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Background: Adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (CS) with right adrenal adenoma combined with HIV infection has rarely been reported. Case presentation: A 39-year-old Chinese male patient with HIV infection was admitted to our hospital due to increased blood pressure in the previous 2 years and weight gain in the previous 6 months. Endocrinological examinations showed that blood cortisol (8 a.m.) was 22.23 μg/dl, the level of ACTH (8 a.m.) was less than 1pg/ml and twenty-four-hour urinary cortisol was 1429 μg/24h. ACTH-independent CS was diagnosed based on low ACTH levels ( 200 cells/μl. Subsequent immunohistochemical staining confirmed right adrenal adenoma. Results: The postoperative recovery was good, and wound healing was possible. After surgical treatment, endocrinological examinations indicated that the level of ACTH increased and the levels of serum cortisol and twenty-four-hour urinary cortisol decreased, which indicated that CS was controlled. CD4/CD8 was 0.47 at reexamination, and the patient's immunity was improved. Conclusion: Due to the potential side effects of steroid drugs, clinicians should use these medications with caution and closely monitor the development of adrenal deficiency.

ObjectiveTo investigate the effects of miRNA-145-5p on the tumor development and progression of prostate cancer (Pca) bone metastasis.MethodsLevels of miRNA-145-5p were assessed by real-time quantitative PCR in PC3 (bone metastatic Pca cells), 22RV1 (non-metastatic Pca cells), RWPE-1 (non-cancerous prostate epithelial cells) and Pca tissues collected from patients with and without bone metastases. The impact of miRNA-145-5p on cell proliferation was tested by CCK8 assay, colony formation assay and flow cytometric cell cycle analysis. Effects on invasion and migration of PC3 cells were determined by Transwell and wound healing assays. Western blotting, enzyme-linked immunosorbent assay, and flow cytometry apoptosis analyses were also performed to assess roles in metastasis.ResultsLevels of miRNA-145-5p were decreased in Pca bone metastases and miRNA-145-5p inhibited cell proliferation, migration and invasion. miRNA-145-5p inhibited the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-β (TGF-β) in PC3 cells. miR-145-5p increased the expression of the epithelial marker E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). It was found that miRNA-145-5p mediated the epithelial-mesenchymal transition (EMT) and induced apoptosis.ConclusionsmiRNA-145-5p negatively regulated the EMT, inhibited Pca bone metastasis and promoted apoptosis in Pca bone metastasis. Mimicry of miRNA-145-5p action raises the possibility of a novel target for treating Pca with bone metastases.

BACKGROUND Emphysema pyelonephritis (EPN) is a very dangerous type of urinary tract infection. It is a lethal disease that develops rapidly and causes the patient to deteriorate rapidly, and it can easily lead to systemic infections and even sepsis. The incidence is extremely low, and it is prevalent in patients with diabetes. We here report a case of EPN in a non-diabetic patient with autosomal dominant polycystic kidney disease (ADPKD). We share the diagnosis and treatment procedure for this extremely rare condition to make this disease easier to identify and address early. CASE SUMMARY A 47-year-old woman presented to the emergency department of our hospital with a high fever and left back pain lasting 4 d. She had a history of autosomal dominant polycystic kidney and polycystic liver. She was diagnosed with left type I EPN and her vital signs deteriorated so quickly that she underwent an emergency operation in which a D-J tube was inserted into her left ureter on the second day after admission. Two months later, she underwent a second-stage flexible ureteroscopy and lithotripsy. Despite postoperative sepsis, she finally recovered after active symptomatic support treatment and effective anti-infective treatment. CONCLUSION Although EPN is more likely to occur in diabetic patients, for non-diabetic patients with ADPKD and upper urinary tract obstruction, the disease also causes rapid deterioration. Early and accurate diagnosis and timely removal of the obstruction by invasive means may be able to save the damaged kidney and the patient’s life.

The main route of metastasis of bladder urothelial carcinoma is through lymph nodes; however, its exact mechanism remains unclear. In this study, we found an association of nucleolar and spindle associated protein 1 (NUSAP1) expression with BUC tissues along with lymph node metastasis and the survival prognosis. A total of 178 pathological specimens following radical bladder cancer resection were obtained. NUSAP1 expression was analyzed by immunohistochemistry. We evaluated the correlation between clinicopathological characteristics and NUSAP1 expression. Logistic regression was used to determine the independent variables that influenced lymph node metastasis. Uni- and multi-factorial Cox regression methods were used to determine the prognostic value of NUSAP1 expression in urothelial carcinoma of the bladder. High expression of NUSAP1 in BUC was not significantly related to the patient’s gender, age, or tumor number (p > 0.05), however was significantly associated with pathological grade, tumor diameter, pathological stage, and lymph node metastasis (p p p = 0.002). In addition, high NUSAP1 expression was an independent prognostic predictor for BUC. In BUC, NUSAP1 showed high expression and was significantly associated with lymph node metastasis, pathological stage, pathological grade, and tumor diameter. NUSAP1 was an independent predictor of lymph node metastasis and prognosis in BUC; higher expression indicated poorer prognosis of BUC patients.

Zhenquan Lu,1,* Jian Hou,1,* Xiao Li,2 Jun Zhou,2 Bingfeng Luo,1 Songwu Liang,1 Richard K Lo,1 Tak Man Wong,2 Guan-Ming Kuang2 1Department of Urology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guan-Ming Kuang, Email kuanggm@hku-szh.orgAbstract: Purpose: The purpose of this study was to identify the potential exosome-derived microRNAs (miRNAs) related to prostate cancer (Pca) bone metastasis.Methods: Two datasets were collected. One dataset was from the authors’ institute, for which two groups of 10 patients each were designed: in the first one, the patients had early-stage localised Pca without bone metastasis, and in the other, the patients presented with Pca with bone metastasis. Then, the miRNA expression profiles of the blood exosomes were obtained and analysed. The other dataset was a public dataset of the miRNA expression transcriptome (GSE26964), which was downloaded from Gene Expression Omnibus (GEO). The results of both datasets were jointly analysed and the most bone-metastatic-related differentially expressed miRNAs (diff-miRNAs) were identified and further validated. Finally, a series of bioinformatics analyses were performed and the relationship between target genes of the diff-miRNAs and the pathogenesis and progression of bone metastasis of Pca were studied.Results: From the authors’ dataset, in all, 313 diff-miRNAs were identified, of which 205 were up-regulated while 108 were down-regulated. From the GSE26964 dataset, 107 diff-miRNAs were found, of which 44 were up-regulated and 63 were down-regulated. Taking the intersection of the results of both datasets, four diff-miRNAs were identified: hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613. In all, 94 target genes of the four diff-miRNAs were predicted. After considering the intersection of the results from the GSE32269 dataset, we obtained 25 target genes. Although either positive or negative correlations were found among the diff-miRNAs with some of the target genes, there is a lack of evidence on how such correlations regulate the development and promotion of Pca bone metastasis.Conclusion: Hsa-miR-125a-3p, hsa-miR-330-3p, hsa-miR-339-5p and hsa-miR-613 are potential biomarkers for Pca bone metastasis.Keywords: prostate cancer, bone metastasis, exosomes, bioinformatics analysis, miRNAs

Background: The bone is the most common site of distant metastasis in prostate cancer. However, treatments for the bone metastasis of prostate cancer remain unsatisfactory. MicroRNAs (miRNAs) are small noncoding RNAs that play a variety of critical roles in tumor development and progression. Studies have confirmed that miRNA mimics could regulate the response to therapy in many cancers. Methods: In this study, a set of forty-four miRNAs were reduced in prostate cancer patients with bone metastases by high-throughput sequencing analysis. Wound healing, transwell assays and western blotting analysis were used to explore the role of miRNA mimic in prostate cancer bone metastasis. Results: Further gene ontology and pathway analysis showed that these miRNAs target genes are mainly involved in cellular metabolic process, intracellular membrane-bounded organelle, as well as proteoglycans in cancer and focal adhesion. Therefore, these down-regulated miRNAs may play a key role for prostate cancer bone metastasis treatment, including hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-133a-3p, hsa-miR-222-5p, hsa-miR-204-3p, hsa-miR-145-5p, hsa-miR-3681-5p, hsa-miR-184, hsa-miR-144-3p, hsa-miR-204-5p, and hsa-miR-221-5p. To further investigate the role of these miRNA mimics on prostate cancer bone metastasis, miR-145-5p was randomly selected for validation. Bioinformatics analysis showed that miR-145-5p target genes significantly affected TGF-beta and adherens junction signaling pathway. Wound healing and transwell assays and western blotting analysis revealed that miR-145-5p mimic inhibited proliferation, migration and invasion. Importantly, miR-145-5p mimic increased the expression of E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9. These results revealed that miR-145-5p mimic mediated epithelial mesenchymal transition. Meanwhile, miR-145-5p mimic enhanced the level of caspase 9, which is an important promoter of apoptosis. Conclusions: These results indicate that miR-145-5p mimic could inhibit the progress of prostate cancer bone metastasis via regulation of epithelial mesenchymal transition. In addition, miR-145-5p mimic could induce the apoptosis of prostate cancer cells with bone metastases. In summary, the miR-145-5p mimic is expected to become a novel strategy for the treatment of tumor metastasis.

Neural network (NN) based data2text models achieve state-of-the-art (SOTA) performance in most metrics, but they sometimes drop or modify the information in the input, and it is hard to control the generation contents. Moreover, it requires paired training data that are usually expensive to collect. Template-based methods have good fidelity and controllability but require heavy human involvement. We propose a novel template-based data2text system powered by a text stitch model. It ensures fidelity and controllability by using templates to produce the main contents. In addition, it reduces human involvement in template design by using a text stitch model to automatically stitch adjacent template units, which is a step that usually requires careful template design and limits template reusability. The text stitch model can be trained in self-supervised fashion, which only requires free texts. The experiments on a benchmark dataset show that our system outperforms SOTA NN-based systems in fidelity and surpasses template-based systems in diversity and human involvement.

Aspect-based sentiment analysis (ABSA) aims to identify the opinion polarity towards a specific aspect. Traditional approaches formulate ABSA as a sentence classification task. However, it is observed that the single sentence classification paradigm cannot take full advantage of pre-trained language models. Previous work suggests it is better to cast ABSA as a question answering (QA) task for each aspect, which can be solved in the sentence-pair classification paradigm. Though QA-style ABSA achieves state-of-the-art (SOTA) results, it naturally separates the prediction process of multiple aspects belonging to the same sentence. It thus is unable to take full advantage of the correlation between different aspects. In this paper, we propose to use the global-perspective (GP) question to replace the original question in QA-style ABSA, which explicitly tells the model the existence of other relevant aspects using additional instructions. In this way, the model can distinguish relevant phrases for each aspect better and utilize the underlying relationship between different aspects. The experimental results on three benchmark ABSA datasets demonstrate the effectiveness of our method.

With studies indicative of altered renal excretion under high altitude-induced hypobaric hypoxia, the consideration of better therapeutic approaches has long been the aim of research on the management of high altitude related illness. The pharmacokinetics of drugs such as furosemide might be altered under hypoxic conditions, making it essential to establish different dose-regimens to maintain therapeutic efficacy or to avoid toxic side effects at high altitude. Simultaneously, drug-drug interactions (DDIs) mediated by OAT1 occur at high altitude, severely affecting furosemide pharmacokinetics. This study investigated the influence of acute exposure to high altitude at 4300 m on the renal excretion of furosemide in rats. Significant changes in physiological parameters and kidney histopathology were found after acute high altitude exposure. Compared with low altitude, the pharmacokinetics of furosemide and the expression level of OAT1 in kidney were significantly changed after rapid ascent to high altitude. Additionally, the down-regulated OAT1 expression further sustained the potential mechanism for the decreased renal excretion of furosemide, resulting in extended residence of the drug in the human body. The elevation of AUC, Cmax , MRT, t1/2 of furosemide, and decreased CL at high altitude further reinforced the current findings. Moreover, the absorption of furosemide was markedly increased and renal excretion significantly declined after co-administration of captopril, resulting in local drug interaction at high altitude. In conclusion, acute exposure to high altitude may significantly affect the renal excretion of furosemide and the pharmacokinetic parameters of furosemide were altered after co-administration of captopril, which may then impact the conventional therapeutic dosage.

Background This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300 m. Methods and Results The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude. The mRNA and protein expression of MRP2 in high altitude group were higher than plain group in rat small intestine and kidney, while was reduced in rat liver. The AUC, K a and C max of norfloxacin were significantly reduced in high altitude group (p 1/2 and Vd were significantly increased (p Conclusions These results indicate that physiological indicators and expression levels of drug transporters MRP2 are changed in responded to high altitude, to severely affect norfloxacin pharmacokinetics. These changes may provide basis and new ideas to adjust the dosage and administration, so as to promote rational drug use in the high altitude.

Cushing's syndrome (CS) during pregnancy is rare. It causes the clinical disorder by overproduction of cortisol. Hypercortisolemia in pregnancy can lead to severe complications, both for the mother and the fetus, including spontaneous abortion, perinatal death, prematurity, maternal hypertension, heart failure, diabetes and opportunistic infections. The most common cause of hypercortisolemia in pregnancy is a cortisol-secreting adrenal tumor. Herein we present a 31 year-old female patient, at 20 weeks' gestation, with CS secondary to a left adrenal tumor. A brief review of reported similar cases is included.

The success of many natural language processing (NLP) tasks is bound by the number and quality of annotated data, but there is often a shortage of such training data. In this paper, we ask the question: "Can we combine a neural network (NN) with regular expressions (RE) to improve supervised learning for NLP?". In answer, we develop novel methods to exploit the rich expressiveness of REs at different levels within a NN, showing that the combination significantly enhances the learning effectiveness when a small number of training examples are available. We evaluate our approach by applying it to spoken language understanding for intent detection and slot filling. Experimental results show that our approach is highly effective in exploiting the available training data, giving a clear boost to the RE-unaware NN., 11 Pages, 2 Figures, Accepted by ACL 2018

Drug efflux transporters plays a key role in pharmacokinetics parameters changes. In recent years, in addition to P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), MRP2 has become an advanced research hotspot. Several signaling pathways andtranscription factors have been reported to be involved in regulation of MRP2 expression in hypoxic microenvironment of tumor, such as peroxisome proliferators-activated receptors (PPARα), nuclear factor κB (NF-κB), pregnane X receptor (PXR), farnesoid X receptor (FXR), constitutive androstane receptor (CAR) and microRNA. But it is not fully understood how MRP2 is regulated under hypoxia. MRP2 is one of the most important efflux transporter proteins. Many drugs or inhibitors have been shown to be its substrate. In the hypoxic environment, changes in expression of MRP2 can significantly affect drug's pharmacokinetics (absorption, distribution, metabolism, excretion). Simultaneously, the regulation of MRP2 expression under hypoxic might involve several signal pathways and many genes, which constitute an integral gene regulatory networks.药物外排转运蛋白对药代动力学参数变化起着关键性作用。近年来研究较多的外排型转运蛋白除了P-糖蛋白(P-glycoprotein，P-gp)、乳腺癌耐药蛋白(breast cancer resistance protein，BCRP)外，多药耐药相关蛋白2(multidrug resistance protein 2，MRP2)逐渐成为了研究的热点。肿瘤微缺氧环境中一些信号转导通路、转录因子参与MRP2基因的表达调控，这些因子包括过氧化物酶体增殖剂激活受体(peroxisome proliferators-activated receptors，PPARα)、核因子-κB(nuclear factor κB，NF -κB)、孕烷X受体(pregnane X receptor，PXR)、法尼醇X受体(farnesoid X receptor，FXR)、组成型雄烷受体(constitutive androstane receptor，CAR)和microRNA等，但MRP2在缺氧条件下的调控机制尚不完全清楚，且是一个很复杂的过程。MRP2作为最主要的外排转运蛋白之一，多种常用药物及抑制剂是其底物，MRP2的表达变化会显著影响这些底物药代动力学(吸收、分布、代谢、排泄)。同时，缺氧状态下MRP2不仅是由单一的信号通路或者某个转录基因调控，而是涉及多个信号通路以及诸多基因，从而构成一个调控网络。.

Distant supervision significantly reduces human efforts in building training data for many classification tasks. While promising, this technique often introduces noise to the generated training data, which can severely affect the model performance. In this paper, we take a deep look at the application of distant supervision in relation extraction. We show that the dynamic transition matrix can effectively characterize the noise in the training data built by distant supervision. The transition matrix can be effectively trained using a novel curriculum learning based method without any direct supervision about the noise. We thoroughly evaluate our approach under a wide range of extraction scenarios. Experimental results show that our approach consistently improves the extraction results and outperforms the state-of-the-art in various evaluation scenarios., Comment: 10 pages, accepted by ACL 2017

In this paper, we deal with the task of extracting first order temporal facts from free text. This task is a subtask of relation extraction and it aims at extracting relations between entity and time. Currently, the field of relation extraction mainly focuses on extracting relations between entities. However, we observe that the multi-granular nature of time expressions can help us divide the dataset constructed by distant supervision into reliable and less reliable subsets, which can help to improve the extraction results on relations between entity and time. We accordingly contribute the first dataset focusing on the first order temporal fact extraction task using distant supervision. To fully utilize both the reliable and the less reliable data, we propose to use curriculum learning to rearrange the training procedure, label dropout to make the model be more conservative about less reliable data, and instance attention to help the model distinguish important instances from unimportant ones. Experiments show that these methods help the model outperform the model trained purely on the reliable dataset as well as the model trained on the dataset where all subsets are mixed together.

Discourse parsing aims to identify the relationship between different discourse units, where most previous works focus on recovering the constituency structure among discourse units with carefully designed features. In this paper, we propose to exploit Long Short Term Memory (LSTM) to properly represent discourse units, while using as few feature engineering as possible. Our transition based parsing model features a multilayer stack LSTM framework to discover the dependency structures among different units. Experiments on RST Discourse Treebank show that our model can outperform traditional feature based systems in terms of dependency structures, without complicated feature design. When evaluated in discourse constituency, our parser can also achieve promising performance compared to the state-of-the-art constituency discourse parsers.

Automatically constructed knowledge bases often suffer from quality issues such as the lack of attributes for existing entities. Manually finding and filling missing attributes is time consuming and expensive since the volume of knowledge base is growing in an unforeseen speed. We, therefore, propose an automatic approach to suggest missing attributes for entities via hierarchical clustering based on the intuition that similar entities may share a similar group of attributes. We evaluate our method on a randomly sampled set of 20,000 entities from DBPedia. The experimental results show that our method can achieve a high precision and outperform existing methods.