Yanan University Affiliated Hospital

Hepatocellular carcinoma (HCC) is the most commonmalignancy. Exsome plays a significant role in the elucidation of signal transduction pathways between hepatoma cells, angiogenesis and early diagnosis of HCC. Exosomes are small vesicular structures that mediate interaction between different types of cells, and contain a variety of components (including DNA, RNA, and proteins). Numerous studies have shown that these substances in exosomes are involved in growth, metastasis and angiogenesis in liver cancer, and then inhibited the growth of liver cancer by blocking the signaling pathway of liver cancer cells. In addition, the exosomal substances could also be used as markers for screening early liver cancer. In this review, we summarized to reveal the significance of exosomes in the occurrence, development, diagnosis and treatment of HCC, which in turn might help us to further elucidate the mechanism of exosomes in HCC, and promote the use of exosomes in the clinical diagnosis and treatment of HCC.

Objective To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. Design This was a nationwide multicentre cross-sectional study. Individuals aged 40–80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti- Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. Results The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12–16) or high-risk (17–25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). Conclusions The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

Using nanoparticles to carry and delivery anticancer drugs holds much promise in cancer therapy, but nanoparticles per se are lacking specificity. Active targeting, that is, using specific ligands to functionalize nanoparticles, is attracting much attention in recent years. Aptamers, with their several favorable features like high specificity and affinity, small size, very low immunogenicity, relatively low cost for production, and easiness to store, are one of the best candidates for the specific ligands of nanoparticle functionalization. This review discusses the benefits and challenges of using aptamers to functionalize nanoparticles for active targeting and especially presents nearly all of the published works that address the topic of using aptamers to functionalize nanoparticles for targeted drug delivery and cancer therapy.

For several years now, scientists have been proposing numerous models for defining anything "as a service (aaS)", including discussions of products, processes, data & information management, and security as a service. In this paper, based on a thorough literature survey, we investigate the vast stream of the state of the art in Everything as a Service (XaaS). We then use this investigation to explore an integrated view of XaaS that will help propose approaches for migrating applications to the cloud and exposing them as services.

In this paper, a novel single layer Multiple Input–Multiple Output (MIMO) antenna for Fifth-Generation (5G) 28 GHz frequency band applications is proposed and investigated. The proposed MIMO antenna operates in the Ka-band, which is the most desirable frequency band for 5G mm-wave communication. The dielectric material is a Rogers-5880 with a relative permittivity, thickness and loss tangent of 2.2, 0.787 mm and 0.0009, respectively, in the proposed antenna design. The proposed MIMO configuration antenna element consists of triplet circular shaped rings surrounded by an infinity-shaped shell. The simulated gain achieved by the proposed design is 6.1 dBi, while the measured gain is 5.5 dBi. Furthermore, the measured and simulated antenna efficiency is 90% and 92%, respectively. One of the MIMO performance metrics—i.e., the Envelope Correlation Coefficient (ECC)—is also analyzed and found to be less than 0.16 for the entire operating bandwidth. The proposed MIMO design operates efficiently with a low ECC, better efficiency and a satisfactory gain, showing that the proposed design is a potential candidate for mm-wave communication.

Depression and anxiety each affect around 1 in 3 people during the first year after a stroke. Suicide causes the death of about 3 to 4/1000 stroke survivors during the first 5 years. This narrative review describes the best available evidence for the epidemiology of depression, anxiety, and suicide; their prevention; and the treatment of anxiety and depression. We conclude with directions for future research.

Four novel ZnII coordination polymers, [Zn(btc)0.5(H2O)]n (1), {[Zn(btc)0.5(4,4‘-bpy)0.5(H2O)]·1.5H2O}n (2), {[Zn2(H2btc)2(4,4‘-bpy)4]·H2O}n (3), [Zn(H2btc)(bpe)]n (4) [H4btc = biphenyl-3,3‘,4,4‘-tetracarboxylic acid, 4,4‘-bpy = 4,4‘-bipyridine, and bpe = 1,2-bis(4-pyridyl)ethane], have been synthesized by hydrothermal reactions. Single-crystal X-ray structural analysis reveals that the four polymers exhibit different novel bilayer architectures. Complex 1 possesses a bilayer structure in which two helical layers are further pillared by (btc)4- ligands into a two-dimensional (2D) bilayer network. Complex 2 is an unusual 2D double-layered supramolecular motif generated by hydrogen bonding interactions of two single-layered networks. Complex 3 displays a 2D supramolecular bilayer network formed by the one-dimensional {[Zn2(H2btc)2(4,4‘-bpy)4]·H2O}n polymer. Complex 4 features a 2D double-layered framework in which two puckering single layers are linked by μ2-carboxylato groups of (H2btc)2- anions. The diverse structures illustrate rational adjustment of the second ligand, and the pH value is a good method to further design bilayer metal−organic compounds with novel structures and properties. In addition, the thermal stabilities and photoluminescence properties of 1−4 were also studied.

perative); but it is not ngape memp==I strike, but memrpin ap-I striking.I think it probable that the aboriginal languages may be divided into two classes.The aborigines evidently belong to two races-one like the Eastern Polynesians, and the other like the Western, or Melanesians.One race has straight hair and a lighter complexion; the other has curly hair, and is darker.And perhaps the characteristic of the languages of the former race may be monosyllabic pronouns, and of the latter race polysyllabic pronouns.This would correspond with the distinction which exists between the same parts of speech in Polynesia and Melanesia.It will be observed that there are many omissions in some of the lists of words.This arises from the persons who collected them not having ascertained the words for those omitted.And I may remark that the omissions of writers of vocabularies are often very unaccountable.Words of the commonest kind are omitted.For instance, Meyer, in his vocabulary of the Encounter Bay dialect of the Narrinyeri, has omitted the word for " small", muralappi, and yet he evidently understood the language well.As it may be desirable to give a sketch of the grammar of an aboriginal language, I proceed to append some account of the grammar of the language of the Narrinyeri.1.This language is called Yarildewallin. 2. There are no articles in this tongue.3. Nouns are declined in the singular, dual, and plural numbers.There are six cases of nouns.The following is the declension of the noun korni, "a man SINGULAR.

The arrival of the monoclonal antibody (mAb) technology in the 1970s brought with it the hope of conquering cancers to the medical community. However, mAbs, on the whole, did not achieve the expected wonder in cancer therapy although they do have demonstrated successfulness in the treatment of a few types of cancers. In 1990, another technology of making biomolecules capable of specific binding appeared. This technique, systematic evolution of ligands by exponential enrichment (SELEX), can make aptamers, single-stranded DNAs or RNAs that bind targets with high specificity and affinity. Aptamers have some advantages over mAbs in therapeutic uses particularly because they have little or no immunogenicity, which means the feasibility of repeated use and fewer side effects. In this review, the general properties of the aptamer, the advantages and limitations of aptamers, the principle and procedure of aptamer production with SELEX, particularly the undergoing studies in aptamers for cancer therapy, and selected anticancer aptamers that have entered clinical trials or are under active investigations are summarized.

Background: Previous studies propose that hypothyroidism might play a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), but findings from published studies on the relationship between hypothyroidism and NAFLD are still controversial. Our study aimed to make a comprehensive evaluation of the relationship between hypothyroidism and NAFLD through a meta-analysis. Methods: PubMed, China Dissertation Database, and EMBASE databases were searched to find observational studies assessing the relationship between hypothyroidism and NAFLD. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the strength of the relationship between hypothyroidism and NAFLD through meta-analysis. Results: Thirteen articles were ultimately included in our meta-analysis. Meta-analysis of the 13 studies found a high correlation between hypothyroidism and NAFLD (OR = 1.52, 95%CI 1.24-1.87, P <0.001). Meta-analysis of 9 studies providing adjusted ORs found that hypothyroidism was independently correlated with NAFLD (OR = 1.72, 95%CI 1.32-2.23, P <0.001). Subgroup analysis found that both overt hypothyroidism and subclinical hypothyroidism were significantly correlated with NAFLD, and the pooled ORs were 1.70 (95%CI 1.23-2.36, P = 0.002) and 1.40 (95%CI 1.10-1.77, P = 0.006), respectively. Besides, meta-analysis of studies providing adjusted ORs also found that both overt hypothyroidism and subclinical hypothyroidism were independently correlated with NAFLD, and the pooled ORs were 1.81 (95%CI 1.30-2.52, P <0.001) and 1.63 (95%CI 1.19-2.24, P = 0.002), respectively. Conclusion: The meta-analysis provides strong epidemiological evidence for the relationship between hypothyroidism and NAFLD. Both individuals with subclinical and overt hypothyroidism are at higher risk for NAFLD than euthyroid subjects.

Alzheimer's disease (AD) is a neurodegenerative disease with complex pathological characteristics, whose etiology and pathogenesis are still unclear. Over the past few decades, the role of the extracellular matrix (ECM) has gained importance in neurodegenerative disease. In this review, we describe the role of the ECM in AD, focusing on the aspects of synaptic transmission, amyloid-β-plaque generation and degradation, Tau-protein production, oxidative-stress response, and inflammatory response. The function of ECM in the pathological process of AD will inform future research on the etiology and pathogenesis of AD.

BACKGROUND: Traditional therapies fail to cure most glioblastoma patients and the 5-year survival rate is less than 10%, highlighting need for new therapeutic approaches. The natural killer group 2 member D ligands (NKG2DLs) are highly expressed in glioblastomas and are considered promising targets for chimeric antigen receptor (CAR) T-cell therapy. The aim of this study was to investigate the effect of NKG2D-expressing CAR-T cells on glioblastomas and glioblastoma stem cells. METHODS: The expression of NKG2DLs was analyzed by flow cytometry and immunohistochemistry. NKG2D-BBz CAR, containing the extracellular domain of NKG2D, was constructed and delivered into T cells by lentiviral particles. In vitro cytotoxicity of the CAR-T cells was assessed by flow cytometry. Release of cytokine, perforin and granzyme B was quantified using enzyme-linked immunosorbent assay kits. The therapeutic efficacy of NKG2D-BBz CAR-T cells in vivo was evaluated using subcutaneous tumor models. The safety of the CAR was analyzed by investigating the effects on proliferation, apoptosis, and karyotype. RESULTS: Our data confirmed the high expression of NKG2DLs in human glioblastoma cells, cancer stem cells, and tumor samples. Further, the NKG2D-BBz CAR-T cells efficiently lysed glioblastoma cells and cancer stem cells in vitro and produced high levels of cytokines, perforin, and granzyme B. The CAR-T cells markedly eliminated xenograft tumors in vivo and did not exhibit significant treatment-related toxicity in the treated mice. The CAR expression also did not exert any obvious effects on cell proliferation, apoptosis, and genomic stability. CONCLUSION: Our findings demonstrated that NKG2D CAR-T cells targeted glioblastoma cells and cancer stem cells in an NKG2D-dependent manner, supporting the use of CAR-T therapy in glioblastoma therapeutic strategies.

Deep reinforcement learning (DRL) has gained great success by learning directly from high-dimensional sensory inputs, yet is notorious for the lack of interpretability. Interpretability of the subtasks is critical in hierarchical decision-making as it increases the transparency of black-box-style DRL approach and helps the RL practitioners to understand the high-level behavior of the system better. In this paper, we introduce symbolic planning into DRL and propose a framework of Symbolic Deep Reinforcement Learning (SDRL) that can handle both high-dimensional sensory inputs and symbolic planning. The task-level interpretability is enabled by relating symbolic actions to options.This framework features a planner – controller – meta-controller architecture, which takes charge of subtask scheduling, data-driven subtask learning, and subtask evaluation, respectively. The three components cross-fertilize each other and eventually converge to an optimal symbolic plan along with the learned subtasks, bringing together the advantages of long-term planning capability with symbolic knowledge and end-to-end reinforcement learning directly from a high-dimensional sensory input. Experimental results validate the interpretability of subtasks, along with improved data efficiency compared with state-of-the-art approaches.

Reinforcement learning and symbolic planning have both been used to build intelligent autonomous agents. Reinforcement learning relies on learning from interactions with real world, which often requires an unfeasibly large amount of experience. Symbolic planning relies on manually crafted symbolic knowledge, which may not be robust to domain uncertainties and changes. In this paper we present a unified framework PEORL that integrates symbolic planning with hierarchical reinforcement learning (HRL) to cope with decision-making in dynamic environment with uncertainties. Symbolic plans are used to guide the agent's task execution and learning, and the learned experience is fed back to symbolic knowledge to improve planning. This method leads to rapid policy search and robust symbolic plans in complex domains. The framework is tested on benchmark domains of HRL.

Ginsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells. We examined the effect of GRh2 on HCT116 cells ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo. The results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. In vivo studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3. The results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

OBJECTIVE: This meta-analysis is to investigate the relationship between the patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 polymorphism and the susceptibility and severity of nonalcoholic fatty liver disease (NAFLD). METHODS: Chinese Journal Full-text Database, Wanfang Database, VIP Database, and PubMed Database were subjected to case-control study retrieving, from January 2008 to December 2014. Following key words were used: fatty liver, PNPLA3, and rs738409 gene or variants or polymorphism or alleles. Meta-analysis was performed based on the retrieved articles. RESULTS: In total 65 studies were first retrieved according to the key words, and finally 21 studies with 14,266 subjects were included. Meta-analysis showed that PNPLA3 rs738409 polymorphism exerted strong influence not only on fatty liver but also on the histological injury. PNPLA3 rs738409 [G] allele was a risk factor for NAFLD (GG vs CC, OR = 4.01, 95% CI 2.93-5.49; GC vs CC, OR = 1.88, 95% CI 1.58-2.24). PNPLA3 gene variant was significantly associated with the increased serum alanine aminotransferase (ALT) levels (GG vs CC, standardized mean difference = 0.47, 95% CI 0.14-0.81). In addition, nonalcoholic steatohepatitis (NASH) was more frequently observed in G allele carriers (GG vs CC, OR = 3.24, 95% CI 2.79-3.76; GC vs CC, OR = 2.14, 95% CI 1.43-3.19). CONCLUSION: PNPLA3 rs738409 polymorphism is not only a factor significantly associated with the susceptibility of NAFLD, but also related to the susceptibility of aggressive diseases.

BACKGROUND: Our purpose was to investigate the association between metabolic syndrome and risk of stroke by meta-analysis. METHODS: Electronic databases through July 2007 were searched to identify prospective cohort studies that examined the association between metabolic syndrome and risk of stroke. Two reviewers independently assessed eligibility and used a standardized form to collect data from published studies. The study quality was assessed by the Newcastle-Ottawa Scale. RESULTS: We found 13 eligible studies that included 92,732 participants. Compared to individuals without metabolic syndrome, subjects with metabolic syndrome had a 1.6-fold increased risk of stroke (95% CI, 1.48-1.75). The relative risk of stroke associated with metabolic syndrome was 2.2 in the studies using the World Health Organization definition and 1.6 in those using the Adult Treatment Panel III definition, but the difference was not statistically significant. CONCLUSIONS: This analysis shows that metabolic syndrome is an important risk factor for incident stroke. A diagnosis of metabolic syndrome may prove useful in clinical management, and its elements should ultimately become important therapeutic targets for the reduction of the stroke burden in the general population.

Three novel heterobimetallic coordination polymers, {Na2[Cd(odpa)(H2O)]}n (1), {Na2[Zn(odpa)(H2O)]}n (2), and {Na2[Cd3(odpa)2(H2O)5]·1.5H2O}n (3) (H4odpa = 4,4′-oxydiphthalic acid), have been prepared under solvothermal conditions and characterized by single-crystal X-ray diffraction. Compounds 1 and 2 are unprecedented 2D bilayer anion networks containing 26- and 24- membered channels made of Cd/Zn polyhedra linked by (odpa)4− ligand, while a novel 2D Na−O network is inserted subtly in the bilayer networks. Compound 3 presents a three-dimensional coordination polymer based on both tetranuclear and hexanuclear heterobimetallic clusters containing one-dimensional hydrophilic channels, where guest water molecules reside. Furthermore, these heterobimetallic clusters connected to each other to build a Cd−Na polyhedral network existing in a 3D anion framework. Compounds 1−3 are all heterobimetallic Cd/Zn−Na compounds containing polymeric anions, which have not been reported in all coordination polymers of (odpa)4− ligand. In 1−3, central CdII/ZnII ions and (odpa)4− ligand display completely different coordination modes and conformations. In addition, the thermal stabilities and photoluminescence properties were also studied.

It is difficult to accurately assess axillary lymph nodes metastasis and the diagnosis of axillary lymph nodes in patients with breast cancer is invasive and has low-sensitivity preoperatively. This study aims to develop a mammography-based radiomics nomogram for the preoperative prediction of ALN metastasis in patients with breast cancer. This study enrolled 147 patients with clinicopathologically confirmed breast cancer and preoperative mammography. Features were extracted from each patient's mammography images. The least absolute shrinkage and selection operator regression method was used to select features and build a signature in the primary cohort. The performance of the signature was assessed using support vector machines. We developed a nomogram by incorporating the signature with the clinicopathologic risk factors. The nomogram performance was estimated by its calibration ability in the primary and validation cohorts. The signature was consisted of 10 selected ALN-status-related features. The AUC of the signature from the primary cohort was 0.895 (95% CI, 0.887-0.909) and 0.875 (95% CI, 0.698-0.891) for the validation cohort. The C-Index of the nomogram from the primary cohort was 0.779 (95% CI, 0.752-0.793) and 0.809 (95% CI, 0.794-0.833) for the validation cohort. Our nomogram is a reliable and non-invasive tool for preoperative prediction of ALN status and can be used to optimize current treatment strategy for breast cancer patients.

BACKGROUND: Despite conflicting evidence, chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia. OBJECTIVES: To assess the effectiveness and safety of chest physiotherapy for pneumonia in adults. SEARCH METHODS: We searched CENTRAL 2012, Issue 11, MEDLINE (1966 to November week 2, 2012), EMBASE (1974 to November 2012), Physiotherapy Evidence Database (PEDro) (1929 to November 2012), CINAHL (2009 to November 2012) and CBM (1978 to November 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing the efficacy of chest physiotherapy for treating pneumonia in adults. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and appraised trial quality. Primary outcomes were mortality and cure rate. We used risk ratios (RR) and mean difference (MD) for individual trial results in the data analysis. We performed meta-analysis and measured all outcomes with 95% confidence intervals (CI). MAIN RESULTS: Six RCTs (434 participants) appraised four types of chest physiotherapy (conventional chest physiotherapy; osteopathic manipulative treatment (which includes paraspinal inhibition, rib raising and myofascial release); active cycle of breathing techniques (which include active breathing control, thoracic expansion exercises and forced expiration techniques); and positive expiratory pressure).None of the physiotherapies (versus no physiotherapy or placebo) improved mortality rates of adults with pneumonia.Conventional chest physiotherapy (versus no physiotherapy), active cycle of breathing techniques (versus no physiotherapy) and osteopathic manipulative treatment (versus placebo) did not increase the cure rate or chest X-ray improvement rate.Osteopathic manipulative treatment (versus placebo) and positive expiratory pressure (versus no physiotherapy) reduced the mean duration of hospital stay by 2.0 days (mean difference (MD) -2.0 days, 95% CI -3.5 to -0.6) and 1.4 days (MD -1.4 days, 95% CI -2.8 to -0.0), respectively. Conventional chest physiotherapy and active cycle of breathing techniques did not.Positive expiratory pressure (versus no physiotherapy) reduced fever duration (MD -0.7 day, 95% CI -1.4 to -0.0). Osteopathic manipulative treatment did not.Osteopathic manipulative treatment (versus placebo) reduced the duration of intravenous (MD -2.1 days, 95% CI -3.4 to -0.9) and total antibiotic treatment (MD -1.9 days, 95% CI -3.1 to -0.7).Limitations of this review are that the studies addressing osteopathic manipulative treatment were small, and that six published studies which appear to meet the inclusion criteria are awaiting classification. AUTHORS' CONCLUSIONS: Based on current limited evidence, chest physiotherapy might not be recommended as routine additional treatment for pneumonia in adults.