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Background: Gastric cancer (GC) remains one of the most common malignancies worldwide. Increasing evidence has demonstrated that circRNAs serve as critical roles in human cancer, including GC. In the present study, we focused on the detailed function and mechanism of circ_0000144 on GC progression. Methods: The levels of circ_0000144, miR-623 and G-protein-coupled receptor, family C, group 5, member A (GPRC5A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Targeted relationships among circ_0000144, miR-623 and GPRC5A were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, colony formation, apoptosis, migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, flow cytometry and transwell assays. Measurement of glutamine and α-ketoglutarate (α-KG) levels was performed using a corresponding assay kit. GPRC5A protein expression was detected using Western blot. In vivo assays were used to explore the impact of circ_0000144 on tumor growth. Results: Our data indicated that circ_0000144 was up-regulated and miR-623 was down-regulated in GC tissues and cells. Circ_0000144 interacted with miR-623 through directly binding to miR-623. Moreover, the knockdown of circ_0000144 weakened GC cell proliferation, colony formation, migration, invasion and glutaminolysis and accelerated cell apoptosis by up-regulating miR-623. GPRC5A was a direct target of miR-623 and circ_0000144 protected against GPRC5A repression through sponging miR-623. Furthermore, miR-623-mediated regulation on GC cell progression was reversed by the stored expression of GPRC5A. Additionally, circ_0000144 depletion inhibited tumor growth in vivo. Conclusion: Our study indicated that circ-0000144 knockdown repressed GC progression at least partly by regulating GPRC5A expression via sponging miR-623, illumining a novel therapeutic target for GC treatment.

Valproic acid is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproic acid augmentation therapy in schizophrenia. Interindividual variability in valproic acid dose and serum concentration may reflect functional consequences of genetic polymorphisms in genes encoding drug-metabolizing enzymes. The aim of this study was to determine the relationship between serum concentrations of valproic acid and single nucleotide polymorphisms of the cytochrome P450 (CYP) 2C19 gene in patients with schizophrenia. All patients had been receiving fixed dose of valproic acid for at least 2 weeks. The daily doses were 0.5–1.5 g. No other drugs except olanzapine were coadministered. Serum concentrations of valproic acid were measured using the ultra-high performance liquid chromatography method with mass-spectrometric detection. The CYP2C19 (CYP2C19*2 G681A and CYP2C19*3 G636A) genotypes were identified by real-time PCR analyses. The mean concentration/dose ratios of valproic acid was significantly higher in patients with 1 (P = 0.029) or 2 (P = 0.007) mutated alleles for CYP2C19 than in those without mutated alleles. The mean concentration/dose ratios of valproic acid was significantly higher in patients with CYP2C19 *1/*2 genotype (P = 0.029) or CYP2C19 *2/*3 genotype (P = 0.014) than in those with CYP2C12 *1/*1 genotype. The findings of this study suggest that CYP2C19 genotypes play an important role in controlling steady-state serum concentrations of valproic acid in Chinese Han population.

Aims Recent studies have shown that the hyperactive Notch pathway is involved in cirrhosis and hepatocellular carcinoma (HCC) development by regulating differentiation of hepatic oval cells (HOCs) into cancer cells. The aim of this study was to investigate whether matrine can alleviate liver injury and promote HOC differentiation into hepatocytes by suppression of Notch pathway. Main methods We evaluated the expression of Notch-1, Jagged-1, and Hes-1 in HCC tissue by immunohistochemistry. Stem cell characteristics of HOCs were evaluated by CCK-8, cell cycle, and apoptosis. The expression of Notch pathway, HOC markers and albumin (ALB) was detected by immunohistochemistry, QRT-PCR and western blotting. The effects of matrine in protecting liver in vivo were investigated in a rat Solt-Farber precancerous model. Key findings We found an abnormal activated Notch pathway in HCC tissue, and the hyperactive Notch pathway was strongly associated with poor liver function in patients with cirrhosis with HCC. Using siNotch-1 to inhibit Notch pathway confirmed that Notch pathway could maintain stem cell characteristics of HOCs. Matrine inhibited stem cell characteristics of HOCs, the expression of Notch pathway and HOC markers but upregulated ALB. Matrine in combined with siNotch-1 RNA decreased the more potently inhibited HOC markers and Notch pathway. In rat Solt-Farber precancerous model, prophylactic application of matrine alleviated liver injury, downregulated Notch pathway and HOC markers, and upregulated ALB in a dose-dependent manner. Significance Matrine could promote the differentiation of HOCs into hepatocytes by inhibiting the Notch signalling pathway and alleviate liver injury.

To explore whether the distance of rectal neuroendocrine neoplasms from the anal margin has an impact on the prognosis of patients and evaluate lymphatic metastases risk score for colorectal neuroendocrine neoplasms (NENs). Clinical pathological and follow-up data of 71 patients identified as colorectal neuroendocrine neoplasms by pathology from July 2011 to July 2019 were carefully collected. Among 71 patients with colorectal NENs, most of the tumors were rectal NENs (62 cases). A total of 26 patients were in the presence of lymph node metastasis, and 44 patients had negative lymph nodes. Patients with lesions from the anal margin > 5 cm in rectum have a better prognosis (P = 0.022). Tumor stage (P = 0.034) and grade (P = 0.001) were independent risk predictors of lymphatic metastases. We developed a lymphatic metastasis risk score for rectal NENs, and patients with the score ≥ 7.5 were more likely to develop lymph node metastases (area 0.958, 95% CI 0.903–1.000, P = 0.000) with a sensitivity of 72.2% and a specificity of 97.3%. Patients with lesions from the anal margin > 5 cm and lymphatic metastasis risk score ≥ 7.5 should be treated actively.

The Yangtze River delta white goat is the only goat breed that produces high-quality brush hair, which is specifically used in top-grade writing brushes. Previous studies have indicated that the CMTM3 and DUSP1 genes are involved in the growth and cycle of high-quality brush hair, and these genes are thought to be involved in the formation of high-quality brush hair traits. In this study, we investigated the relationship between methylation of CMTM3 and DUSP1 and such traits. The results indicated that the relative expression levels of the CMTM3 and DUSP1 genes were higher in non-high-quality brush hair than in high-quality brush hair. Furthermore, the CpG sites of the DUSP1 gene were not methylated, and the methylation level of CMTM3 was negatively correlated with the gene expression level. We believe that the DUSP1 gene regulates the formation of high-quality brush hair by non-methylated, and that methylation of the CMTM3 gene results in a decrease in its expression, causing an increase in the activity of the androgen receptor and the level of androgen. This high androgen level promotes the growth of high-quality brush hair. These study results provide a theoretical basis for further elucidating the molecular mechanism of the formation of high-quality brush hair characteristics, and provide scientific reference for the molecular breeding of high-quality brush hair.

Background: CDC25 is a dual-specificity phosphatase that was first identified in the yeast Schizosaccharomyces pombe as a cell cycle-defective mutant. Although CDC25 is involved in the cell cycle of ovarian granulosa cells, the CDC25 signaling pathway has not been clarified fully. To explore the role of CDC25C in the cell cycle of goat ovarian granulosa cells, a CDC25C-overexpressing vector, pCMV-HA-CDC25C, was constructed and transfected into granulosa cells from adult and young white goats from Jiangsu Nantong. RT-PCR was used to measure CDC25C, CDK1, and WEE1 gene expression levels, and flow cytometry was used to distinguish ovarian granulosa cells in different phases of the cell cycle. Progesterone and estradiol levels in transfected ovarian granulosa cells were also measured. Results: In adult goat follicular granulosa cells transfected with pCMV-HA-CDC25C, CDC25C expression increased significantly, which greatly increased the relative gene expression levels of both CDK1 and WEE1. Additionally, progesterone and estradiol levels were increased in goat follicular granulosa cells overexpressing CDC25C. And the cell cycle results showed that transfection of pCMV-HA-CDC25C leads to a higher proportion of cells in S phase compared to the no vector-transfected groups. Conclusions: The results of this study indicated that the overexpression of CDC25C may increase the gene expression levels of both WEE1 and CDK1 in S phase and accelerate the transition of cells from G1 phase to S phase.

The pitch deviation caused by machining error affects the transmission stationarity of the spur gear pair. It results in time-variation of the contact ratio for the system by corner contact. Meshing characteristics of the spur gear pair with the pitch deviation are studied in order to analyze the time-varying contact ratio and motion characteristics of the system. The mathematical model of time-varying contact ratio is established to explore its time-varying characteristics. Dynamics model of the spur gear pair with the pitch deviation considering time-varying contact ratio under multi-state meshing is proposed. The transmission stationarity of the spur gear pair are explored by dynamic meshing forces. The influence of system parameters and operating parameters on dynamics characteristics of the spur gear pair with the pitch deviation considering time-varying contact ratio is studied by bifurcation diagrams, phase portraits and Poincare maps. Results show that the pitch deviation as a short-period error in the spur gear pair leads to complex periodic motions. The possibility of the tooth disengagement, back-side teeth contacting and chaotic motion for the spur gear pair increases with the increase of complexity of pitch deviation values. The transmission accuracy and stationarity for the spur gear pair decrease when pitch deviation values are complex. This study provides a theoretical basis for dynamics modeling and stationarity analysis of the spur gear transmission system and other gear transmission systems.

The pitch deviation of gears caused by machining leads to corner contact in actual meshing process. In order to study the influence of the pitch deviation on motion characteristics of the spur gear pair, meshing state functions are constructed to reflect multi-state meshing including mesh-in at corner contact, mesh-out at corner contact, single and double pair drive-side teeth mesh, single and double pair back-side teeth contact and tooth disengagement. The nonlinear dynamics model of spur gear pair with pitch deviations under multi-state meshing is established. Variation laws of dynamic meshing forces and meshing states for the spur gear pair are analyzed. The influence of main parameters on nonlinear dynamics of the spur gear pair with pitch deviations is investigated. Results indicate that the pitch deviation results in complex periodic motion as a short-period error in spur gear pair. It mainly affects transmission stability of the spur gear pair by changing meshing states. This investigation provides a theoretical basis for the parameter design of the spur gear transmission system and the influence of pitch deviation in other gear transmission systems.

The safe operation of gear pairs is the basic safety guarantee of the machine. The safety of the gear pair may be destroyed due to transfinite of kinematic variables and system parameters. In order to reveal its evolutionary mechanism, the safety characteristics of the spur gear pair are researched under the established safety domain. A nonlinear dynamics model of the spur gear pair considered multi-state meshing is introduced. The comprehensive teeth contact safety domain of the spur gear pair to prevent tooth surface contact fatigue, tooth surface plastic deformation and tooth root bending fatigue is established. A method of judging safety characteristics of the system is given. The safety basins, phase portraits and Poincare mappings are computed to reveal the distribution of the coexistence attractors and judge the safety characteristics of the system motions under the established safety domain in the state space. Multi-initial values bifurcation diagrams and the corresponding top Lypunov exponents (TLE) via the change of the backlash, the fluctuation coefficient of the comprehensive transmission error and the external load are used to catch the motions in the studied state space and study their transition. Bifurcation & safety dendrograms are constructed to study the evolutionary processes of the system safety characteristics. System parameters are divided into two types according to their influence on the erosion and bifurcation of the system safety basins. Two patterns to change the system safety characteristics from safe to unsafe are found. The sensitive parameters of meshing state change the safety characteristics by one-to-two bifurcation. The sensitive parameters of dynamic characteristics mainly affect the safety characteristics by changing the amplitude of kinematic variables and the dynamic response of the tooth disengagement or back-side teeth contacting state. The study is helpful in the selection of system parameters for mitigation and design against fatigue.

The feasibility of near-infrared spectroscopy (NIRS) combined with chemometrics for the rapid detection of the cellulose and hemicellulose contents in corn stover is discussed. Competitive adaptive reweighted sampling (CARS) and genetic simulated annealing algorithm (GSA) were combined (CARS-GSA) to select the characteristic wavelengths of cellulose and hemicellulose and to reduce the dimensionality and multicollinearity of the NIRS data. The whole spectra contained 1845 wavelength variables. After CARS-GSA optimization, the number of characteristic wavelengths of cellulose (hemicellulose) was reduced to 152 (260), accounting for 8.24% (14.09%) of all wavelengths. The coefficients of determination of the regression models for predicting the cellulose and hemicellulose contents were 0.968 and 0.996, the root mean square errors of prediction (RMSEPs) were 0.683 and 0.648, and the residual predictive deviations (RPDs) were 5.213 and 16.499, respectively. The RMSEP of the cellulose and hemicellulose regression models was 0.152 and 0.190 lower for CARS-GSA than for the full-spectrum, and the RPD was increased by 0.949 and 3.47, respectively. The results showed that the CARS-GSA model substantially reduced the number of characteristic wavelengths and significantly improved the predictive ability of the regression model.

Kaida Jiang,1 Lingjiang Li,2 Xueyi Wang,3 Maosheng Fang,4 Jianfei Shi,5 Qiuyun Cao,6 Jincai He,7 Jinan Wang,8 Weihao Tan,8 Cuili Hu8 1Psychiatry Department, Shanghai Mental Health Center, Shanghai, 2Psychiatry Department,The Second Xiangya Hospital, Central South University, Changsha, 3Psychiatry Department, First affiliated Hospital of Hebei Medical University, Shijiazhuang, 4Psychiatry Department, Wuhan Mental Health Center, Wuhan, 5Psychiatry Department, Hangzhou the 7th Hospital, Hangzhou, 6Psychology Department, Nanjing Drum Tower Hospital, Nanjing, 7Neurology Department, First affiliated Hospital of Wenzhou Medical University, Wenzhou, 8Medical Affairs Department, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Background: Significant anxiety symptoms are associated with poor clinical course and outcome in major depressive disorder (MDD). This single-arm, open-label study aimed to evaluate the efficacy and tolerability of escitalopram treatment in patients with MDD and anxiety symptoms. Methods: Adult patients with MDD and anxiety symptoms (Montgomery–Asberg Depression Rating Scale [MADRS] ≥22 and Hamilton Anxiety Rating Scale [HAM-A] ≥14) were enrolled and received escitalopram (10–20 mg/day) treatment for 24 weeks. Symptom status was assessed by MADRS, 17-item-Hamilton Depression Rating Scale, HAM-A, and Clinical Global Impression Scale at baseline and the following visits. Quality of life was assessed by Short Form-12, and safety was evaluated by adverse events, laboratory investigations, vital signs, and physical findings. Results: Overall, 200 of 318 (66.2%) enrolled patients completed the 24-week treatment. The remission (MADRS ≤10 and HAM-A ≤7) rate in the full analysis set (N=285) was 73.3% (95% confidence interval: 67.80, 78.38) at week 24. Mean (± standard deviation) MADRS total score was 33.4 (±7.13) and HAM-A score was 27.6 (±7.26) at baseline, which reduced to 6.6 (±10.18) and 6.0 (±8.39), respectively, at week 24. Patients with higher baseline depression and anxiety level took longer to achieve similar remission rates. Overall, 80 of the 302 (26.5%) patients included in the safety set reported at least 1 treatment-emergent adverse event (TEAE). Most frequently reported TEAEs (>2%) were headache (4.0%), nasopharyngitis (3.6%), nausea (3.0%), and dizziness (2.6%). Serious TEAEs were reported by 1.3% patients; no deaths were reported. Conclusion: Escitalopram 10–20 mg/day was effective and well-tolerated in the long-term treatment of MDD with anxiety symptoms in adult Chinese population. Keywords: anxiety, Chinese, escitalopram, long term, major depressive disorder

Matrine (C15H24N2O) is an alkaloid extracted from the Chinese herb Sophora flavescens that has anti-fibrotic and anti-cancer properties. The aim of the present study was to determine the chemopreventive effect of matrine on the development of primary hepatocellular carcinoma (HCC) and its possible association with the suppression of the Notch signaling pathway. The rats were randomly divided into four groups: Control, model, low-dose matrine and high-dose matrine groups. The model was established by combining a partial hepatectomy with diethylnitrosamine (DEN) + 2-acetylaminofluorene (2-AAF). Low- and high-dose matrine groups received intragastric administration of matrine (0.25 and 2.5 g/l of matrine, respectively). DEN + 2-AAF injections and hepatectomy were not performed in the control group. All rats were sacrificed 2, 4 and 7 weeks after hepatectomy. HCC-like histopathological lesions were detected using hematoxylin and eosin staining. The expression levels of α-1-fetoprotein (AFP), albumin (ALB), Notch1 and Hes1 were analyzed using immunohistochemistry. Hepatic lobule structure loss, liver tissue necrosis and inflammatory cell infiltration, and edema degeneration were observed in the model group. By contrast, hepatocyte cord structure was restored and hepatocyte edema degeneration was significantly reduced after 7 weeks of treatment with matrine. In addition, compared with the model group, matrine reduced the expression of AFP, increased the expression of ALB and reduced the expression of Notch1 and Hes1 (only for high-dose matrine; all P

Olanzapine is an atypical antipsychotic drug that has been increasingly used for treatment in schizophrenia. It has been observed that olanzapine responses in schizophrenia patients vary individually, but the reason has not been elucidated. In the study, we aimed to comprehensively explore the relationships between olanzapine responses and genetic polymorphisms of drug metabolizing enzymes, transporters and target receptors, and so as to interpret the reason of good and poor responses of olanzapine. A total of 241 Chinese Han paranoid schizophrenia who treated with olanzapine alone for 4 weeks were recruited. The positive and negative symptom scale (PANSS) was used to evaluate the efficacy of olanzapine. The genetic polymorphisms were detected by improved multiple ligase detection reaction (iMLDR). Multivariate logistic regression analysis suggested that the genetic polymorphisms of CYP1A2 rs762551, UGT1A4 rs2011425, ABCB1 rs1045642, DRD2 rs1799732 and rs1799978, 5-HTR2A rs6311 were significantly associated with olanzapine response. Multifactor dimensionality reduction (MDR) analysis showed that there was a negative interaction between CYP1A2 rs762551, ABCB1 rs1045642, DRD2 rs1799978, 5-HTR2A rs6311 and the interaction model was the optimal model. Our findings could partially explain the different olanzapine outcome and provided evidence for clarifying the predictive indicators of olanzapine response in further.

Phosphorus (P) is one of nutrients essential for plant growth. The differences in P content, accumulation, and distribution among 98 rapeseed (Brassica napus) varieties with different P use efficiency for grain production (PUEg) were studied. The results showed that there were highly significant differences in P contents of the whole plant and various organs among different rapeseed varieties. Furthermore, PUEg had significantly negative correlations with P accumulations in whole plant, stems, shells, and seeds. The correlation analysis showed that the correlation coefficient of PUEg and P distribution ratio in stems was smaller, and it was significantly negatively correlated in shells, while it showed highly positive correlations in seeds. It indicated that P content in rapeseed plant stems and shells appeared to be transported into seeds to increase P distribution in seedpods at the late maturity stage, which could help improve PUEg.

Backlash plays a significant role in gear design and geared dynamics analysis. This study aims to establish a model of the time-varying backlash for a standard involute spur gear pair. The elastic deformations, thermal deformations and film thickness deformation at the meshing point are considered in this model. Asperity and fluid loads are included in film thickness. A time-varying backlash model with contact ratio is developed according to the force analysis at the meshing point. The contributions and effects of the various deformations on the backlash are analyzed. The effects of rotation speed, torque load and tooth surface temperature on the time-varying backlash are studied. Results show that the influence of various parameters on the backlash cannot be ignored. The time-varying backlash is less affected by elastic deformation and oil film thickness deformation, and is greatly affected by the thermal deformation. The time-varying backlash increases with the increase of torque load and the decreases of rotation speed and tooth surface temperature. Tooth surface temperature is validated experimentally due to its importance in the established model.

A face-gear drive system has been extensively used in important transmission devices with strict requirements for size and weight such as helicopter reducer and so on. Its dynamic characteristics directly affect the stability and reliability of the equipment. A piecewise torsional-bending-pendular nonlinear dynamics model of the face-gear drive system is established to study its nonlinear dynamics and dynamic characteristics. The multi-state engagements including drive-side teeth engaging, teeth disengagement, back-side teeth engaging, and alternate engaging between single-teeth pair and double-teeth pairs caused by the couple of the backlash and the contact ratio being greater than 1.0 is considered. The change of the dynamic engaging force and load distribution ratio for the system is analyzed by numerical results under three different states engagement. The effects of the load coefficient, meshing frequency and the comprehensive transmission error on the dynamic characteristics and nonlinear dynamics of the system are studied based on three different Poincare mappings defined by bifurcation diagrams, top Lyapunov exponent diagrams, phase portraits and variation curve of the dynamic engaging force. Results show that the complex phenomena such as teeth disengagement, drive-side and back-side impact occur with alternating meshing of the single and double pair teeth via the change of studied parameters. The research is helpful for the optimization of the face-gear drives.

Summary Background The China Mental Health Survey was set up in 2012 to do a nationally representative survey with consistent methodology to investigate the prevalence of mental disorders and service use, and to analyse their social and psychological risk factors or correlates in China. This paper reports the prevalence findings. Methods We did a cross-sectional epidemiological survey of the prevalence of mental disorders (mood disorders, anxiety disorders, alcohol-use and drug-use disorders, schizophrenia and other psychotic disorders, eating disorder, impulse-control disorder, and dementia) in a multistage clustered-area probability sample of adults from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Face-to-face interviews were done with a two-stage design by trained lay interviewers and psychiatrists with the Composite International Diagnostic Interview, the Structured Clinical Interview for DSM-IV Axis I disorders, the Community Screening Instrument for Dementia from the 10/66 dementia diagnostic package, and the Geriatric Mental State Examination. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted to adjust for differential probabilities of selection and differential response as well as to post-stratify the sample to match the population distribution. Findings 32 552 respondents completed the survey between July 22, 2013, and March 5, 2015. The weighted prevalence of any disorder (excluding dementia) was 9·3% (95% CI 5·4–13·3) during the 12 months before the interview and 16·6% (13·0–20·2) during the participants' entire lifetime before the interview. Anxiety disorders were the most common class of disorders both in the 12 months before the interview (weighted prevalence 5·0%, 4·2–5·8) and in lifetime (7·6%, 6·3–8·8). The weighted prevalence of dementia in people aged 65 years or older was 5·6% (3·5–7·6). Interpretation The prevalence of most mental disorders in China in 2013 is higher than in 1982 (point prevalence 1·1% and lifetime prevalence 1·3%), 1993 (point prevalence 1·1% and lifetime prevalence 1·4%), and 2002 (12-month prevalence 7·0% and lifetime prevalence 13·2%), but lower than in 2009 (1-month prevalence 17·5%). The evidence from this survey poses serious challenges related to the high burdens of disease identified, but also offers valuable opportunities for policy makers and health-care professionals to explore and address the factors that affect mental health in China. Funding National Health Commission of Health (Ministry of Health) and Ministry of Science and Technology of China.

The aim of the present study was to evaluate the efficacy and safety of a combination of intra-arterial and intravenous chemotherapy in the treatment of unresectable, advanced gastric cancer, and assess which patients are likely to benefit from combined treatment. The clinical data of 128 patients diagnosed with unresectable, advanced gastric cancer at The Fourth Hospital of Hebei Medical University (Shijiazhuang, China) from January 2009 to September 2012 were retrospectively analyzed. The patients were divided into two groups as follows: Those who received regional intra-arterial chemoembolization plus systemic chemotherapy (combined group; n=62) and those who received systemic chemotherapy only (venous group; n=66). The clinical response, overall survival (OS) and toxic effects in the two groups were compared. Univariate and multivariate analyses were performed to identify the primary factors affecting the survival time of patients in the combined group. The overall response rate was significantly increased (35.5%) in the combined group compared with the venous group (19.7%; P=0.045). The median OS was 14 months in the combined group and 13 months in the venous group, and the 1-year and 2-year survival rates in the two groups were 45.2 and 9.7%, and 40.9 and 6.1%, respectively. There were significant differences between the survival curves (P=0.044). The median time to progression in the combined group and the venous group was 10 months and 6 months, respectively, and the difference was statistically significant (P=0.003). Multivariate analysis revealed that tumor-node-metastasis (TNM)-stage and the degree of tumor staining were independent factors affecting OS. No differences in adverse reactions between the two groups were observed (P>0.05). The combination of intra-arterial and intravenous chemotherapy may effectively improve the rate of clinical response, prolong OS and time to symptomatic progression in patients with unresectable, advanced gastric cancer, in particular those with an earlier TNM stage and distinct tumor staining.

In this paper, a graph coloring-based spectrum allocation algorithm in cognitive radio networks combined with analytic hierarchy process is proposed. By analyzing several key factors that affect the quality of the leased spectrum, the algorithm combines the graph algorithm and analytic hierarchy process to assign the optimal spectrum to cognitive users orderly. Simulation results show that the proposed algorithm can effectively improve the network efficiency compared with original algorithms and arose inconspicuous loss to the whole network’s fairness. The proposal not only improves the efficiency of spectrum allocation, but also balances the requirements of the overall fairness of cognitive radio networks.

The classification and recognition technology of underwater acoustic signal were always an important research content in the field of underwater acoustic signal processing. Currently, wavelet transform, Hilbert-Huang transform, and Mel frequency cepstral coefficients are used as a method of underwater acoustic signal feature extraction. In this paper, a method for feature extraction and identification of underwater noise data based on CNN and ELM is proposed. An automatic feature extraction method of underwater acoustic signals is proposed using depth convolution network. An underwater target recognition classifier is based on extreme learning machine. Although convolution neural networks can execute both feature extraction and classification, their function mainly relies on a full connection layer, which is trained by gradient descent-based; the generalization ability is limited and suboptimal, so an extreme learning machine (ELM) was used in classification stage. Firstly, CNN learns deep and robust features, followed by the removing of the fully connected layers. Then ELM fed with the CNN features is used as the classifier to conduct an excellent classification. Experiments on the actual data set of civil ships obtained 93.04% recognition rate; compared to the traditional Mel frequency cepstral coefficients and Hilbert-Huang feature, recognition rate greatly improved.

A nonlinear dynamic model of a 3-DOF gear system is established to study the influence of the tooth contact temperature in the meshing surface on the dynamics in the system. The nonlinear factors such as the tooth contact temperature, the time-varying stiffness, the meshing friction, the comprehension transmission error and backlash are considered. The flash temperature of tooth surface of pinion and gear is formulated according to Blok’s flash temperature theory. The mathematical expression of tooth surface contact temperature varied with time is derived. The temperature stiffness is put forward and added to the nonlinear dynamic model. The expression of the mesh stiffness varied with the flash temperature of the tooth surface is derived based on Hertz contact theory. The dynamical characteristics of the system such as chaos, doubling bifurcation and Hopf bifurcation are analyzed.

We demonstrate that a four-ion cluster state can be used to realize the quantum state transfer in the ion-trap systems. The scheme does not involve Bell-state measurement and is insensitive to both the initial motional state and heating.

Caveolin-1 and flotillin-1 are considered as markers of lipid rafts which can be regarded as sorting platforms for targeted transport of transmembrane proteins and are involved in fundamental cellular events such as signal transduction, cell adhesion, lipid/protein sorting, and human cancer. We addressed caveolin-1 and flotillin-1 expression in 90 human hepatocellular carcinoma (HCC) and adjacent noncancerous tissues (ANT) samples by SDS-PAGE and immunoblotting with specific antibodies. Significant caveolin-1 and flotillin-1 overexpression was found in HCC tissues compared to ANT and was confirmed by immunohistochemistry. Raft-associated Akt signaling pathway components involved in the regulation of cell survival were altered by western blotting in HCC microdomain-enriched subcellular fractions purified from paired HCC and ANT samples. Our results demonstrated that the activity of raft-associated but not total membrane Akt determines its cellular functions. Lipid rafts differ in different types of tissues, which allows for the possibility of tissue-type-specific targeting for cell survival.

Worldwide, hepatitis B virus (HBV) infection is one of the leading causes of chronic liver disease. Because HBV is not a cytopathogenic virus, host immune responses induced by viral persistence are generally thought to be responsible for the disease progression of chronic HBV infection.1 Generally, HBV-specific T cells were believed to play important roles in inducing hepatocellular damage during chronic HBV infection2,3; however, recent studies have shown that these cells often display functional impairment, such as T cell exhaustion by up-regulation of programmed death 1,4,5 T cell attrition through the B cell lymphoma 2 interacting mediator,6 and impaired T cell receptor signaling through the ζ-chain.7 T cell impairment is even more pronounced in the livers of patients with chronic hepatitis B (CHB) versus their blood.5 Furthermore, activated HBV-specific CD8 T cells are often found to be present in the livers of patients without evident liver immunopathology, whereas non–virus-specific lymphocytes have usually massively infiltrated the livers of patients with hepatocellular damage.8 A model of HBV-transgenic mice has further confirmed that non–virus-specific lymphocytes can exacerbate the liver inflammation initiated by virus-specific CD8 T cells.9,10 These findings suggest that non–virus-specific inflammatory cells infiltrating the liver may actively participate in HBV-associated liver pathogenesis. Natural killer (NK) cells are abundant in the liver and serve as a major innate immune component against microbial infection.11 Recent studies have clearly suggested that NK cells may contribute to liver pathogenesis in rodent models12 and in patients with chronic hepatitis C virus (HCV) or HBV infection.13–16 Particularly during HCV infection, the viral infection results in an elevation of interferon-α (IFN-α) that subsequently polarizes NK cells toward cytolytic activity to induce liver injury.15 Emerging evidence indicates that during HBV infection, the early NK cell responses may lead to the initial control of the acute infection and allow the timely and efficient development of an adaptive immune response.17,18 However, if the virus persists, activated NK cells can mediate hepatocyte apoptosis by up-regulating tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in hepatitis B e antigen (HBeAg)–negative patients with hepatic flares14 and Fas ligand (FasL) in patients with HBV-associated acute-on-chronic liver failure.16 Although these studies have partially defined the role of NK cells in liver injury, NK cells may also use some other ligands to mediate liver injury in various disease progression phases of chronic HBV infection. In addition, recently available data about NK cells in CHB patients were primarily obtained from the peripheral compartments18,19; detailed information about the roles of NK cells in the liver pathogenesis of chronic HBV infection is scarce, especially for HBeAg-positive subjects. HBeAg-positive individuals with chronic HBV infection are generally divided into two groups: immune-tolerant (IT) carriers and immune-activated (IA) patients. The former group is characterized by minimal liver damage, normal alanine aminotransferase (ALT) levels, and active viral replication; the latter, generally after the IT phase, have increased liver injury and decreased viral replication.1,20 In this study, we comprehensively characterized the hepatic NK cells in these HBV-infected individuals and demonstrated that NK cell–mediated liver pathogenesis depended on an imbalanced cytokine milieu in the livers of these IA patients. Our findings may facilitate the rational development of immunotherapeutic strategies for enhancing viral control while limiting or blocking liver injury and inflammation.

To study the expressions of β-catenin in hepatocellular carcinoma (HCC) tissue, adjacent cirrhotic liver tissue and hemangioma-surrounding liver tissue to understand whether their difference in expression will influence on the prognosis and to study the relationship between Wnt/β-catenin signaling pathway and HNF-1α expression.50 specimens of HCC, 50 specimens of adjacent cirrhotic liver tissue and 7 specimens of hemangioma-surrounding liver tissue were used to detect the differences in the expression of β-catenin and HNF-1α in them by immunohistochemistry.The expression rate of β-catenin was 74.0% (37/50) in the HCC tissue, 18.0% (9/50) in cirrhotic liver tissue, and 14.3% (1/7) in hemangioma-surrounding liver tissue. The expression rate of β-catenin in HCC tissue was significantly higher than that in the hemangioma-surrounding liver tissue (P = 0.002) and cirrhotic liver tissue (P0.001). The patients with abnormal expression had worse prognosis. Among the 50 HCC cases, the expression of HNF-1α was negative in 20.0% (10/50), weak positive in 40.0% (20/50), moderately positive in 26.0% (13/50), and strong positive in 14.0% (7/50). Among the 50 adjacent cirrhotic liver tissues, the expression of HNF-1α was negative in 12.0% (6/50), weak positive in 20.0% (10/50), moderately positive in 52.0% (26/50) and strong positive in 16.0% (8/50). In the 7 cases of hemangioma-surrounding liver tissue, the expression of HNF-1α was negative in 0(0/7), weak positive in 14.3% (1/7), moderately positive in 28.6% (2/7) and strong positive in 57.1% (4/7). The positive expression rate of HNF-1α in the HCC tissue was significantly lower than that in the hemangioma-surrounding liver tissues (P = 0.029) and adjacent cirrhotic liver tissues (P = 0.008). The patients with positive HNF-1α expression had a better prognosis. The abnormal expression of β-catenin was negatively correlated with positive HNF-1α expression (r = -0.673, P0.001).The occurrence and development of HCC is related to the abnormal β-catenin expression. There is a negative correlation between Wnt/β-catenin signaling pathway and HNF-1α expression.

Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

Children with Developmental Coordination Disorder (DCD) have multiple impairments in movement, in learning, and in the activities of daily living. Studies from other countries have associated these impairments with cognitive function, particularly executive functioning, but these findings have not been confirmed in China.Compare the executive functioning of children with DCD with that of normal children.The Wisconsin Card Sorting Test (WCST) was administered to 39 children who met DSM-IV criteria of DCD identified at the Seventh People's Hospital of Hangzhou from March 2008 through March 2010. The WCST was also administered to a control group of 39 randomly selected children from one elementary school in Hangzhou.The total responses on the WCST and the number of non-perseverative errors for cases and controls were similar, but cases had significantly more errors, more perseverative responses and more perseverative errors; moreover, they completed fewer categories than controls and required more trials to complete the first category.Our study confirms previous studies which show significantly impaired executive functioning in patients with DCD. Collectively, these studies suggest that the deficits in executive functioning of children with DCD significantly impair their intellectual and social development.发育性协调运动障碍（Developmental Coordination Disorder，DCD）患儿存在明显的运动能力、学习和日常生活能力的下降。国外研究表明，患儿的这些能力下降与其认知功能尤其是执行功能的受损有关，但国内尚无此类研究证实来这些结果。比较发育性协调运动障碍儿童与正常儿童的执行功能。对2008年3月至2010年3月在杭州市第七人民医院就诊并符合DSM-IV发育性协调运动障碍诊断的39例患儿采用威斯康星分类卡片测验（Wisconsin Card Sorting Test，WCST）进行评估。另外，在杭州某小学随机抽取39名健康儿童作为对照组，同样对他们进行WCST评估。两组在WCST的总应答数及非持续错误数相似，但是研究组的错误应答数、持续性应答数和持续性错误数均显著高于对照组。另外，研究组患儿完成分类数低于对照组，完成第一个分类所需的应答数也高于对照组。本研究证实了先前一些研究的结果，即发育性协调运动障碍儿童存在明显的执行功能缺陷。所有这些研究均提示，患儿的执行功能缺陷显著影响了其智能和社会功能的发展。

The role of CD4+ cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC) remains obscure. This study characterized CD4+ CTLs in HCC patients and further elucidated the associations between CD4+ CTLs and HCC disease progression. In all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis (LC) patients, and 88 healthy individuals were enrolled in the study. CD4+ CTLs were defined by flow cytometry, immunohistochemistry, and lytic granule exocytosis assays. A multivariate analysis of prognostic factors for overall survival was performed using the Cox proportional hazards model. Circulating and liver-infiltrating CD4+ CTLs were found to be significantly increased in HCC patients during early stage disease, but decreased in progressive stages of HCC. This loss of CD4+ CTLs was significantly correlated with high mortality rates and reduced survival time of HCC patients. In addition, the proliferation, degranulation, and production of granzyme A, granzyme B, and perforin of CD4+ CTLs were inhibited by the increased forkhead/winged helix transcription factor (FoxP3+) regulatory T cells in these HCC patients. Further analysis showed that both circulating and tumor-infiltrating CD4+ CTLs were independent predictors of disease-free survival and overall survival after the resection of the HCC. Conclusion: The progressive deficit in CD4+ CTLs induced by increased FoxP3+ regulatory T cells was correlated with poor survival and high recurrence rates in HCC patients. These data suggest that CD4+ CTLs may represent both a potential prognostic marker and a therapeutic target for the treatment of HCC. (HEPATOLOGY 2013)