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Background: Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model. Methods: Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) KrasG12D+/-; p53fl/fl; myristolated-p110αfl/fl-ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40–41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed. Results: Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p<0.001) post-injection. In addition, CIH increases variability in tumor volume on day 19 (p<0.0001), day 26 (p<0.0001), day 33 (p = 0.025) and day 40 (p = 0.004). Finally, metastases are frequently detected in heart, mediastinal lymph nodes, and right lung using H&E and immunohistochemistry. Conclusions: Using a GEM mouse model of metastatic lung cancer, we report that male mice with solitary lung cancer have accelerated malignant progression and increased variability in tumor growth when exposed to cyclical intermittent hypoxia. Our results indicate that cyclical intermittent hypoxia is a pathogenic factor in non-small cell lung cancer that promotes the more rapid growth of developing tumors. [ABSTRACT FROM AUTHOR]

Recent advance in the direct-acting antivirals (DAAs) offers the potentials to eradicate hepatitis C virus (HCV) worldwide and makes universal screening more urgent. A point-of-care (POC) oral anti-HCV assay, the Fortune assay, was developed and its performance was evaluated. Individuals with or without HCV infection were recruited in three Centers. Paired oral and serum samples were tested using the Fortune and InTec anti-HCV assays. The Kehua serum anti-HCV assay served as a supplemental test to verify the discordant results. Some oral samples were also tested using the OraQuick anti-HCV assay. Furthermore, the Fortune assay results were compared with the documented RNA results. Sensitivity, specificity, and accuracy of the Fortune assay was 93.11%, 98.48%, and 96.58%, respectively (n = 1,022). Consistency between the Fortune and OraQuick assays was 96.35% (264/274); the Fortune assay detected additional 8 positive oral samples missed by the OraQuick assay. The Fortune assay demonstrated a 97.46% (115/118) positivity among the viremic patients. Furthermore, its sensitivity was HCV genotype independent. In conclusion, the Fortune assay was highly specific and accurate. It had comparable sensitivity as the serum assays for the diagnosis of active HCV infection. It provides a completely non-invasive and reliable tool for HCV screening in the DAA era. [ABSTRACT FROM AUTHOR]

With wetlands categorized as one of the three major ecosystems, the study of wetland health has global environmental implications. Multiple regression models were employed to establish relationships between Landsat-8 images, vegetation indices and field measured biomass in the Yellow River Delta Nature Reserve. These models were then used to estimate the spatial distribution of wetland vegetative biomass. The relationships between wetland vegetative biomass and soil factors (organic matter, nitrogen, phosphorus, potassium, water soluble salt, pH and moisture) were modeled. We were able to achieve higher correlations and improved model fits using vegetative indices and spectral bands 1–5 as independent variables. Several important soil factors were isolated, including soil moisture and salt concentrations, which affect wetland biomass spatial distributions. Overall, wetland biomass decreased from land to the ocean and from the river courses outward. [ABSTRACT FROM AUTHOR]

Neuromuscular electrical stimulation (NMES) has been used to improve muscle strength and decrease spasticity of the ankle joint in stroke patients. However, it is unclear how NMES could influence dynamic spasticity of ankle plantarflexors and gait asymmetry during walking. The study aimed to evaluate the effects of applying NMES over ankle dorsiflexors or plantarflexors on ankle control during walking and gait performance in chronic stroke patients. Twenty-five stroke participants with inadequate ankle control were recruited and randomly assigned to an experimental or a control group. The experimental group received 20 minutes of NMES on either the tibialis anterior muscle (NMES-TA) or the medial gastrocnemius muscle (NMES-MG). The control group received 20 minutes of range of motion and stretching exercises. After the 20 minutes of NMES or exercises, all participants received ambulation training for 15 minutes. Training sessions occurred 3 times per week for 7 weeks. The pre- and post-training assessments included spatio-temporal parameters, ankle range of motion, and dynamic spasticity of ankle plantarflexors during walking. Muscle strength of ankle dorsiflexors and plantarflexors as well as static spasticity of ankle plantarflexors were also examined. The results showed that the static and dynamic spasticity of ankle plantarflexors of the NMES-TA group were significantly decreased after training. Reduction in dynamic spasticity of ankle plantarflexors of the NMES-TA group was significantly greater than that of the NMES-MG group. When compared to the control group, the NMES-TA group had greater improvements in spatial asymmetry, ankle plantarflexion during push off, and muscle strength of ankle dorsiflexors, and the NMES-MG group showed a significant decrease in temporal asymmetry. In summary, NMES on ankle dorsiflexors could be an effective management to enhance gait performance and ankle control during walking in chronic stroke patients. NMES on ankle plantarflexors may improve gait symmetry. [ABSTRACT FROM AUTHOR]

Necroptosis is a programmed necrosis, regulated by receptor interacting protein kinase 1(RIP1) and receptor interacting protein kinase 3(RIP3), and could be inhibited by necrostatin-1(Nec-1) specifically. This study aims to evaluate the effect of Nec-1 on LPS-treated periodontal ligament stem cells (PDLSCs). In the research, three groups were established: normal cultured PDLSCs, Porphyromonas gingivalis (Pg)-LPS stimulated PDLSCs and Pg-LPS+Nec-1 treated PDLSCs. The expression of RIP1 and RIP3 and osteogenic differentiation of PDLSCs in three groups were analyzed. Then, we constructed cell aggregates (CA) using PDLSCs, then PDLSCs-CA were combined with Bio-Oss in three groups were transplanted subcutaneously in nude mice to assess their potentials of periodontal tissue regeneration. The results showed that RIP1 and RIP3 were fully expressed in Pg-LPS stimulated PDLSCs and the level increased significantly. Nec-1 inhibited RIP1-RIP3 interaction, and further inhibited necroptosis of PDLSCs in inflammatory state. Moreover, Nec-1 pretreatment ameliorates the osteogenic differentiation of LPS-treated PDLSCs and can effectively promote the cementum like structure ectopic regenerative ability of PDLSCs in nude mice. These findings show RIP1/RIP3-mediated necroptosis is an important mechanism of cell death in PDLSCs. Nec-1 has a protective effect in reducing cell death and promotes ectopic periodontal tissue like structure regeneration by inhibiting necroptosis. Nec-1 is a hopeful therapeutic agent which protects cells from necroptosis and ameliorates functional outcome. [ABSTRACT FROM AUTHOR]

Phylogeny of hard ticks (Ixodidae) remains unresolved. Mitochondrial genomes (mitogenomes) are increasingly used to resolve phylogenetic controversies, but remain unavailable for the entire large Hyalomma genus. Hyalomma asiaticum is a parasitic tick distributed throughout the Asia. As a result of great morphological variability, two subspecies have been recognised historically; until a morphological data-based synonymization was proposed. However, this hypothesis was never tested using molecular data. Therefore, objectives of this study were to: 1. sequence the first Hyalomma mitogenome; 2. scrutinise the proposed synonymization using molecular data, i.e. complete mitogenomes of both subspecies: H. a. asiaticum and kozlovi; 3. conduct phylogenomic and comparative analyses of all available Ixodidae mitogenomes. Results corroborate the proposed synonymization: the two mitogenomes are almost identical (99.6%). Genomic features of both mitogenomes are standard for Metastriata; which includes the presence of two control regions and all three "Tick-Box" motifs. Gene order and strand distribution are perfectly conserved for the entire Metastriata group. Suspecting compositional biases, we conducted phylogenetic analyses (29 almost complete mitogenomes) using homogeneous and heterogeneous (CAT) models of substitution. The results were congruent, apart from the deep-level topology of prostriate ticks (Ixodes): the homogeneous model produced a monophyletic Ixodes, but the CAT model produced a paraphyletic Ixodes (and thereby Prostriata), divided into Australasian and non-Australasian clades. This topology implies that all metastriate ticks have evolved from the ancestor of the non-Australian branch of prostriate ticks. Metastriata was divided into three clades: 1. Amblyomminae and Rhipicephalinae (Rhipicephalus, Hyalomma, Dermacentor); 2. Haemaphysalinae and Bothriocrotoninae, plus Amblyomma sphenodonti; 3. Amblyomma elaphense, basal to all Metastriata. We conclude that mitogenomes have the potential to resolve the long-standing debate about the evolutionary history of ticks, but heterogeneous evolutionary models should be used to alleviate the effects of compositional heterogeneity on deep-level relationships. [ABSTRACT FROM AUTHOR]

Peroxiredoxin Q (PrxQ) that belonged to the cysteine-based peroxidases has long been identified in numerous bacteria, but the information on the physiological and biochemical functions of PrxQ remain largely lacking in Corynebacterium glutamicum. To better systematically understand PrxQ, we reported that PrxQ from model and important industrial organism C. glutamicum, encoded by the gene ncgl2403 annotated as a putative PrxQ, played important roles in adverse stress resistance. The lack of C. glutamicum prxQ gene resulted in enhanced cell sensitivity, increased ROS accumulation, and elevated protein carbonylation levels under adverse stress conditions. Accordingly, PrxQ-mediated resistance to adverse stresses mainly relied on the degradation of ROS. The physiological roles of PrxQ in resistance to adverse stresses were corroborated by its induced expression under adverse stresses, regulated directly by the stress-responsive ECF-sigma factor SigH. Through catalytical kinetic activity, heterodimer formation, and bacterial two-hybrid analysis, we proved that C. glutamicum PrxQ catalytically eliminated peroxides by exclusively receiving electrons from thioredoxin (Trx)/thioredoxin reductase (TrxR) system and had a broad range of oxidizing substrates, but a better efficiency for peroxynitrite and cumene hydroperoxide (CHP). Site-directed mutagenesis confirmed that the conserved Cys49 and Cys54 are the peroxide oxidation site and the resolving Cys residue, respectively. It was also discovered that C. glutamicum PrxQ mainly existed in monomer whether under its native state or functional state. Based on these results, a catalytic model of PrxQ is being proposed. Moreover, our result that C. glutamicum PrxQ can prevent the damaging effects of adverse stresses by acting as thioredoxin-dependent monomeric peroxidase could be further applied to improve the survival ability and robustness of the important bacterium during fermentation process. [ABSTRACT FROM AUTHOR]

Background: Acupuncture has been demonstrated to be effective and safe for chronic severe functional constipation (CSFC). However, which patients with CSFC will have a better response to acupuncture remains unclear. Objective: To explore factors related to acupuncture response in patients with CSFC. Methods: We performed a secondary analysis of a previous multicenter randomized controlled trial consisting of a 2-week run-in period, 8-week treatment, and 12-week follow-up without treatment in which patients with CSFC were randomly allocated to an electroacupuncture group or a sham electroacupuncture group. Responders were defined as participants with an increase of at least one complete spontaneous bowel movement (CSBM) in week 20 compared with the baseline period. The CSBM responder rate in both groups was described, and the baseline characteristics of participants potentially related to acupuncture response were mainly analyzed using logistic regression analysis with bootstrapping techniques. Results: A total of 1021 participants were analyzed in this study, of whom 516 (50.5%) were classified as responders. The CSBM responder rate in week 20 was significantly greater in the electroacupuncture group than in the sham electroacupuncture group (62.9% vs. 37.9%, respectively; P<0.001). Both age and comorbidity were negatively associated with clinical response: with every one-year increase in age, the likelihood of clinical response was reduced by 1.2% (OR 0.988, 95%CI 0.980 to 0.996; P = 0.005), and patients with comorbidities were approximately 42% less likely to respond to treatment (OR 0.581, 95%CI 0.248 to 0.914; P = 0.001). Conclusion: CSFC patients with increasing age and comorbidity may be less likely to respond to acupuncture. These findings contribute to guiding clinical practice in terms of pretreatment patient selection. Further research is needed to confirm the association. [ABSTRACT FROM AUTHOR]

Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys’ thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance. Both the young and the old transgenic mice had significantly higher serum uric acid and its catabolic product, allantoin, than age-matched wild-type mice. This THP mutation apparently caused primary defects in TAL by compromising the luminal translocation and reabsorptive functions of NKCC2 and ROMK and secondary responses in proximal tubules by upregulating NHE3 and URAT1. Our results strongly suggest that the progressive worsening of kidney functions reflects the accumulation of the deleterious effects of the misfolded mutant THP and the compensatory responses. Transgenic mice recapitulating human THP/uromodulin-associated kidney diseases could be used to elucidate their pathogenesis and test novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Adeno-associated virus (AAV) vectors are important gene delivery tools for the treatment of many recessively inherited retinal diseases. For example, a wild-type (WT) AAV5 vector can deliver a full-length Cnga3 (cyclic nucleotide-gated channel alpha-3) cDNA to target cells of the cone photoreceptor function loss 5 (cpfl5) mouse, a spontaneous animal model of achromatopsia with a Cnga3 mutation. Gene therapy restores cone-mediated function and blocks cone degeneration in the mice. However, since transgene expression delivered by an AAV vector shows relatively short-term effectiveness, this cannot be regarded as a very successful therapy. AAV2 and AAV8 vectors with capsid mutations have significantly enhanced transduction efficiency in retinas compared to WT AAV controls. In this study, AAV8 (Y447, 733F+T494V)-treated cpfl5 retinas showed greater preservation of short-term cone electroretinogram (ERG) responses than AAV8 (Y447, 733F)- or AAV2 (Y272, 444, 500, 730F+T491V)-mediated treatments. To explore the long-term rescue effect, AAV8 (Y447, 733F+T494V)-treated cpfl5 retinas were evaluated at 9 months following postnatal day 14 (P14) treatment. Rescued ERG responses in the cones of treated cpfl5 eyes decreased with increasing age, but still maintained more than 60% of the WT mouse responses at the oldest time point examined. Expression of CNGA3 and M/S-opsins was maintained in cone outer segments of the treated cpfl5 eyes and was equal to expression in age-matched WT retinas. Near-normal cone-mediated water maze behavior was observed in the treated cpfl5 mice. As these are the longest follow-up data reported thus far, AAV8 with capsid Y-F and T-V mutations may be one of the most effective AAV vectors for long-term treatment in a naturally occurring mouse model of CNGA3 achromatopsia. [ABSTRACT FROM AUTHOR]

Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases. [ABSTRACT FROM AUTHOR]

Cavities are important in clinical diagnosis of pulmonary tuberculosis (TB) infected by Mycobacterium tuberculosis. Although microRNAs (miRNAs) play a vital role in the regulation of inflammation, the relation between plasma miRNA and pulmonary tuberculosis with cavity remains unknown. In this study, plasma samples were derived from 89 cavitary pulmonary tuberculosis (CP-TB) patients, 89 non-cavitary pulmonary tuberculosis (NCP-TB) patients and 95 healthy controls. Groups were matched for age and gender. In the screening phase, Illumina high-throughput sequencing technology was employed to analyze miRNA profiles in plasma samples pooled from CP-TB patients, NCP-TB patients and healthy controls. During the training and verification phases, quantitative RT-PCR (qRT-PCR) was conducted to verify the differential expression of selected miRNAs among groups. Illumina high-throughput sequencing identified 29 differentially expressed plasma miRNAs in TB patients when compared to healthy controls. Furthermore, qRT-PCR analysis validated miR-769-5p, miR-320a and miR-22-3p as miRNAs that were differently present between TB patients and healthy controls. ROC curve analysis revealed that the potential of these 3 miRNAs to distinguish TB patients from healthy controls was high, with the area under the ROC curve (AUC) ranged from 0.692 to 0.970. Moreover, miR-320a levels were decreased in drug-resistant TB patients than pan-susceptible TB patients (AUC = 0.882). In conclusion, we identified miR-769-5p, miR-320a and miR-22-3p as potential blood-based biomarkers for TB. In addition, miR-320a may represent a biomarker for drug-resistant TB. [ABSTRACT FROM AUTHOR]

This paper forecasts the 2016 canine Anaplasma spp. seroprevalence in the United States from eight climate, geographic and societal factors. The forecast’s construction and an assessment of its performance are described. The forecast is based on a spatial-temporal conditional autoregressive model fitted to over 11 million Anaplasma spp. seroprevalence test results for dogs conducted in the 48 contiguous United States during 2011–2015. The forecast uses county-level data on eight predictive factors, including annual temperature, precipitation, relative humidity, county elevation, forestation coverage, surface water coverage, population density and median household income. Non-static factors are extrapolated into the forthcoming year with various statistical methods. The fitted model and factor extrapolations are used to estimate next year’s regional prevalence. The correlation between the observed and model-estimated county-by-county Anaplasma spp. seroprevalence for the five-year period 2011–2015 is 0.902, demonstrating reasonable model accuracy. The weighted correlation (accounting for different sample sizes) between 2015 observed and forecasted county-by-county Anaplasma spp. seroprevalence is 0.987, exhibiting that the proposed approach can be used to accurately forecast Anaplasma spp. seroprevalence. The forecast presented herein can a priori alert veterinarians to areas expected to see Anaplasma spp. seroprevalence beyond the accepted endemic range. The proposed methods may prove useful for forecasting other diseases. [ABSTRACT FROM AUTHOR]

Background: Bortezomib is recently studied as a novel agent in indolent lymphoma. The optimal schedule of bortezomib used in indolent lymphoma is still uncertain. Methods: We did a systematic review and meta-analysis of the clinical trials comparing the efficacy and toxicity of the weekly and biweekly schedules of bortezomib in patients with indolent lymphoma. We searched Pubmed, Cochrane Library and Emabase from inception to July 29, 2016. The primary outcome was the overall response rate including the complete response rate and the partial response rate. The secondary outcomes were the proportions of patients in each group experiencing the adverse events including the neutropathy, fatigue, diarrhea, nausea and neutropenia. Findings: After final screening, six trials were considered eligible for analysis. The results showed that the overall response rate of biweekly schedule was higher than that of weekly schedule in indolent lymphoma (OR 1.691;95%CI 1.02–2.80). Furthermore, there were no significant differences between the two schedules of bortezomib for the main adverse events. Interpretation: The biweekly schedule of bortezomib was more effective than the weekly schedule in indolent lymphoma, with similar proportion of toxicities. [ABSTRACT FROM AUTHOR]

The modified multiple platform method (MMPM) is a classical sleep deprivation model. It has been widely used in behavioral and brain research, due to its effects on physical and mental functions. However, different MMPM protocols can promote distinct effects in rats. Although the MMPM has been proved to induce central fatigue, the effects of different durations of subjection to the MMPM remain undetermined. This study aims to investigate the changes in behavior, N-Methyl-d-Aspartate receptor 1 (NR1) and 2A (NR2A), as well as the ultrastructural alteration in the hippocampus after different MMPM modelling, to compare the central fatigue effect induced by dynamic MMPM. Rats were randomly divided into four groups: 5-, 14- and 21- day MMPM groups, and a control group. Each MMPM group underwent a 14-hour daily MMPM modelling. After each training session, open field and elevated plus maze tests were performed. Corticosterone levels were detected by ELISA, and the hippocampal NR1 and NR2A were measured by RT-PCR and Western blot analysis. In addition, ultrastructural changes in the hippocampal cornu ammonis 1(CA1) region were determined by transmission electron microscopy (TEM). The findings showed that the 5 and 14 days of MMPM induced a high-stress state, while the 21 days of MMPM induced anxiety and degenerative alteration in the hippocampal morphology. Additionally, hippocampal NR1 and NR2A gene expression decreased in all MMPM groups, whereas the protein expression only decreased in the 21-day group. Overall, different durations of MMPM caused distinct behavioral and brain changes, and the 21 days of MMPM could induce central fatigue. [ABSTRACT FROM AUTHOR]

Ulinastatin, is a broad-spectrum protease inhibitor purified from human urine, inhibits endogenous proteases such as trypsin, α-chymotrypsin, hyaluronidase, and plasmin. It is widely being used at increasingly higher doses for the treatment of acute or chronic pancreatitis, severe infection, and acute organ failure. We aimed to evaluate the safety and tolerability of high-dose ulinastatin in healthy volunteers in our single center, randomized, double-blind, placebo-controlled, single-dose escalation study. Fifty-one healthy Chinese subjects were enrolled in 9 dose cohorts (3×105 U, 6×105 U, 12×105 U, 20×105 U, 30×105 U, 45×105 U, 60×105 U, 70×105 U, or 80×105 U of ulinastatin) and randomized to UTI or matching placebo (n = 1). Each dose cohort was composed of 3–7 subjects. All subjects were required to have 2 h of intravenous infusion. Safety and tolerability were assessed throughout the study via monitoring of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and interviews with the subjects about adverse events. Fifty-one subjects (35 men and 16 women) completed the study. A total of 13 AEs were reported by 10 subjects: 11 adverse events in the ulinastatin groups and 2 adverse events in the placebo group. Twelve of the adverse events were possibly related to the study drug. The most common drug-related adverse events included dizziness, pain at injection site, and a decrease in white blood cell count. All adverse events were of mild severity; none were serious. In conclusion, 2 hours of intravenous infusion of ulinastatin (3×105 to 80×105 U) was well tolerated by healthy Chinese subjects. [ABSTRACT FROM AUTHOR]

This paper models the prevalence of antibodies to Borrelia burgdorferi in domestic dogs in the United States using climate, geographic, and societal factors. We then use this model to forecast the prevalence of antibodies to B. burgdorferi in dogs for 2016. The data available for this study consists of 11,937,925 B. burgdorferi serologic test results collected at the county level within the 48 contiguous United States from 2011-2015. Using the serologic data, a baseline B. burgdorferi antibody prevalence map was constructed through the use of spatial smoothing techniques after temporal aggregation; i.e., head-banging and Kriging. In addition, several covariates purported to be associated with B. burgdorferi prevalence were collected on the same spatio-temporal granularity, and include forestation, elevation, water coverage, temperature, relative humidity, precipitation, population density, and median household income. A Bayesian spatio-temporal conditional autoregressive (CAR) model was used to analyze these data, for the purposes of identifying significant risk factors and for constructing disease forecasts. The fidelity of the forecasting technique was assessed using historical data, and a Lyme disease forecast for dogs in 2016 was constructed. The correlation between the county level model and baseline B. burgdorferi antibody prevalence estimates from 2011 to 2015 is 0.894, illustrating that the Bayesian spatio-temporal CAR model provides a good fit to these data. The fidelity of the forecasting technique was assessed in the usual fashion; i.e., the 2011-2014 data was used to forecast the 2015 county level prevalence, with comparisons between observed and predicted being made. The weighted (to acknowledge sample size) correlation between 2015 county level observed prevalence and 2015 forecasted prevalence is 0.978. A forecast for the prevalence of B. burgdorferi antibodies in domestic dogs in 2016 is also provided. The forecast presented from this model can be used to alert veterinarians in areas likely to see above average B. burgdorferi antibody prevalence in dogs in the upcoming year. In addition, because dogs and humans can be exposed to ticks in similar habitats, these data may ultimately prove useful in predicting areas where human Lyme disease risk may emerge. [ABSTRACT FROM AUTHOR]

Burkitt lymphoma (BL) is a rare and highly aggressive type of non-Hodgkin lymphoma. The mortality rate of BL patients is very high due to the rapid growth rate and frequent systemic spread of the disease. A better understanding of the pathogenesis, more sensitive diagnostic tools and effective treatment methods for BL are essential. Metabolomics, an important aspect of systems biology, allows the comprehensive analysis of global, dynamic and endogenous biological metabolites based on their nuclear magnetic resonance (NMR) and mass spectrometry (MS). It has already been used to investigate the pathogenesis and discover new biomarkers for disease diagnosis and prognosis. In this study, we analyzed differences of serum metabolites in BL mice and normal mice by NMR-based metabolomics. We found that metabolites associated with energy metabolism, amino acid metabolism, fatty acid metabolism and choline phospholipid metabolism were altered in BL mice. The diagnostic potential of the metabolite differences was investigated in this study. Glutamate, glycerol and choline had a high diagnostic accuracy; in contrast, isoleucine, leucine, pyruvate, lysine, α-ketoglutarate, betaine, glycine, creatine, serine, lactate, tyrosine, phenylalanine, histidine and formate enabled the accurate differentiation of BL mice from normal mice. The discovery of abnormal metabolism and relevant differential metabolites may provide useful clues for developing novel, noninvasive approaches for the diagnosis and prognosis of BL based on these potential biomarkers. [ABSTRACT FROM AUTHOR]

Staphylococcus hyicus has caused great losses in the swine industry by inducing piglet exudative epidermitis (EE), sow mastitis, metritis, and other diseases and is a threat to human health. The pathogenesis of EE, sow mastitis, and metritis involves the interaction between the host and virulent protein factors of S. hyicus, however, the proteins that interact with the host, especially the host immune system, are unclear. In the present study, immunoproteomics was used to screen the immunogenic proteins of S. hyicus strain ZC-4. The cellular and secreted proteins of S. hyicus strain ZC-4 were obtained, separated by 2D gel electrophoresis, and further analyzed by western blot with S. hyicus strain ZC-4-infected swine serum. Finally, 28 specific immunogenic proteins including 15 cellular proteins and 13 secreted proteins, 26 of which were novel immunogenic proteins from S. hyicus, were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. To further verify their immunogenicity, two representative proteins (acetate kinase [cellular] and enolase [secreted]) were chosen for expression, and the resultant recombinant proteins could react with S. hyicus ZC-4-infected swine serum. In mice, both acetate kinase and enolase activated the immune response by increasing G-CSF and MCP-5 expression, and acetate kinase further activated the immune response by increasing IL-12 expression. Enolase can confer better protection against S.hycius than acetate kinase in mice. For the first time to our knowledge, our results provide detailed descriptions of the cellular and secreted proteins of S. hyicus strain ZC-4. These immunogenic proteins may contribute to investigation and elucidation of the pathogenesis of S. hyicus and provide new candidates for subunit vaccines in the future. [ABSTRACT FROM AUTHOR]

To analyze intensities of ocular exposure to direct (Eo,dir), reflected (Eo,refl), and diffuse (Eo,diff) ultraviolet (UV) irradiance at different solar elevation angles (SEAs), a rotating manikin and dual-detector spectrometer were used to monitor the intensity of ocular exposure to UV irradiation (Eo) and ambient UV radiation (UVR) under clear skies in Sanya, China. Eo,dir was derived as the difference between maximum and minimum measured Eo values. Eo,refl was converted from the value measured at a height of 160 cm. Eo,diff was calculated as the minimum measured Eo value minus Eo,refl. Regression curves were fitted to determine distributions of intensities and growth rates at different wavelengths and SEAs. Eo,dir differed from ambient UVR exposure. Linear, quadratic, and linear Eo,dir distributions were obtained in SEA ranges of 14°–30°, 30°–50°, and 50°–90°, respectively, with maximum Eo,dir at 32°–38° SEA. Growth rates of Eo,dir with increasing wavelength were fitted with quadratic functions in all SEA ranges. Distributions and growth rate of Eo,refl values were fitted with quadratic functions. Maximum Eo,diff was achieved at the same SEA for all fitted quadratic functions. Growth rate of Eo,diff with increasing wavelength was fitted with a linear function. Eo,dir distributions were fitted with linear or quadratic functions in different SEA ranges. All Eo,refl and Eo,diff distributions were fitted with quadratic functions. As SEA increased, the Eo,dir portion of Eo increased and then decreased; the Eo,refl portion increased from an initial minimum; and the Eo,diff portion first decreased and then increased. The findings may provide data supporting on construction of a mathematical model of ocular UV exposure. [ABSTRACT FROM AUTHOR]

Vibrio mimicus is a pathogen that causes ascites disease in fish. We have previously demonstrated that the outer membrane protein U (OmpU) is an important adhesin in V. mimicus. Here eight specific OmpU-binding phage clones, which presented three different OmpU-binding peptides (designated P1, P2, P3), were screened from a commercially available phage displayed 12-mer peptide library using rOmpU protein as target. Then, synthetic OmpU-binding peptides were measured for their adhesion antagonistic activity and binding affinity via adhesion inhibition test and non-competitive ELISA, respectively. The results showed that after co-incubated with the mixture of rOmpU and P3, visible green fluorescence could be observed on the epithelioma papulosum cyprinidi (EPC) cells surface; while the EPC cells co-incubated with the mixture of rOmpU and P1/P2 exhibited little green fluorescence. The average adhesion number of V. mimicus 04–14 isolate before and after treatment with peptide was 21.4 ± 1.5, 20.8 ± 0.8 (irrelevant peptide), 20.2 ± 0.5 (P3), 5.1 ± 0.7 (P1) and 3.4 ± 0.8 (P2), respectively. There was a significant decrease in the adhesive level of 04–14 isolate treated with P1/ P2 compared to the untreated isolate (p<0.01). The affinity constants of P1 and P2 were (6.17 ± 0.19) × 108 L/mol and (1.24 ± 0.56) × 109 L/mol, respectively. Furthermore, protective effects of P1 and P2 on grass carps challenged with V. mimicus were preliminary detected. It was found there was delayed death of fish in the groups treated with P1/P2, and the survival rate of challenged fish improved with the increase of the dose of adhesion antagonistic peptide. Taken together, two novel OmpU-binding peptides, which possessed adhesion antagonistic activity, high affinity and a certain degree of antibacterial activity against V. mimicus, were screened and identified. [ABSTRACT FROM AUTHOR]

Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins. [ABSTRACT FROM AUTHOR]

Quaternary climate fluctuations have profoundly affected the current distribution patterns and genetic structures of many plant and animal species in the Qinghai-Tibetan Plateau (QTP) and adjacent mountain ranges, e.g. Tianshan (TSR), Altay, etc. In this greater area disjunct distributions are prominent but have nevertheless received little attention with respect to the historical processes involved. Here, we focus on Pedicularis kansuensis to test whether the current QTP and TSR disjunction is the result of a recent Holocene range expansion involving dispersal across arid land bridge(s) or a Pleistocene range fragmentation involving persistence in refugia. Two chloroplast DNA spacers were sequenced for 319 individuals from 34 populations covering the entire distribution range of this species in China. We found a total of 17 haplotypes of which all occurred in the QTP, and only five in the TSR. Overall genetic diversity was high (HT = 0.882, HS = 0.559) and higher in the QTP than in the TSR. Genetic differentiation among regions and populations was relatively low (GST = 0.366) and little evidence for a phylogeographic pattern emerged. The divergence times for the four main lineages could be dated to the early Pleistocene. Surprisingly, the two ubiquitous haplotypes diverged just before or around the Last Glacial Maximum (LGM) and were found in different phylogenetic lineages. The Species Distribution Model suggested a disappearance of P. kansuensis from the TSR during the LGM in contrast to a relatively constant potential distribution in the QTP. We conclude that P. kansuensis colonized the TSR after the LGM. The improbable long-distance dispersal by wind or water across arid land seed flow may well have had birds or men as vector. [ABSTRACT FROM AUTHOR]

In the internal dose evaluation, the specific absorbed fraction (SAF) and S-value are calculated from the reference phantom based on Caucasian data. The differences in height and weight between Caucasian and Asian may lead to inaccurate dose estimation. In this study, we developed the Taiwanese reference phantoms. 40 volunteers were recruited. Magnetic resonance images (MRI) were obtained, and the contours of 15 organs were drawn. The Taiwanese reference man (TRM) and Taiwanese reference woman (TRW) were constructed. For the SAF calculation, the differences in the self-absorption SAF (self-SAF) between the TRM, TRW, and Oak Ridge National Laboratory (ORNL) adult phantom were less than 10% when the difference in organ mass was less than 20%. The average SAF from liver to pancreas of TRM was 38% larger than that of the ORNL adult phantom, and the result of TRW was 2.02 times higher than that of the ORNL adult phantom. For the S-value calculation, the ratios of TRW and ORNL adult phantom ranged from 0.91 to 1.57, and the ratios of TRM and ORNL adult phantom ranged from 1.04 to 2.29. The SAF and S-value results were dominantly affected by the height, weight, organ mass, and geometric relationship between organs. By using the TRM and TRW, the accuracy of internal dose evaluation can be increased for radiation protection and nuclear medicine. [ABSTRACT FROM AUTHOR]

Replanting disease is a major factor limiting the artificial cultivation of the traditional Chinese medicinal herb Salvia miltiorrhiza. At present, little information is available regarding the role of miRNAs in response to replanting disease. In this study, two small RNA libraries obtained from first-year (FPR) and second-year plant (SPR) roots were subjected to a high-throughput sequencing method. Bioinformatics analysis revealed that 110 known and 7 novel miRNAs were annotated in the roots of S. miltiorrhiza. Moreover, 39 known and 2 novel miRNAs were identified and validated for differential expression in FPR compared with SPR. Thirty-one of these miRNAs were further analyzed by qRT-PCR, which revealed that 5 miRNAs negatively regulated the expression levels of 7 target genes involved in root development or stress responses. This study not only provides novel insights into the miRNA content of S. miltiorrhiza in response to replanting disease but also demonstrates that 5 miRNAs may be involved in these responses. Interactions among the differentially expressed miRNAs with their targets may form an important component of the molecular basis of replanting disease in S. miltiorrhiza. [ABSTRACT FROM AUTHOR]

Background: Since the discovery of cell-free foetal DNA in the plasma of pregnant women, many non-invasive prenatal testing assays have been developed. In the area of skeletal dysplasia diagnosis, some PCR-based non-invasive prenatal testing assays have been developed to facilitate the ultrasound diagnosis of skeletal dysplasias that are caused by de novo mutations. However, skeletal dysplasias are a group of heterogeneous genetic diseases, the PCR-based method is hard to detect multiple gene or loci simultaneously, and the diagnosis rate is highly dependent on the accuracy of the ultrasound diagnosis. In this study, we investigated the feasibility of using targeted capture sequencing to detect foetal de novo pathogenic mutations responsible for skeletal dysplasia. Methodology/Principal Findings: Three families whose foetuses were affected by skeletal dysplasia and two control families whose foetuses were affected by other single gene diseases were included in this study. Sixteen genes related to some common lethal skeletal dysplasias were selected for analysis, and probes were designed to capture the coding regions of these genes. Targeted capture sequencing was performed on the maternal plasma DNA, the maternal genomic DNA, and the paternal genomic DNA. The de novo pathogenic variants in the plasma DNA data were identified using a bioinformatical process developed for low frequency mutation detection and a strict variant interpretation strategy. The causal variants could be specifically identified in the plasma, and the results were identical to those obtained by sequencing amniotic fluid samples. Furthermore, a mean of 97% foetal specific alleles, which are alleles that are not shared by maternal genomic DNA and amniotic fluid DNA, were identified successfully in plasma samples. Conclusions/Significance: Our study shows that capture sequencing of maternal plasma DNA can be used to non-invasive detection of de novo pathogenic variants. This method has the potential to be used to facilitate the prenatal diagnosis of skeletal dysplasia. [ABSTRACT FROM AUTHOR]

The current study aimed to determine whether dietary nucleotides supplementation could improve growth performance, intestinal development and immune function of intra-uterine growth restricted (IUGR) neonate using pig as animal model. A total of 14 pairs of normal birth weight (NBW) and IUGR piglets (7 days old) were randomly assigned to receive a milk-based control diet (CON diet) or diet supplemented with nucleotides (NT diet) for a period of 21 days. Blood samples, intestinal tissues and digesta were collected at necropsy and analyzed for morphology, digestive enzyme activities, microbial populations, peripheral immune cells, expression of intestinal innate immunity and barrier-related genes and proteins. Compared with NBW piglets, IUGR piglets had significantly lower average daily dry matter intake and body weight gain (P<0.05). Moreover, IUGR markedly decreased the villous height and villi: crypt ratio in duodenum (P<0.05), as well as the maltase activity in jejunum (P<0.05). In addition, IUGR significantly decreased the serum concentrations of IgA, IL-1βand IL-10 (P<0.05), as well as the percentage of peripheral lymphocytes (P<0.05). Meanwhile, the down-regulation of innate immunity-related genes such as TOLLIP (P<0.05), TLR-9 (P = 0.08) and TLR-2 (P = 0.07) was observed in the ileum of IUGR relative to NBW piglets. Regardless of birth weight, however, feeding NT diet markedly decreased (P<0.05) feed conversion ratio, increased the villous height in duodenum (P<0.05), activities of lactase and maltase in jejunum (P<0.05), count of peripheral leukocytes (P<0.05), serum concentrations of IgA and IL-1β as well as gene expressions of TLR-9, TLR-4 and TOLLIP in ileum (P<0.05). In addition, expressions of tight junction proteins (Claudin-1 and ZO-1) in ileum were markedly increased by feeding NT diet relative to CON diet (P<0.05). These results indicated that IUGR impaired growth performance, intestinal and immune function, but dietary nucleotides supplementation improved nutrients utilization, intestinal function and immunity. [ABSTRACT FROM AUTHOR]

For centuries, mulberry leaf has been used in traditional Chinese medicine for the treatment of diabetes. This study aims to test the prevention effects of a proprietary mulberry leaf extract (MLE) and a formula consisting of MLE, fenugreek seed extract, and cinnamon cassia extract (MLEF) on insulin resistance development in animals. MLE was refined to contain 5% 1-deoxynojirimycin by weight. MLEF was formulated by mixing MLE with cinnamon cassia extract and fenugreek seed extract at a 6:5:3 ratio (by weight). First, the acute toxicity effects of MLE on ICR mice were examined at 5 g/kg BW dose. Second, two groups of normal rats were administrated with water or 150 mg/kg BW MLE per day for 29 days to evaluate MLE’s effect on normal animals. Third, to examine the effects of MLE and MLEF on model animals, sixty SD rats were divided into five groups, namely, (1) normal, (2) model, (3) high-dose MLE (75 mg/kg BW) treatment; (4) low-dose MLE (15 mg/kg BW) treatment; and (5) MLEF (35 mg/kg BW) treatment. On the second week, rats in groups (2)-(5) were switched to high-energy diet for three weeks. Afterward, the rats were injected (ip) with a single dose of 105 mg/kg BW alloxan. After four more days, fasting blood glucose, post-prandial blood glucose, serum insulin, cholesterol, and triglyceride levels were measured. Last, liver lysates from animals were screened with 650 antibodies for changes in the expression or phosphorylation levels of signaling proteins. The results were further validated by Western blot analysis. We found that the maximum tolerance dose of MLE was greater than 5 g/kg in mice. The MLE at a 150 mg/kg BW dose showed no effect on fast blood glucose levels in normal rats. The MLE at a 75 mg/kg BW dose and MLEF at a 35 mg/kg BW dose, significantly (p < 0.05) reduced fast blood glucose levels in rats with impaired glucose and lipid metabolism. In total, 34 proteins with significant changes in expression and phosphorylation levels were identified. The changes of JNK, IRS1, and PDK1 were confirmed by western blot analysis. In conclusion, this study demonstrated the potential protective effects of MLE and MLEF against hyperglycemia induced by high-energy diet and toxic chemicals in rats for the first time. The most likely mechanism is the promotion of IRS1 phosphorylation, which leads to insulin sensitivity restoration. [ABSTRACT FROM AUTHOR]

Background: Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma. Methods: We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events. Results: Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR]  = 1.60, 95% confidence interval [CI]: 1.27–2.01) and 1-year survival (combined RR = 1.26, 95% CI: 1.14–1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR = 1.23, 95% CI: 1.10–1.36), vomiting (combined RR = 1.73, 95% CI: 1.41–2.12) and neutropenia (combined RR = 1.75, 95% CI: 1.42–2.16) compared to the group for DTIC alone. Conclusion: These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion. [ABSTRACT FROM AUTHOR]

β-lactam antibiotics are widely used in clinic. Filamentous fungus Acremonium chrysogenum is an important industrial fungus for the production of CPC, one of the major precursors of β-lactam antibiotics. Although its fermentation yield has been bred significantly over the past decades, little is known regarding molecular changes between the industrial strain and the wild type strain. This limits the possibility to improve CPC production further by molecular breeding. Comparative transcriptome is a powerful tool to understand the molecular mechanisms of CPC industrial high yield producer compared to wild type. A total of 57 million clean sequencing reads with an average length of 100 bp were generated from Illumina sequencing platform. 22,878 sequences were assembled. Among the assembled unigenes, 9502 were annotated and 1989 annotated sequences were assigned to 121 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Furthermore, we compared the transcriptome differences between a high-yield and a wild-type strain during fermentation. A total of 4329 unigenes with significantly different transcription level were identified, among which 1737 were up-regulated and 2592 were down-regulated. 24 pathways were subsequently determined which involve glycerolipid metabolism, galactose metabolism, and pyrimidine metabolism. We also examined the transcription levels of 18 identified genes, including 11 up-regulated genes and 7 down-regulated genes using reverse transcription quantitative -PCR (RT-qPCR). The results of RT-qPCR were consistent with the Illumina sequencing. In this study, the Illumina sequencing provides the most comprehensive sequences for gene expression profile of Acremonium chrysogenum and allows de novo transcriptome assembly while lacking genome information. Comparative analysis of RNA-seq data reveals the complexity of the transcriptome in the fermentation of different yield strains. This is an important public information platform which could be used to accelerate the research to improve CPC production in Acremonium chrysogenum. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1) thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2) Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3) ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by affecting ET-1 expression and the function of PAECs and PASMCs. [ABSTRACT FROM AUTHOR]

Daphnetin, a plant-derived dihydroxylated derivative of coumarin, is an effective compound extracted from a plant called Daphne Korean Nakai. Coumarin derivates were known for their antithrombotic, anti-inflammatory, and antioxidant activities. The present study was aimed to determine the immunosuppressive effects and the underlying mechanisms of daphnetin on concanavalin A (ConA) induced T lymphocytes in mice. We showed that, in vitro, daphnetin suppressed ConA-induced splenocyte proliferation, influenced production of the cytokines and inhibited cell cycle progression through the G0/G1 transition. The data also revealed that daphnetin could down-regulate activation of ConA induced NF-κB and NFAT signal transduction pathways in mouse T lymphocyte. In vivo, daphnetin treatment significantly inhibited the 2, 4- dinitrofluorobenzene (DNFB) -induced delayed type hypersensitivity (DTH) reactions in mice. Collectively, daphnetin had strong immunosuppressive activity both in vitro and in vivo, suggesting a potential role for daphnetin as an immunosuppressive agent, and established the groundwork for further research on daphnetin. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficiency and safety of the transperitoneal approaches with retroperitoneal approaches in laparoscopic partial nephrectomy for renal cell carcinoma and provide evidence-based medicine support for clinical treatment. Methods: A systematic computer search of PUBMED, EMBASE, and the Cochrane Library was executed to identify retrospective observational and prospective randomized controlled trials studies that compared the outcomes of the two approaches in laparoscopic partial nephrectomy. Two reviewers independently screened, extracted, and evaluated the included studies and executed statistical analysis by using software STATA 12.0. Outcomes of interest included perioperative and postoperative variables, surgical complications and oncological variables. Results: There were 8 studies assessed transperitoneal laparoscopic partial nephrectomy (TLPN) versus retroperitoneal laparoscopic partial nephrectomy (RLPN) were included. RLPN had a shorter operating time (SMD = 1.001,95%confidence interval[CI] 0.609–1.393,P<0.001), a lower estimated blood loss (SMD = 0.403,95%CI 0.015–0.791,P = 0.042) and a shorter length of hospital stay (WMD = 0.936 DAYS,95%CI 0.609–1.263,P<0.001) than TLPN. There were no significant differences between the transperitoneal and retroperitoneal approaches in other outcomes of interest. Conclusions: This meta-analysis indicates that, in appropriately selected patients, especially patients with intraperitoneal procedures history or posteriorly located renal tumors, the RLPN can shorten the operation time, reduce the estimated blood loss and shorten the length of hospital stay. RLPN may be equally safe and be faster compared with the TLPN. [ABSTRACT FROM AUTHOR]