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Abstract Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I–III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p

Abstract Schizophrenia (SCZ), which affects approximately 1% of the world’s population, is a global public health concern. It is generally considered that the interplay between genes and the environment is important in the onset and/or development of SCZ. Although several whole-exome sequencing studies have revealed rare risk variants of SCZ, no rare coding variants have been strongly replicated. Assessing isolated populations under extreme conditions might lead to the discovery of variants with a recent origin, which are more likely to have a higher frequency than chance to reflect gene-environment interactions. Following this approach, we examined a unique cohort of Tibetans living at an average altitude above 4500 meters. Whole-exome sequencing of 47 SCZ cases and 53 controls revealed 275 potential novel risk variants and two known variants (12:46244485: A/G and 22:18905934: A/G) associated with SCZ that were found in existing databases. Only one gene (C5orf42) in the gene-based statistics surpassed the exome-wide significance in the cohort. Metascape enrichment analysis suggested that novel risk genes were strongly enriched in pathways relevant to hypoxia, neurodevelopment, and neurotransmission. Additionally, 47 new risk genes were followed up in Han sample of 279 patients with SCZ and 95 controls, only BAI2 variant appearing in one case. Our findings suggest that SCZ patients living at high altitudes may have a unique risk gene signature, which may provide additional information on the underlying biology of SCZ, which can be exploited to identify individuals at greater risk of exposure to hypoxia.

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

ABSTRACT: Objectives: This study was conducted in Jilin Province to investigate the mechanism involved in the antibiotic resistance and pathogenicity of Klebsiella pneumoniae. Methods: Lung samples were collected from large-scale pig farms in Jilin Province. Antimicrobial susceptibility and mouse lethality assays were carried out. K. pneumoniae isolate JP20, with high virulence and antibiotic resistance, was chosen for whole-genome sequencing. The complete sequence of its genome was annotated, and the virulence and antibiotic resistance mechanism were analysed. Results: A total of 32 K. pneumoniae strains were isolated and tested for antibiotic resistance and pathogenicity. Among them, the JP20 strain showed high levels of resistance to all tested antimicrobial agents and strong pathogenicity in mice (lethal dose of 1.35 × 1011 CFU/mL). Sequencing of the multidrug-resistant and highly virulent K. pneumoniae JP20 strain revealed that the antibiotic resistance genes were mainly carried by an IncR plasmid. We speculate that extended-spectrum β-lactamases and loss of outer membrane porin OmpK36 play an important role in carbapenem antibiotic resistance. This plasmid contains a mosaic structure consisting of a large number of mobile elements. Conclusion: Through genome-wide analysis, we found that an lncR plasmid carried by the JP20 strain may have evolved in pig farms, possibly leading to multidrug resistance in the JP20 strain. It is speculated that the antibiotic resistance of K. pneumoniae in pig farms is mainly mediated by mobile elements (insertion sequences, transposons, and plasmids). These data provide a basis for monitoring the antibiotic resistance of K. pneumoniae and lay a foundation for an improved understanding of the genomic characteristics and antibiotic resistance mechanism of K. pneumoniae.

Summary: Background: Improved markers for predicting recurrence are needed to stratify patients with localised (stage I–III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities—clinical, genomic, and histopathological—to improve the predictive accuracy for localised renal cell carcinoma recurrence. Methods: In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI). Findings: The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825–0·876 vs 0·608–0·793; p

Multidrug-resistant Enterococcus faecalis (E. faecalis) often cause intestinal infections in cats. The aim of this study was to investigate a multidrug-resistant E. faecalis isolate for plasmidic and chromosomal antimicrobial resistance and their genetic environment. E. faecalis strain ESC1 was obtained from the feces of a cat. Antimicrobial susceptibility testing was carried out using the broth microdilution method. Conjugation experiments were performed using Escherichia coli and Staphylococcus aureus as receptors. Complete sequences of chromosomal DNA and plasmids were generated by whole genome sequencing (WGS) and bioinformatics analysis for the presence of drug resistance genes and mobile elements. Multidrug-resistant E. faecalis ESC1 contained a chromosome and three plasmids. The amino acid at position 80 of the parC gene on the chromosome was mutated from serine to isoleucine, and hence the amino acid mutation at this site led to the resistance of ESC1 strain to fluoroquinolones. Eleven antibiotic resistance genes were located on two plasmids. We identified a novel composite transposon carrying two aminoglycoside resistance genes aac(6′)-aph(2″). This study reported the coexistence of a novel 5.4 kb composite transposon and a resistance plasmid with multiple homologous recombination in an isolate of E. faecalis ESC1. This data provides a basis for understanding the genomic signature and antimicrobial resistance mechanisms of this pathogen.

Recovering dynamic magnetic resonance imaging (MRI) from highly undersampled raw data is of great significance, and is an important approach for achieving both high temporal and spatial resolution in dynamic contrast enhanced imaging. In this study, a method for 3D dynamic MRI with high spatiotemporal resolution and motion insensitivity was developed, which combines golden angle variable density spiral trajectory, parallel imaging and homotopic l0 minimization-based compressed sensing. Golden angle variable density spiral trajectory, which has the advantages of high data acquisition efficiency and motion insensitivity, was used to acquire k-space data. In the reconstruction algorithm, multicoil sparsity constrain was applied in the temporal total variation domain and l0 minimization, instead of traditional l1 minimization, was adopted, which could further increase the undersampling rate. Simulations and in vivo experiments demonstrated that high spatial resolution and temporal resolution can be achieved by the proposed method while maintaining the image quality. This study also suggested the advantages of homotopic l0 norm-based 3D dynamic MRI reconstruction and its clinical potential.

BackgroundFecal microbiota transplantation (FMT) is an effective treatment for intestinal and extra-intestinal disorders. Nonetheless, long-term safety and efficacy remain major challenges for FMT applications. To date, few long-term follow-up studies have been published on FMT in children.MethodsRetrospective reviewed the medical charts of 74 patients who underwent 508 FMT courses between August 2014 and July 2019 at our medical center. All the FMT procedures followed uniform standards. Baseline characteristics pre-FMT and follow-up data were collected at 1, 3, 6, 12, 36, 60, and 84 months after FMT. All potential influencing factors for adverse events (AEs) were analyzed and assessed using regression analyses.ResultsA total of 70 (13.7%) short-term AEs occurred in twenty-six patients (35.1%). Most AEs (88.5%) occurred within 2 days post-FMT. A total of 91.4% of the AEs were self-limiting. Ulcerative colitis (UC) and within four times of FMT were associated with a higher rate of AEs (p = 0.028 and p = 0.021, respectively). The primary clinical remission rate after FMT was as high as 72.9%. Twenty-five children were followed for more than 5 years after FMT. The clinical remission rates gradually decreased over time after FMT. During follow-up, none of the patients developed autoimmune, metabolic, or rheumatologic disorders or tumor-related diseases. However, nine children developed rhinitis, five developed rhinitis, were underweight, and six developed constipation.ConclusionsFMT is a safe and effective treatment for dysbiosis in children. The long-term efficacy of FMT for each disease decreased over time. Moreover, multiple FMTs are recommended 3 months post-FMT for recurrent diseases.

Several studies have confirmed that microglia are involved in neuropathic pain. Inhibition of guanosine-5′-triphosphate cyclohydrolase 1 (GTPCH1) can reduce the inflammation of microglia. However, the precise mechanism by which GTPCH1 regulates neuropathic pain remains unclear. In this study, BV2 microglia were transfected with adenovirus to knockdown GTPCH1 expression. High throughput sequencing analysis revealed that the mitogen-activated protein kinase (MAPK) related pathways and proteins were the most significantly down-regulated molecular function. Co-expression network analysis of Mapk14 mRNA and five long noncoding RNAs (lncRNAs) revealed their correlation. Quantitative reverse transcription-polymerase chain reaction revealed that among five lncRNAs, ENSMUST00000205634, ENSMUST00000218450 and ENSMUST00000156079 were related to the downregulation of Mapk14 mRNA expression. These provide some new potential targets for the involvement of GTPCH1 in neuropathic pain. This study is the first to note the differential expression of lncRNAs and mRNA in GTPCH1 knockdown BV2 microglia. Findings from this study reveal the mechanism by which GTPCH1 activates microglia and provide new potential targets for microglial activation in neuropathic pain.

PurposeTo assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level.MethodsPenile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB.ResultsDisease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED.ConclusionsOur study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.

Preclinical and clinical studies have suggested that fibroblast growth factor (FGF) system contributed to the onset and development of schizophrenia (SCZ). However, there was no strong clinical evidence to link an individual FGF with SCZ. In this study, we aim to measure blood FGF9 levels in the patients with SCZ with and/or without medication, and test whether FGF9 has a potential to be a biomarker for SCZ. We recruited 130 patients with SCZ and 111 healthy individuals, and the ELISA and qRT-PCR assays were used to measure serum FGF9 levels in the participants. ELISA assay demonstrated that serum FGF9 protein levels were dramatically reduced in first-episode, drug-free patients, but not in chronically medicated patients when compared to healthy control subjects. Further analysis showed that treatment of the first-episode, drug-free SCZ patients with antipsychotics for 8 weeks significantly increased the serum FGF9 levels. In addition, we found that blood FGF9 mRNA levels were significantly lower in first-onset SCZ patients than controls. Under the receiver operating characteristic curve, the optimal cutoff values for FGF9 protein level as an indicator for diagnosis of drug-free SCZ patients was projected to be 166.4 pg/ml, which yielded a sensitivity of 0.955 and specificity of 0.86, and the area under the curve was 0.973 (95% CI, 0.954-0.993). Furthermore, FGF9 had good performance to discriminate between drug-free SCZ patients and chronically medicated patients, the optimal cutoff value for FGF9 concentration was projected to be 165.035 pg/ml with a sensitivity of 0.86 and specificity of 0.919, and the AUC was 0.968 (95% CI, 0.944, 0.991). Taken together, our results for the first time demonstrated the dysregulation of FGF9 in SCZ, and FGF9 has the potential to be served as a biomarker for SCZ.

Pasteurella multocida (Pm) is one of the major pathogens of bovine respiratory disease (BRD), which can develop drug resistance to many of the commonly used antibiotics. Our earlier research group found that with clinical use of enrofloxacin, Pm was more likely to develop drug resistance to enrofloxacin. In order to better understand the resistance mechanism of Pm to enrofloxacin, we isolated PmS and PmR strains with the same PFGE typing in vitro, and artificially induced PmR to obtain the highly resistant phenotype, PmHR. Then transcriptome sequencing of clinically isolated sensitive strains, resistant and highly drug-resistant strains, treated with enrofloxacin at sub-inhibitory concentrations, were performed. The satP gene, of which the expression changed significantly with the increase in drug resistance, was screened. In order to further confirm the function of this gene, we constructed a satP deletion (ΔPm) strain using suicide vector plasmid pRE112, and constructed the C-Pm strain using pBBR1-MCS, and further analyzed the function of the satP gene. Through a continuously induced resistance test, it was found that the resistance rate of ΔPm was obviously lower than that of Pm in vitro. MDK99, agar diffusion and mutation frequency experiments showed significantly lower tolerance of ΔPm than the wild-type strains. The pathogenicity of ΔPm and Pm was measured by an acute pathogenicity test in mice, and it was found that the pathogenicity of ΔPm was reduced by about 400 times. Therefore, this study found that the satP gene was related to the tolerance and pathogenicity of Pm, and may be used as a target of enrofloxacin synergistic effect.

Previous research has demonstrated aberrations in the levels of inflammatory cytokines in patients with schizophrenia (SCZ), but most of the respective studies have tested a narrow set of inflammatory cytokines. Here, we aimed to analyze broad immune profiles in the peripheral blood of the first-episode drug-free (FEDF) patients with SCZ at baseline and after an 8-week treatment with atypical antipsychotics. Serum samples from 24 FEDF patients with SCZ and 25 healthy control (HC) subjects were tested using Luminex multiplex analysis for 30 cytokines, chemokines, and growth factors. Multiple comparison tests demonstrated that interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-γ), monokine induced by IFN-γ, and granulocyte colony-stimulating factor (G-CSF) levels were significantly increased, whereas those of the epidermal growth factor were significantly decreased in the FEDF patients with SCZ. Moreover, the levels of the 6 dysregulated cytokines as well as those of 12 additional soluble factors in FEDF patients with SCZ were significantly decreased after 8 weeks of antipsychotic treatment. Furthermore, the transcription of G-CSF and IFN-γ was significantly increased in FEDF patients with SCZ when compared with controls, and G-CSF and IFN-γ mRNA levels were highly correlated with their respective protein concentrations. Receiver operating characteristic curves showed that G-CSF and IFN-γ had good performance in differentiating between FEDF patients with SCZ and HC subjects. Taken together, our data revealed that FEDF patients with SCZ were accompanied by a unique pattern of immune profile, and antipsychotic medications seemed to suppress the immune function in these patients, which could be used to develop novel targets for the diagnosis and treatment of SCZ.

Bovine milk-derived extracellular vesicles (BM-EVs) are recognized as promising nanoscale delivery vectors owing to their large availability. However, few isolation methods can achieve high purity and yield simultaneously. Therefore, we developed a novel and cost-effective procedure to separate BM-EVs via “salting-out.” First, BM-EVs were isolated from skimmed milk using ammonium sulfate. The majority of BM-EVs were precipitated between 30 and 40% saturation and 34% had a relatively augmented purity. The separated BM-EVs showed a spherical shape with a diameter of 60–150 nm and expressed the marker proteins CD63, TSG101, and Hsp70. The purity and yield were comparable to the BM-EVs isolated via ultracentrifugation while ExoQuick failed to separate a relatively pure fraction of BM-EVs. The uptake of BM-EVs into endothelial cells was dose- and time-dependent without significant cytotoxicity. The levels of endothelial nitric oxide syntheses were regulated by BM-EVs loaded with icariside II and miRNA-155-5p, suggesting their functions as delivery vehicles. These findings have demonstrated that it is an efficient procedure to isolate BM-EVs via “salting-out,” holding great promise toward therapeutic applications.

This paper is to elucidate the correlation between different symptoms of UTUC and the clinicopathological characteristics and prognosis. The clinicopathological data of 700 consecutive patients with UTUC who were treated with radical nephroureterectomy were reviewed, and symptoms were categorized into three groups: S1-no direct symptoms, S2-local symptoms (including hematuria and flank pain) and S3-systemic symptoms. We found that the distributions of patients in the S1, S2 and S3 groups were 96 (13.7%), 601 (85.9%) and 3 (0.4%), respectively, and most patients in S1 were incidentally found to have abnormal findings on ultrasound during regular health examination. Altogether, 534 patients (76.3%) presented with gross hematuria, and 111 (15.9%) presented with flank pain. Patients in S1 had a higher rate of hydronephrosis (p

Abstract Background To evaluate the prognostic significance of the novel index combining preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) in renal cell carcinoma (RCC) patients. Methods We enrolled 1360 patients who underwent nephrectomy in our institution from 2001 to 2010. The cutoff values for HALP, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were defined by using X-tile software. Survival was analyzed by the Kaplan–Meier method, with differences analyzed by the log-rank test. Multivariate Cox proportional-hazards model was used to evaluate the prognostic significance of HALP for RCC. Results Low HALP was significantly associated with worse clinicopathologic features. Kaplan-Meier and log-rank tests revealed that HALP was strongly correlated with cancer specific survival (P

We aimed to investigate the prognostic value of chromogranin A (CgA) in castration-resistant prostate cancer (CRPC). We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows: progression-free survival (PFS) was associated with CgA level (hazard ratio [HR] = 2.47, 95% confidence interval [CI]: 1.47–4.14, P = 0.0006); PFS was relative to CgA change (HR = 9.22, 95% CI: 3.03–28.05, P < 0.0001); and overall survival (OS) was relative to CgA level (HR = 1.47, 95% CI: 1.15–1.87, P = 0.002). When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 (95% CI: 1.09–1.45, P = 0.001) in the first-line hormonal therapy group, and an HR of 2.33 (95% CI: 1.40–3.89, P = 0.001) in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.

Abstract Background To explore the prognostic significance of preoperative prognostic nutritional index (PNI) in bladder cancer after radical cystectomy and compare the prognostic ability of inflammation-based indices. Methods We retrospectively analyzed data for 516 patients with bladder cancer who underwent radical cystectomy in our institution between 2006 to 2012. Clinicopathologic characteristics and inflammation-based indices (PNI, neutrophil/lymphocyte ratio [NLR], platelet/lymphocyte ratio [PLR], lymphocyte/monocyte ratio [LMR]) were evaluated by pre-treatment measurements. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method and compared by log-rank test. Multivariate analysis with a Cox proportional hazards model was used to confirm predictors identified on univariate analysis. The association between clinicopathological characteristics and PNI or NLR was tested. Results Among the 516 patients, the median follow-up was 37 months (interquartile range 20 to 56). On multivariate analysis, PNI and NLR independently predicted OS (PNI: hazard ratio [HR] = 1.668, 95% CI: 1.147–2.425, P = 0.007; NLR: HR = 1.416, 95% CI:1.094–2.016, P = 0.0149) and PFS (PNI: HR = 1.680, 95% CI:1.092–2.005, P = 0.015; NLR: HR = 1.550, 95% CI:1.140–2.388, P = 0.008). Low PNI predicted worse OS for all pathological stages and PFS for T1 and T2 stages. Low PNI was associated with older age (>65 years), muscle-invasive bladder cancer, high American Society of Anesthesiologists grade and anemia. Conclusion PNI and NLR were independent predictors of OS and PFS for patients with bladder cancer after radical cystectomy and PNI might be a novel reliable biomarker for bladder cancer.

Background: The pretreatment neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic factor in various types of carcinomas. The aim of this study was to investigate the prognostic value of pretreatment NLR in a large cohort of Chinese patients with upper tract urothelial carcinoma (UTUC). Methods: We retrospectively analyzed the medical data of 656 UTUC patients who underwent radical nephroureterectomy (RNU) from 2001 to 2011 at Peking University First Hospital. Receiver operating characteristic (ROC) curve analysis was performed to calculate the optimal cutoff point of pretreatment NLR. Uni- and multi-variate analyses were used to identify the prognostic factors for cancer-specific survival (CSS) and intravesical recurrence-free survival (IVRFS). Results: The optimal cutoff point of pretreatment NLR was 2.40 by ROC curves, by which patients with high NLR (NLR ≥2.40) and low NLR (NLR 5 cm (χ2 = 8.213, P= 0.005), ipsilateral hydronephrosis (χ2 = 4.624, P= 0.033), and concomitant carcinoma in situ(CIS) (χ2 = 9.517, P= 0.003). A high pretreatment NLR (hazard ratio [HR] = 1.820, P= 0.001), main tumor diameter >5 cm (HR = 1.789, P= 0.009), lymph node metastasis (HR = 1.863, P= 0.024), and high tumor stage (HR = 1.745, P< 0.001) independently predicted poor CSS after surgery, while only concomitant carcinoma in situ(CIS) (HR = 2.164, P= 0.034), ureteroscopy before surgery (HR = 1.701, P= 0.015), and high tumor grade (HR = 1.645, P= 0.018) were independent predictors of IVRFS after RNU. Conclusions: The pretreatment NLR was related to some adverse clinicopathological features and was an independent predictor of CSS, although not IVRFS, in Chinese UTUC patients.

Objective: To review hot issues and future direction of renal tumor biopsy (RTB) technique. Data Sources: The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015. Study Selection: We included all the relevant articles on RTB technique in English, with no limitation of study design. Results: Computed tomography and ultrasound were usually used for guiding RTB with respective advantages. Core biopsy is more preferred over fine needle aspiration because of superior accuracy. A minimum of two good-quality cores for a single renal tumor is generally accepted. The use of coaxial guide is recommended. For biopsy location, sampling different regions including central and peripheral biopsies are recommended. Conclusion: In spite of some limitations, RTB technique is relatively mature to help optimize the treatment of renal tumors.

Adipokines such as leptin play important roles in the regulation of energy metabolism, particularly in the control of appetite. Here, we describe a hormone, mimecan, which is abundantly expressed in adipose tissue. Mimecan was observed to inhibit food intake and reduce body weight in mice. Intraperitoneal injection of a mimecan-maltose binding protein (-MBP) complex inhibited food intake in C57BL/6J mice, which was attenuated by pretreatment with polyclonal antibody against mimecan. Notably, mimecan-MBP also induced anorexia in Ay/a and db/db mice. Furthermore, the expression of interleukin (IL)-1β and IL-6 was up-regulated in the hypothalamus by mimecan-MBP, as well as in N9 microglia cells by recombinant mouse mimecan. Taken together, the results suggest that mimecan is a satiety hormone in adipose tissue, and that mimecan inhibits food intake independently of leptin signaling by inducing IL-1β and IL-6 expression in the hypothalamus.

Objective: To review the natural history and growth kinetics of small renal masses (SRMs). Data Sources: The literature concerning natural history and growth kinetics of SRMs was collected from PubMed published from 1990 to 2014. Study Selection: We included all the relevant articles on the active surveillance (AS) or delayed treatment for SRMs in English, with no limitation of study design. Results: SRMs under AS have a slow growth potential in general. The mean linear growth rate is 0.33 cm/year, the mean volumetric growth rate is 9.48 cm 3 /year. The rate of metastasis during AS is below 2%. Some factors are associated with the growth rate of SRMs, including tumor grade, histological subtype, initial tumor size, age, radiographic characteristics, and molecular markers. No definite predictor of growth rate of SRMs is defined at present. SRMs with high tumor grade and the subtype of clear cell renal cell carcinoma may have aggressive growth potential. Conclusions: AS is a reasonable choice for elderly patients with SRMs, who are at high risk from surgery. Progression during observation is the biggest concern while performing AS. There is no definite predictor of progression for SRMs under AS. Percutaneous renal biopsy providing immunohistological and genic biomarkers may improve the understanding of natural history of SRMs.

There is currently no consensus about the pattern and risk factors of bladder recurrence after nephroureterectomy, especially in the Chinese population. We evaluated the pattern and risk factors based on data from a large Chinese center. Methods: The clinical and pathological data of 438 patients with upper tract urothelial carcinoma (UTUC), who underwent nephroureterectomy at Peking University First Hospital, Beijing, China between 2000 and 2010, was retrospectively analyzed. Univariate analysis by log-rank test and multivariate analysis by Cox proportional hazards regression model were used to determine the independent risk factors. Results: A total of 135 patients (30.8%) developed intravesical recurrence within a median follow-up of 45 months (range: 12–144 months). The median interval of bladder recurrence was 15 months (range: 2.0–98.0 months), and the two peaks for recurrence were 4–6 months and 17–19 months. Lower tumor grade, tumor multifocality, concomitant carcinoma in situ (CIS) and tumors located in the lower ureter were significant risk factors by univariate and multivariate analysis. A risk-scoring system was developed and a significant difference was found between different risk evaluations. Patients with concomitant CIS tended to develop a late bladder recurrence. One hundred and eighteen patients (87.4%) received transurethral resection after bladder tumor recurrence. Conclusion: Lower tumor grade, tumor multifocality, concomitant CIS and tumors located in the lower ureter tend to be predictive for bladder recurrence after nephroureterectomy, although the underlying mechanism is not fully elucidated, and the scoring system could help risk stratification. Most recurrent tumors could be treated by transurethral resection and there were two peaks for recurrence, which is probably related to the mechanisms and may be unique to the Chinese population.

The rice blast, caused by fungus Magnaporthe oryzae, is a major constraint to the world food security. Hyphal growth is the foundation of fungal development and proliferation of fungi. To investigate genes involved in hyphal growth of this fungus, digital gene expression tag profiling was used to compare a previously generated temperature-sensitive mutant which defect at hyphae growth and reduction on pathogenicity, with its related wildtype strain. 416 genes were detected as differential expression, 178 of which were specifically expressed in Guy-11 but down-regulated expression in the mutant. Functional classification analysis revealed the phenotype mutation may be mainly caused by a defection in translational and vacuole-related processes. The results and the protocol used will improve our knowledge on morphogenesis and promote the further study on M. oryzae pathogenesis.

Diatoms are important components of marine ecosystems and contribute greatly to the world's primary production. Despite their important roles in ecosystems, the molecular basis of how diatoms cope with oxidative stress caused by nutrient fluctuations remains largely unknown. Here, an isobaric tags for relative and absolute quantitation (iTRAQ) proteomic method was coupled with a series of physiological and biochemical techniques to explore oxidative stress- and cell fate decision-related cellular and metabolic responses of the diatom Thalassiosira pseudonana to nitrate (N) and inorganic phosphate (P) stresses. A total of 1151 proteins were detected; 122 and 56 were significantly differentially expressed from control under N- and P-limited conditions, respectively. In N-limited cells, responsive proteins were related to reactive oxygen species (ROS) accumulation, oxidative stress responses and cell death, corresponding to a significant decrease in photosynthetic efficiency, marked intracellular ROS accumulation, and caspase-mediated programmed cell death activation. None of these responses were identified in P-limited cells; however, a significant up-regulation of alkaline phosphatase proteins was observed, which could be the major contributor for P-limited cells to cope with ambient P deficiency. These findings demonstrate that fundamentally different metabolic responses and cellular regulations are employed by the diatom in response to different nutrient stresses and to keep the cells viable.

The performance of a low/high-pressure-stage centrifugal compressor in a land-use MW-level gas turbine with a pressure ratio of approximately 11 is analyzed and optimized with a 1D aerodynamic design and modeling optimization system. 1D optimization results indicate that the diameter ratio of the low-pressure-stage centrifugal compressor with a vane-less diffuser, and the divergent angle of the high-pressure-stage centrifugal compressor with a vaned diffuser, are extremely large and result in low efficiency. Through modeling design and optimization system analysis, a tandem vaned diffuser is used in the low-pressure stage, and a tandem vaned diffuser with splitter vanes is adopted in the high-pressure stage. Computational fluid dynamics (CFD) results show that the pressure ratio and efficiency of the optimized low/high-pressure-stage centrifugal compressor are significantly improved. Coupling calculations of the low/high-pressure stage of the original and optimized designs are conducted based on the results of MW-level gas turbine cycles. CFD results show that the pressure ratio and efficiency of the optimized two-stage centrifugal compressor increase by approximately 8% and 4%, respectively, under three typical load conditions of 100%, 90%, and 60%.

We consider a new system of multivalued mixed variational inequality problem, which includes some known systems of variational inequalities as special cases. Under suitable conditions, the existence of solutions for the system of multivalued mixed variational inequality problem and the convergence of iterative sequences generated by the generalized f-projection algorithm are proved. A perturbational algorithm for solving a special case of multivalued mixed variational inequality problem is formally constructed. The results concerned with the existence of solutions and the convergence of iterative sequences generated by the perturbational algorithm are also given. Some known results are improved and generalized.

By using surjectivity theorem of pseudomonotone and coercive operators rather than the KKM theorem and fixed point theorem used in recent literatures, we obtain some conditions under which a system of generalized variational-hemivariational inequalities concerning set-valued mappings, which includes as special cases many problems of hemivariational inequalities studied in recent literatures, is solvable. As an application, we prove an existence theorem of solutions for a system of generalized variational-hemivariational inequalities involving integrals of Clarke's generalized directional derivatives.

This paper is devoted to the convergence of the implicit Ishikawa iteration processes for approximating a common fixed point of nonexpansive semigroup in CAT(0) spaces. We obtain the Δ-convergence results of the implicit Ishikawa iteration sequences for a family of nonexpansive mappings in CAT(0) spaces. Under certain and different conditions, we also get the strong convergence theorems of implicit Ishikawa iteration sequences for nonexpansive semigroups in the CAT(0) spaces. The results presented in this paper extend and generalize some previous results.

Relatively nonexpansive mappings and equilibrium problems are considered based on a shrinking projection method. Using properties of the generalized f-projection operator, a strong convergence theorem for relatively nonexpansive mappings and equilibrium problems is proved in Banach spaces under some suitable conditions.

We generalize the concept of well-posedness by perturbations for optimization problem to a class of variational-hemivariational inequalities. We establish some metric characterizations of the well-posedness by perturbations for the variational-hemivariational inequality and prove their equivalence between the well-posedness by perturbations for the variational-hemivariational inequality and the well-posedness by perturbations for the corresponding inclusion problem.

We study the strong convergence of two kinds of viscosity iteration processes for approximating common fixed points of the pseudocontractive semigroup in uniformly convex Banach spaces with uniformly Gâteaux differential norms. As special cases, we get the strong convergence of the implicit viscosity iteration process for approximating common fixed points of the nonexpansive semigroup in Banach spaces satisfying some conditions. The results presented in this paper extend and generalize some results concerned with the nonexpansive semigroup in (Chen and He, 2007) and the pseudocontractive mapping in (Zegeye et al., 2007) to the pseudocontractive semigroup in Banach spaces under different conditions.

ABSTRACT Objectives: To evaluate the prognosis of non-metastatic T3a renal cell carcinoma (RCC) with partial nephrectomy (PN). Patients and Methods: We retrospectively evaluated 125 patients with non-metastatic T3a RCC. Patients undergoing PN and radical nephrectomy (RN) were strictly matched by clinic-pathologic characteristics. Log-rank test and Cox regression model were used for univariate and multivariate analysis. Results: 18 pair patients were matched and the median follow-up was 35.5 (10-86) months. PN patients had a higher postoperative eGFR than RN patients (P=0.034). Cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ between two groups (P=0.305 and P=0.524). On multivariate analysis, CSS decreased with positive surgical margin and anemia (both P

ABSTRACT Purpose: To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). Materials and Methods: We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent diagnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multivariate analyses were used to determine the independent risk factors. Results: The median follow-up time was 48 months (interquartile range (IQR): 31-77 months). Patients who underwent ureteroscopy were more likely to have a small (p

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH. [ABSTRACT FROM AUTHOR]

The reaction order plays a crucial role in evaluating the response rate of acid-rock. However, the conventional two-scale model typically assumes that the reaction order is constant as one, which can lead to significant deviations from reality. To address this issue, this study proposes a novel multi-order dynamic model for acid-rock reaction by combining rotating disk experimental data with theoretical derivation. Through numerical simulations, this model allows for the investigation of the impact of acidification conditions on different orders of reaction, thereby providing valuable insights for on-site construction. The analysis reveals that higher response orders require higher optimal acid liquid flow rates, and lower optimal Hþ diffusion coefficients, and demonstrate no significant correlation with acid concentration. Consequently, it is recommended to increase the displacement and use high-viscosity acid for reservoirs with high calcite content, while reducing the displacement and using low-viscosity acid for reservoirs with high dolomite content. [ABSTRACT FROM AUTHOR]