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Background: Duck circovirus (DuCV) infections commonly induce immunosuppression and secondary infections in ducks, resulting in significant economic losses in the duck breeding industry. Currently, effective vaccines and treatments for DuCV have been lacking. Therefore, rapid, specific, and sensitive detection methods are crucial for preventing and controlling DuCV., Methods: A lateral flow strip (LFS) detection method was developed using recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 12a (Cas12a). The RPA-CRISPR/Cas12a-LFS targeted the DuCV replication protein (Rep) and was operated at 37 ℃ and allowed for visual interpretation without requiring sophisticated equipment., Results: The results revealed that the reaction time of RPA-CRISPR/Cas12a-LFS is only 45 min. This method achieved a low detection limit of 2.6 gene copies. Importantly, this method demonstrated high specificity and no cross-reactivity with six other avian viruses. In a study involving 97 waterfowl samples, the Rep RPA-CRISPR/Cas12a-LFS showed 100% consistency and agreement with real-time quantitative polymerase chain reaction., Conclusion: These findings underscored the potential of this user-friendly, rapid, sensitive, and accurate detection method for on-site DuCV detection., Competing Interests: Declarations. Ethics approval and consent to participate: The clinical samples collection was approved by Fujian Academy of Agricultural Sciences. Consent for publication: All authors consent for publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The anti-HER2 antibody trastuzumab is a standard treatment for gastric carcinoma with HER2 overexpression, but not all patients benefit from treatment with HER2-targeted therapies due to intrinsic and acquired resistance. Thus, more precise predictors for selecting patients to receive trastuzumab therapy are urgently needed., Methods: We applied mass spectrometry-based proteomic analysis to 38 HER2-positive gastric tumor biopsies from 19 patients pretreated with trastuzumab (responders n = 10; nonresponders, n = 9) to identify factors that may influence innate sensitivity or resistance to trastuzumab therapy and validated the results in tumor cells and patient samples., Results: Statistical analyses revealed significantly lower phosphorylated ribosomal S6 (p-RPS6) levels in responders than nonresponders, and this downregulation was associated with a durable response and better overall survival after anti-HER2 therapy. High p-RPS6 levels could trigger AKT/mTOR/RPS6 signaling and inhibit trastuzumab antitumor efficacy in nonresponders. We demonstrated that RPS6 phosphorylation inhibitors in combination with trastuzumab effectively suppressed HER2-positive GC cell survival through the inhibition of the AKT/mTOR/RPS6 axis., Conclusions: Our findings provide for the first time a detailed proteomics profile of current protein alterations in patients before anti-HER2 therapy and present a novel and optimal predictor for the response to trastuzumab treatment. HER2-positive GC patients with low expression of p-RPS6 are more likely to benefit from trastuzumab therapy than those with high expression. However, those with high expression of p-RPS6 may benefit from trastuzumab in combination with RPS6 phosphorylation inhibitors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To compare the 5-year follow-up outcomes of radiofrequency catheter ablation (RFCA) combined with left atrial appendage closure (LAAC) and long-term oral anticoagulant (OAC) after RFCA in patients with atrial fibrillation. Methods: This retrospective cross-sectional study included patients with atrial fibrillation who underwent"one-stop"procedure in the First Affiliated Hospital of Ningbo University from September 2015 to December 2017 (RFCA+LAAC group). Baseline data of patients were collected. Propensity score matching at the ratio of 1∶1 was used to select patients with atrial fibrillation who took long-term OAC after RFCA (RFCA+OAC group). The maintenance rate of sinus rhythm and the incidence of adverse events during follow-up were compared between the two groups. Results: A total of 110 patients were enrolled in the RFCA+LAAC group and RFCA+OAC group, respectively. Age of patients was (67.4±8.8) years in RFCA+LAAC group, and there were 42 (38.2%) female patients. Age of patients was (67.3±7.9) years in RFCA+OAC group, and there were 47 (42.7%) female patients. The patients were followed up for mean of (5.3±1.1) years. There was no significant difference in the maintenance rate of sinus rhythm (log-rank: χ 2 =0.277, P =0.602) and incidence of ischemic stroke events (2.7% (3/110) vs. 4.5% (5/110), P =0.719) during follow-up between the two groups. The incidence of bleeding events (6.4% (7/110) vs. 18.2% (20/110), P =0.008) and major bleeding events (1.8% (2/110) vs. 8.2% (9/110), P =0.030) was significantly higher in the RFCA+OAC group than in the RFCA+LAAC group. Conclusion: There is no significant difference between RFCA+LAAC group and RFCA+OAC group in maintenance rate of sinus rhythm and incidence of ischemic stroke events. Patients in the RFCA+LAAC group have a lower risk of bleeding events compared to the RFCA+OAC group.

Objectives: Primary tumor tissue is often analyzed to search for predictive biomarkers and DNA-guided personalized therapies, but there is an incomplete understanding of the discrepancies in the genomic profiles between primary tumors and metastases, such as liver and lung metastases., Methods: We performed in-depth targeted next-generation sequencing of 520 key cancer-associated genes for 47 matched primary and metastatic tumor samples which were retrospectively collected., Results: A total of 699 mutations were detected in the 47 samples. The coincidence rate of primary tumors and metastases was 51.8% (n = 362), and compared to patients with liver metastases, patients with lung metastases had a significantly greater coincidence rate ( P =  .021). The number of specific mutations for the primary tumors and liver and lung metastases was 186 (26.6%), 122 (17.5%), and 29 (4.1%), respectively. Analysis of a patient with all three occurrences, including a primary tumor, liver metastasis, and lung metastasis, indicated a possible polyclonal seeding mechanism for liver metastases. Remarkably, multiple samples from patients with primary and metastatic tumors supported a mechanism of synchronous parallel dissemination from primary tumors to metastatic tumors that were not mediated through pre-metastatic tumors. We also found that the PI3K-Akt signaling pathway significantly altered lung metastases compared to matched primary tumors ( P =  .001). In addition, patients with mutations in CTCF, PIK3CA, or TP53 and LRP1B, AURKA, FGFR1, ATRX, DNMT3B, or GNAS had larger primary tumor sizes and metastases, especially patients with both LRP1B and AURKA mutations. Interestingly, CRC patients with TP53 -disruptive mutations were more likely to have liver metastases ( P =  .016)., Conclusion: In this study, we demonstrate significant differences in the genomic landscapes of colorectal cancer patients based on the site of metastasis. Notably, we observe a larger genomic variation between primary tumors and liver metastasis compared to primary tumors and lung metastasis. These findings can be used for tailoring treatments based on the specific metastatic site.

Objective: To evaluate the feasibility and safety of the LAmbre occluder for large-diameter left atrial appendage occlusion. Methods: This study was a retrospective cohort study. Patients with large orifice of the left atrial appendage (≥31 mm) and occlusion with the LAmbre device in the Arrhythmia Center of Ningbo First Hospital were included from June 2018 to March 2020. Baseline data were collected and major perioperative complications of left atrial appendage occlusion (including death, stroke, instrumental embolism, cardiac tamponade, and major bleeding events) were recorded. Patients were followed up 45 days, 6 months and 12 months after surgery. The shunt and device-related thrombosis were recorded by esophageal cardiac ultrasound or pulmonary vein CT, and the occurrence of postoperative thromboembolism, bleeding events, death and other serious adverse events were recorded. Results: The average age and left atrial appendage ostial dimension of 32 patients (37.5% women) included in this research were (70.4±8.4) years old and (34.4±2.9) mm. The LAmbre device was successfully implanted in 31(96.9%) patients. No major complications occurred during the perioperative period. During the 12-month follow-up, pericardial tamponade occurred in 1(3.2%) patient and was recovered after treatment. There was no occluder edge shunt>5 mm in patients followed up by esophageal echocardiography. No significant peri-device leak, device-related thrombus, thromboembolism or death event has occurred. Conclusion: The LAmbre occluder may be feasible and safe for large-diameter left atrial appendage occlusion.

Avian leukosis virus (ALV) induces multiple tumors in chicken and is still prevalent in a lot of local flocks in China. In this study, we analyzed the ALV infection status in an Anyi tile-like gray chicken flock by DF1-cells isolation, virus identification, and genome sequencing. Results showed a 29% (29/100) ALV positive rate in this flock. Homology analysis based on env genes illustrated that all these stains belong to subgroup J (92-100% identities) and can be further divided into 5 batches, suggesting a higher diversity of ALV-J within the same flock. The whole-genome analysis of representative stains from each batch confirmed the close relationship between these isolated strains with previously reported strains from different regions (Guangxi, Shandong, and Heilongjiang), revealing the enrichment of different strains in Anyi tile-like grey chickens. This study provides the epidemiological data of ALV-J in a special chicken flock and a reference for the further eradication of ALV in China., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Innovations in genomics have enabled the development of low-cost, high-resolution, single nucleotide polymorphism (SNP) genotyping arrays that accelerate breeding progress and support basic research in crop science. Here, we developed and validated the SoySNP618K array (618,888 SNPs) for the important crop soybean. The SNPs were selected from whole-genome resequencing data containing 2,214 diverse soybean accessions; 29.34% of the SNPs mapped to genic regions representing 86.85% of the 56,044 annotated high-confidence genes. Identity-by-state analyses of 318 soybeans revealed 17 redundant accessions, highlighting the potential of the SoySNP618K array in supporting gene bank management. The patterns of population stratification and genomic regions enriched through domestication were highly consistent with previous findings based on resequencing data, suggesting that the ascertainment bias in the SoySNP618K array was largely compensated for. Genome-wide association mapping in combination with reported quantitative trait loci enabled fine-mapping of genes known to influence flowering time, E2 and GmPRR3b, and of a new candidate gene, GmVIP5. Moreover, genomic prediction of flowering and maturity time in 502 recombinant inbred lines was highly accurate (>0.65). Thus, the SoySNP618K array is a valuable genomic tool that can be used to address many questions in applied breeding, germplasm management, and basic crop research., (© 2021 Institute of Botany, Chinese Academy of Sciences.)

Several outbreaks of duck hepatitis A virus type 1 (DHAV-1), which were characterized by yellow coloration and hemorrhage in pancreatic tissues, have occurred in China. The causative agent is called pancreatitis-associated DHAV-1. The mechanisms involved in pancreatitis-associated DHAV-1 infection are still unclear. Transcriptome analysis of duck pancreas infected with classical-type DHAV-1 and pancreatitis-associated DHAV-1 was carried out. Deep sequencing with Illumina-Solexa resulted in a total of 53.9 Gb of clean data from the cDNA library of the pancreas, and a total of 29,597 unigenes with an average length of 993.43 bp were generated by de novo sequence assembly. The expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase, which are involved in glycine, serine, and threonine metabolism pathways, were significantly downregulated in ducks infected with pancreatitis-associated DHAV-1 compared with those infected with classical-type DHAV-1. These findings provide information regarding differences in expression levels of metabolism-associated genes between ducks infected with pancreatitis-associated DHAV-1 and those infected with classical-type DHAV-1, indicating that intensive metabolism disorders may contribute to the different phenotypes of DHAV-1-infection., (© 2021. The Author(s).)

Feature screening is an important and challenging topic in current class-imbalance learning. Most of the existing feature screening algorithms in class-imbalance learning are based on filtering techniques. However, the variable rankings obtained by various filtering techniques are generally different, and this inconsistency among different variable ranking methods is usually ignored in practice. To address this problem, we propose a simple strategy called rank aggregation with re-balance (RAR) for finding key variables from class-imbalanced data. RAR fuses each rank to generate a synthetic rank that takes every ranking into account. The class-imbalanced data are modified via different re-sampling procedures, and RAR is performed in this balanced situation. Five class-imbalanced real datasets and their re-balanced ones are employed to test the RAR's performance, and RAR is compared with several popular feature screening methods. The result shows that RAR is highly competitive and almost better than single filtering screening in terms of several assessing metrics. Performing re-balanced pretreatment is hugely effective in rank aggregation when the data are class-imbalanced.

Tumor-associated macrophages (TAMs) regulate tumor immunity. Previous studies have shown that the programmed cell death protein 1 (PD-1)-positive TAMs have an M2 macrophage phenotype. CD68 is a biomarker of TAMs and is considered to be a poor prognostic marker of several malignancies. Our results show that PD-1-positive TAMs can be a negative survival indicator in patients with muscle-invasive bladder cancer (MIBC), and that the mechanistic effects could result due to a combination of PD-1 and CD68 activity. We analyzed 22 immune cell types using data from 402 patients with MIBC from the TCGA database, and found that a high immune score and M2 TAMs were strongly associated with poor clinical outcomes in patients with MIBC. Further, we analyzed resected samples from 120 patients with MIBC and found that individuals with PD-1-positive TAMs showed a reduction in 5-year overall survival and disease-free survival. Additionally, PD-1-positive TAMs showed a significant association with higher programmed death-ligand 1 (PD-L1) expression, the Ki67 index, the pT stage and fewer CD8-positive T cells. Through the co-immunoprecipitation (co-IP) assay of THP-1 derived macrophages, we found that CD68 can bind to PD-1. The binding of CD68 and PD-1 can induce M2 polarization of THP-1 derived macrophages and promote cancer growth. The anti-CD68 treatment combined with peripheral blood mononuclear cells (PBMC) showed obvious synergy effects on inhibiting the proliferation of T24 cells. Together, these results indicate for the first time that CD68/PD-1 may be a novel target for the prognosis of patients with MIBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiang, Zhang, Chen, He, Liu, Han, Shi, Yang, Mu, Fu and Gao.)

Aims: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder of substantial heritability, yet emerging evidence suggests that key risk variants might reside in the noncoding regions of the genome. Our study explored the association of lncRNAs (long noncoding RNAs) with ADHD as represented at three different phenotypic levels guided by the Research Domain Criteria (RDoC) framework: (i) ADHD caseness and symptom dimension, (ii) executive functions as functional endophenotype, and (iii) potential genetic influence on white matter architecture as brain structural endophenotype., Methods: Genotype data of 107 tag single nucleotide polymorphisms (SNP) from 10 candidate lncRNAs were analyzed in 1040 children with ADHD and 630 controls of Chinese Han descent. Executive functions including inhibition and set-shifting were assessed by STROOP and trail making tests, respectively. Imaging genetic analyses were performed in a subgroup of 33 children with ADHD and 55 controls using fractional anisotropy (FA)., Results: One SNP rs3908461 polymorphism in RNF219-AS1 was found to be significantly associated with ADHD caseness: with C-allele detected as the risk genotype in the allelic model (P = 8.607E-05) and dominant genotypic model (P = 9.628E-05). Nominal genotypic effects on inhibition (p = 0.020) and set-shifting (p = 0.046) were detected. While no direct effect on ADHD core symptoms was detected, mediation analysis suggested that SNP rs3908461 potentially exerted an indirect effect through inhibition function [B = 0.21 (SE = 0.12), 95% CI = 0.02-0.49]. Imaging genetic analyses detected significant associations between rs3908461 genotypes and FA values in corpus callosum, left superior longitudinal fasciculus, left posterior limb of internal capsule, left posterior thalamic radiate (include optic radiation), and the left anterior corona radiate (P FWE corrected  < 0.05)., Conclusion: Our present study examined the potential roles of lncRNA in genetic etiological of ADHD and provided preliminary evidence in support of the potential RNF219-AS1 involvement in the pathophysiology of ADHD in line with the RDoC framework., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Patients with HER2-positive gastric cancer (GC) can benefit from the addition of trastuzumab. However, not all patients with HER2-positive GC respond to trastuzumab. Biomarkers affecting its efficacy in patients with advanced gastric cancer (AGC) are largely unknown. Therefore, classifying GC into molecularly distinct subtypes to accurately distinguish between GC patients who would and would not benefit from trastuzumab is worthwhile. Tumor mutation burden (TMB) is a notable feature in GC and whether TMB influences trastuzumab efficacy is still unknown. Herein, we report the case of a 61-year-old man who was diagnosed with metastatic HER2-positive gastric adenocarcinoma that had spread to the liver (T4aN0M1, stage IV). Esophagogastroduodenoscopy revealed a circular ulcer in the posterior wall of the stomach. A computed tomography (CT) scan revealed a 2-cm diameter liver metastasis. Immunohistochemical analysis of the endoscopic biopsy tumor revealed 3+ positive expression for HER2. Whole-exome sequencing (WES) of the tumor tissue revealed 3,736 somatic mutations in 2,423 genes and a very high TMB of 50.3 mutations/Mb. Immunohistochemistry revealed that the patient had mismatch repair-proficient (pMMR) GC. The patient received first-line trastuzumab-containing chemotherapy, and after 2 courses of sequential metronomic trastuzumab-containing chemotherapy, restaging CT showed that the liver metastasis had disappeared. Following resection, the patient had no recurrence and no new tumor metastasis after a follow-up of period nearly 7 years. This study is the first to report that pMMR GC with a high TMB has a favorable response to trastuzumab. The combination of HER2 positivity and a high TMB may be sufficiently predictive of sensitivity to trastuzumab in AGC.

Colorectal cancer (CRC) is one of the most malignant cancers, and its incidence is still steadily increasing. The DDX RNA helicase family members have been found to play a role in various cancers; however, the role of DDX54 in colorectal cancer is still unclear and needed to be defined. Here, we found DDX54 was overexpressed in CRC tissues by the label-free mass spectrum, which was also verified in tissue microarray of colon cancer, as well as the CRC cell lines and TCGA database. High DDX54 level was correlated with tumor stage and distant metastasis, which always indicated a poor prognosis to the CRC patients. DDX54 could promote the proliferation and mobility of CRC cells through increasing the phosphorylation level p65 and AKT leading to the tumorigenesis. Here, we have preliminarily studied the function of DDX54 in CRC, which would improve our understanding of the underlying biology of CRC and provide the new insight that could be translated into novel therapeutic approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Wang, Meng, Hu, Yan, He, Shi, Fu and Zu.)

Objective: To investigate the safety and efficacy of percutaneous left atrial appendage closure (LAAC) in nonvalvular atrial fibrillation patients (NVAF) with left atrial spontaneous echocardiographic contrast (LA SEC). Methods: A total of 95 NVAF patients treated in the Department of Cardiology of Ningbo First Hospital from July 2018 to June 2019 were enrolled in this study. The study population was divided into two group according to the presence or absence of LA SEC detected by transesophageal echocardiography (TEE). TEE was scheduled 45 days post-procedure to detect device-related thrombus (DRT). Stroke and bleeding events were recorded during follow-up. Periprocedural complications and follow-up results were compared between the two groups. Results: LA diameters were smaller in non-LA SEC group than LA SEC group ((44.0±7.4)mm vs (47.3±6.6)mm, P =0.033). Watchman device was successfully implanted into all the enrolled patients. No death, transient ischemic attack (TIA)/stroke, device embolization and major bleeding events occurred. Fifty patients (90.2%) in LA SEC group and 31 patients (91.2%) in non-LA SEC group finished TEE follow-up 45 days post-procedure. No device-related thrombus was detected in non-LA SEC group, while 2 cases (6.5%) were detected in LA SEC group, but there was no significant differences in the incidence between the two groups ( P =0.127). The LA SEC group and non-LA SEC group were followed-up for (12.3±3.8) months and (12.9±3.3) months, respectively; and there was no significant differences in the incidence of death, TIA/stroke, major and minor bleeding events between two groups during the follow-up (all P >0.05). Conclusion: LAAC in NVAF patients with LA SEC was safe and effective. However, the incidence of DRT was slightly higher.

Background: Gastric cancer (GC) is a common form of malignant cancer in worldwide which has a poor prognosis. Despite recent improvements in the treatment of GC, the prognosis is not yet satisfactory for GC patients. CYT997, a novel microtubule-targeting agent, recently has been identified to be a promising anticancer candidate for the treatment of cancers; however, the effects of CYT997 in GC remain largely unknown., Methods: Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry. The mitochondrial ROS were detected by confocal microscope and flow cytometry. Gastric cancer patient-derived xenograft (PDX) model was used to evaluate its antitumor activity of CYT997 in vivo., Results: CYT997 inhibited gastric cancer cell proliferation and induced cell apoptosis and triggered autophagy. CYT997 induced apoptosis through triggering intracellular mitochondrial ROS generation in GC cells. ROS scavengers N-acetylcysteine (NAC) and Mitoquinone (MitoQ) distinctly weakened CYT997-induced cell cycle G2/M arrest and apoptosis in GC cells. Pretreatment with autophagy inhibitor 3-MA promoted the effect of CYT997 on cells apoptosis. Mechanistically, CYT997 performed its function through regulation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in GC cells. In addition, CYT997 inhibited growth of gastric cancer patient-derived xenograft (PDX) tumors., Conclusions: CYT997 induces autophagy and apoptosis in gastric cancer by triggering mitochondrial ROS accumulation to silence JAK2/STAT3 pathway. CYT997 might be a potential antitumor drug candidate to treat GC.

Background/objectives: For treatment of large bone defects challenging in orthopaedic clinics, bone graft substitutes are commonly used for the majority of surgeons. It would be proposed in the current study that our bioactive scaffolds could additionally serve as a local delivery system for therapeutic small molecule agents capable of providing support to enhance biological bone repair., Methods: In this study, composite scaffolds made of poly (lactic-co-glycolic acid) (PLGA) and tricalcium phosphate (TCP) named by P/T was fabricated by a low-temperature rapid prototyping technique. For optimizing the scaffolds, the phytomolecule icaritin (ICT) was incorporated into P/T scaffolds called P/T/ICT. The osteogenic efficacies of the two groups of scaffolds were compared in a successfully established calvarial defect model in rats. Bone regeneration was evaluated by X-ray, micro-computerised tomography (micro-CT), and histology at weeks 4 and/or 8 post-implantation. In vitro induction of osteogenesis and osteoclastogenesis was established for identification of differentiation potentials evoked by icaritin in primary cultured precursor cells., Results: The results of radiographies and decalcified histology demonstrated more area and volume fractions of newly formed bone within bone defect sites implanted with P/T/ICT scaffold than that with P/T scaffold. Undecalcified histological results presented more osteoid and mineralized bone tissues, and also more active bone remodeling in P/T/ICT group than that in P/T group. The results of histological staining in osteoclast-like cells and newly formed vessels indicated favorable biocompatibility, rapid bioresorption and more new vessel growth in P/T/ICT scaffolds in contrast to P/T scaffolds. Based on in vitro induction, the results presented that icaritin could significantly facilitate osteogenic differentiation, while suppressed adipogenic differentiation. Meanwhile, icaritin demonstrated remarkable inhibition of osteoclastogenic differentiation., Conclusion: The finding that P/T/ICT composite scaffold can enhance bone regeneration in calvarial bone defects through facilitating effective bone formation and restraining excessive bone resorption., The Translational Potential of This Article: The osteogenic bioactivity of icaritin facilitated PLGA/TCP/icartin composite scaffold to exert significant bone regeneration in calvarial defects in rat model. It might form an optimized foundation for potential clinical validation in bone defects application., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2020 The Authors.)

Background: Feature selection in class-imbalance learning has gained increasing attention in recent years due to the massive growth of high-dimensional class-imbalanced data across many scientific fields. In addition to reducing model complexity and discovering key biomarkers, feature selection is also an effective method of combating overlapping which may arise in such data and become a crucial aspect for determining classification performance. However, ordinary feature selection techniques for classification can not be simply used for addressing class-imbalanced data without any adjustment. Thus, more efficient feature selection technique must be developed for complicated class-imbalanced data, especially in the context of high-dimensionality., Results: We proposed an algorithm called sssHD to achieve stable sparse feature selection applied it to complicated class-imbalanced data. sssHD is based on the Hellinger distance (HD) coupled with sparse regularization techniques. We stated that Hellinger distance is not only class-insensitive but also translation-invariant. Simulation result indicates that HD-based selection algorithm is effective in recognizing key features and control false discoveries for class-imbalance learning. Five gene expression datasets are also employed to test the performance of the sssHD algorithm, and a comparison with several existing selection procedures is performed. The result shows that sssHD is highly competitive in terms of five assessment metrics. In addition, sssHD presents limited differences between performing and not performing re-balance preprocessing., Conclusions: sssHD is a practical feature selection method for high-dimensional class-imbalanced data, which is simple and can be an alternative for performing feature selection in class-imbalanced data. sssHD can be easily extended by connecting it with different re-balance preprocessing, different sparse regularization structures as well as different classifiers. As such, the algorithm is extremely general and has a wide range of applicability.

Objective : Integrin β3 is one of the main integrin heterodimer receptors on the surface of cardiac myocytes. Our previous studies showed that hypoxia induces apoptosis and increases integrin β3 expression in cardiomyocytes. However, the exact mechanism by which integrin β3 protects against apoptosis remains unclear. Hence, the present investigation aimed to explore the mechanism of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis. Methods : Stable cells and in vivo acute and chronic heart failure rat models were generated to reveal the essential role of integrin β3 in cardiomyocyte proliferation and apoptosis. Western blotting and immunohistochemistry were employed to detect the expression of integrin β3 in the stable cells and rat cardiac tissue. Flow cytometer was used to investigate the role of integrin β3 in hypoxia-induced cardiomyocyte apoptosis. Confocal microscopy was used to detect the localization of integrin β3 and integrin αv in cardiomyocytes. Results : A cobaltous chloride-induced hypoxic microenvironment stimulated cardiomyocyte apoptosis and increased integrin β3 expression in H9C2 cells, AC16 cells, and cardiac tissue from acute and chronic heart failure rats. The overexpression of integrin β3 promoted cardiomyocyte proliferation, whereas silencing integrin β3 expression resulted in decreased cell proliferation in vitro . Furthermore, knocking down integrin β3 expression using shRNA or the integrin β3 inhibitor cilengitide exacerbated cobaltous chloride-induced cardiomyocyte apoptosis, whereas overexpression of integrin β3 weakened cobaltous chloride-induced cardiomyocytes apoptosis. We found that integrin β3 promoted cardiomyocytes proliferation through the regulation of the PTEN/Akt/mTOR and ERK1/2 signaling pathways. In addition, we found that knockdown of integrin αv or integrin β1 weakened the effect of integrin β3 in cardiomyocyte proliferation. Conclusion : Our findings revealed the molecular mechanism of the role of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis, providing new insights into the mechanisms underlying myocardial protection., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Elastic net (Enet) and sparse partial least squares (SPLS) are frequently employed for wavelength selection and model calibration in analysis of near infrared spectroscopy data. Enet and SPLS can perform variable selection and model calibration simultaneously. And they also tend to select wavelength intervals rather than individual wavelengths when the predictors are multicollinear. In this paper, we focus on comparison of Enet and SPLS in interval wavelength selection and model calibration for near infrared spectroscopy data. The results from both simulation and real spectroscopy data show that Enet method tends to select less predictors as key variables than SPLS; thus it gets more parsimony model and brings advantages for model interpretation. SPLS can obtain much lower mean square of prediction error (MSE) than Enet. So SPLS is more suitable when the attention is to get better model fitting accuracy. The above conclusion is still held when coming to performing the strongly correlated NIR spectroscopy data whose predictors present group structures, Enet exhibits more sparse property than SPLS, and the selected predictors (wavelengths) are segmentally successive., Competing Interests: The authors declare that they have no conflicts of interest.

An issue for class-imbalanced learning is what assessment metric should be employed. So far, precision-recall curve (PRC) as a metric is rarely used in practice as compared with its alternative of receiver operating characteristic (ROC). This study investigates the performance of PRC as the evaluating criterion to address the class-imbalanced data and focuses on the comparison of PRC with ROC. The advantages of PRC over ROC on assessing class-imbalanced data are also investigated and tested on our proposed algorithm by tuning the whole model parameters in simulation studies and real data examples. The result shows that PRC is competitive with ROC as performance measurement for handling class-imbalanced data in tuning the model parameters. PRC can be considered as an alternative but effective assessment for preprocessing (such as variable selection) skewed data and building a classifier in class-imbalanced learning., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Halofuginone, which is the main active ingredient of Dichroa fabrifuga, was used to inhibit the synthesis of type I collagen and played increasingly important roles in tumor therapy. This study aims to investigate the protective effects of halofuginone on human umbilical vein endothelial cells (HUVECs) from H2O2-induced apoptosis and oxidative stress., Methods: Propidium iodide and Annexin-V double staining assay was used to measure the apoptosis. Cell viability assay, the measurements of reactive oxygen species (ROS) parameters malondialdehyde and superoxide dismutase, western-blot assays, and quantitative PCR were used to elucidate the effects and mechanisms of halofuginone in protecting H2O2-induced injury., Results: The results showed that halofuginone counteracted H2O2-induced cell viability decline and PCNA downregulation. Furthermore, halofuginone decreased ROS levels and protected HUVECs from H2O2-induced apoptosis. In detail, it showed that H2O2 induced a transient activation of Mitogen-activated protein kinases members ERK1/2 and p38, whereas induced a sustained activation of c-Jun N-terminal kinase (JNK), which play dominant roles in triggering apoptosis. Inhibition of JNK activation also inhibited H2O2-mediated apoptosis. Finally, it was shown that halofuginone upregulated VEGF expressions, which functioned by inhibiting sustained JNK activation, thus protecting HUVECs., Conclusion: Halofuginone has powerful effects in protecting HUVECs from H2O2-induced apoptosis, via upregulating VEGF and inhibiting overactivated JNK phosphorylation. Halofuginone might be a promising preventive drug for cardiovascular diseases.

This study sought to determine whether the in situ tumor-infiltrating immune lymphocytes, as a novel companion to the Immunoscore analysis, could be a promising, valuable prognostic and predictive marker in patients with head and neck squamous cell carcinoma (HNSCC). Total (CD3+) and cytotoxic (CD8+) T lymphocytes were assessed using immunohistochemistry in tumor nests and stroma obtained from patient surgical specimens. The "Immunoscore" methodology has been defined to quantify the amount of in situ immune infiltrate (from I0 to I4). Survival curves were measured using the Kaplan-Meier method, and differences in survival and response to therapy between the groups were estimated using the log-rank test. The prognostic value of the Immunoscore was determined using Cox multivariate analysis. The density and location of CD3+ and CD8+ lymphocytes and the associated Immunoscore correlated significantly with differences in disease-free survival (DFS) and overall survival (OS) (all P < .005). Compared with tumor-node-metastasis (TNM) staging, the Immunoscore was found to have an advantage in predicting survival (P = .000). In addition, a high Immunoscore was associated with the tumors of advanced-stage patients who underwent different treatment regimens. The Immunoscore could be a useful prognostic marker. The measurement of CD3+ and CD8+ cell infiltration may be beneficial in HNSCC patients and may help determine which patients may benefit most from definitive chemoradiotherapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

To understand the niche characteristics of main woody species in Pterocarya stenoptera community, we investigated P. stenoptera communities in riparian zone of Lijiang River, China. The niche characteristics of main species in tree layers and shrub layers were quantified with the indices of Levins niche breadth, Shannon niche breadth, Schoener niche similarities and Pianka niche overlap. The results showed that P. stenoptera in the tree layer, and Ficus abelii and Morus alba in the shrub layer had higher niche breadth than other species. The species with larger importance values generally had larger niche breadth, but the rank orders of which were not exactly the same. The niche similarity of main populations in the tree layer was generally smaller than that in the shrub layer. The mean value of niche similarity of main populations in the tree layer and shrub layer was 0.151 and 0.236, respectively. There was a low degree of niche similarity among species within the community, indicating that they had a low similarity in resource use. The niche overlap of main populations in the tree layer was generally smaller than that in the shrub layer, with the mean value of niche overlap of main populations in the tree layer and shrub layer being 0.217 and 0.273, respectively. The niche overlap between the main species in the community was relatively lower. There was no significant correlation between niche breadth and niche similarity. The species with larger niche breadth often had more opportunities to overlap with other species. However, their overlap value was not necessarily larger. Larger niche similarity was often associated with higher degrees of niche overlap. The P. stenoptera community in riparian zone of Lijiang River was the climax community, the relationship among species was relatively stable, the population regeneration was very slow, and the development trend of this community was declining in the future.

Objective: To investigation the situation of cold chain on vaccine in parts of Zhejiang Province and to provide recommendations for the management. Methods: From October to December, 2016, we each selected an immunization clinic in Cangnan County of Wenzhou, Yongkang City of Jinhua, Jianggan District of Hangzhou. Temperature recorder and vaccine viral monitor (VVM) labels were used to monitor the cold chain during all the storage and transportation process. In Jianggan District, we use optical density sensor to detected 20 VVM labels every time when the vaccine was stock in and out. Results: In total, 54 958 records were collected by temperature recording devices in all the three immunization clinic. 275 records exceeded the temperature limit required for store and transportation, of which 270 (98.2%) were above 8 ℃ and 5 (1.9%) were under 2 ℃. Excessive temperature exposure mainly occurred during the transportation (38.2%, n= 105), followed by storage process in CDCs at different levels (26.2%, n= 72), stock in and out (20.7%, n= 50) and storage in the refrigerators in immunization clinics (14.9%, n= 41). The average optical density difference between VVM labels and the reference circular decreased from 0.404 to 0.344 when the vaccines were delivered from the Zhejiang provincial CDC to immunization clinics. The color of VVMs did not significantly changed before use. Conclusions: The potential risk of vaccine cold chain in the monitoring sites is over-temperature. The weak links of cold chain management include the transportation, storage process, and stock in and out.

Background: Dabigatran is a kind of oral anticoagulant and there was little review only about dabigatran and warfarin used in patients with atrial fibrillation. This meta-analysis only assesses the dabigatran and warfarin used in patients with atrial fibrillation., Design: Cochrane Library, PubMed, Clinical Trials.gov, CNKI, and WanFang databases were searched. The primary endpoint was the incidence of stroke and the second endpoints were the incidence of bleeding and embolic events., Results: Six RCTs and 20086 patients were included in our meta-analysis. No significant difference was obtained between 110 mg dabigatran and warfarin on the endpoint of stroke (risk ratio (RR), 0.90; 95% confidence interval [CI], 0.71-1.12; P = .34; I = 0%) and embolic events p (RR, 0.89; 95% CI, 0.71-1.12; P = .32; I = 0%). However, the 110 mg dabigatran associated lower incidence of bleeding (RR, 0.81; 95% CI, 0.69-0.95; P = .01; I = 0%) compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower rate of stroke (RR, 0.96; 95% CI, 0.83-1.12; P = .62; I = 0%) and embolic events (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%) but similar in the incidence of bleeding (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%)., Conclusion: No significant difference was obtained between 110 mg dabigatran and warfarin in the incidence of stroke and embolic events. However, the 110 mg dabigatran associated lower incidence of bleeding compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower incidence of stroke and embolic events but similar in the incidence of bleeding.

Recently, dedicator of cytokinesis 2 (DOCK2) has been reportedly exhibited high mutation prevalence in the Asian colorectal cancer (CRC) cohort. However, the expression pattern of DOCK2 and its clinical significance in CRC were still unknown. To characterize the role of DOCK2, a tissue microarray (TMA) containing 481 archived paraffin-embedded CRC specimens was performed by immunohistochemistry. Among which, 54 primary CRC tissues showed high expression of DOCK2 protein, while others were negative. Moreover, DOCK2 expression was positively associated with invasion depth (P < .001) and tumor size (P = .016). Significantly, Kaplan-Meier survival analysis revealed that patients with higher DOCK2 expression had a longer overall survival time (P = .017). Furthermore, univariate and multivariate Cox regression analysis confirmed that DOCK2 is an independent prognostic marker in CRC (P = .049,; HR, 0.519; 95% CI, 0.270 to 0.997). In addition, we observed a strong correlation between the infiltration of CD8 + T lymphocytes and DOCK2 expression (P = .0119). Our findings demonstrated that overexpressed DOCK2 might involve in recruiting CD8 + T lymphocytes and serve as a novel prognostic indicator and indicated a potential therapeutic strategy by restoring DOCK2 for CRC., (© 2018 Wiley Periodicals, Inc.)

Background: During electricity generation of nuclear power plant, heat energy cannot be completely converted into electrical energy, and a part of it is lost in the form of thermal discharge into the environment. The thermal discharge is harmful to flora and fauna leading to environmental deterioration, biological diversity decline, and even biological extinction., Results: The present study investigated the influence of thermal discharge from a nuclear power plant on the growth and development of Pacific oyster Crassostrea gigas which is widely used as bio indicator to monitor environmental changes. The growth of soft part and the gonad development of oysters were inhibited due to thermal discharge. During winter season, temperature elevation caused by thermal discharge promoted the growth of oyster shells. During summer season, the growth rate of oysters in thermal discharge area was significantly lower than that of the natural sea area., Conclusions: The results of this study provided a better understanding of assessing the impact of thermal discharge on the marine ecological environment and mariculture industry. It also provided a scientific basis for defining a safe zone for aquaculture in the vicinity of nuclear power plants.

Background: Gastrin is an important gastrointestinal hormone produced primarily by G-cells in the antrum of the stomach. It normally regulates gastric acid secretion and is implicated in a number of human disease states, but how its function affects breast cancer (BC) development is not documented. The current study investigated the suppressive effects of gastrin on BC and its underlying mechanisms., Methods: Serum levels of gastrin were measured by enzyme-linked immunosorbent assay (ELISA) and correlation between gastrin level and development of BC was analyzed by chi-square test. Inhibitory effects of gastrin on BC were investigated by CCK-8 assay and nude mice models. Expressions of CCKBR/ERK/P65 in BC patients were determined through immunohistochemistry (IHC) and Western blot. Survival analysis was performed using the log-rank test., Results: The results indicated that the serum level of gastrin in BC patients was lower compared with normal control. Cellular and molecular experiments indicated that reduction of gastrin is associated with inactivation of cholecystokinin B receptor (CCKBR)/ERK/P65 signaling in BC cells which is corresponding to molecular type of estrogen receptor (ER) positive BC. Furthermore, we found that low expression of gastrin/CCKBR/ERK /P65 was correlated to worse prognosis in BC patients. Gastrin or ERK/P65 activators inhibited ER + BC through CCKBR-mediated activation of ERK/P65. Moreover, combination treatment with gastrin and tamoxifen more efficiently inhibited ER + BC than tamoxifen alone., Conclusions: We concluded that low serum gastrin is related to increased risk of ER + BC development. The results also established that CCKBR/ERK/P65 signaling function is generally tumor suppressive in ER + BC, indicating therapies should focus on restoring, not inhibiting, CCKBR/ERK/P65 pathway activity.

Background: To test the hypothesis that activated extracellular signal-regulated kinase (ERK) regulates P65-miR23a/27a/24 axis in gastric cancer (GC) and the ERK-P65-miR23a/27a/24 axis plays an important role in the development of GC, and to evaluate the role of gastrin in GC progression and ERK-P65-miR23a/27a/24 axis., Methods: The component levels of the ERK-P65-miR23a/27a/24 axis in four fresh GC tissues, 101 paraffin-embedded GC tissues and four GC cell lines were determined by Western blotting, immunohistochemistry (IHC) or qRT-PCR. The effects of gastrin on GC were first evaluated by measuring gastrin serum levels in 30 healthy and 70 GC patients and performing a correlation analysis between gastrin levels and survival time in 27 GC patients after eight years of follow-up, then evaluated on GC cell lines, GC cell xenograft models, and patient-derived xenografts (PDX) mouse models. The roles of ERK-P65-miR23a/27a/24 axis in GC progression and in the effects of gastrin on GC were examined., Results: ERK- P65-miR23a/27a/24 axis was proved to be present in GC cells. The levels of components of ERK-P65-miR23a/27a/24 axis were decreased in GC tissue samples and PGC cells. The decreased levels of components of ERK-P65-miR23a/27a/24 axis were associated with poor prognosis of GC, and ERK-P65-miR23a/27a/24 axis played a suppressive role in GC progression. Low blood gastrin was correlated with poor prognosis of the GC patients and decreased expression of p-ERK and p-P65 in GC tissues. Gastrin inhibited proliferation of poorly-differentiated GC (PGC) cells through activating the ERK-P65-miR23a/27a/24 axis. Gastrin inhibited GC growth and enhanced the suppression of GC by cisplatin in mice or PGC cell culture models through activating the ERK-P65-miR23a/27a/24 axis or its components., Conclusions: ERK-P65-miR23a/27a/24 axis is down-regulated, leading to excess GC growth and poor prognosis of GC. Low gastrin promoted excess GC growth and contributed to the poor prognosis of the GC patients by down-regulating ERK-P65-miR23a/27a/24 axis. Gastrin inhibits gastric cancer growth through activating the ERK-P65-miR23a/27a/24 axis.

Transmembrane-4-L-six-family member-1 (TM4SF1), a tumor-associated antigen, is overexpressed in most epithelial cell carcinomas and a potential target for antibody-mediated therapy. However, the role of TM4SF1 in gastric cancer has not been elucidated. The aim of this study was to investigate the clinical significance of TM4SF1 expression in gastric carcinoma (GC) tissues using 152 GC tissue samples and matched adjacent nontumor tissue samples analyzed by immunohistochemistry, and 13 fresh GC tissue samples analyzed by Western blotting. The results showed that TM4SF1 was heterogeneously expressed in normal gastric mucosa, with a high expression rate in fundus mucosa. Higher levels and strong expression rate of TM4SF1 were associated with GC tissues of higher-grade differentiation. TM4SF1 levels were lower in gastric cancer tissues than gastric noncancerous tissues. Expression of TM4SF1 was not correlated with USP10 (P = 0.157), S100A12 (P = 0.479), p53 (P = 0.249), or Ki67 (P = 0.166) in GC. The expression of TM4SF1 was significantly and negatively correlated with depth of invasion (P = 0.031), nodal metastasis (P = 0.042), TNM stage (P = 0.030), and Lauren classification (P = 0.026). There was no significant correlation between TM4SF1 expression and age, gender, tumor size, or distant metastasis (P > 0.05). The expression of TM4SF1 was associated with well overall survival (P = 0.0164). The 5-year survival rate for patients with GC showing TM4SF1 positive was 58.82% (10/17), and the median survival time was 78 months, higher than that (12.90%, 12/93) of patients who were TM4SF1 negative, whose median survival time was 62 months. These data suggested that low expression of TM4SF1 is associated with carcinogenesis and development, tumor progression and invasion of gastric cancer, and poor overall survival of patients with GC. TM4SF1 is a tumor suppressor for GC and a novel prognostic marker for patients with GC., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Using an ORF1b-based astrovirus-specfic reverse transcription (RT)-PCR assay, a novel astrovirus-like was detected from domestic geese in China. Pairwise comparisons and phylogenetic analyzes suggested that a novel group of goose astrovirus, different with previously known astroviruses in the genus Avastrovirus, was found circulating in geese. This study has expanded our understanding about the role of domestic waterfowls as reservoirs for diverse astroviruses.

Background: The smartphone-based whole slide imaging (WSI) system represents a low-cost and effective alternative to automatic scanners for telepathology. In a previous study, the development of one such solution, named scalable whole slide imaging (sWSI), was presented and analyzed. A clinical evaluation of its iOS version with 100 frozen section samples verified the diagnosis-readiness of the produced virtual slides., Objective: The first aim of this study was to delve into the quantifying issues encountered in the development of an Android version. It should also provide insights into future high-resolution real-time feedback medical imaging apps on Android and invoke the awareness of smartphone manufacturers for collaboration. The second aim of this study was to further verify the clinical value of sWSI with cytology samples. This type is different from the frozen section samples in that they require finer detail on the cellular level., Methods: During sWSI development on Android, it was discovered that many models do not support uncompressed camera pixel data with sufficient resolution and full field of view. The proportion of models supporting the optimal format was estimated in a test on 200 mainstream Android models. Other factors, including slower processing speed and camera preview freezing, also led to inferior performance of sWSI on Android compared with the iOS version. The processing speed was mostly determined by the central processing unit frequency in theory, and the relationship was investigated in the 200-model simulation experiment with physical devices. The camera preview freezing was caused by the lag between triggering photo capture and resuming preview. In the clinical evaluation, 100 ThinPrep cytology test samples covering 6 diseases were scanned with sWSI and compared against the ground truth of optical microscopy., Results: Among the tested Android models, only 3.0% (6/200) provided an optimal data format, meeting all criteria of quality and efficiency. The image-processing speed demonstrated a positive relationship with the central processing unit frequency but to a smaller degree than expected and was highly model-dependent. The virtual slides produced by sWSI on Android and iOS of ThinPrep cytology test samples achieved similar high quality. Using optical microscopy as the ground truth, pathologists made a correct diagnosis on 87.5% (175/200) of the cases with sWSI virtual slides. Depending on the sWSI version and the pathologist in charge, the kappa value varied between .70 and .82. All participating pathologists considered the quality of the sWSI virtual slides in the experiment to be adequate for routine usage., Conclusions: Limited by hardware and operating system support, the performance of sWSI on mainstream Android smartphones did not fully match the iOS version. However, in practice, this difference was not significant, and both were adequate for digitizing most of the sample types for telepathology consultation., (©Yu-Ning Huang, Xing-Chun Peng, Shuoxin Ma, Hong Yu, Yu-Biao Jin, Jun Zheng, Guo-Hui Fu. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 04.04.2018.)

Objective: To investigate the effect of dexmedetomidine at maintenance dose on the postoperative function of elder patients after general anesthesia for laparoscopic ovarian cystectomy., Methods: We enrolled a total of 96 elder patients who were admitted to this hospital for laparoscopic ovarian cystectomy under general anesthesia between March 2015 and March 2017, and divided them into two groups, Group A (n = 48) and B (n = 48). Patients in both groups received the same methods for anesthesia induction and maintenance drugs. At the beginning of operation, patients in Group A received the intravenous injection of dexmedetomidine (0.8 μg/kg) followed by maintenance dose [0.5 μg/(kg h)] to the end of operation, while those in Group B underwent intravenous injection of 0.9% normal saline at the same rate, during which blood pressure, heart rate, oxyhemoglobin saturation and dosage of anesthetics at T1 (5 min after being delivered into the operation room), T2 (immediately after anesthesia induction), T3 (immediately after intubation), T4 (immediately after operation), T5 (immediately after end of operation) and T6 (immediately after extubation). Then, the levels of NSE, IL-6, CRP and HMGB1 were compared between two groups at 24 h before the operation, at the end, 24 h, 3 d and 7 d after operation. Besides, we also compared the postoperative cognitive functions and incidence of adverse reactions at 1 d before, 1, 2, 3 and 7 d after operation through MOCA scales., Results: At T3, T4 and T6, comparisons of the average arterial pressure and heart rate showed that the differences between the two groups had statistical significance ( p  < .05). At the end of operation, and at 24 h, 3 d and 7 d after operation, we found that the levels of IL-6 and CRP in patients of two groups were all significantly elevated when compared with those before operation; at the end of operation and at 24 h and 3 d after operation, the levels of IL-6 and CRP in the Group B were higher than those in the Group A, and the differences had statistical significance ( p  < .05). At the end of operation and at 24 h and 3 d after operation, the levels of NSE and HMGB1 in two group were higher than those before operation, and a more significant elevation was identified in Group B with statistically significant differences ( p  < .05); at 7 d after operation, a decreasing trend was found in the level of HMGB1, which, however, remained higher than the preoperative level, and the level in Group B was still higher than that in Group A with statistically significant differences ( p  < .05). At 2 d after operation, we found that the scores of MOCA in the Group B were remarkably decreased in comparison with the scores in Group A with a statistically significant difference ( p  < .05). Moreover, the incidence rate of postoperative cognitive dysfunction (POCD) in the Group A was significantly lower than that in the Group B, and the difference had statistical significance ( p  < .05)., Conclusion: Dexmedetomidine can ameliorate the postoperative cognitive functions of elder patients who received the laparoscopic ovarian cystectomy under general anesthesia, and effectively decrease the incidence rate of POCD without any obvious or severe adverse reaction. Thus, it can serve as a kind of adjuvant drug for general anesthesia in clinical practice.

Background: A direct correlation between hepatitis B virus DNA (HBV-DNA) and liver markers has not been identified in chronic hepatitis B (CHB) patients. However, the effect of HBV-DNA changes on liver markers remains unclear. We explored the association between decreased HBV-DNA and liver makers in CHB patients., Methods: Chronic hepatitis B patients who visited Jinhua Central Hospital twice were selected for analysis. Finally, 171 participants with a 1-log reduction in HBV-DNA between the two visits were enrolled as the case group, and 158 participants with no significant changes in HBV-DNA were enrolled as the control group., Results: There was no significant correlation between HBV-DNA and liver markers (P>.05). However, in longitudinal analysis, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT) were significantly different between the two tests (P<.05) in the case group. Conversely, there was no significant difference in the control group. When HBV-DNA decreased >26 times, ALT was reduced by half or more. A similar trend was observed with a decrease of >63 times for AST and a decrease of >76 times for GGT., Conclusions: A large change in HBV-DNA can lead to a significant variation in liver markers. In particular, ALT was more sensitive than other liver markers to a reduction in HBV-DNA., (© 2017 Wiley Periodicals, Inc.)

N-stearoylthrosine (NST), a synthesized anandamide (AEA) analogue, plays a neuroprotective role in neurodegenerative diseases and cerebrovascular diseases. Several studies have demonstrated that the endocannabinoids systems (ECS) are involved in the neuroprotective effects against cerebral ischemic injury. Oxygen-glucose deprivation (OGD)-induced neuronal injury elevated the levels of endocannabinoids and activated ECS. This research was conducted to investigate the neuroprotective effect of NST against OGD-induced neuronal injury in cultured primary cortical neurons and the potential mechanism involved. Cortical neurons were treated with NST at indicate concentrations for 30min prior to injury and OGD injured neurons were incubated with normal conditions for 0-24h. The best neuroprotective effect of NST against OGD-induced injury occurred at 10μM. All data indicated that the neuroprotective effect of NST against OGD-induced injury resulted from blocking anandamide membrane transporter (AMT) (IC 50 =11.74nM) and inhibiting fatty acid amide hydrolase activity (FAAH) (IC 50 =16.54nM). Our findings demonstrated that NST has an important role in cerebral ischemic injury pathological progression through activating cannabinoid receptors by inhibiting AEA inactivation system. These data suggested a potential role for NST in the therapeutic consideration of cerebral ischemic injury. However, inhibition of AEA inactivation system may provide a neuroprotective effect during cerebral ischemic injury., (Copyright © 2017. Published by Elsevier B.V.)

Zinc pyrithione (ZPT) is a broad-spectrum antibacterial and antifungal agent; therefore, it is widely used in industry and civilian life. It is discharged into the aquatic environment with industrial and civilian waste water. Carassius sp. is one of the most widely distributed and farmed fish in China. The effects of aquatic ZPT on Carassius sp. remain unknown. In this study, we determined the acute toxicity of ZPT on Carassius sp. The results showed that the median lethal concentration (LC50 96 h) of ZPT on Carassius sp. cultivated in freshwater or water with 1.5 or 3 ‰ salinity was 0.163, 0.126, and 0.113 mg/L, respectively. ZPT has a higher affinity to the liver than the kidney, with a prolonged tissue residual time. P-glycoprotein (P-gp), an ATP-binding cassette transporter, was found to be induced in the liver and kidney tissues of these Carassius spp. after ZPT treatment, based on the determination of its mRNA and protein levels by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry, respectively. The ZPT accumulation and magnitude of P-gp induction were also affected by the salinity of the cultivation water. These results suggest that aquatic ZPT is potentially toxic to Carassius sp. We speculate that P-gp induction may play a protective role for Carassius sp. Our findings provide a basis for assessing the potential risk of ZPT to aquatic animals including Carassius sp.

Gastric cancer (GC) is a leading cause of cancer-related death worldwide and the pathogenesis of GC remains largely unknown. Here, we demonstrate a novel mechanism by which P300/CBP associating factor (PCAF) acts as a tumor suppressor in GC cells. We showed that both PCAF mRNA and protein were downregulated in GC cells, and that this downregulation correlated with poor survival. Meanwhile, the interaction between human anion exchanger 1 (AE1) and p16 is a key event in GC development. We found that PCAF inhibited GC growth by interacting with AE1 and p16 to promote ubiquitin-mediated degradation of AE1 and p16 upregulation and translocation into the nucleus. Binding of nuclear p16 to CDK4 prevented the CDK4-Cyclin D1 interaction to inhibit GC proliferation. Furthermore, reduced PCAF levels in GC cells were associated with intracellular alkalinization and decreased immunity. Together these results suggest that PCAF acts as a GC suppressor through a novel PCAF-p16-CDK4 axis. The downregulation of PCAF expression in GC cells that follows intracellular alkalinization and decreased immune response, indicates that GC therapies should focus on restoring PCAF levels.

Objective: Previous animal studies showed contradictory clinical observations on whether acute hyperglycemia contributes to poor outcome in traumatic brain injury (TBI). Herein, we tried to clarify this issue., Methods: Striking with depths of 3.0-4.25mm at right occipitoparietal brain region and with depth of 3.75mm at right/left occipitoparietal or right/left frontoparietal brain region were performed, respectively. Blood glucose and insulin levels were traced every four hours from 1 to 72h after striking. HOMA2-%S and HOMA2-%β were calculated. Modified neurological severity scores (mNSS) were used to evaluate neurological deficit within 72h., Results: Striking with depths of 3.5-4.25mm induced increase in blood glucose lasting up to 24h after striking. The levels of blood glucose after striking with depths of 3.75-4.25mm were significantly different from that of striking with the depth of 3.0mm. Striking with depth of 3.75mm at right/left occipitoparietal region induced higher blood glucose in 24h than that at right/left frontoparietal region. Insulin concentration increased slowly during 72h after striking. Striking also induced decrease in insulin sensitivity and secretion lasting 72h. Evaluation of mNSS revealed that severe striking (beyond 3.75mm) worsened nerve function than slight striking (<3.0mm). Intervention of acute hyperglycemia could decrease the mNSS from 2 to 7 days after TBI., Conclusion: Our results suggested that only severe TBI could induce acute hyperglycemia by itself, and early care of acute hyperglycemia could benefit the outcome of TBI patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Human anion exchanger 1 and 2 (AE1 and AE2) mediate the exchange of Cl(-)/HCO3 (-) across the plasma membrane and regulate intracellular pH (pHi). AE1 is specifically expressed on the surface of erythrocytes, while AE2 is widely expressed in most tissues, and is particularly abundant in parietal cells. Previous studies showed that an interaction between AE1 and p16 is a key event in gastric cancer (GC) progression, but the importance of AE2 in GC is unclear., Methods: The relationship among AE1, AE2 and p16 in GC cells was characterized by molecular and cellular experiments. AE2 expression and pHi were measured after knockdown or forced expression of AE1 or p16 in GC cells. The effect of AE2 on GC growth and the correlation of AE2 expression with differentiation and prognosis of GC were also evaluated. The effect of gastrin on AE2 expression and GC growth was investigated in cellular experiments and mouse xenograft models., Results: p16 binds to both AE1 and AE2 simultaneously. AE1 or p16 silencing elevated AE2 expression on the plasma membrane where it plays a role in pHi regulation and GC suppression. AE2 expression was decreased in GC tissue, and these decreased levels were correlated with poor differentiation and prognosis of GC. The low AE2 protein levels are due to rapid ubiquitin-mediated degradation that was facilitated in the presence of p16. Gastrin inhibited the growth of GC cells at least partially through up-regulation of AE2 expression., Conclusion: AE1/p16 expression promoted AE2 degradation in GC cells. Gastrin is a potential candidate drug for targeted therapies for AE1- and p16-positive GC.

A restriction fragment length polymorphism combined with direct PCR technique to differentiate goose and Muscovy duck parvoviruses (GPV and MDPV) was developed based on comparison of the NS gene of GPV and MDPV. Both GPV and MDPV genomic DNA can be amplified with 641 bp using the specific PCR primers. The PCR fragments can be cut into 463 bp and 178 bp only in the case of MDPV-derived PCR products, whereas the GPV-derived PCR products cannot. The method established in this study can be used to differentiate GPV and MDPV with high specificity and precision, by using a direct PCR kit and QuickCut enzyme, as quickly as conventional PCR.

The pathogenesis of osteosarcoma involves complex genetic and epigenetic factors. This study was to explore the impact and clinical relevance of long non-coding RNA (lncRNA), Taurine up-regulated gene 1 (TUG1) on patients with osteosarcoma. Seventy-six osteosarcoma tissues and matched adjacent normal tissues were included for analysis. The plasma samples were obtained from 29 patients with osteosarcoma at pre-operation and post-operation, 42 at newly diagnosed, 18 who experienced disease progression or relapse, 45 post-treatment, 36 patients with benign bone tumor, and 20 healthy donors. Quantitative real-time reverse transcript polymerase chain reactions were used to assess the correlation of the expression levels of TUG1 with clinical parameters of osteosarcoma patients. TUG1 was significantly overexpressed in the osteosarcoma tissues compared with matched adjacent normal tissues (P < 0.01) and was closely correlated with tumor size, post-operative chemotherapy, and Enneking surgical stage. Upregulation of TUG1 strongly correlated with poor prognosis and was an independent prognostic indicator for overall survival (HR = 2.78, 95% CI = 1.29-6.00, P = 0.009) and progression-free survival (HR = 1.81, 95% CI = 1.01-3.54, P = 0.037). Our constructed nomogram containing TUG1 had more predictive accuracy than that without TUG1 (c-index 0.807 versus 0.776, respectively). In addition, for plasma samples, TUG1 expression levels were obviously decreased in post-operative patients (mean ΔCT -4.98 ± 0.22) compared with pre-operation patients (mean ΔCT -6.09 ± 0.74), and the changes of TUG1 expression levels were significantly associated with disease status. Receiver operating characteristic (ROC) curve analysis demonstrated that TUG1 could distinguish patients with osteosarcoma from healthy individuals compared with alkaline phosphatase (ALP) (the area under curve 0.849 versus 0.544). TUG1 was overexpressed in patients with osteosarcoma and strongly correlated with disease status. In addition, TUG1 may serve as a molecular indicator in maintaining surveillance and forecasting prognosis.

Residual periosteum developed periosteal bone formation in the pocket 10 years after cranioplasty, lumpectomy was conducted on the left lower abdomen under local anesthesia. Pathological sections revealed abundant osteocytes and mature bone matrix, and confirmed the bone formation on the residual periosteum.

Tilapia is the common name for a group of cichlid fishes. Identification of DNA markers significantly associated with important traits in candidate genes may speed up genetic improvement. L-Amino acid oxidase (LAO) plays a crucial role in the innate immune defences of animals. Previously, whether LAO variants were associated with economic traits had not been studied in fish. We characterized the cDNA sequence of the LAO gene of hybrid tilapia (Oreochromis spp.). Its ORF was 1536 bp, encoding a flavoenzyme of 511 amino acids. This gene consisted of seven exons and six introns. Its expression was detected in the intestine, blood, kidney, skin, liver. It was highly expressed in the intestine. After a challenge with a bacterial pathogen, Streptococcus agalactiae, its expression was up-regulated significantly in the liver, intestine and spleen (P < 0.05). We identified one SNP in the genomic sequence of the gene and found that this SNP was associated significantly with body length (P < 0.05), but not with resistance to S. agalactiae. The results of this study suggest that the LAO gene plays an important role in innate immune responses to the bacterial pathogen in tilapia. The investigation of relationship between polymorphism of LAO gene and disease resistance and growth in tilapia showed that one SNP was associated significantly with body length. Further experiments on whether SNPs in the LAO gene are associated with growth in tilapia and other populations could be useful in understanding more functions of the LAO gene.

Background: Administration of trastuzumab, a fully humanized monoclonal antibody targeted to the human epidermal growth factor receptor 2 (HER2, p185), has improved outcomes for patients with HER2-positive gastric cancer (GC), but some relevant issues remain to be investigated and will emerge with new anti-GC drugs. Gastrin is a major gastrointestinal hormone proven to have an inhibitory effect on GC in vitro and in vivo., Aim: To explore the sympathetic role of trastuzumab and gastrin on inhibition of GC., Methods: The HER2-positive and HER2-negative GC cell lines were treated with trastuzumab, gastrin, or their combination in vitro and in xenograft model. The synergistical role of trastuzumab and gastrin and related mechanisms were investigated., Results: We found the synergistic inhibitory effects of trastuzumab and gastrin on HER2-negative GC cells through the gastrin/cholecystokinin B receptor (CCKBR) pathway. Trastuzumab upregulated CCKBR protein levels but could not initiate its signal transduction, whereas gastrin increased the levels and activation of CCKBR. Molecular experiments indicated that trastuzumab and gastrin co-treatment synergistically enhanced the stability of CCKBR. Moreover, their combined treatment synergistically arrested GC cells at G0/G1 phase, down-regulated levels of GC-related proteins, including anion exchanger 1 (AE1), cyclin D1, β-catenin, and cytoplasmic p16, and promoted nuclear translocation of p16. In addition, combination treatment upregulated AE2 levels, which are reduced in GC tissues. The in vivo synergistic anti-GC effect of combined treatment was confirmed in xenograft experiments., Conclusions: Trastuzumab plus gastrin inhibit growth of Her2-negative GC by targeting cytoplasmic AE1 and p16.