A novel four-gene signature for predicting the prognosis of hepatocellular carcinoma.

OBJECTIVE: To identify and utilize gene signatures for the prognostic evaluation of postoperative patients with hepatocellular carcinoma (HCC). METHODS: The gene mRNA expression profiles and corresponding clinicopathological data of postoperative patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Highly differentially expressed genes (DEGs) in tumor tissues compared to adjacent tissues were identified, and their associations with the overall survival (OS) of HCC patients were analyzed. The strongly associated genes were used to develop a prognostic score for the survival stratification of HCC, and the underlying mechanisms were analyzed using bioinformatics. RESULTS: A total of 376 DEGs were identified and four DEGs (ADH4, COL15A1, RET and KCNJ16) were independently associated with OS. A prognostic score derived from the four genes could effectively stratify HCC patients with different OS outcomes, independent of clinical parameters. Patients with high scores exhibited poorer OS than patients with low scores (HR 5.526, 95% CI: 2.451-12.461, p < .001). The four genes were involved in cancer-related biological processes and were independent of each other in bioinformatics analyses. CONCLUSION: Four genes strongly associated with the prognosis of postoperative patients with HCC were identified, and the derived prognostic score was simple and valuable for overall survival prediction.

Pirfenidone ameliorates silica-induced lung inflammation and fibrosis in mice by inhibiting the secretion of interleukin-17A.

Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown. Here, we evaluated the efficacy of pirfenidone in the treatment of early and advanced silicosis in an experimental mouse model and explored its potential pharmacological mechanisms. We found that pirfenidone alleviated silica-induced lung dysfunction, secretion of inflammatory cytokines (TNF-α, IL-1ß, IL-6) and deposition of fibrotic proteins (collagen I and fibronectin) in both early and advanced silicosis models. Moreover, we observed that both 100 and 200 mg/kg pirfenidone can effectively treat early-stage silicosis, while 400 mg/kg was recommended for advanced silicosis. Mechanistically, antibody array and bioinformatic analysis showed that the pathways related to IL-17 secretion, including JAK-STAT pathway, Th17 differentiation, and IL-17 pathway, might be involved in the treatment of silicosis by pirfenidone. Further in vivo experiments confirmed that pirfenidone reduced the production of IL-17A induced by silica exposure via inhibiting STAT3 phosphorylation. Neutralizing IL-17A by anti-IL-17A antibody improved lung function and reduced pulmonary inflammation and fibrosis in silicosis animals. Collectively, our study has demonstrated that pirfenidone effectively ameliorated silica-induced lung dysfunction, pulmonary inflammation and fibrosis in mouse models by inhibiting the secretion of IL-17A.

Metal ions/nucleotide coordinated nanoparticles comprehensively suppress tumor by synergizing ferroptosis with energy metabolism interference.

BACKGROUND: Ferroptosis holds promise as a potential tumor therapy by programming cell death with a hallmark of reactive oxygen species (ROS)-induced lipid peroxidation. However, vigorous energy metabolism may assist tumors to resist oxidative damage and thus weaken the effects of ferroptosis in tumor treatment. RESULTS: Herein, a bifunctional antitumor platform was constructed via coordinated interactions between metal ions and nucleotides to synergistically activate ferroptosis and interrupt energy metabolism for tumor therapy. The designed nanoparticles were composed of Fe2+/small interfering RNA (siRNA) as the core and polydopamine as the cloak, which responded to the tumor microenvironment with structural dissociation, thereby permitting tumor-specific Fe2+ and siRNA release. The over-loaded Fe2+ ions in the tumor cells then triggered ferroptosis, with hallmarks of lipid peroxidation and cellular glutathione peroxidase 4 (GPX4) down-regulation. Simultaneously, the released siRNA targeted and down-regulated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in the tumor to inhibit glycolytic pathway, which interfered with tumor energy metabolism and enhanced Fe2+-induced ferroptosis to kill tumor cells. CONCLUSIONS: This study presents a concise fabrication of a metal ion/nucleotide-based platform to integrate ferroptosis and energy metabolism intervention in one vehicle, thereby providing a promising combination modality for anticancer therapy.

Depth estimation method of surface of micropart in microassembly space based on microscopic vision tomographic scanning images.

Three-dimensional (3D) morphology of microparts has an important influence on performance of microassembly system that mainly assembles microparts in millimetre and micron scale. Because 3D morphology of microparts cannot be accurately obtained by conventional microscopic vision system, a depth estimation method of surface of micropart in microassembly space based on microscopic vision tomographic scanning (MVTS) images is proposed in this paper. The proposed method uses the positions of pixels with the largest focus values in MVTS image to construct the isodepth contours of surface of micropart and obtains the depth values of micropart's surface at the positions of MVTS by assigning depth values to corresponding isodepth contours. The MVTS images are obtained by MVTS and pixels with the largest focus values in MVTS image are obtained by focus measurement of MVTS images of micropart in microassembly space. On these bases, 3D spatial interpolation method is applied to map depth value of space between adjacent isodepth contours and to obtain depth values of all surface of micropart. Simulation experiments are carried out to verify the proposed method by generating simulated MVTS image array from two simulation objects, and the influence parameters of the proposed method are analysed. In established experimental setup of microassembly that can realise MVTS, experimental verification for the proposed depth estimation method are carried out by using cone cavity and end jaws of microgripper. 3D morphologies of depth maps of cone cavity and end jaws of microgripper are registered with their respective CAD models using iterative nearest point registration algorithm to quantify accuracy of depth estimation. The research results show that 3D morphology of micropart can be obtained by the proposed method and has better accuracy than those by conventional shape from focus method. This method provides a new way to obtain the morphology of microparts and lays a foundation for improving the accuracy and efficiency of gripping, alignment and approaching microparts in microassembly systems.

YAP1 is an independent prognostic marker in pancreatic cancer and associated with extracellular matrix remodeling.

BACKGROUND: Pancreatic cancer is a major cause of cancer-related mortality. The identification of effective biomarkers is essential in order to improve management of the disease. Yes-associated protein 1 (YAP1) is a downstream effector of the Hippo pathway, a signal transduction system implicated in tissue repair and regeneration, as well as tumorigenesis. Here we evaluate the biomarker potential of YAP1 in pancreatic cancer tissue. METHODS: YAP1 was selected as a possible biomarker for pancreatic cancer from global protein sequencing of fresh frozen pancreatic cancer tissue samples and normal pancreas controls. The prognostic utility of YAP1 was evaluated using mRNA expression data from 176 pancreatic cancer patients in The Cancer Genome Atlas (TCGA), as well as protein expression data from immunohistochemistry analysis of a local tissue microarray (TMA) cohort comprising 140 pancreatic cancer patients. Ingenuity Pathway Analysis was applied to outline the interaction network for YAP1 in connection to the pancreatic tumor microenvironment. The expression of YAP1 target gene products was evaluated after treatment of the pancreatic cancer cell line Panc-1 with three substances interrupting YAP-TEAD interaction, including Super-TDU, Verteporfin and CA3. RESULTS: Mass spectrometry based proteomics showed that YAP1 is the top upregulated protein in pancreatic cancer tissue when compared to normal controls (log2 fold change 6.4; p = 5E-06). Prognostic analysis of YAP1 demonstrated a significant correlation between mRNA expression level data and reduced overall survival (p = 0.001). In addition, TMA and immunohistochemistry analysis suggested that YAP1 protein expression is an independent predictor of poor overall survival [hazard ratio (HR) 1.870, 95% confidence interval (CI) 1.224-2.855, p = 0.004], as well as reduced disease-free survival (HR 1.950, 95% CI 1.299-2.927, p = 0.001). Bioinformatic analyses coupled with in vitro assays indicated that YAP1 is involved in the transcriptional control of target genes, associated with extracellular matrix remodeling, which could be modified by selected substances disrupting the YAP1-TEAD interaction. CONCLUSIONS: Our findings indicate that YAP1 is an important prognostic biomarker for pancreatic cancer and may play a regulatory role in the remodeling of the extracellular matrix.

Community-based rehabilitation service in Chengdu, Southwest China: a cross-sectional general survey.

BACKGROUND: World Health Organization initiated community-based rehabilitation (CBR) in 1978, and by now, it has been an essential process of medical services worldwide. China had strengthened primary health care on building more than 35,000 community health centers (CHCs) in cities, and more than 34,000 township health centers (THCs) in the rural area. Nevertheless, it remains unclear that if these primary health centers could provide optional rehabilitation services for disabilities. And this study aims at evaluating the supply capacity of rehabilitation service in primary health centers of Chengdu, a regional center city of southwest China. METHOD: We conducted a general investigation of primary health centers in Chengdu, a city located in southwest China with more than 15 million population. Our investigation covered all of Chengdu's 390 primary health centers from October to November 2016. We researched these primary health centers on basic rehabilitation services, diseases, and rehabilitation equipment quantity and quality, and traditional Chinese medicine (TCM) physiotherapy. RESULT: Rehabilitation therapy is available in 88.9% (337 of 379) of all primary health centers. Meanwhile, CHCs slightly surpass THCs with an available rate of 92.2% (106 of 115) and 87.5% (231 of 264), respectively. Traditional Chinese Medicine (TCM) physiotherapy is available in 97.1% (368 of 379) of all primary health centers, 97.3% (112 of 115) of CHCs and 97.0% (256 of 264) of THCs. Quantitative analysis showed that substantial factors which could make an impact on the number of patients per year contain: categories of rehabilitation disease (P < 0.001, 95% confidence interval (CI) [- 1.571, - 0.702]),number of rehabilitation bed (P < 0.001, 95%CI [- 1.249, - 0.290]). CONCLUSION: CBR and TCM physiotherapy has become accessible for disabilities in most basic health centers of Chengdu City, whereas, available rate of CBR in THCs is lesser than in CHCs, which suggests an imbalance in primary health service development between rural and urban area. Categories of rehabilitation diseases, and the number of rehabilitation beds constitute co-factors that make an impact on the CBR capacity of basic health centers.

Anodic Voltage Dependence of Ti-6Al-4V Substrates and Hydroxyapatite Coating.

Ti-6Al-4V alloys were anodized in a solution containing 0.15 M HF and 2 M H3PO4 for 30 min under different voltages and then coated with hydroxyapatite (HA) by hydrothermal-electrochemical deposition. The effects of anodizing voltage on the morphology and bioactivity of the HA coating and on the bonding strength between the HA coating and the anodized substrates were investigated. Results indicated that highly ordered amorphous TiO2 nanotube arrays formed on the Ti-6Al-4V surface after anodic oxidation. The pore size of the nanotube increased up to approximately 100 nm with increasing anodic voltage until 25 V. The nanotube was damaged at anodic voltages above 25 V. The crystal structure of TiO2 changed from amorphous to anatase when the anodized substrates were heated at 450 °C for 3 h. The contact angle between the Ti-6Al-4V surfaces and the simulated body fluid evidently decreased after anodic oxidation. The roughness increased with increasing anodic voltage, and Ra reached about 0.56 µm under 25 V. The HA coating exhibited layered growth. The deposition of rod-like HA crystals as well as the crystallinity of the HA coating initially increased and then decreased with the further increase of the anodic volatage. The degree of crystallinity reached the maximum of approximately 73% at 25 V. The bonding strength between the coating and the anodized substrates increased and then slightly decreased with increasing voltage. The bonding strength was about 20.0 MPa when titanium substrate was anodized under 25 V. The results of simulated body fluid immersing experiments suggest that the HA coating exhibits promising bioactivity.

The chondroprotective effect of diosmin on human articular chondrocytes under oxidative stress.

Excessive oxidative stress, which can amplify inflammatory responses, is involved in the pathologic progression of knee osteoarthritis. Diosmin is known to possess a variety of biological functions such as antiinflammatory and antioxidant activities. We therefore demonstrated the chondroprotective potentials of diosmin on human articular chondrocytes under oxidative stress. The cytotoxicity of diosmin (5, 10, 50, and 100 µM) to chondrocytes was first evaluated. Subsequently, the cells were treated with diosmin (5 and 10 µM) after hydrogen peroxide (H2 O2 ) exposure. We found that the cytotoxicity of diosmin occurred in a dose-dependent manner (10, 50, and 100 µM), and low-dose diosmin (5 µM) slightly impaired cell viability. Diosmin supplementations (5 and 10 µM) did not show beneficial effects on mitochondrial activity, cytotoxicity, proliferation, and survival and the cell senescence was ameliorated in H2 O2 -exposed chondrocytes. On the other hand, diosmin down-regulated the mRNA levels of iNOS, COX-2, IL-1ß, COL1A1, MMP-3, and MMP-9; up-regulated TIMP-1 and SOX9; and improved COL2A1 in chondrocytes under oxidative stresses. Furthermore, diosmin also regulated glutathione reductase and glutathione peroxidase of H2 O2 -exposed chondrocytes. In conclusion, diosmin displayed a remarkable antiinflammatory effect compared with the antioxidant capacity on human chondrocytes. Diosmin can maintain the homeostasis of extracellular matrix of articular cartilage.

Gas chromatography-mass spectrometry based metabolomics profile of hippocampus and cerebellum in mice after chronic arsenic exposure.

Intake of arsenic (As) via drinking water has been a serious threat to global public health. Though there are numerous reports of As neurotoxicity, its pathogenesis mechanisms remain vague especially its chronic effects on metabolic network. Hippocampus is a renowned area in relation to learning and memory, whilst recently, cerebellum is argued to be involved with process of cognition. Therefore, the study aimed to explore metabolomics alternations in these two areas after chronic As exposure, with the purpose of further illustrating details of As neurotoxicity. Twelve 3-week-old male C57BL/6J mice were divided into two groups, receiving deionized drinking water (control group) or 50 mg/L of sodium arsenite (via drinking water) for 24 weeks. Learning and memory abilities were tested by Morris water maze (MWM) test. Pathological and morphological changes of hippocampus and cerebellum were captured via transmission electron microscopy (TEM). Metabolic alterations were analyzed by gas chromatography-mass spectrometry (GC-MS). MWM test confirmed impairments of learning and memory abilities of mice after chronic As exposure. Metabolomics identifications indicated that tyrosine increased and aspartic acid (Asp) decreased simultaneously in both hippocampus and cerebellum. Intermediates (succinic acid) and indirect involved components of tricarboxylic acid cycle (proline, cysteine, and alanine) were found declined in cerebellum, indicating disordered energy metabolism. Our findings suggest that these metabolite alterations are related to As-induced disorders of amino acids and energy metabolism, which might therefore, play an important part in mechanisms of As neurotoxicity.

Lipoxin A4 and its analog suppress hepatocarcinoma cell epithelial-mesenchymal transition, migration and metastasis via regulating integrin-linked kinase axis.

Epithelial-mesenchymal Transition (EMT) and migration play an important role in tumor progression, and lipoxin (LX), the 'stop signal' for inflammation, has been studied in basic research for its anti-inflammatory or inflammatory pro-resolving properties. Here, in the in vitro experiment, we showed that LXA4 could inhibit the EMT and migration in phorbol myristate acetate (PMA) or activated conditioned medium (ACM)-stimulated Hep3B cells by downregulation of integrin-linked kinase (ILK), a pseudokinase in cytoplasm and these effects were via inhibiting the phosphorylation of Akt and GSK3ß. Morover, LXA4 could not affect the EMT and migration of PMA-stimulated Hep3B cells by knockdown of ILK. In the in vivo experiment, BML-111 (the analog of LXA4) could inhibit the EMT and metastasis of hepatocarcinoma cells. We also demonstrated that ILK siRNA inhibited phosphorylation of downstream signaling targets Akt and GSK3ß, decreased expression of MMP-2 and MMP-9. These results showed that LXA4 could be a possible candidate for liver cancer therapy, and blocking ILK axis would be an effective drug target.

Role of Neuroinflammation in Opioid Tolerance: Translational Evidence from Human-to-Rodent Studies.

Opioid analgesics remain the most effective and widely used analgesics for the management of moderate to severe pain, including cancer pain and chronic non-cancer pain. However, the efficacy of long-term opioid analgesics is attenuated by tolerance and/or hyperalgesia after long-term use, preventing adequate pain relief under stable opioid dosages for chronic pain patients. Classical neuron-centered concepts about tolerance, such as internalization of opioid receptors, upregulation of N-methyl-D-aspartate receptor function, or downregulation of glutamate transporter activity, can only partially explain the phenomenon of tolerance. Recent evidence revealing glial activation and upregulation of inflammatory mediators in the rodent central nervous system has confirmed the pivotal role of neuroinflammation in neuropathic pain or opioid tolerance, or both. However, human evidence is still sparse.Based on our clinical practice, we conducted translational research by investigating the cerebrospinal fluid (CSF) cytokine and chemokine profiles of opioid-tolerant patients after research ethic committee approval. CSF samples from opioid-tolerant patients and opioid-naive subjects were compared. We found CXCL1, CXCL12, and leukemia inhibitory factor (LIF) were significantly upregulated among the opioid-tolerant patients and positively correlated with the opioid dosage.We translated these findings back to lab animal experiment; after induction of tolerance by morphine infusion, the spinal cord expression of CXCL1, CXCL12, and LIF were all upregulated. Although CXCL1 and CXCL12 infusion alone did not affect baseline tail-flick latency, morphine analgesic efficacy dropped significantly after intrathecal infusion of CXCL1 and CXCL12. After establishing tolerance by intrathecal continuous infusion of morphine, tolerance development was accelerated by co-administration of CXCL1 and CXCL12. In parallel, the effect was attenuated by co-administration of CXCL1- or CXCL12-neutralizing antibody or concordant receptor antagonists.On the contrary, although chronic morphine administration still induced LIF upregulation in rat spinal cords, intrathecal injection of LIF potentiated the analgesic action of morphine and delayed the development of morphine tolerance. Upregulation of endogenously released LIF by long-term use of opioids might counterbalance the tolerance induction effects of other pro-inflammatory cytokines.CXCL1, CXCL12, and LIF are upregulated in both opioid-tolerant patients and rodents. The onset and extent of opioid tolerance were affected by modulating the intrathecal CXCL1/CXCR2, CXCL12/CXCR4, and LIF signaling and could be novel drug targets for the treatment of opioid tolerance.

Public Key-Based Authentication and En-Route Filtering Scheme in Wireless Sensor Networks.

The existing public key-based en-route filtering schemes are vulnerable to report disruption attacks or selective forwarding attacks, and they fail to consider any measure to detect and punish the malicious nodes. The authors propose a series of public key-based security mechanisms for wireless sensor networks (WSNs) in this paper, including a mechanism for verifying the partial signatures, a substitution mechanism, an effective report forwarding protocol, and a trust value-based mechanism to identify and punish the malicious nodes. Finally, the authors develop a public key-based authentication and en-route filtering scheme (PKAEF), which can resist false data injection attacks, report disruption attacks and selective forwarding attacks, and can mitigate the impact of malicious nodes. Detailed performance analysis and evaluation show that, in most cases, PKAEF outperforms previous works in terms of safety, filtering efficiency, and data availability.

[A new triterpenic acid from the roots of Rosa laevigata].

This study was designed to investigate triterpenoids from the roots of Rosa laevigata Michx. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity and chemical constitution. Spectroscopy methods were used to determine their structures. Five constituents were isolated and identified as19α-OH-3ß-E-feruloyl corosolic acid (1), 23-hydroxy-tormentic acid (2), 2α, 3ß, 19α, 23- tetrahydroxy-12-en-28-oleanolic acid (3), 2α, 3α, 20ß- trihydroxyurs-13 (18)-en-28-oic-acid (4), 2α, 3ß, 20ß-trihydroxyurs-13 (18)-en-28-oic-acid (5). Compound 1 was assigned as a new compound, compounds 4, 5 were obtained from the genus Rosa for the first time.

[Investigation and genetic identification on Babesia infection in rodents in some areas of Fujian Province].

Objective: To explore the status of Babesia infection in rodents and the genetic characteristics of Babesia spp. in Fujian Province. Methods: Rodents were captured by the night trapping method in Shaowu, Qingliu, Shunchang, Yong'an, Changle and Youxi during 2014-2015. The rodent species was identified, and information on the time and place of capture, species and sex of rodents was recorded. Blood samples was collected, in which the fragment of 18S rRNA gene of Babesia spp. was amplified by PCR. The PCR products were sequenced and the phylogenetic tree was constructed for homology analysis. Data on positive rate were analyzed with Chi-square or Fisher exact test. Results: Two hundred and nine rats were captured, comprising of 71 domestic and 138 wild rats. The overall positive rate was 9.6%(20/209). The positive rate in domestic rats was 2.8%(2/71), including one Rattus norvebicus and one Rattus flavipectus. The positive rate in wild rats was 13.0%(18/138), including 13 Bandicota indica, one Rattus losea, 2 Rattus confucianus and 2 Rattus fulvescens. The positive rate was significantly higher in wild rats than in domestic rats (P < 0.05). The Youxi region had the highest positive rate(14.9%,13/87), followed by Yong'an(13.6%, 3/22), and no positive rat was found in Qingliu. The positive rate in the male rats was 7.9%(9/114), and that in the females was 11.6%(11/95). The positive rate was highest in adult rats (10.4%,18/173), followed by young ones (6.3%,2/32). No positive rat was found in old rats. There was no significant difference in positive rate among different regions, between male and female rats, or among different ages (P > 0.05). The sequences of PCR products had a 100% homology. The BLAST results revealed the species to be Babesia microti. The phylogenetic tree showed that the sample sequence was the most homologous with Babesia microti from Zhejiang Province(GenBank Accession No: JQ609305). Conclusion: There occurs Babesia microti infection in rats in part areas of Fujian Province. The positive rate was higher in wild rats than in domestic rats.

[Effect of air pollution on respiratory health in school-aged children in the main urban area of Chongqing, China].

OBJECTIVE: To investigate the effect of air pollution on respiratory health in school-aged children in the main urban area of Chongqing, China. METHODS: The main urban area of Chongqing was divided into polluted area and clean area according to the air pollution data shown on the Environmental Protection Agency Website of Chongqing between 2010 and 2015. A cluster sampling method was used to select 695 third- or fourth-grade children from 2 primary schools in the clean or polluted area as study subjects, with 313 children from the clean area and 382 children from the polluted area. Pulmonary function was examined for all children and a standard American epidemiological questionnaire (ATS-DLD-78-C) was used to investigate the prevalence of respiratory diseases and symptoms. RESULTS: Compared with the clean area, the polluted area had significantly higher concentrations of inhalable particles (PM10), fine particulate matter (PM2.5), and nitric oxide (NOX) (P<0.05). The multivariate logistic regression analysis was performed after adjustment for confounding factors, and the results showed that compared with those in the clean area, the children in the polluted area had significantly higher risks of cough (OR=1.644), cough during cold (OR=1.596), expectoration during cold (OR=2.196), persistent expectoration (OR=1.802), and wheezing (OR=2.415). The boys and girls in the clean area had significantly higher forced vital capacity and forced expiratory volume in one second than those in the polluted area (P<0.05). CONCLUSIONS: Air pollution in the main urban area of Chongqing is associated with the increased prevalence of respiratory symptoms in school-aged children and has certain effect on children's pulmonary function.

[Application of esmolol in severe hand, foot, and mouth disease].

OBJECTIVE: To study the clinical effect and mechanism of action of esmolol in the treatment of severe hand, foot, and mouth disease (HFMD). METHODS: A prospective randomized controlled trial was performed. A total of 102 children with severe HFMD were enrolled in the study and were randomly divided into conventional treatment and esmolol treatment groups (n=51 each). The children in the conventional treatment group were given conventional treatment according to the guidelines for the diagnosis and treatment of HFMD. Those in the esmolol treatment group were given esmolol in addition to the conventional treatment. The heart rate (HR), systolic blood pressure (SBP), and respiratory rate (RR) were continuously monitored for all children. Blood samples were collected from all children before treatment and 1, 3, and 5 days after treatment to measure the levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-κB) p65 in mononuclear cells. Serum levels of myocardial enzymes and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before treatment and after 5 days of treatment. RESULTS: There were no significant differences in HR, SBP, RR, NE, TNF-α, IL-6, NF-κB p65, serum myocardial enzymes, and NT-proBNP before treatment between the conventional treatment and esmolol treatment groups. Both groups had significant reductions in these parameters at each time point (P<0.05). Compared with the conventional treatment group, the esmolol treatment group had significant improvements in the above parameters after 1 and 3 days of treatment (P<0.05). After 5 days of treatment, the esmolol treatment group had significant improvements in serum levels of myocardial enzymes and NT-proBNP compared with the conventional treatment group (P<0.05). CONCLUSIONS: Early application of esmolol can effectively stabilize the vital signs of the children with severe HFMD. Its mechanism of action may be related to reducing serum catecholamine concentration, alleviating myocardial damage, improving cardiac function, and reducing inflammatory response.

CSRQ: Communication-Efficient Secure Range Queries in Two-Tiered Sensor Networks.

In recent years, we have seen many applications of secure query in two-tiered wireless sensor networks. Storage nodes are responsible for storing data from nearby sensor nodes and answering queries from Sink. It is critical to protect data security from a compromised storage node. In this paper, the Communication-efficient Secure Range Query (CSRQ)-a privacy and integrity preserving range query protocol-is proposed to prevent attackers from gaining information of both data collected by sensor nodes and queries issued by Sink. To preserve privacy and integrity, in addition to employing the encoding mechanisms, a novel data structure called encrypted constraint chain is proposed, which embeds the information of integrity verification. Sink can use this encrypted constraint chain to verify the query result. The performance evaluation shows that CSRQ has lower communication cost than the current range query protocols.

[Research on Life Quality Scale for Patients with Idiopathic Pulmonary Fibrosis].

OBJECTIVE: To develop a life quality scale suitable for idiopathic pulmonary fibrosis (IPF) patients, objectively reflecting its changes. METHODS: Authors first put forward a theoretical structure model of a scale according to patient-reported outcome (PRO) scale formulation principle by combining basic theories of Chinese medicine (CM). Then authors developed an initial scale on the basis of various life quality scales for respiratory disease patients by using structural decision making. Totally 34 patients with confirmed diagnosis of IPF were tested by questionnaire. Items were screened using expert importance scoring method, factor analysis, correlation coefficient method, Cronbach's alpha coefficient method. IPF patient reported outcomes (IPF PRO, IP) were finally defined. RESULTS: A new IP scale was developed covering three areas and 38 items. Pearson correlation coefficient for correlation analysis of clinical symptom scores in ST-George Respiratory Questionnaire and IP scale was 0.828 (P < 0.01). Pearson correlation coefficient for correlation analysis of activity ability scores was 0.929 (P < 0.01). Pearson correlation coefficient for correlation analysis of total scores was 0.862 (P < 0.01). By reliability of IP scale itself (reliability) analysis, Cronbach's alpha coefficient was 0.713. By using factor analysis method for data analysis, KMO statistics was 0.902. CONCLUSION: IP scale fully reflected the connotation of IPF patients' quality of life, so it could be used as CM clinical therapeutic effect evaluation tool.

[Triterpenoids from roots of Rosa laevigata].

To study the triterpenoids from the roots of Rosa laevigata. The silica gel column chromatography was used to separate the chemical constituents from the roots of Rosa laevigata Michx. HPLC was used to analyze its purity, chemical and spectroscopy methods were used to determine their structures. 12 constituents were isolated and identified as(2R, 19R)methyl 2-acetyloxy-19- hydroxyl-3-oxo-urs-12-en-28-carboxylate(1), pomonic acid (2), 18, 19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11, 13(18)-dien-28-oic acid(3), swinhoeic acid (4), myrianthic acid(5), 2α, 3ß, 19α-trihydroxy-24-oxo-urs-12-en-oic acid (6), tormentic acid(7), arjunic acid (8), 1ß-hydroxyeuscaphic acid(9), quadranoside Ⅷ (10), alpinoside(11), rubuside B (12). Compounds 1-4, 6, 9, 11-12 were obtained from this plant for the first time. Compounds 2-4, 6, 11-12 were obtained from the genus Rosa for the first time.

[Expression of vasoactive intestinal peptide in peripheral blood of children with hand, foot and mouth disease].

OBJECTIVE: To investigate the expression of vasoactive intestinal peptide (VIP) in peripheral blood of children with hand, foot and mouth disease and its significance. METHODS: According to the condition of the disease, 86 children with hand, foot and mouth disease were classified into phase 1 group (19 children) and phase 2 group (67 children). ELISA was used to measure the concentrations of plasma VIP, interferon-γ (IFN-γ), and interleukin-4 (IL-4) in peripheral blood. Flow cytometry was used to measure CD3+, CD4+, and CD8+ T lymphocyte subsets. RT-PCR was used for qualitative detection of enterovirus 71 (EV71) RNA in stool. RESULTS: Compared with the phase 1 group, the phase 2 group had a significantly higher positive rate of EV71-RNA (P<0.05) and significantly higher serum levels of IgG, IgA, IgM, and C3 (P<0.05). The phase 2 group had significantly lower proportions of peripheral CD3+, CD4+, and CD8+ T lymphocyte subsets than the phase 1 group (P<0.05), as well as significantly lower proportion of peripheral B cells and CD4+/CD8+ ratio than the phase 1 group (P<0.05). The phase 2 group also had a significantly lower concentration of VIP in peripheral blood than the phase 1 group (P<0.05). In the 86 children with hand, foot and mouth disease, the concentration of VIP in peripheral blood was positively correlated with the proportion of CD4+ T lymphocyte subset and CD4+/CD8+ ratio (r=0.533 and 0.532 respectively; P<0.05). CONCLUSIONS: VIP may be an important marker of the severity of hand, foot and mouth disease.