasters are vital for safe mining. To investigate the time-frequency features of induced charge signals with coal damage and failure of roadways, the generation mechanism of free charge in loaded coal is analyzed and the induced charge monitoring test is conducted. According to the stress-induced charge-time curves, the time-domain features of charge signals at each loading stage are obtained. The wavelet threshold denoising approach and generalized Morse wavelet transform method are applied to denoise the raw signals and study the frequency-domain features. Further, the quantitative relationship between the de-noised induced charge signals and the degree of coal damage is established. The results show that the event number, amplitude and fluctuation degree of available induced charge signals are all at a low level in the compaction and elastic stages of the coal, which are mainly generated by the piezoelectric effect and predominantly represent discreteness. When entering the plastic and failure stages, the available signals are primarily produced by the crack propagation and triboelectric effects, with a significant increase in the event number, amplitude, and fluctuation degree. Then the induced charge signals gradually transit from discrete to continuous. Generally, the dominant frequency of the available induced charge signals during the coal damage process is concentrated at 0 ~ 11 Hz. The available induced charge is positively correlated with the degree of coal damage, which can perform the damage degree of coal mass, providing a new approach to evaluate the stability of roadway surrounding rocks.

A Rat Dry Eye Model with Lacrimal Gland Dysfunction Induced by Scopolamine.

Aqueous-deficient dry eye (ADDE) is a type of dry eye disease that can result in the reduction of tear secretion quantity and quality. Prolonged abnormal tear production can lead to a disturbance in the ocular surface environment, including corneal damage and inflammation. In severe cases, ADDE can cause vision loss or even blindness. Currently, dry eye treatment is limited to eye drops or physical therapy, which can only alleviate eye discomfort symptoms and cannot fundamentally cure dry eye syndrome. To restore the function of the lacrimal gland in dry eye, we have created an animal model of lacrimal gland dysfunction in rats induced by scopolamine. Through the comprehensive evaluation of the lacrimal gland, corneas, conjunctivas, and other factors, we aim to provide a full understanding of the pathological changes of ADDE. Compared with the current dry eye mouse model, this ADDE animal model includes a functional evaluation of the lacrimal gland, providing a better platform for studying lacrimal gland dysfunction in ADDE.

eIF4A3-mediated circEHMT1 regulation in retinal microvascular endothelial dysfunction in diabetic retinopathy.

BACKGROUND AND OBJECTIVE: Literature has reported that circular RNAs (circRNAs) are crucially associated with diabetic retinopathy (DR). Furthermore, circEHMT1 has been identified to maintain endothelial cell barrier function. This study aimed to investigate the mechanisms that regulate aberrant circEHMT1 expression and its role in the pathogenesis of DR. METHODS: In this study, retinal microvascular endothelial cells were exposed to a high glucose (HG) environment, and subsequently, tube formation and intercellular junction proteins were evaluated. Furthermore, the biological functions of circEHMT1 and its potential regulatory factor, eIF4A3, in microvascular endothelial cells under HG conditions were also assessed. In addition, the regulatory role of eIF4A3 on circEHMT1 expression was confirmed. Moreover, to elucidate the in vivo functions of eIF4A3 and circEHMT1, streptozotocin (STZ) was used to establish a DR model in rats. RESULTS: It was revealed that HG condition decreased circEHMT1 and eIF4A3 expressions and reduced ZO-1, Claudin-5, and Occludin levels in retinal microvascular endothelial cells. Furthermore, it was observed that eIF4A3 could regulate the expression of circEHMT1. Overexpression of eIF4A3 or circEHMT1 under HG conditions improved endothelial cell injury and decreased tube-formation ability. Additionally, in the DR rat model, eIF4A3 overexpression restored circEHMT1 levels and ameliorated retinal vasculature changes. CONCLUSION: Altogether, eIF4A3 regulates circEHMT1 expression, thereby affecting microvascular endothelial cell injury and tube formation. Further understanding the regulatory effect of eIF4A3 on circEHMT1 may provide novel therapeutic targets for DR.

Analysis of the impact of the combined use of rebar bolts and FRP bolts in the roadway enclosure.

In order to investigate the support effect of the combination of FRP bolts and rebar bolts in the roadway, taking a coal mine as the background of the project, research and analysis of the engineering geological conditions of the mine and the layout of the mining roadway, stress analysis of the roadway peripheral rock, and put forward the combination of rebar and FRP bolts in the roadway peripheral rock support program. Based on different scenarios, FLAC3D was applied to simulate and analyze the distribution of axial force, maximum principal stress of the surrounding rock, yield damage of the surrounding rock, and displacement of the surrounding rock under three conditions: no support, full rebar bolt support, and combined rebar and FRP bolt support. The results show that (1) In the pre-action period between the bolt and the surrounding rock of the roadway, the FRP bolt carries the force first; in the late action period, the rebar bolt and the FRP bolt carry the force together. (2) From the analysis of the stress concentration degree of the maximum principal stress of the roadway surrounding rock, the horizontal displacement of the roadway surrounding rock and the distribution characteristics of the plastic zone of the roadway surrounding rock, it can be concluded that the support strength of FRP bolts is slightly lower than that of rebar bolts. (3) Under the state of combined support of FRP and rebar bolts, the range of plastic zone of surrounding rock in the roadway is analyzed in comparison with the effect of full rebar bolt support, and the range of reduction of plastic zone of surrounding rock is not obvious, and the effect of full rebar bolt support and combined support of FRP and rebar bolts on controlling the damage of surrounding rock is similar. (4) The side part of the roadway perimeter rock mining adopts FRP bolts instead of rebar bolts, and if the FRP bolts are not damaged, the combination of FRP and rebar bolts can be used for support, which can maintain the stability of the roadway perimeter rock.

TLR7 Agonists Modulate the Activation of Human Conjunctival Epithelial Cells Induced by IL-1ß via the ERK1/2 Signaling Pathway.

Conjunctival epithelia cells play an important role in the development of allergic reactions. TLR7 agonists have been shown in studies to increase the body's immunological tolerance by controlling the proportion of Th1/Th2 cells, although it is still unknown what impact this has on conjunctival epithelial cells. In this study, we examined the effect of TLR7 agonists on the inflammatory-activation of conjunctival epithelial cells induced by IL-1ß. Quantitative PCR and ELISA analysis confirmed that TLR7 agonists could impair the proinflammatory cytokines released by the epithelia cells, whereas pro-inflammatory cytokines led to subsequent reactive oxygen species and neutrophil chemotaxis. Phosphorylation analysis and nucleocytoplasmic separation further confirmed that TLR7 agonists inhibit IL-1ß-induced epithelia cells activation and ATP depletion via modulating the cytoplasmic residence of ERK1/2. Our finding indicated that TLR7 of conjunctival epithelia cells could be as a potent anti-inflammatory target for the ocular surface. And TLR7 agonists may become potential new drug for the treatment of allergic conjunctivitis.

Applications of hydrogel materials in different types of corneal wounds.

Severe corneal injury can lead to a decrease in light transmission and even blindness. Currently, corneal transplantation has been applied as the primary treatment for corneal blindness; however, the worldwide shortage of suitable corneal donor tissue means that a large proportion of patients have no access to corneal transplants. This situation has contributed to the rapid development of various corneal substitutes. The development and optimization of novel hydrogels that aim to replace partial or full-thickness pathological corneas have advanced in the last decade. Meanwhile, with the help of 3D bioprinting technology, hydrogel materials can be molded to a refined and controllable shape, attracting many scientists to the field of corneal reconstruction research. Although hydrogels are not yet available as a substitute for traditional clinical methods of corneal diseases, their rapid development makes us confident that they will be in the near future. We summarize the application of hydrogel materials for various types of corneal injuries frequently encountered in clinical practice, especially focusing on animal experiments and preclinical studies. Finally, we discuss the development and achievements of 3D bioprinting in the treatment of corneal injury.

Immunotherapies of retinoblastoma: Effective methods for preserving vision in the future.

Retinoblastoma is the most common intraocular tumor in children. Patients can be cured by enucleation, but it can lead to vision loss. Chemotherapy is the main method of treatment for RB currently. Unfortunately, chemoresistant and tumor metastasis often happen, resulting in a relatively poor prognosis. Therefore, immunotherapy becomes one of the optimal choices. Targeting not only tumor cells but also the active tumor microenvironment is a novel strategy for RB treatment. Here, we conclude several potential targets for RB immunotherapy, including gangliosides GD2, PD-1 and PD-L1, B7H3, EpCAM and SYK. We also review the techniques for CART, bispecific antibodies and genetically modified Dendritic cells according to the characteristics of different targets and discuss the feasibility of immunotherapy with different targets.

Mechanism of nonylphenol induced gastric inflammation through NF-κB/NLRP3 signaling pathway.

Studies have found that the intake of environmental endocrine disruptors was positively correlated with the occurrence of gastric diseases. The aim of this study was to determine whether nonylphenol (NP) exposure can induce gastric inflammation and whether its mechanism was related to NF-κB/NLRP3 signaling pathway. In vivo, male SD rats were randomly divided into 4 groups (12 rats/group): control group (corn oil), NP low (0.4 mg/kg), medium (4 mg/kg), and high (40 mg/kg) dose groups. After 33 weeks of NP chronic exposure, it was found pathological changes in gastric tissues, increase the release of inflammatory factors, and effects expressions of genes related to the NF-κB/NLRP3 signaling pathway. In vitro, the GES-1 cell experiments, which included four groups: control (0 µmol/L NP), L (2.5 µmol/L NP), M (40 µmol/L NP), and H (60 µmol/L NP), confirmed that NP increased the release of inflammatory factors in the cells, and up-regulated the expression of proteins related to NF-κB/NLRP3 signaling pathway. Furthermore, when pyrrolidinedithiocarbamate ammonium (PDTC) blocked the NF-κB signaling pathway, it was found that the expression of related proteins in the NF-κB/NLRP3 signaling pathway was decreased, and the release of inflammatory factors in GES-1 cells caused by NP was also attenuated. The results of this study indicated that NP can induce inflammation in the stomach in vivo and in vitro, and its mechanism was related to the NF-κB/NLRP3 signaling pathway. These findings provided a new perspective on the mechanism of inflammatory response induced by exposure to environmental endocrine disruptors. Also, these findings indicated that therapeutic strategies for the NF-κB/NLRP3 signaling pathway may be new methods to treat inflammatory diseases.

Effect of nonylphenol on the colonic mucosa in rats and intervention with zinc-selenium green tea (Camellia sinensis).

To investigate the effect of nonylphenol (NP) exposure on the colonic mucosa in rats, and the protective effects of Guizhou zinc-selenium tea (Zn-Se tea) on the damage induced by NP, sixty Sprague-Dawley rats were randomly divided into 6 groups (n = 10 in each group): control group (corn oil), and rats gavaged with NP at the doses of 0.4 mg/kg/d (Low NP group), 4 mg/kg/d (Medium NP group), 40 mg/kg/d (High NP group), and 40 mg/kg NP combined with green tea group at the doses of 0.2 g/ml (NP + GT group) and 0.2 g/ml Zn-Se tea group (NP + ZST group). NP at 40 mg/kg/d was administered to the tea groups for 3 months, followed by NP + green tea and NP + Zn-Se tea for 4 months, and the rest of the groups were gavaged for 7 months. With the increase of NP concentration, NP accumulation in colon gradually increased (P < 0.05), colonic villi shortened, tight junctions between cells widened, intestinal integrity was impaired, and goblet cells, intraepithelial lymphocytes and mast cells were significantly lower in NP high-dose group than in control group (P < 0.05). Meanwhile, the protein expression of Caspase-1, IL-1ß and Pro-IL-1ß in NP high-dose group was significantly higher than that in control group (P < 0.05). Zn-Se tea increased the number of goblet cells in colon and decreased the accumulation of NP in colon (P < 0.05); Zn-Se tea and common green tea decreased the expression of Caspase-1 and Pro-IL-1ß protein (P < 0.05). NP exposure can destroy intestinal morphology, reduce the number of intestinal immune cells, reduce intestinal immunity and increase the release of inflammatory factors; Guizhou Zn-Se tea has a certain protective effect on colon damage caused by NP.

Transesophageal electrophysiology study in the diagnosis of dual atrioventricular nodal nonreentrant tachycardia.

"Double fire" is generally characterized by 1:2 atrioventricular conduction of sinus beats traveling down fast and slow pathways that result in double ventricular response. When this phenomenon repeats rapidly, dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) occurs. We report a case of an irregular tachycardia with a comprehensive record that includes an electrocardiogram, a transesophageal electrophysiology study, and an intracardiac electrophysiology study. This is the first report of transesophageal electrophysiology study in the diagnosis of DAVNNT. A diagnosis of DAVNNT was deduced, and the patient was successfully treated with radiofrequency ablation of the slow pathway.

Association of endocrine disrupting chemicals levels in serum, environmental risk factors, and hepatic function among 5- to 14-year-old children.

Endocrine-disrupting chemicals (EDCs) might increase the risk of childhood diseases by disrupting hormone-mediated processes that are critical for growth and development during childhood, however, the association among the exposure level of EDCs such as Nonylphenol (NP), Bisphenol A (BPA), Dimethyl phthalate (DMP) in children and environmental risk factors, as well as hepatic function has not been elaborated. This study aimed to discuss this interesting relationship among NP, BPA, DMP concentrations in serum, environmental risk factors, hepatic function of 5- to 14-year-old children in industrial zone, residential zone and suburb in northern district of Guizhou Province, China. In Zunyi city, 1006 children participated in cross-sectional health assessments from July to August 2018, and their parents completed identical questionnaires on the environmental risk factors of EDCs exposure to mothers and children. Serum NP, BPA and DMP concentrations were measured by high performance liquid chromatography (HPLC). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were detected with automatic biochemical analyzer. The median concentrations of serum NP, BPA, and DMP in the participants were 45.85 ng/mL, 26.31 ng/mL and 31.62 ng/mL, respectively, which were higher than the environmental concentration limits of the U.S. National Environmental Protection Agency (EPA). Hair gels used during pregnancy, types of domestic drinking water, nail polish and cosmetics used by children were significantly positive correlated with serum NP concentration (P < 0.05). Gender, feeding pattern, plastic water cup used during pregnancy, hair spray and perfume use for children, duration of children birth, materials for baby bottle or cup and ways to plastic products were significantly positively correlated with serum BPA concentration (P < 0.05). Gender, perms used during pregnancy, hair spray and perfume use for children, using plastic lunch box during pregnancy, duration of children birth, exposure to pesticides, parents' occupations were significantly positively correlated with serum DMP concentrations (P < 0.05). Serum NP (ß = 0.296, P = 0.036) and DMP (ß = 0.316, P = 0.026) concentrations and TBIL level were significantly positively correlated. Serum NP concentration and the levels of IBIL (ß = 0.382, P = 0.006) are significantly positively correlated. Cosmetics used during pregnancy significantly increased AST level (ß = 2.641, P = 0.021). There was a positive correlation between the frequency of hair spray and perfume use for children and the AST (ß = 4.241, P = 0.022). NP, BPA and DMP, which were commonly detected in the serum of children aged 5-14 years old in Zunyi City, Northern Guizhou Province, China, were closely related to the environmental risk factors of exposure environment during pregnancy, infancy and school age. Exposure to NP, BPA and DMP would have negative effects on hepatic function, and these effects showed differences in gender and geographical location. Notably,The relationships were more evident in girls than in boys.

Correction to: Correlation between indoor air pollution and adult respiratory health in Zunyi City in Southwest China: situation in two different seasons.

It has been highlighted that the original article [1] contained some errors in the Result section of the Abstract. The incorrect and correct statement is shown in the Correction article.

Correlation between indoor air pollution and adult respiratory health in Zunyi City in Southwest China: situation in two different seasons.

BACKGROUND: Indoor environmental quality significantly influences the occurrence of asthma attack. Zunyi District has abundant coal reserves and is regarded as one of the cities that are most severely polluted by high levels of particulate matter in China. This study aimed to examine the correlation of indoor exposure with adult respiratory health, as well as the differences in effect between winter and summer. METHODS: A cross-sectional epidemiological study was conducted among 1207 adult residents in Zunyi, Guizhou Province of Southwest China in winter and summer. Data on health variables related to asthma and home environmental factors were collected using a modified European Community Respiratory Health Survey II questionnaire. The following data were obtained: samples of particulate matter 2.5 (PM2.5) inside and outside the households under study (n = 20); lung function status, including peak expiratory flow rate, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC ratio. RESULT: The odds ratio (OR) for asthma-like symptoms and asthma in adults using coal stove for cooking or warming, relative to non-users, was 1.73 (95% CI, 1.11-2.69) in winter vs. 1.30 (95% CI, 0.79-2.14) in summer. Adult residents with exposure to cooking oil fumes were at a considerably higher risk of asthma-like symptoms and asthma [OR = 2.65 (95% CI, 1.25 to 5.61) in winter vs. OR = 7.93 (95% CI, 2.54 to 24.75] in summer] than those without such exposure. The prevalence of asthma-like symptoms and asthma was significantly higher in adults with high kitchen risk scores or high sleeping-area risk scores than in those with low scores in both seasons (p < 0.05). The relative kitchen and sleeping area PM2.5 concentrations were higher in winter than in summer (p < 0.05). Lung function was negatively associated with indoor kitchen and sleeping area relative PM2.5 concentration in winter rather than summer (p < 0.001). The effect of exposure to indoor risk factors on lung function among the residents was greater in winter than in summer (p < 0.001). CONCLUSION: Exposure to indoor risk factors, such as aerocontaminants from coal combustion, causes asthma symptoms and reduces pulmonary function. The effect of indoor risk factors on respiratory health among adults with such exposure was greater in winter than in summer.

The effects of different shapes of capsulorrhexis on postoperative refractive outcomes and the effective position of the intraocular lens in cataract surgery.

BACKGROUND: To evaluate the effects of anterior capsular opening size on deviation from predicted refraction and the effective position of the intraocular lens (ELP) in cataract surgery. METHODS: Nonrandomized clinical trial. Eighty patients (80 eyes) with simple age-related cataracts were treated from May 2018 to September 2018 at the Fourth Affiliated Hospital of China Medical University. All patients undergoing phacoemulsification received intraocular lens based on the voluntary principle. Forty eyes were implanted with the C-loop haptic intraocular lens (AMO Tecnis ZCB00) while the other 40 eyes were implanted with the plate haptic intraocular lens (CT ASPHINA 509 M). Follow-up visits were conducted postoperatively at 1 week, 1 month, and 3 months during which patients underwent refraction and data collection after pupil dilation, which included anterior segment photography and Scheimpflug imaging by Pentacam. The area, horizontal and vertical diameter of the capsulorrhexis, circularity, decentration, and package were analysed using the image analysis software Image-Pro-Plus 6.0,then evaluated the relationship between the different shapes of capsulorrhexis with deviation from predicted refraction and ELP in cataract surgery. RESULTS: Deviation from predicted refraction and all of the parameters of capsulorrhexis were not correlative in the 509 M IOL group, however, in the Tecnis IOL group, while the deviation from predicted refraction and all of the capsulorrhexis parameters were not correlative at 1 week, the deviation from predicted refraction did correlate with capsulorrhexis area, horizontal diameter at 1 month (P = 0.029, P = 0.048), and with capsulorrhexis area, vertical diameter at 3 months (P = 0.03, P = 0.017). The ELP correlated with package in both groups postoperatively (r > 0, P < 0.05), but there is no other capsulorrhexis parameters correlated with ELP in the 509 M IOL group (all P > 0.05). For the Tecnis IOL group, the ELP and capsulorrhexis area were correlated at 1 week and 1 month, while the ELP and horizontal diameter, the ELP and vertical diameter were correlated at 1 week, but did not correlate with the other capsulorrhexis parameters in the Tecnis IOL group (all P > 0.05). CONCLUSIONS: The shape of the capsulorrhexis has an effect on postoperative refractive outcomes and the effective position of the intraocular lens in cataract surgery, and plate haptic intraocular lenses have better refractive stability than C-loop haptic intraocular lenses. TRIAL REGISTRATION: ChiCTR1800015638 ,2018-04-12.

Comparison of VerifyNow P2Y12 and thrombelastography for assessing clopidogrel response in stroke patients in China.

Poor response to clopidogrel is often associated with recurrent ischemic events, and reliable platelet function tests are needed to identify clopidogrel low response (CLR). The aim of the study was to compare the consistency of VerifyNow P2Y12 and thrombelastography (TEG) in acute ischemic stroke patients treated with clopidogrel. Patients hospitalized in Changhai Hospital from August 2012 to September 2013 and assigned to treatment with a daily 75-mg dose of clopidogrel. The blood samples were taken on the 5-7th day to assess the capability of VerifyNow P2Y12 and TEG for evaluation of clopidogrel response, and all instrument parameters were used to perform correlation analysis. Patients with CLR were detected by using the methods and criteria published earlier (PRU ≥ 230 assayed by VerifyNow P2Y12 or TEG-Inhib% ≤30 % measured by TEG). Totally 58 patients were enrolled for the study and there were wide varieties in parameters of VerifyNow P2Y12 and TEG. Results showed a total of 17 and 9 patients, respectively, identified as CLR assessed by VerifyNow P2Y12 and TEG, but only three patients were detected to be clopidogrel low responders with both tests. The kappa consistency analysis showed poor consistency between VerifyNow P2Y12 and TEG results in terms of CLR (Kappa = -0.0349, p = 0.7730). Linear regression also demonstrated poor correlation between VerifyNow-PRU/VerifyNow-Inhib% and TEG-Inhib% (p = 0.07901 and p = 0.3788, respectively). Our study demonstrated that there was poor correlation between VerifyNow P2Y12 and TEG results, and VerifyNow P2Y12 showed a larger proportion of CLR than TEG.

Sensitivity and Specificity of Double-Track Sign in the Detection of Transverse Sinus Stenosis: A Multicenter Retrospective Study.

BACKGROUND: Transverse sinus stenosis (TSS) is common among patients with cerebral venous sinus thrombosis. No previous studies have reported on double-track sign detected on axial Gd-enhanced T1WI in TSS. This study aimed to determine the sensitivity and specificity of the double-track sign in the detection of TSS. METHODS: We retrospectively reviewed medical records of 383 patients with transverse sinus thrombosis (TST) and 30 patients with normal transverse sinus from 5 participating hospitals in china from January 2008 to June 2014. 167 feasible transverse sinuses included in this study were categorized into TSS (n = 76), transverse sinus occlusion (TSO) (n = 52) and transverse sinus normal (TSN) groups (n = 39) according to imaging diagnosis on digital subtraction angiography (DSA) or magnetic resonance venography (MRV). Double-track sign on axial Gd-enhanced T1WI was compared among the three groups. Sensitivity and specificity of double-track sign in detection of TSS were calculated, with final imaging diagnosis of TSS on DSA or MRV as the reference standard. RESULTS: Of 383 patients with TST recruited over a 6.5-year period, 128 patients were enrolled in the study, 255 patients were excluded because of insufficient clinical data, imaging finding and delay time, and 30 matched patients with normal transverse sinus were enrolled in the control group. Therefore, double-track sign assessment was conducted in 167 available transverse sinuses of 158 patients. Of the 76 sinuses in TSS group, 51 had double-track sign. Of the other 91 sinuses in TSO and TSN groups, 3 had a false-positive double-track sign. Thus, double-track sign on axial Gd-enhanced T1WI was 67.1% (95% CI 55.3-77.2) sensitive and 96.7% (95% CI 89.9-99.1) specific for detection of TSS. CONCLUSIONS: The double-track sign on axial Gd-enhanced T1WI is highly specific and moderate sensitive for detection of TSS. Nevertheless, it could be a direct sign and might provide an early clue for TSS.

Influence of Genetic Polymorphisms on Clopidogrel Response and Clinical Outcomes in Patients with Acute Ischemic Stroke CYP2C19 Genotype on Clopidogrel Response.

OBJECTIVES: This study sought to evaluate the influence of the genetic polymorphisms on platelet reactivity and clinical outcomes in acute ischemic stroke patients taking clopidogrel. BACKGROUND: Little research has been published on relationships between genetic polymorphisms, platelet reactivity, and clinical outcomes in stroke patients treated with clopidogrel. METHODS: Patients hospitalized in Changhai Hospital with acute ischemic stroke were randomly enrolled into treatment with a 75-mg daily maintenance dose of clopidogrel. Genotyping was detected by the MassARRAY iPLEX genotyping system (Sequenom Inc, San Diego, CA), and platelet reactivity was evaluated by the VerifyNow P2Y12 test (Accumetrics Inc., San Diego, CA). Sixteen single nucleotide polymorphisms (SNPs) within 9 genes were selected and high on-clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) value ≥230. The primary endpoint was ischemic events, including major adverse cardiac events (MACE), recurrence of stroke, transient ischemic attack (TIA), and the composite of vascular death, and the secondary endpoint was bleeding. RESULTS: Of the 345 patients recruited, 275 (79.7%) patients were followed up for 1 year and 122 (35.4%) patients were categorized as HPR. Among the SNPs selected, only the CYP2C19*2 allele and the CYP2C19*3 allele were statistically significantly associated with PRU (P < 0.001 and P = 0.003, respectively). Similarly, the prevalence of HPR was associated with CYP2C19*2 and CYP2C19*3 (P < 0.001 and P = 0.001, respectively). During the 1 year of follow-up, a total of 64 (23.3%) cases of clinical events occurred, including 60 ischemic events and 4 bleeding events. There were no correlation between CYP2C19 variant alleles and clinical outcomes (P > 0.05), but a statistically significant relevance was found between the HPR and the ischemic events in 1 year of follow-up (P = 0.001). CONCLUSIONS: CYP2C19*2 and CYP2C19*3 had a significant impact on clopidogrel response, but was not associated with ischemic events during 1 year of follow-up in patients with acute ischemic stroke. HPR was an independent risk factor for ischemic events, and the VerifyNow P2Y12 test may be available to guide individualized antiplatelet therapies in stroke patients in China.