Search

BackgroundThe Chinese government recently introduced a program to buy medical supplies in bulk to reduce the patient cost burden. For patients undergoing percutaneous coronary intervention (PCI), little is known about the effect on outcomes of this bulk-buy program.AimsThis study investigated whether the bulk-buy program to decrease the price of stents used in PCI affected clinical decision-making and outcomes.MethodsThis single-center study enrolled patients undergoing PCI from January 2020-December 2021. Prices decreased for stents on January 1, 2021, and balloons on March 1, 2021. Patients were grouped by surgical year as either before (2020) or after (2021) policy implementation. All clinical data were collected. To examine whether clinical decision-making for PCI was affected by the bulk-buy program, procedure appropriateness was analyzed using the 2017 appropriate use criteria (AUC). To assess outcomes, the rates of major adverse cardiac and cerebrovascular events (MACCE) and complications were compared between groups.ResultsStudy participants were 601 patients in 2020 (before bulk buying) and 699 patients in 2021 (after bulk buying). Results of analysis by AUC for procedure appropriateness were 74.5% appropriate, 21.6% may be appropriate, and 3.8% rarely appropriate in 2020, with no differences for patients who underwent PCI in 2021. Between-group comparisons showed MACCE rates of 0.5% in 2020 and 0.6% in 2021, whereas complication rates were 5.5% and 5.7%, respectively. No statistically significant differences were found between groups (p > 0.05).ConclusionThe bulk-buy program did not impact physician clinical decision-making or surgical outcomes for patients undergoing PCI.

BackgroundAnopheles stephensi Listen (1901) is a major vector of malaria in Asia and has recently been found in some regions of Africa. The An. stepehnsi species complex is suspected to have three sibling species: type, intermediate, and mysorensis, each with its own vector competence to the malaria parasite and ecology. To identify the members of the species complex in our An. stephensi insectary colony, we used the morphological features of eggs and genetic markers such as AnsteObp1 (Anopheles stephensi odorant binding protein 1), mitochondrial oxidases subunit 1 and 2 (COI and COII), and nuclear internal transcribed spacer 2 locus (ITS2).MethodsEggs were collected from individual mosquitoes (n = 50) and counted for the number of ridges under stereomicroscope. Genomic DNA was extracted from female mosquitoes. After the amplification of partial fragments of AnsteObp1, COI, COII and ITS2 genes, the PCR products were purified and sequenced. Phylogenetic analysis was performed after aligning query sequences against the submitted sequences in GenBank using MEGA 7.ResultsThe range of ridges number on each egg float was 12-13 that corresponds to the mysorensis form of An. stephensi. The generated COI, COII and ITS2 sequences showed 100%, 99.46% and 99.29% similarity with the sequences deposited for Chinese, Indian and Iranian strains of An. stephensi, respectively. All the generated AnsteObp1 intron I region sequences matched 100% with the sequences deposited for An. stephensi sibling species C (mysorensis form) from Iran and Afghanistan.ConclusionsThis manuscript precisely describes the morphological and molecular details of the 'var mysorensis' form of An. stephensi that could be exploited in elucidating its classification as well as in differentiation from other biotypes of the same or other anopheline species. Based on our findings, we recommend AnsteObp1 as a robust genetic marker for rapid and accurate discrimination (taxonomic identification) of the An. stephensi species complex, rather than the COI, COII, and ITS2 marker, which could only be utilized for interspecies (Anopheles) differentiation.

In the field of object detection, domain adaptation is one of popular solution to align the distribution between the real scene (target domain) and the training scene (source domain) by adversarial training. However, only global features are applied to the Domain Adaptive Faster R-CNN (DA Faster R-CNN) method. The lack of local features reduces the performance of domain adaptation. Therefore, a novel method for domain adaptive detection called Skip-Layer Network with Optimization (SLNO) method is proposed in this paper. Three improvements are presented in SLNO. Firstly, different level convolutional features are fused by a multi-level features fusion component for domain classifier. Secondly, a multi-layer domain adaptation component is developed to align the image-level and the instance-level distributions simultaneously. Among this component, domain classifiers are used in both image-level and instance-level distributions through the skip layer. Thirdly, the cuckoo search (CS) optimization method is applied to search for the best coefficient of SLNO. As a result, the capability of domain alignment is strengthened. The Cityscapes, Foggy Cityscapes, SIM10K, KITTI data sets are applied to test our proposed novel approach. Consequently, excellent results are achieved by our proposed methods against state-of-the-art object detection methods. The results demonstrate our improvements are effective on domain adaptation detection.

Unmanned ground vehicles (UGVs) are an important research application of artificial intelligence. In particular, the deep learning-based object detection method is widely used in UGV-based environmental perception. Good experimental results are achieved by the deep learning-based object detection method Faster region-based convolutional neural network (Faster R-CNN). However, the exploration space of the region proposal network (RPN) is restricted by its expression. In our paper, a boosted RPN (BRPN) with three improvements is developed to solve this problem. First, a novel enhanced pooling network is designed in this paper. Therefore, the BRPN can adapt to objects with different shapes. Second, the expression of BRPN loss function is improved to learn the negative samples. Furthermore, the grey wolf optimizer (GWO) is used to optimize the parameters of the improved BRPN loss function. Thereafter, the performance of the BRPN loss function is promoted. Third, a novel GA-SVM classifier is applied to strengthen the classification capacity. The PASCAL VOC 2007, VOC 2012 and KITTI datasets are used to test the BRPN. Consequently, excellent experimental results are obtained by our deep learning-based object detection method.

Accurate and reliable state estimation and mapping are the foundation of most autonomous driving systems. In recent years, researchers have focused on pose estimation through geometric feature matching. However, most of the works in the literature assume a static scenario. Moreover, a registration based on a geometric feature is vulnerable to the interference of a dynamic object, resulting in a decline of accuracy. With the development of a deep semantic segmentation network, we can conveniently obtain the semantic information from the point cloud in addition to geometric information. Semantic features can be used as an accessory to geometric features that can improve the performance of odometry and loop closure detection. In a more realistic environment, semantic information can filter out dynamic objects in the data, such as pedestrians and vehicles, which lead to information redundancy in generated map and map-based localization failure. In this paper, we propose a method called LiDAR inertial odometry (LIO) with loop closure combined with semantic information (LIO-CSI), which integrates semantic information to facilitate the front-end process as well as loop closure detection. First, we made a local optimization on the semantic labels provided by the Sparse Point-Voxel Neural Architecture Search (SPVNAS) network. The optimized semantic information is combined into the front-end process of tightly-coupled light detection and ranging (LiDAR) inertial odometry via smoothing and mapping (LIO-SAM), which allows us to filter dynamic objects and improve the accuracy of the point cloud registration. Then, we proposed a semantic assisted scan-context method to improve the accuracy and robustness of loop closure detection. The experiments were conducted on an extensively used dataset KITTI and a self-collected dataset on the Jilin University (JLU) campus. The experimental results demonstrate that our method is better than the purely geometric method, especially in dynamic scenarios, and it has a good generalization ability.

[This corrects the article DOI: 10.1371/journal.pone.0050093.].

Nuclear factor erythroid 2-related factor 2 (NRF2) functions as a transcription factor and regulates a wide array of antioxidant and stress-responsive genes. NRF2 has been widely implicated in different types of cancers, but only limited studies concerning the relationship between NRF2 expression and tumour invasion or prognosis in lung cancer. Therefore, we conducted a meta-analysis to determine the prognostic value of NRF2 in patients with non-small cell lung cancer (NSCLC). The relationship between NRF2 expression in NSCLC patients and clinicopathological features was also investigated. Overall survival (OS) and treatment response rate were evaluated using STATA software. Twenty eligible articles with 2530 lung cancer patients were included in this meta-analysis. The results revealed that high expression level of NRF2 was associated with pathologic distant metastasis (odds ratio (OR) = 2.64, 95% confidence interval (CI) 1.62-4.31; P < 0.001), lymph node metastasis (OR = 2.14, 95% CI: 1.53-3.00; P < 0.001), and tumour node metastasis (TNM) stage (OR = 1.95, 95% CI: 1.52-2.49, P < 0.001). High NRF2 expression was associated with low treatment response rate in platinum-based chemotherapy (HR = 0.11, 95% CI 0.02-0.51; P = 0.005). High expression level of NRF2 is predictive for poor overall survival rate (HR = 1.86, 95% CI 1.44-2.41, P < 0.001) and poor progression-free survival (PFS) (HR = 2.27, 95% CI 1.26-4.09, P = 0.006). Compared to patients with a low level of NRF2 expression, patients with high NRF2 expression levels were associated with worse OS and PFS when given the chemotherapy or EGFR-TKI. Together, our meta-analysis results suggest that NRF2 can act as a potential indicator of NSCLC tumour aggressiveness and help the prognosis and design of a better treatment strategy for NSCLC patients.

Bike-sharing systems (BSS) have widely spread over many cities in the world as an environmentally friendly means to reduce air pollution and traffic congestion. This paper focuses on the bike-sharing rebalancing problem (BRP), which consists of two aspects: determining desired demands at each station and designing routes to redistribute bikes among stations. For the first task, we firstly apply the random forest, a very efficient machine learning algorithm, to forecast desired demands for each station, which can be easily implemented with distributed computing. For the second task, it belongs to the broad class of the vehicle routing problem with pickup and delivery (VRPPD). In most existing settings, all of the demands being strictly satisfied can lead to longer routes and add operational costs. In this paper, we propose a new model with unserved demands by relaxing demands satisfying constraints. Then, we design a distributed ant colony optimization (ACO) based algorithm with some specific modifications to increase its efficiency for the proposed model. We propose to use the percentage of average cost saving per bike as a metric to evaluate the performance of our method on cost-reducing and compare with existing methods and best-known values. Computational results on benchmarks show the advantage of our approach. Finally, we provide a real case study of BSS in Hangzhou, China, with insightful elaborations.

ObjectiveAn early onset of menarche and, later, menopause are well-established risk factors for the development of breast cancer and endometrial cancer. Although the largest GWASs have identified 389 independent signals for age at menarche (AAM) and 44 regions for age at menopause (ANM), GWAS can only identify the associations between variants and traits. The aim of this study was to identify genes whose expression levels were associated with AAM or ANM due to pleiotropy or causality by integrating GWAS data with genome-wide expression quantitative trait loci (eQTLs) data. We also aimed to identify the pleiotropic genes that influenced both phenotypes.MethodWe employed GWAS data of AAM and ANM and genome-wide eQTL data from whole blood. The summary data-based Mendelian randomization method was used to prioritize the associated genes for further study. The colocalization analysis was used to identify the pleiotropic genes associated with both phenotypes.ResultsWe identified 31 genes whose expression was associated with AAM and 24 genes whose expression was associated with ANM due to pleiotropy or causality. Two pleiotropic genes were identified to be associated with both phenotypes.ConclusionThe results point out the most possible genes which were responsible for the association. Our study prioritizes the associated genes for further functional mechanistic study of AAM and ANM and illustrates the benefit of integrating different omics data into the study of complex traits.

[This corrects the article DOI: 10.1371/journal.pone.0108324.].

Ascorbic acid (AsA), chlorophyll and carotenoid contents and their associated gene expression patterns were analysed in Actinidia chinensis 'Hongyang' outer pericarp. The results showed chlorophyll degradation during fruit development and softening, exposed the yellow carotenoid pigments. LHCB1 and CLS1 gene expressions were decreased, while PPH2 and PPH3 gene expressions were increased, indicating that downregulation of chlorophyll biosynthesis and upregulation of its degradation, caused chlorophyll degradation. A decrease in the expression of the late carotenoid biosynthesis and maintenance genes (LCYB1, LCYE1, CYP1, CYP2, ZEP1, VDE1, VDE2, and NCED2) and degradation gene (CCD1), showed biosynthesis and degradation of carotenoid could be regulatory factors involved in fruit development. Most genes expression data of L-galactose and recycling pathway were agreement with the AsA concentrations in the fruit, suggesting these are the predominant pathways of AsA biosynthesis. GMP1, GME1 and GGP1 were identified as the key genes controlling AsA biosynthesis in 'Hongyang' outer pericarp.

Faster Region-based Convolutional Network (Faster R-CNN) is a state-of-the-art object detection method. However, the object detection effect of Faster R-CNN is not good based on the Region Proposal Network (RPN). Inspired by RPN of Faster R-CNN, we propose a novel proposal generation method called Enhanced Region Proposal Network (ERPN). Four improvements are presented in ERPN. Firstly, our proposed deconvolutional feature pyramid network (DFPN) is introduced to improve the quality of region proposals. Secondly, novel anchor boxes are designed with interspersed scales and adaptive aspect ratios. Thereafter, the capability of object localization is increased. Thirdly, a particle swarm optimization (PSO) based support vector machine (SVM), termed PSO-SVM, is developed to distinguish the positive and negative anchor boxes. Fourthly, the classification part of multi-task loss function in RPN is improved. Consequently, the effect of classification loss is strengthened. In this study, our proposed ERPN is compared with five object detection methods on both PASCAL VOC and COCO data sets. For the VGG-16 model, our ERPN obtains 78.6% mAP on VOC 2007 data set, 74.4% mAP on VOC 2012 data set and 31.7% on COCO data set. The performance of ERPN is the best among the comparison object detection methods. Furthermore, the detection speed of ERPN is 5.8 fps. Additionally, ERPN obtains good effect on small object detection.

Androgen receptor (AR) is a member of the steroid receptor family and a therapeutic target for all stages of prostate cancer. AR is activated by ligand binding within its C-terminus ligand-binding domain (LBD). Here we show that overexpression of the AR NTD to generate decoy molecules inhibited both the growth and progression of prostate cancer in castrated hosts. Specifically, it was shown that lentivirus delivery of decoys delayed hormonal progression in castrated hosts as indicated by increased doubling time of tumor volume, prolonged time to achieve pre-castrate levels of serum prostate-specific antigen (PSA) and PSA nadir. These clinical parameters are indicative of delayed hormonal progression and improved therapeutic response and prognosis. Decoys reduced the expression of androgen-regulated genes that correlated with reduced in situ interaction of the AR with androgen response elements. Decoys did not reduce levels of AR protein or prevent nuclear localization of the AR. Nor did decoys interact directly with the AR. Thus decoys did not inhibit AR transactivation by a dominant negative mechanism. This work provides evidence that the AR NTD plays an important role in the hormonal progression of prostate cancer and supports the development of AR antagonists that target the AR NTD.

With the rapid development of information technology, scientific social networks (SSNs) have become the fastest and most convenient way for researchers to communicate with each other. Many published papers are shared via SSNs every day, resulting in the problem of information overload. How to appropriately recommend personalized and highly valuable papers for researchers is becoming more urgent. However, when recommending papers in SSNs, only a small amount of positive instances are available, leaving a vast amount of unlabelled data, in which negative instances and potential unseen positive instances are mixed together, which naturally belongs to One-Class Collaborative Filtering (OCCF) problem. Therefore, considering the extreme data imbalance and data sparsity of this OCCF problem, a hybrid approach of Social and Content aware One-class Recommendation of Papers in SSNs, termed SCORP, is proposed in this study. Unlike previous approaches recommended to address the OCCF problem, social information, which has been proved playing a significant role in performing recommendations in many domains, is applied in both the profiling of content-based filtering and the collaborative filtering to achieve superior recommendations. To verify the effectiveness of the proposed SCORP approach, a real-life dataset from CiteULike was employed. The experimental results demonstrate that the proposed approach is superior to all of the compared approaches, thus providing a more effective method for recommending papers in SSNs.

Altered brain function in patients with major depressive disorder (MDD) has been repeatedly demonstrated by task-based and resting-state studies, respectively. However, less is known concerning whether overlapped abnormalities in functional activities across modalities exist in MDD patients. To find out the answer, we implemented an fMRI experiment and collected both task and resting-state data from 19 MDD patients and 19 matched, healthy, controls. A distraction paradigm involving emotionally valenced pictures was applied to induce affective responses in subjects. As a result, concurrent deficits were found in arousing activation during a positive task in both the reward circuit and salience network (SN) that is composed of the dorsal part of anterior cingulate cortex (dACC) and bilateral anterior insulae (AI) in only the MDD group. Subsequent amplitude of low frequency fluctuations (ALFF) and functional connectivity analyses based on resting-state data exhibited consistent alterations in the bilateral AI of MDD patients, and indicated patients' difficulties in regulating the balance between central executive network (CEN) and default mode network (DMN) due to altered connectivity among the CEN, DMN, and SN. Our findings provide new evidence demonstrating impaired salience processing and resulting alterations in responses to positive stimuli in MDD patients. Furthermore, brain abnormalities synchronized across functional states in MDD patients can be evidenced by a combination of task and resting-state fMRI analyses.

This study evaluated the working memory performance of 18 patients experiencing their first onset of mild depression without treatment and 18 healthy matched controls. The results demonstrated that working memory impairment in patients with mild depression occurred when memorizing the position of a picture but not when memorizing the pictures themselves. There was no significant difference between the two groups in the emotional impact on the working memory, indicating that the attenuation of spatial working memory was not affected by negative emotion; however, cognitive control selectively affected spatial working memory. In addition, the accuracy of spatial working memory in the depressed patients was not significantly reduced, but the reaction time was significantly extended compared with the healthy controls. This finding indicated that there was no damage to memory encoding and function maintenance in the patients but rather only impaired memory retrieval, suggesting that the extent of damage to the working memory system and cognitive control abilities was associated with the corresponding depressive symptoms. The development of mild to severe depressive symptoms may be accompanied by spatial working memory damage from the impaired memory retrieval function extending to memory encoding and memory retention impairments. In addition, the impaired cognitive control began with an inadequate capacity to automatically process internal negative emotions and further extended to impairment of the ability to regulate and suppress external emotions. The results of the mood-congruent study showed that the memory of patients with mild symptoms of depression was associated with a mood-congruent memory effect, demonstrating that mood-congruent memory was a typical feature of depression, regardless of the severity of depression. This study provided important information for understanding the development of cognitive dysfunction.

Some studies reported that probiotic could relieve allergy-induced damage to the host, but how to get a useful probiotic is still a challenge. In this study, the protective effects of three lactic acid bacteria (La, Lp and Lc) were evaluated in a mouse model, and its relationship with the in vitro properties was analyzed. The in vitro results indicated that La with the capacity to inhibit IL-4 production could have a better anti-allergy effect in vivo than two others. However, the animal trials showed that all LAB strains could alleviate allergen-induced airway inflammation. Among them, LAB strain Lp had a better effect in inhibiting allergic response through a modulation of Th1/Th2 balance and an increase of regulatory T cells. This difference could be explained by that different LAB strains have a strain-specific effect on gut microbiota closely associated with host immune responses. Finally, this study did not only obtain an effective anti-allergy probiotic strain via animal study, but also indicate that probiotic-induced effect on intestinal microbiota should be considered as an important screening index, apart from its inherent characteristics.

Although microbial activity and associated iron (oxy)hydroxides are known in general to affect the environmental dynamics of 4-hydroxy-3-nitrobenzenearsonic acid (roxarsone), the mechanistic understanding of the underlying biophysico-chemical processes remains unclear due to limited experimental information. We studied how Shewanella oneidensis MR-1 -a widely distributed metal-reducing bacterium, in the presence of dissolved Fe(III), affects roxarsone transformations and biogeochemical cycling in a model aqueous system. The results showed that the MR-1 strain was able to anaerobically use roxarsone as a terminal electron acceptor and to convert it to a single product, 3-amino-4-hydroxybenzene arsonic acid (AHBAA). The presence of Fe(III) stimulated roxarsone transformation via MR-1-induced Fe(III) reduction, whereby the resulting Fe(II) acted as an efficient reductant for roxarsone transformation. In addition, the subsequent secondary Fe(III)/Fe(II) mineralization created conditions for adsorption of organoarsenic compounds to the yielded precipitates and thereby led to arsenic immobilization. The study provided direct evidence of Shewanella oneidensis MR-1-induced direct and Fe(II)-associated roxarsone transformation. Quantitative estimations revealed a candidate mechanism for the early-stage environmental dynamics of roxarsone in nature, which is essential for understanding the environmental dynamics of roxarsone and successful risk assessment.

Fusarium oxysporum is a soil-born fungus that induces wilt and root rot on a variety of plants. F. oxysporum f. sp. conglutinans (Foc) can cause wilt disease on cabbage. This study showed that a homolog of SIX1 protein in the Arabidopsis infecting isolate Fo5176 (Fo5176-SIX1) had four isoforms in the conidia of Foc by proteomic analysis. Thus, we analyzed the roles of protein Foc-SIX1. Gene expression analysis showed that, compared to the expression in mycelia, dramatically altered expression of Foc-SIX1 could be detected after infecting cabbages, and Foc-SIX1 was highly expressed in conidia under axenic culture condition. Furthermore, we knocked out the Foc-SIX1 gene and found that Foc-ΔSIX1 mutants had significantly reduced virulence compared with wild type isolate, and full virulence was restored by complementation of Foc-ΔSIX1 mutants with Foc-SIX1. Thus, we concluded that SIX1 in Foc was required for full virulence on cabbage. We also complemented Foc-ΔSIX1 with SIX1 gene in F. oxysporum f. sp. lycopersici (Fol) and found Foc-ΔSIX1::Fol-SIX1 mutants did not affect the virulence of Foc-ΔSIX1. The results confirmed that Fol-SIX1 was not capable of replacing the role of Foc-SIX1 in Foc on the disease symptom development of cabbage. The roles of Fol-SIX1 on virulence might rely on host specificity.

Acquired resistance to tamoxifen remains a major obstacle in breast cancer (BC) treatment, since the underlying mechanism has not been fully elucidated. The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated and plays important roles in progression of breast cancer. In the present study, we aimed to investigate the biological role and clinical significance of UCA1 in BC drug resistance. Hence, we used quantitative PCR assay to evaluate the UCA1 expression in tissues from patients with BC as well as established tamoxifen-resistant BC cell lines in vitro. We tested the viability, invasive ability and apoptosis rate in MCF-7 and T47D cells using MTT assay, transwell assay and flow cytometry assay, respectively. The influence of UCA1 on tumorigenesis was monitored by in vivo mice xenograft model. The activation of Wnt/β-catenin signaling pathway was evaluated by immunofluorescence assay, western blot assay and luciferase reporter assay, respectively. We found that the expression of UCA1 positively correlated with the pathological grade and mortality of breast cancer patients, moreover, expressions of UCA1 was increased significantly in the tamoxifen-resistant cell lines compared with the wild type parental cells. Ectopic expression of UCA1 promoted cell survival and resistance to tamoxifen treatment, whereas inhibition of UCA1 enhanced tamoxifen sensitivity of BC cells and induced more apoptotic cells. In addition, tamoxifen-resistant cells exhibited increased Wnt signaling activation as measured by the TOP/FOP Wnt luciferase reporter assay and β-catenin protein level compared with parental MCF-7 and T47D cells, respectively. In line with these data, UCA1 depletion attenuated the activity of Wnt/β-catenin pathway activation and the tumorigenicity of the tamoxifen-resistant BC cells. Taken together, our data highlights the pivotal role of UCA1-Wnt/β-catenin signaling pathway in the tamoxifen resistance in breast cancer, which could be targeted to improve the effectiveness and efficacy of tamoxifen treatment in breast cancer.

Duration of untreated psychosis (DUP) is a potentially modifiable prognostic factor of course and prognosis of psychiatric disorders. Few studies have demonstrated that different cultural backgrounds or perspectives on psychosis may be important factors to the DUP. This study attempted to explore whether the DUP was different in Chinese and Mauritians and to clarify potential influencing factors to a long DUP (>3 months).200 patients from China and 100 patients from Mauritius were enrolled in the study. Their respective family members were also recruited. Demographic and clinical characteristics were collected, and the Internalized Stigma of Mental Illness (ISMI) scale was adapted to measure the stigma in all subjects. Binary logistic regression analysis was used to find the potential influencing factors to the long DUP.35.3% of the enrolled patients had a long DUP. No significant difference was found in frequency of long DUP between the two countries. Chinese patients had relatively less perceptions of stigma. Furthermore, Chinese patients with a long DUP had more perception of breakup due to mental illness (OR = 2.22, p = 0.04) and more families' perception of the patient being disinherited due to mental illness (OR = 6.47, p = 0.01). Mauritian patients with a long DUP were less likely to have high monthly income (OR = 0.12, p

Previously, we demonstrated that the highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) HuN4 strain causes obvious thymic atrophy and thymocytes apoptosis in infected piglets after birth, which is more severe than that induced by classical PRRSV. In this study, we investigated apoptosis and autophagy in the thymus of piglets infected with the HP-PRRSV HuN4 strain, and found that both apoptosis and autophagy occurred in the thymus of piglets infected with HP-PRRSV. In addition to a few virus-infected cells, CD14+ cells, the main autophagic cells in the thymus were thymic epithelial cells. These findings demonstrated that HP-PRRSV induces apoptosis in bystander cells, and induces autophagy in both infected and bystander cells in the thymus of infected piglets. Herein, we first present new data on the thymic lesions induced by HP-PRRSV, and show that apoptosis and autophagy are key mechanisms involved in cell survival and determinants of the severity of thymic atrophy in infected piglets. Finally, future studies of the mechanism underlying immune responses are proposed based on our current understanding of PRRSV-host interactions.

Antioxidant activity of lactic acid bacteria is associated with multiple health-protective effects. Traditional indexes of chemical antioxidant activities poorly reflect the antioxidant effects of these bacteria in vivo. Cellular antioxidant activity (CAA) assay was used in this study to determine the antioxidant activity of cell-free supernatants (CFSs) of 10 Lactobacillus strains. The performance of the CAA assay was compared with that of four chemical antioxidant activity assays, namely, DPPH radical scavenging, hydroxyl radical scavenging (HRS), reducing power (RP), and inhibition of linoleic acid peroxidation (ILAP). Results of the CAA assay were associated with those of DPPH and ILAP assays, but not with those of RP and HRS assays. The inter- and intra-specific antioxidant activities of CFS were characterized by chemical and CAA assays. L. rhamnosus CCFM 1107 displayed a high antioxidative effect similar to positive control L. rhamnosus GG ATCC 53103 in all of the assays. The CAA assay is a potential method for the detection of antioxidant activities of lactobacilli CFSs.

Microwaves are used in one method of physical therapy and can increase muscle tissue temperature which is useful for improving muscle, tendon and bone injuries. In the study, we sought to determine whether titanium alloy internal fixations influence apoptosis in tissues subjected to microwave treatments at 2,450 MHz and 40 W during the healing of fractures because this issue is not yet fully understood.In this study, titanium alloy internal fixations were used to treat 3.0-mm transverse osteotomies in the middle of New Zealand rabbits' femurs. After the operation, 30-day microwave treatments were applied to the 3.0 mm transverse osteotomies 3 days after the operation. The changes in the temperatures of the muscle tissues in front of the implants or the 3.0 mm transverse osteotomies were measured during the microwave treatments. To characterize the effects of titanium alloy internal fixations on apoptosis in the muscles after microwave treatment, we performed TUNEL assays, fluorescent real-time (quantitative) PCR, western blotting analyses, reactive oxygen species (ROS) detection and transmission electron microscopy examinations.The temperatures were markedly increased in the animals with the titanium alloy implants. Apoptosis in the muscle cells of the implanted group was significantly more extensive than that in the non-implanted control group at different time points. Transmission electron microscopy examinations of the skeletal muscles of the implanted groups revealed muscular mitochondrial swelling, vacuolization. ROS, Bax and Hsp70 were up-regulated, and Bcl-2 was down-regulated in the implanted group.Our results suggest that titanium alloy internal fixations caused greater muscular tissue cell apoptosis following 2,450 MHz, 40 W microwave treatments in this rabbit femur fracture models.

Since the association of serum uric acid and kidney transplant graft outcome remains disputable, we sought to evaluate the predictive value of uric acid level for graft survival/function and the factors could affect uric acid as time varies. A consecutive cohort of five hundred and seventy three recipients transplanted during January 2008 to December 2011 were recruited. Data and laboratory values of our interest were collected at 1, 3, 6, 12, 24 and 36 months post-transplant for analysis. Cox proportional hazard model, and multiple regression equation were built to adjust for the possible confounding variables and meet our goals as appropriate. The current cohort study lasts for 41.86 ± 15.49 months. Uric acid level is proven to be negatively associated with eGFR at different time point after adjustment for age, body mass index and male gender (standardized β ranges from -0.15 to -0.30 with all P

Recently, using the patient's genotype to guide warfarin dosing has gained interest; however, whether pharmacogenetics-based dosing (PD) improves clinical outcomes compared to conventional dosing (CD) remains unclear. Thus, we performed a meta-analysis to evaluate these two strategies.The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese VIP and Chinese Wan-fang databases were searched. The Cochrane Collaboration's tool was used to assess the risk of bias in randomized controlled trials (RCTs). The primary outcome was time within the therapeutic range (TTR); the secondary end points were the time to maintenance dose and time to first therapeutic international normalized ratio (INR), an INR greater than 4, adverse events, major bleeding, thromboembolism and death from any cause.A total of 11 trials involving 2,678 patients were included in our meta-analysis. The results showed that PD did not improve the TTR compared to CD, although PD significantly shortened the time to maintenance dose (MD = -8.80; 95% CI: -11.99 to -5.60; P

To evaluate the diagnostic value of the Inlet-to-outlet median nerve area ratio (IOR) in patients with clinically and electrophysiologically confirmed carpal tunnel syndrome (CTS).Forty-six wrists in 46 consecutive patients with clinical and electrodiagnostic evidence of CTS and forty-four wrists in 44 healthy volunteers were examined with ultrasonography. The cross-sectional area (CSA) of the median nerve was measured at the carpal tunnel inlet (the level of scaphoid-pisiform) and outlet (the level of the hook of the hamate), and the IOR was calculated for each wrist. Ultrasonography and electrodiagnostic tests were performed under blinded conditions. Electrodiagnostic testing combined with clinical symptoms were considered to be the gold standard test. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value between the inlet CSA and IOR.The study population included 16 men and 30 women (mean age, 45.3 years; range, 18-83 years). The control population included 18 men and 26 women (mean age, 50.4 years; range, 18-79 years). The mean inlet CSA was 8.7 mm2 in healthy controls and 14.6mm2 in CTS group (P

Lactobacillus plantarum CCFM8246, which has a relatively strong copper binding capacity and tolerance to copper ions, was obtained by screening from 16 lactic acid bacteria in vitro. The selected strain was then applied to a mouse model to evaluate its protective function against copper intoxication in vivo. The experimental mice were divided into an intervention group and a therapy group; mice in the intervention group received co-administration of CCFM8246 and a copper ion solution by gavage, while mice in the therapy group were treated with CCFM8246 after 4 weeks of copper exposure. In both two groups, mice treated with copper alone and that treated with neither CCFM8246 nor copper served as positive and negative controls, respectively. At the end of the experimental period, the copper content in feces and tissues, the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, and oxidation stress indices in liver and kidney tissue were determined. Learning and memory ability was evaluated by Morris water maze experiments. The results indicated that treatment with CCFM8246 significantly increased the copper content in feces to promote copper excretion, reduce the accumulation of copper in tissues, reverse oxidative stress induced by copper exposure, recover the ALT and AST in serum and improve the spatial memory of mice.

BackgroundOur prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set?MethodThree levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.ResultsWe confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19-5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58-3.15), genital (OR 5.24, 95% CI 3.52-8.15) and intercourse (OR 10.65, 95% CI 5.56-23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11-2.27) and phobia (OR 1.41, 95%CI 1.09-1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20-1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02-2.02). Intercourse (OR 3.47, 95%CI 1.66-8.22), use of force and threats (OR 1.95, 95%CI 1.05-3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20-1.64) were significantly associated with recurrent MD.ConclusionsIn Chinese women CSA is strongly associated with recurrent MD and this association increases with greater severity of CSA. Depressed women with CSA have some specific clinical traits. Some features of CSA were associated with greater likelihood of developing recurrent MD.

Designer nucleases such as TALENS and Cas9 have opened new opportunities to scarlessly edit the mammalian genome. Here we explored several parameters that influence Cas9-mediated scarless genome editing efficiency in murine embryonic stem cells. Optimization of transfection conditions and enriching for transfected cells are critical for efficiently recovering modified clones. Paired gRNAs and wild-type Cas9 efficiently create programmed deletions, which facilitate identification of targeted clones, while paired gRNAs and the Cas9D10A nickase generated smaller targeted indels with lower chance of off-target mutagenesis. Genome editing is also useful for programmed introduction of exogenous DNA sequences at a target locus. Increasing the length of the homology arms of the homology-directed repair template strongly enhanced targeting efficiency, while increasing the length of the DNA insert reduced it. Together our data provide guidance on optimal design of scarless gene knockout, modification, or knock-in experiments using Cas9 nuclease.

BACKGROUND: The extent to which co-evolutionary processes shape morphological traits is one of the most fascinating topics in evolutionary biology. Both passive and active pollination modes coexist in the fig tree (Ficus, Moraceae) and fig wasp (Agaonidae, Hymenoptera) mutualism. This classic obligate relationship that is about 75 million years old provides an ideal system to consider the role of pollination mode shifts on pollen evolution. METHODS AND MAIN FINDINGS: Twenty-five fig species, which cover all six Ficus subgenera, and are native to the Xishuangbanna region of southwest China, were used to investigate pollen morphology with scanning electron microscope (SEM). Pollination mode was identified by the Anther/Ovule ratio in each species. Phylogenetic free regression and a correlated evolution test between binary traits were conducted based on a strong phylogenetic tree. Seventeen of the 25 fig species were actively pollinated and eight species were passively pollinated. Three pollen shape types and three kinds of exine ornamentation were recognized among these species. Pollen grains with ellipsoid shape and rugulate ornamentation were dominant. Ellipsoid pollen occurred in all 17 species of actively pollinated figs, while for the passively pollinated species, two obtuse end shapes were identified: cylinder and sphere shapes were identified in six of the eight species. All passively pollinated figs presented rugulate ornamentation, while for actively pollinated species, the smoother types - psilate and granulate-rugulate ornamentations - accounted for just five and two among the 17 species, respectively. The relationship between pollen shape and pollination mode was shown by both the phylogenetic free regression and the correlated evolution tests. CONCLUSIONS: Three pollen shape and ornamentation types were found in Ficus, which show characteristics related to passive or active pollination mode. Thus, the pollen shape is very likely shaped by pollination mode in this unique obligate mutualism.

Under normal conditions, loading activities result in microdamage in the living skeleton, which is repaired by bone remodeling. However, microdamage accumulation can affect the mechanical properties of bone and increase the risk of fracture. This study aimed to determine the effect of microdamage on the mechanical properties and composition of bone. Fourteen male goats aged 28 months were used in the present study. Cortical bone screws were placed in the tibiae to induce microdamage around the implant. The goats were euthanized, and 3 bone segments with the screws in each goat were removed at 0 days, 21 days, 4 months, and 8 months after implantation. The bone segments were used for observing microdamage and bone remodeling, as well as nanoindentation and bone composition, separately. Two regions were measured: the first region (R1), located 1.5 mm from the interface between the screw hole and bone; and the second region (R2), located>1.5 mm from the bone-screw interface. Both diffuse and linear microdamage decreased significantly with increasing time after surgery, with the diffuse microdamage disappearing after 8 months. Thus, screw implantation results in increased bone remodeling either in the proximal or distal cortical bone, which repairs the microdamage. Moreover, bone hardness and elastic modulus decreased with microdamage repair, especially in the proximal bone tissue. Bone composition changed greatly during the production and repair of microdamage, especially for the C (Carbon) and Ca (Calcium) in the R1 region. In conclusion, the presence of mechanical microdamage accelerates bone remodeling either in the proximal or distal cortical bone. The bone hardness and elastic modulus decreased with microdamage repair, with the micromechanical properties being restored on complete repair of the microdamage. Changes in bone composition may contribute to changes in bone mechanical properties.

PURPOSE: Dual-energy (DE) radiographic imaging improves tissue discrimination by separating soft from hard tissues in the acquired images. This study was to establish a mathematic model of DE imaging based on intrinsic properties of tissues and quantitatively evaluate the feasibility of applying the DE imaging technique to tumor localization in radiotherapy. METHODS: We investigated the dependence of DE image quality on the radiological equivalent path length (EPL) of tissues with two phantoms using a stereoscopic x-ray imaging unit. 10 lung cancer patients who underwent radiotherapy each with gold markers implanted in the tumor were enrolled in the study approved by the hospital's Ethics Committee. The displacements of the centroids of the delineated gross tumor volumes (GTVs) in the digitally reconstructed radiograph (DRR) and in the bone-canceled DE image were compared with the averaged displacements of the centroids of gold markers to evaluate the feasibility of using DE imaging for tumor localization. RESULTS: The results of the phantom study indicated that the contrast-to-noise ratio (CNR) was linearly dependent on the difference of EPL and a mathematical model was established. The objects and backgrounds corresponding to ΔEPL less than 0.08 are visually indistinguishable in the bone-canceled DE image. The analysis of patient data showed that the tumor contrast in the bone-canceled images was improved significantly as compared with that in the original radiographic images and the accuracy of tumor localization using the DE imaging technique was comparable with that of using fiducial makers. CONCLUSION: It is feasible to apply the technique for tumor localization in radiotherapy.

AIM: To investigate the incidence and risk factors of microscopically positive proximal margins in Chinese patients with adenocarcinoma of the gastroesophageal junction. METHODS: The medical records of 483 patients, who underwent surgical treatment with curative intent for adenocarcinoma of the gastroesophageal junction in a single high-volume tertiary medical center, were reviewed. Demographic, radiographic, endoscopic, pathologic, and treatment-related variables were evaluated. All proximal margins were re-evaluated by two experienced pathologists, and a positive proximal margin was defined as the microscopic presence of invasive tumor cells seen at the esophageal transaction margin submitted en face on final paraffin sections. RESULTS: The incidence of positive proximal margins was 23.81% in this series. Siewert type, depth of tumor invasion, lymph node involvement, presence of vascular or lymphatic invasion, and presence of perineural invasion were significantly associated with positive proximal margins. On multivariate analysis, the presence of vascular or lymphatic invasion and advanced-stage disease were independent risk factors for positive proximal margins in patients with adenocarcinoma of the gastroesophageal junction. CONCLUSION: Residual cancer at proximal resection margins remains a major issue for the surgical treatment of adenocarcinoma of the gastroesophageal junction in China.

Acetylcholinesterase resistance has been well documented in many insects, including several mosquito species. We tested the resistance of five wild, Chinese strains of the mosquito Culex pipiens quinquefasciatus to two kinds of pesticides, dichlorvos and propoxur. An acetylcholinesterase gene (ace1) was cloned and sequenced from a pooled sample of mosquitoes from these five strains and the amino acids of five positions were found to vary (V185M, G247S, A328S, A391T, and T682A). Analysis of the correlation between mutation frequencies and resistance levels (LC50) suggests that two point mutations, G247S (r2 = 0.732, P = 0.065) and A328S (r2 = 0.891, P = 0.016), are associated with resistance to propoxur but not to dichlorvos. Although the V185M mutation was not associated with either dichlorvos or propoxur resistance, its RS genotype frequency was correlated with propoxur resistance (r2 = 0.815, P = 0.036). And the HWE test showed the A328S mutation is linked with V185M, also with G247S mutation. This suggested that these three mutations may contribute synergistically to propoxur resistance. The T682A mutation was negatively correlated with propoxur (r2 = 0.788, P = 0.045) resistance. Knowledge of these mutations may help design strategies for managing pesticide resistance in wild mosquito populations.

To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers.We examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status.Among the recurrent MDD patients there were 216(3.6%) current smokers, 117 (2.0%) former smokers and 333(5.6%) lifetime smokers. Lifetime smokers had a slightly more severe illness, characterized by more episodes, longer duration, more comorbid illness (panic and phobias), with more DSM-IV A criteria and reported more symptoms of fatigue and suicidal ideation or attempts than never smokers. Some known risk factors for MDD were also differentially represented among smokers compared to non-smokers. Smokers reported more stressful life events, were more likely to report childhood sexual abuse, had higher levels of neuroticism and an increased rate of familial MDD. Only neuroticism was significantly related to nicotine dependence.Although depressed women smokers experience more severe illness, smoking rates remain low in MDD patients. Family history of MDD and environmental factors contribute to lifetime smoking in Chinese women, consistent with the hypothesis that the association of smoking and depression may be caused by common underlying factors.

BACKGROUND: A tumor is considered a heterogeneous complex in a three-dimensional environment that is flush with pathophysiological and biomechanical signals. Cell-stroma interactions guide the development and generation of tumors. Here, we evaluate the contributions of normal fibroblasts to gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: By coculturing normal fibroblasts in monolayers of BGC-823 gastric cancer cells, tumor cells sporadically developed short, spindle-like morphological characteristics and demonstrated enhanced proliferation and invasive potential. Furthermore, the transformed tumor cells demonstrated decreased tumor formation and increased lymphomatic and intestinal metastatic potential. Non-transformed BGC-823 cells, in contrast, demonstrated primary tumor formation and delayed intestinal and lymph node invasion. We also observed E-cadherin loss and the upregulation of vimentin expression in the transformed tumor cells, which suggested that the increase in metastasis was induced by epithelial-to-mesenchymal transition. CONCLUSION: Collectively, our data indicated that normal fibroblasts sufficiently induce epithelial-to-mesenchymal transition in cancer cells, thereby leading to metastasis.

The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years.We report results from 3,639 Chinese women with recurrent MDD and 3,800 controls. Highly significant odds ratios (ORs) were observed between MDD and full time employment (OR = 0.36, 95% CI = 0.25-0.46, logP = 78), social status (OR = 0.83, 95% CI = 0.77-0.87, logP = 13.3) and education attainment (OR = 0.90, 95% CI = 0.86-0.90, logP = 6.8). We found a monotonic relationship between increasing age and increasing levels of educational attainment. Those with only primary school education have significantly more episodes of MDD (mean 6.5, P-value = 0.009) and have a clinically more severe disorder, while those with higher educational attainment are likely to manifest more comorbid anxiety disorders.In China lower socioeconomic position is associated with increased rates of MDD, as it is elsewhere in the world. Significantly more episodes of MDD occur among those with lower educational attainment (rather than longer episodes of disease), consistent with the hypothesis that the lower socioeconomic position increases the likelihood of developing MDD. The phenomenology of MDD varies according to the degree of educational attainment: higher educational attainment not only appears to protect against MDD but alters its presentation, to a more anxious phenotype.

Classical Swine Fever (CSF) is a highly infectious fatal pig disease, resulting in huge economic loss to the swine industry. Integrins are membrane-bound signal mediators, expressed on a variety of cell surfaces and are known as receptors or co-receptors for many viruses. However, the role of integrin β3 in CSFV infection is unknown. Here, through quantitive PCR, immunofluorescence (IFC) and immunocytohistochemistry (ICC), we revealed that ST (swine testicles epithelial) cells have a prominent advantage in CSFV proliferation as compared to EC (swine umbilical vein endothelial cell), IEC (swine intestinal epithelial cell) and PK (porcine kidney epithelial) cells. Meanwhile, ST cells had remarkably more integrin β3 expression as compared to EC, IEC and PK cells, which was positively correlated with CSFV infection and proliferation. Integrin β3 was up-regulated post CSFV infection in all the four cell lines, while the CSFV proliferation rate was decreased in integrin β3 function-blocked cells. ShRNA1755 dramatically decreased integrin β3, with a deficiency of 96% at the mRNA level and 80% at the protein level. CSFV proliferation was dramatically reduced in integrin β3 constantly-defected cells (ICDC), with the deficiencies of 92.6%, 99% and 81.7% at 24 h, 48 h and 72 h post CSFV infection, respectively. These results demonstrate that integrin β3 is required in CSFV infection and proliferation, which provide a new insight into the mechanism of CSFV infection.

Mucosal vaccine based on lactic acid bacteria is an attractive concept for the prevention and treatment of allergic diseases, but their mechanisms of action in vivo are poorly understood. Therefore, we sought to investigate how recombinant major dust mite allergen Der p2-expressing Lactococcus lactis as a mucosal vaccine induced the immune tolerance against house dust mite allergy in a mouse model.Three strains of recombinant L. lactis producing Der p2 in different cell components (extracellular, intracellular and cell wall) were firstly constructed. Their prophylactic potential was evaluated in a Der p2-sensitised mouse model, and immunomodulation properties at the cellular level were determined by measuring cytokine production in vitro.Der p2 expressed in the different recombinant L. lactis strains was recognized by a polyclonal anti-Der p2 antibody. Oral treatment with the recombinant L. lactis prior sensitization significantly prevented the development of airway inflammation in the Der p2-sensitized mice, as determined by the attenuation of inflammatory cells infiltration in the lung tissues and decrease of Th2 cytokines IL-4 and IL-5 levels in bronchoalveolar lavage. In addition, the serum allergen-specific IgE levels were significantly reduced, and the levels of IL-4 in the spleen and mesenteric lymph nodes cell cultures were also markedly decreased upon allergen stimulation in the mice fed with the recombinant L. lactis strains. These protective effects correlated with a significant up-regulation of regulatory T cells in the mesenteric lymph nodes.Oral pretreatment with live recombinant L. lactis prevented the development of allergen-induced airway inflammation primarily by the induction of specific mucosal immune tolerance.

In grassland ecosystems, N and P fertilization often increase plant productivity, but there is no concensus if fertilization affects soil C fractions. We tested effects of N, P and N+P fertilization at 5, 10, 15 g m-2 yr-1 (N5, N10, N15, P5, P10, P15, N5P5, N10P10, and N15P15) compared to unfertilized control on soil C, soil microbial biomass and functional diversity at the 0-20 cm and 20-40 cm depth in an alpine meadow after 5 years of continuous fertilization. Fertilization increased total aboveground biomass of community and grass but decreased legume and forb biomass compared to no fertilization. All fertilization treatments decreased the C:N ratios of legumes and roots compared to control, however fertilization at rates of 5 and 15 g m-2 yr-1 decreased the C:N ratios of the grasses. Compared to the control, soil microbial biomass C increased in N5, N10, P5, and P10 in 0-20 cm, and increased in N10 and P5 while decreased in other treatments in 20-40 cm. Most of the fertilization treatments decreased the respiratory quotient (qCO2) in 0-20 cm but increased qCO2 in 20-40 cm. Fertilization increased soil microbial functional diversity (except N15) but decreased cumulative C mineralization (except in N15 in 0-20 cm and N5 in 20-40 cm). Soil organic C (SOC) decreased in P5 and P15 in 0-20 cm and for most of the fertilization treatments (except N15P15) in 20-40 cm. Overall, these results suggested that soils will not be a C sink (except N15P15). Nitrogen and phosphorus fertilization may lower the SOC pool by altering the plant biomass composition, especially the C:N ratios of different plant functional groups, and modifying C substrate utilization patterns of soil microbial communities. The N+P fertilization at 15 g m-2 yr-1 may be used in increasing plant aboveground biomass and soil C accumulation under these meadows.

The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD.A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol.A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P0.05) among three groups.BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general.Chinese Clinical Trial Register center ChiCTR-TRC-09000530.

BACKGROUND: Evidence implicated the diagnostic significance of microRNAs in whole urine/urine sediments in urothelial carcinoma of the bladder (UCB). However, the contaminated blood cells in patients with haematouria significantly altered the expression profiles of urinary microRNA, influencing the test accuracy. METHODS: MicroRNA profiles of the urine supernatants of UCB patients and controls without any malignancy and profiles of malignant and corresponding normal mucosa tissues from the patients were determined by microRNA microarray and compared to identify differentially expressed microRNAs. The differential expression was verified in the tissues of an independent patient cohort by RT-qPCR. The diagnostic significance of selected microRNAs as biomarkers in the urine supernatant was investigated in the expanded cohorts. RESULTS: MicroRNA-99a and microRNA-125b were down-regulated in the urine supernatants of UCB patients. The degree of down-regulation was associated with the tumor grade. A diagnostic model was developed using a combined index of the levels of microRNA-99a and microRNA-125b in the urine supernatant with a sensitivity of 86.7%, a specificity of 81.1% and a positive predicted value (PPV) of 91.8%. Discriminating between high- and low-grade UCB, the model using the level of microRNA-125b alone exhibited a sensitivity of 81.4%, a specificity of 87.0% and a PPV of 93.4%. CONCLUSIONS: The results revealed a unique microRNA expression signature in the urine supernatants of UCB patients for the development of molecular diagnostic tests. An effective cell-free urinary microRNA-based model was developed using a combined index of the levels of microRNA-99a and microRNA-125b to detect UCB with good discriminating power, high sensitivity and high specificity.

The correspondence between species distribution and the environment depends on species' ability to track favorable environmental conditions (via dispersal) and to maintain competitive hierarchy against the constant influx of migrants (mass effect) and demographic stochasticity (ecological drift). Here we report a simulation study of the influence of landscape structure on species distribution. We consider lottery competition for space in a spatially heterogeneous environment, where the landscape is represented as a network of localities connected by dispersal. We quantified the contribution of neutrality and species sorting to their spatial distribution. We found that neutrality increases and the strength of species-sorting decreases with the centrality of a community in the landscape when the average dispersal among communities is low, whereas the opposite was found at elevated dispersal. We also found that the strength of species-sorting increases with environmental heterogeneity. Our results illustrate that spatial structure of the environment and of dispersal must be taken into account for understanding species distribution. We stress the importance of spatial geographic structure on the relative importance of niche vs. neutral processes in controlling community dynamics.

The relationship between suicidality and major depression is complex. Socio- demography, clinical features, comorbidity, clinical symptoms, and stressful life events are important factors influencing suicide in major depression, but these are not well defined. Thus, the aim of the present study was to assess the associations between the above-mentioned factors and suicide ideation, suicide plan, and suicide attempt in 6008 Han Chinese women with recurrent major depression (MD). Patients with any suicidality had significantly more MD symptoms, a significantly greater number of stressful life events, a positive family history of MD, a greater number of episodes, a significant experience of melancholia, and earlier age of onset. Comorbidity with dysthymia, generalized anxiety disorder (GAD), social phobia, and animal phobia was seen in suicidal patients. The present findings indicate that specific factors act to increase the likelihood of suicide in MD. Our results may help improve the clinical assessment of suicide risk in depressed patients, especially for women.

The variations of SORCS1 gene may play potential key roles in late-onset Alzheimer's disease (LOAD). To evaluate the relationship between the polymorphism of SORCS1 gene and LOAD in the ethnic Han Chinese, we conducted a case-control study to investigate the association between the single-nucleotide polymorphisms (SNPs) in intron 1 of SORCS1 and LOAD in Chinese Han population. Six reported SNPs in intron 1 of SORCS1 were analyzed by Snapshot, genotyping and haplotyping in 236 Chinese LOAD cases and 233 matched controls. The significant differences in frequencies of two SNPs (rs10884402, rs950809) were found between the two groups. In addition, haplotype analyses revealed that, in the LOAD group, the frequency of haplotypes C-C-G-T-C (alleles in order of rs17277986, rs6584777, rs10884402, rs7078098, rs950809 polymorphisms) were significantly higher (Psim

The pathogenesis of bullous pemphigoid (BP) is characterized by the T cell-dependent production of autoantibodies. Recent studies have indicated that follicular T helper cells (Tfh), the key modulator of B cell activation and autoantibody production, are critical in the development of several autoimmune diseases. Tfh cells perform their functions via IL-21, their hallmark cytokine. In the present study, the frequencies of Tfh cells were investigated in the peripheral blood samples of BP patients to evaluate whether Tfh cells involve in this clinical entity. Significantly higher Tfh cell counts were observed in the peripheral blood of BP patients than those in healthy controls (median: 11.25% vs. 4.95%, respectively; P

BACKGROUND: Abnormalities in large-scale, structural and functional brain connectivity have been increasingly reported in patients with major depressive disorder (MDD). However, MDD-related alterations in functional interaction between the cerebral hemispheres are still not well understood. Resting state fMRI, which reveals spontaneous neural fluctuations in blood oxygen level dependent signals, provides a means to detect interhemispheric functional coherence. We examined the resting state functional connectivity (RSFC) between the two hemispheres and its relationships with clinical characteristics in MDD patients using a recently proposed measurement named "voxel-mirrored homotopic connectivity (VMHC)". METHODOLOGY/PRINCIPAL FINDINGS: We compared the interhemispheric RSFC, computed using the VMHC approach, of seventeen first-episode drug-naive patients with MDD and seventeen healthy controls. Compared to the controls, MDD patients showed significant VMHC decreases in the medial orbitofrontal gyrus, parahippocampal gyrus, fusiform gyrus, and occipital regions including the middle occipital gyrus and cuneus. In MDD patients, a negative correlation was found between VMHC of the fusiform gyrus and illness duration. Moreover, there were several regions whose VMHC showed significant negative correlations with the severity of cognitive disturbance, including the prefrontal regions, such as middle and inferior frontal gyri, and two regions in the cereballar crus. CONCLUSIONS/SIGNIFICANCE: These findings suggest that the functional coordination between homotopic brain regions is impaired in MDD patients, thereby providing new evidence supporting the interhemispheric connectivity deficits of MDD. The significant correlations between the VMHC and clinical characteristics in MDD patients suggest potential clinical implication of VMHC measures for MDD. Interhemispheric RSFC may serve as a useful screening method for evaluating MDD where neural connectivity is implicated in the pathophysiology.

Dyschromatosis universalis hereditaria (DUH) is a rare heterogeneous pigmentary genodermatosis, which was first described in 1933. The genetic cause has recently been discovered by the discovery of mutations in ABCB6. Here we investigated a Chinese family with typical features of autosomal dominant DUH and 3 unrelated patients with sporadic DUH.Skin tissues were obtained from the proband, of this family and the 3 sporadic patients. Histopathological examination and immunohistochemical analysis of ABCB6 were performed. Peripheral blood DNA samples were obtained from 21 affected, 14 unaffected, 11 spouses in the family and the 3 sporadic patients. A genome-wide linkage scan for the family was carried out to localize the causative gene. Exome sequencing was performed from 3 affected and 1 unaffected in the family. Sanger sequencing of ABCB6 was further used to identify the causative gene for all samples obtained from available family members, the 3 sporadic patients and a panel of 455 ethnically-matched normal Chinese individuals.Histopathological analysis showed melanocytes in normal control's skin tissue and the hyperpigmented area contained more melanized, mature melanosomes than those within the hypopigmented areas. Empty immature melanosomes were found in the hypopigmented melanocytes. Parametric multipoint linkage analysis produced a HLOD score of 4.68, with markers on chromosome 2q35-q37.2. A missense mutation (c.1663 C>A, p.Gln555Lys) in ABCB6 was identified in this family by exome and Sanger sequencing. The mutation perfectly cosegregated with the skin phenotype. An additional mutation (g.776 delC, c.459 delC) in ABCB6 was found in an unrelated sporadic patient. No mutation in ABCB6 was discovered in the other two sporadic patients. Neither of the two mutations was present in the 455 controls. Melanocytes showed positive immunoreactivity to ABCB6.Our data add new variants to the repertoire of ABCB6 mutations with DUH.