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Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer's test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S/D-SEDs. In conclusion, this preclinical study supports the possibility of using S/D virally inactivated SEDs to treat DES and restore a normal epithelium.

Objective Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to examine prescribing patterns of antidepressants, antipsychotics and mood stabilizers in BD patients misdiagnosed with MDD in China. Methods A total of 1487 patients originally diagnosed with MDD were consecutively screened for diagnostic revision in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses. Data on psychotropic prescriptions were collected by a review of medical records. Results Three hundred and nine of the 1487 patients (20.8%) fulfilled DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. Of the BD patients (n = 309), 227 (73.5%) received any use of antidepressants, 73 (23.6%) antipsychotics and 33 (10.7%) mood stabilizers. In multiple logistic regression analyses, compared with those with MDD, patients with BD-I were more likely to receive antidepressants (OR 1.7, 95% CI 1.1–2.8, p = 0.02), antipsychotics (OR 1.6, 95% CI 1.04–2.5, p = 0.04) and mood stabilizers (OR 3.9, 95% CI 2.1–7.2, p

Background Bipolar disorder (BD) is a recurrent, complex illness and often misdiagnosed and treated as a major depressive disorder (MDD). This study set out (1) to investigate the proportion of BD in patients treated for MDD using DSM-IV diagnostic criteria; (2) to test the usefulness of the screening tool — the 32-item Hypomania Checklist (HCL-32) in Chinese patients; and (3) to assess whether MDD patients with subthreshold manic features (patients who screened positive for BD on the HCL-32, but did not meet the diagnostic criteria for DSM-IV BD as measured by Mini International Neuropsychiatric Interview (MINI)) differ from those with BD, and from those suffering from MDD without manic features in terms of basic demographic and clinical variables. Methods A total of 1487 patients treated for MDD were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The HCL-32 was self-completed by patients to identify hypomanic symptoms, and the MINI was used by clinicians to establish DSM-IV diagnoses. Results The proportions of undiagnosed BD (all types), BD-I and BD-II were 20.8%, 7.9% and 12.8%, respectively. The HCL-32 had low positive predictive value (0.43). Compared to MDD patients without subthreshold manic features, MDD patients with subthreshold manic features were younger at onset, less likely to be married and had more depressive episodes on a seasonal basis, and more frequent depressive episodes overall. Compared to BD patients, MDD patients with subthreshold manic features had an older age at onset and less frequent depressive episodes and less family history of psychiatric disorders, appetite, weight gain and time spent sleeping, suicide ideation and attempts and psychotic symptoms. Conclusions At least one fifth of Chinese patients treated for MDD may have an undiagnosed BD. The HCL-32 is useful to identify broader subthreshold bipolar features. The findings need to be confirmed by longitudinal studies using more comprehensive, standardized instruments.

Background Synaptic mechanisms and neuronal oscillations have been proposed to be responsible for neuropathic pain formation. Many studies have also highlighted the important role of electrical synapses in synaptic plasticity and in neuronal oscillations. Thus, electrical synapses may contribute to neuropathic pain generation. However, previous studies have primarily focused on the role of chemical synapses, while ignoring the role of electrical synapses, in neuropathic pain generation. Methods The authors adopted microinjection, RNA interference techniques, and behavioral tests to verify the link between connexin 36 (Cx36) and neuropathic pain. They also studied the selective Cx36 blocker mefloquine in rat chronic constriction injury and spared nerve injury model of neuropathic pain. Electrophysiologic recordings were used to further confirm the behavioral data. Results The authors found that Cx36, which constitutes the neuron–neuron electrical synapses, was up-regulated in the anterior cingulate cortex after nerve injury (n = 5). Meanwhile, Cx36-mediated neuronal oscillations in the gamma frequency range (30 to 80 Hz) (n = 7 to 8) and the neuronal synaptic transmission (n = 13 to 19) were also enhanced. Neuropathic pain was relieved by disrupting Cx36 function or expression in the anterior cingulate cortex. They also found that mefloquine, which are clinically used for treating malaria, affected gamma oscillations and synaptic plasticity, leading to a sustained pain relief in chronic constriction injury and spared nerve injury models (n = 7 to 12). Conclusion The electrical synapses blocker mefloquine could affect gamma oscillations and synaptic plasticity in the anterior cingulate cortex and relieve neuropathic pain. Cx36 may be a new therapeutic target for treating chronic pain.

Elevated compression tests were conducted on 2205 duplex stainless steel using a Gleeble 3800 thermal simulator under constant strain rates ranging from 0.1 s−1 to 50 s−1 and at deformation temperatures ranging from 900°C to 1200°C for the sample. All tests were performed at a total true strain of 0.9. The elevated temperature deformation behavior of the 2205 duplex stainless steel was characterized based on an analysis of the stress–strain curves. A set of constitutive equations for 2205 duplex stainless steel was proposed by employing hyperbolic sine function. The equations revealed the dependence of flow stress on strain, strain rate and temperature. In order to evaluate the accuracy of the constitutive equations, the mean errors of flow stress between the experimental data and predicted results were calculated. The results showed that there was a good agreement between the prediction and experimental values.

Quantum key distribution with polarized qubits has not yet been realized over the aerial fiber, due to rapid polarization changes. Here, we report our recent work towards quantum communication through an aerial fiber channel. We designed a fast polarization feedback module featuring high efficiency, fast speed, and good stability. With this module, we implemented long-distance quantum key distribution over different types of aerial fiber links based on polarization encoding. Our work takes a significant step towards the application of quantum communications in complex environments.

In this study, the effect of original thicknesses of plate, the thicknesses of plate after rolling and rolling reduction on the strength in 301 stainless steel was modeled by means of artificial neural network (ANN). The experimental data were collected to obtain training set and testing set. The normalization method was employed for avoiding over-fitting. The optimal ANN method architecture was determined by according to the trial and error procedure. The results of the ANN model were in good agreement with experimental data. As can be seen from the result, we believe that the neural network model can efficiently predict the relationship between mechanical properties and rolling reduction in 301 austenitic stainless steel.

In this paper, artificial neural networks (ANN) has been proposed to determine the stresses of 13Cr supermartensitic stainless steel (SMSS) welds based on various deformation temperatures and strains using experimental data from tensile tests. The experiments provided the required data for training and testing. A three layer feed-forward network, deformation temperature and strain as input parameters while stress as the output, was trained with automated regularization (AR) algorithm for preventing overfitting. The results showed that the best fitting training dataset was obtained with ten units in the hidden layer, which made it possible to predict stress accurately. The correlation coefficients (R-value) between experiments and prediction for the training and testing dataset were 0.9980 and 0.9943, respectively, the biggest absolute relative error (ARE) was 6.060 %. As seen that the ANN model was an efficient quantitative tool to evaluate and predict the deformation behavior of type 13Cr SMSS welds during tensile test under different temperatures and strains.

Background and Aims: Src family kinases have been suggested to be associated with the metastasis of tumors, but their related mechanisms remain unclear. The aims of the present study were to assess the possible mechanisms by which the inhibition of Fyn activation regulates pancreatic cancer metastasis. Methods: We examined the expressions of Fyn in human pancreatic cancer tissues by immunohistochemistry and systematically investigated the relationship between Fyn expression and pancreatic cancer metastasis. A nude mouse xenograft model induced by BxPC3 cells with or without the inhibition of Fyn activation was used to explore the effect of the inhibition of Fyn on metastasis in vivo. Methyl thiazolyl tetrazolium and terminal deoxynucleotidyl transferase-labeling assays were used to examine the effect of the inhibition of Fyn on the cell proliferation of BxPC3 pancreatic cancer cells in vitro. Reverse transcription polymerase chain reaction and Western blot analysis were performed to explore the possible mechanism of Fyn-induced metastasis. Results: We found that the upregulation of Fyn expression was correlated with human pancreatic cancer metastasis. In BxPC3 pancreatic cancer cells, the inhibition of Fyn activation by kinase-dead Fyn transfection decreased liver metastasis in nude mice. Further analyses showed that Fyn activity modulated pancreatic cell metastasis through the regulation of proliferation and apoptosis. Conclusions: Our results suggest a possible mechanism by which Fyn activity regulates cell proliferation and apoptosis that exerts an effect on pancreatic cancer metastasis.

Purpose: Interaction between tumor cells and surrounding stromal fibroblast (SF) plays a critical role in tumor growth and invasion. The aim of the study is to determine the role of SF in regulating the invasive behaviors of pancreatic cancer by evaluating the mode of SF activating the urokinase plasminogen activator (uPA)-plasmin-matrix metalloproteinase (MMP)-2 cascade. Experimental Design: The expression patterns of uPA, MMP-2, and uPA receptor (uPAR) in human metastatic pancreatic cancer were analyzed by immunohistochemistry and the roles of SF in activation of the uPA-plasmin-MMP-2 cascade were evaluated by coculturing pancreatic cancer cell lines with SF. Results: uPA expression and fibroblastic uPAR expression were correlated with liver metastasis of human pancreatic cancer. MMP-2 rather than MMP-9 was activated in the metastatic pancreatic cancer. In the in vitro culture system, the coculture of peritumor fibroblasts with metastatic pancreatic cancer BxPc3 cells resulted in activation of MMP-2 and up-regulation of uPAR expression. In this coculture system, the uPA-plasminogen cascade was involved in MMP-2 activation. This activation required a direct interaction between SF and cancer cells. In the coculture system, intergrin α6β1 expression was increased in BxPc3 cells, and blocking the function of integrin α6β1 decreased the activation of uPA and MMP-2. This suggests that interaction between integrins of cancer cells and the uPARs of the SF might be involved in the activation of the uPAR-uPA-MMP-2 cascade. Conclusion: Our results suggest that SF plays a role in promoting pancreatic cancer metastasis via activation of the uPA-plasminogen-MMP-2 cascade.

Little has been reported about the demographic and clinical features of major depressive disorder (MDD) with comorbid dysthymia in Chinese patients. This study examined the frequency of comorbid dysthymia in Chinese MDD patients together with the demographic and clinical correlates and prescribing patterns of psychotropic drugs.Consecutively collected sample of 1178 patients with MDD were examined in 13 major psychiatric hospitals in China. Patients' demographic and clinical characteristics and psychotropic drugs prescriptions were recorded using a standardized protocol and data collection procedure. The diagnosis of dysthymia was established using the Mini International Neuropsychiatric Interview. Medications ascertained included antidepressants, antipsychotics, benzodiazepines, and mood stabilizers.One hundred and three (8.7%) patients fulfilled criteria for dysthymia. In multiple logistic regression analyses, compared to non-dysthymia counterparts, MDD patients with dysthymia had more depressive episodes with atypical features including increased appetite, sleep, and weight gain, more frequent lifetime depressive episodes, and less likelihood of family history of psychiatric disorders. There was no significant difference in the pattern of psychotropic prescription between the 2 groups.There are important differences in the demographic and clinical features of comorbid dysthymia in Chinese MDD patients compared with previous reports. The clinical profile found in this study has implications for treatment decisions.

Dry eye syndrome (DES) is a common eye disease. Artificial tears (AT) are used to treat DES, but they are not effective. In this study, we assessed the anti-inflammatory effect of AT containing epigallocatechin gallate (EGCG) and hyaluronic acid (HA) on DES. Human corneal epithelial cells (HCECs) were used in the WST-8 assay to determine the safe dose of EGCG. Lipopolysaccharide-stimulated HCECs showing inflammation were treated with EGCG/HA. The expression of IL-1s, IL-6, IL-8, and TNF-α was assessed by real-time PCR and AT physical properties such as the viscosity, osmolarity, and pH were examined. AT containing EGCG and HA were topically administered in a rabbit DES model established by treatment with 0.1% benzalkonium chloride (BAC). Tear secretion was assessed and fluorescein, H&E, and TUNEL staining were performed. Inflammatory cytokine levels in the corneas were also examined. The non-toxic optimal concentration of EGCG used for the treatment of HCECs in vitro was 10 μg/mL. The expression of several inflammatory genes, including IL-1s, IL-6, IL-8, and TNF-α, was significantly inhibited in inflamed HCECs treated with 10 μg/mL EGCG and 0.1% (w/v) HA (E10/HA) compared to that in inflamed HCECs treated with either EGCG or HA alone. AT containing E10/HA mimic human tears, with similar osmolarity and viscosity and a neutral pH. Fluorescence examination of the ocular surface of mouse eyes showed that HA increased drug retention on the ocular surface. Topical treatment of DES rabbits with AT plus E10/HA increased tear secretion, reduced corneal epithelial damage, and maintained the epithelial layers and stromal structure. Moreover, the corneas of the E10/HA-treated rabbits showed fewer apoptotic cells, lower inflammation, and decreased IL-6, IL-8, and TNF-α levels. In conclusion, we showed that AT plus E10/HA had anti-inflammatory and mucoadhesive properties when used as topical eye drops and were effective for treating DES in rabbits.

Activation of hepatic stellate cells (HSC) plays a pivotal role in the development of hepatic fibrosis. Transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor responsible for the activation of HSC. Diosgenin is a steroidal saponin found in several plants including Solanum and Dioscorea species, and it inhibited high glucose-induced renal tubular fibrosis. However, the effects of diosgenin against hepatic fibrosis remain elusive. Therefore, in this study, we investigated the effects of diosgenin on TGF-β1-induced HSCs and elucidate the possible mechanism of its anti-fibrotic effect. Our results demonstrated that diosgenin inhibited TGF-β1-induced HSC proliferation, reduced the expression of collagen I and α-smooth muscle actin (α-SMA), as well as the expression of TGF-β receptor I (TGF-β RI) and II. Moreover, diosgenin suppressed TGF-β1-induced phosphorylation of Smad3 in HSCs. In conclusion, our data demonstrate that diosgenin inhibited HSC-T6 cell proliferation and activation, at least in part, via the TGF-β1/Smad signaling pathway. These results provide that diosgenin may have potential to treat liver fibrosis.

To explore the mechanism of three kinds extracts (saponins, volatile components, polysaccharide components) of Qingxin Kaiqiao Recipe (QKR) in improving learning and memory capabilities of Alzheimer's disease (AD) rats.A controlled comparison method was used. Totally 56 male SD rats were randomly divided into seven groups, i.e., the normal control group, the sham-operation group, the model group, the Aricept group, the saponin group, the benzene group, and the polysaccharide group, 8 in each group. AD rat model was established by bilateral hippocampus injection of Aβ1-40 (2 µL, 2.5 µg/µL). The next day after modeling rats in the saponin group, the benzene group, and the polysaccharide group, the saponin group, the Aricept group were intragastrically administered with saponin (at the daily dose of 9 mL/kg, 2.1 g/mL) , benzene (at the daily dose of 3.33 mL/kg, 5.7 g/mL) , polysaccharide (at the daily dose of 8.33 mL/kg, 2.28 g/mL), Aricept (at the daily dose of 1.67 mg/kg), respectively, once a day for 2 consecutive weeks from 10 am every day. Equal volume of normal saline was intragastrically administered to rats in the normal control group and the model group. Learning and memory capabilities were detected using water maze 2 weeks later. Expression levels of synaptotagmin-1 (Syt-1), interleukin-1β (IL-1β), glia fibrillary acidic protein (GFAP), and β-amyloid precursor protein (βAPP) in the cortex and hippocampus of AD rats were detected using immunohistochemistry.Learning and memory capabilities could be improved by three kinds extracts of QKR. There was no statistical difference in the escape latency between the polysaccharide group and the model group (P0. 05). The escape lacency was shortened in the rest treatment groups (P0.05). The escape latency was obviously prolonged in three kinds extracts of QKR groups, when compared with the Aricept group (P0.05, P0.01). Compared with the model group, times for crossing platforms were significantly increased in the saponin group and the Aricept group (P0.05). Compared with the Aricept group, average times for crossing platforms were significantly lessened in three kinds extracts of QKR groups (P0.01). Compared with the sham-operation group, expression levels of Syt-1, IL-1β, GFAP, and βAPP in the cortex and hippocampus were increased in the model group (P0.01). Compared with the model group, the expression of cortical Syt-1 increased in the saponin group and the benzene group; the expression of cortical IL-1β increased in the benzene group and the polysaccharide group; the expression of hippocampal GFAP increased in the three kinds extracts of QKR groups; expression levels of Syt-1, IL-1β, GFAP, and β-APP in the cortex and hippocampus decreased in the rest treatment groups (all P0.05, P0.01). Compared with the Aricept group, expression levels of Syt-1, IL-1β, GFAP, and βAPP in the cortex and hippocampus were significantly increased in three kinds extracts of QKR groups (P0.05, P0.01).Three kinds extracts of QKR might play roles in anti-AD possibly by decreasing expression levels of Syt-1, IL-1β, GFAP, and βAPP in the cortex and hippocampus.

The main objective of this study is to establish a virtual prototyping model of a flexible four-bar mechanism and perform co-simulations using both mechanism model construction and control strategy development tools for the structure. Taking the four-bar mechanism as an example, a co-simulation control approach is introduced to study multi-body flexible dynamics. Lagrange approach is first implemented to study the dynamics model of a rigid four-bar mechanism, and co-simulations are conducted to investigate the responses of its flexible form made of various materials. Then, controller strategies are exercised to demand the four-bar mechanism to response as requested. The study verifies the feasibility to control of flexible multi-body mechanisms' traces.

Highway construction obviously led to the social and economic benefits. This article uses the basis data of economic and social statistics in 2005-2014 of Guangdong Province, combines the qualitative and quantitative methods, Index system and analyze the impact of the economic and social benefits of the highway, establish and simulation the system dynamics causal diagram and system dynamics flow diagram. Research on the effects of highway construction of the socio-economic within the system dynamic model, proposed the method of development and construction of the highway project. Provide theoretical support of relevant policy recommendations to promote economic and social development to give full play to highway function 1 .

Dry eye syndrome (DES) is one of the most common types of ocular diseases. There is a major need to treat DES in a simple yet efficient way. Artificial tears (AT) are the most commonly used agents for treating DES, but are not very effective. Herbal extractions of ferulic acid (FA), an anti-oxidant agent, and kaempferol (KM), an anti-inflammatory reagent, were added to buffer solution (BS) to replace ATs for DES treatment. The cytotoxicity and anti-inflammatory effects were examined in vitro by co-culture with human corneal epithelial cells (HCECs) to obtain the optimal concentration of KM and FA for treating HCECs. Physical properties of BS, such as pH value, osmolality, and refractive index were also examined. Then, rabbits with DES were used for therapeutic evaluation. Tear production, corneal damage, and ocular irritation in rabbits’ eyes were examined. The non-toxic concentrations of KM and FA for HCEC cultivation over 3 days were 1 µM and 100 µM, respectively. Live/dead stain results also show non-toxicity of KM and FA for treating HCECs. Lipopolysaccharide-stimulated HCECs in inflammatory conditions treated with 100 µM FA and 1 µM KM (FA100/KM1) showed lower IL-1B, IL-6, IL-8, and TNFα expression when examined by real-time PCR. The BS with FA100/KM1 had neutral pH, and a similar osmolality and refractive index to human tears. Topical delivery of BS + FA100/KM1 showed no irritation to rabbit eyes. The corneal thickness in the BS + FA100/KM1 treated group was comparable to normal eyes. Results of DES rabbits treated with BS + FA100/KM1 showed less corneal epithelial damage and higher tear volume than the normal group. In conclusion, we showed that the combination of FA (100 µM) and KM (1 µM) towards treating inflamed HCECs had an anti-inflammatory effect, and it is effective in treating DES rabbits when BS is added in combination with these two herbal supplements and used as a topical eye drop.

Background 3-Hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitors or statins are competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis. Currently, statins are used as first-line therapy in the treatment of diabetic dyslipidemia. However, effects of statins on β cell function remains unclear. This study aims to examine effects of atorvastatin treatment on pancreatic β cell function in obese C57BL/6 J mice and the possible mechanisms. Methods Diet-induced obesity (DIO) C57BL/6 J mice were treated with atorvastatin (30 mg/kg/day) for 58 days. β cell function was assessed by hyperglycemic clamp and the area of insulin-positive β cells was examined by immunofluorescence. Gene expression was assessed by RT-PCR, and endoplasmic reticulum (ER) stress related proteins were examined by Western blot. Additionally, cell viability and apoptosis of the cholesterol-loaded NIT-1 cells were investigated after atorvastatin treatment. Results Hyperglycemic clamp study revealed that glucose infusion rate (GIR) and insulin stimulation ratio in atorvastatin-treated DIO mice were markedly higher than control mice (P

Background The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting. Methods 1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II. Results Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24). Conclusion The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored.

The aim of this current study is to investigate the potential role of AMP-activated protein kinase (AMPK) in hydrogen peroxide (H2O2)-induced cardiomyocyte death, and focused on the signaling mechanisms of AMPK activation by H2O2. We observed a significant AMPK activation in H2O2-treated cardiomyocytes (both primary cells and H9c2 line). Inhibition of AMPK by its inhibitor or RNAi-reduced H2O2-induced cardiomyocyte death. We here proposed that transforming growth factor-β-activating kinase 1 (TAK1) might be the upstream kinase for AMPK activation by H2O2. H2O2-induced TAK1 activation, which recruited and activated AMPK. TAK1 inhibitor significantly suppressed H2O2-induced AMPK activation and following cardiomyocyte death, while over-expression of TAK1-facilitated AMPK activation and aggregated cardiomyocyte death. Importantly, heat shock protein-70 (HSP-70)-reduced H2O2-induced reactive oxygen species (ROS) accumulation, the TAK1/AMPK activation and cardiomyocyte death. In conclusion, we here suggest that TAK1 activates AMPK-dependent cell death pathway in H2O2-treated cardiomyocytes, and HSP-70 inhibits the signaling pathway by reducing ROS content.

Introduction Little has been reported about the demographic and clinical features of major depressive disorder (MDD) with comorbid dysthymia in Chinese patients. This study examined the frequency of comorbid dysthymia in Chinese MDD patients together with the demographic and clinical correlates and prescribing patterns of psychotropic drugs. Methods Consecutively collected sample of 1178 patients with MDD were examined in 13 major psychiatric hospitals in China. Patients' demographic and clinical characteristics and psychotropic drugs prescriptions were recorded using a standardized protocol and data collection procedure. The diagnosis of dysthymia was established using the Mini International Neuropsychiatric Interview. Medications ascertained included antidepressants, antipsychotics, benzodiazepines, and mood stabilizers. Results One hundred and three (8.7%) patients fulfilled criteria for dysthymia. In multiple logistic regression analyses, compared to non-dysthymia counterparts, MDD patients with dysthymia had more depressive episodes with atypical features including increased appetite, sleep, and weight gain, more frequent lifetime depressive episodes, and less likelihood of family history of psychiatric disorders. There was no significant difference in the pattern of psychotropic prescription between the 2 groups. Conclusions There are important differences in the demographic and clinical features of comorbid dysthymia in Chinese MDD patients compared with previous reports. The clinical profile found in this study has implications for treatment decisions.

A low-cost process with electron beam evaporator deposition for amorphous layers was demonstrated in hetero-junction with intrinsic thin layer (HIT) solar cell. The cleaning process with saw damage removal procedure and the annealing temperature are also discussed in this work. The open-circuit voltage (Voc) and short-circuit current density (Jsc) were obtained as 285 mV and 2.9 mA/cm², respectively, with 5 min saw damage removal and 450°C forming gas annealing. Therefore, the low-cost process with the electron beam evaporator deposition could possibly fabricate the HIT solar cell and be a candidate for future higher performance photovoltaic device with optimisation process condition.

Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to examine prescribing patterns of antidepressants, antipsychotics and mood stabilizers in BD patients misdiagnosed with MDD in China.A total of 1487 patients originally diagnosed with MDD were consecutively screened for diagnostic revision in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses. Data on psychotropic prescriptions were collected by a review of medical records.Three hundred and nine of the 1487 patients (20.8%) fulfilled DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. Of the BD patients (n = 309), 227 (73.5%) received any use of antidepressants, 73 (23.6%) antipsychotics and 33 (10.7%) mood stabilizers. In multiple logistic regression analyses, compared with those with MDD, patients with BD-I were more likely to receive antidepressants (OR 1.7, 95% CI 1.1-2.8, p = 0.02), antipsychotics (OR 1.6, 95% CI 1.04-2.5, p = 0.04) and mood stabilizers (OR 3.9, 95% CI 2.1-7.2, p0.001), whereas patients with BD-II were more likely to receive mood stabilizers (OR 2.4, 95% CI 1.3-4.4, p = 0.003). There was no difference in the use of antidepressants (OR 1.1, 95% CI 0.8-1.5, p = 0.7) and antipsychotics (OR 1.3, 95% CI 0.9-1.9, p = 0.2) between BD-II and MDD. In addition, there was no difference between BD-I and BD-II in any use of antidepressants, antipsychotics and mood stabilizers.The prescription of antidepressants for BD patients misdiagnosed with MDD is very common, and only a very small proportion of patients received guideline-concordant treatment. Considering the potentially hazardous effects of inappropriate pharmacotherapy in this population, continuing education and training addressing the correct diagnosis of BD and rational use of psychotropic medications are needed in China.

BackgroundNon-Hodgkin's lymphoma (NHL) has been reported to be associated with autoimmune and pro-inflammatory response, and genetic polymorphisms of candidate genes involved in autoimmune and pro-inflammatory response may influence the susceptibility to NHL. To evaluate the role of such genetic variations in risk of NHL, we conducted a case-control study of 514 NHL patients and 557 cancer-free controls in a Chinese population.MethodWe used the Taqman assay to genotype six potentially functional single nucleotide polymorphisms (SNPs) in six previously reported inflammation and immune-related genes (TNF rs1799964T>C, LTA rs1800683G>A, IL-10 rs1800872T>G, LEP rs2167270G>A, LEPR rs1327118C>G, TNFAIP8 rs1045241C>T). Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI).ResultsWe observed a significantly increased risk of NHL associated with the TNFAIP8 rs1045241C>T polymorphism (adjusted OR = 3.03; 95% CI = 1.68-5.45 for TT vs. CC and adjusted OR = 2.03; 95% CI = 1.53-2.69 for CT/TT vs. CC). The risk associated with the T allele was more evident in subgroups of 40-60 year-old, non-smokers or light-smokers (less than 25 pack-years), and subjects with normal weight or overweight. Risk for both B and T cell non-Hodgkin's lymphoma was elevated for CT/TT genotypes (adjusted OR = 1.95, 95% CI = 1.41-2.70 for B cell NHL and adjusted OR = 2.22, 95% CI = 1.49-3.30 for T cell NHL), particularly for DLBCL (adjusted OR = 2.01, 95%CI = 1.41-2.85) and FL (adjusted OR = 2.53, 95% CI = 1.17-5.45). These risks were not observed for variant genotypes of other five SNPs compared with their common homozygous genotypes.ConclusionsThe polymorphism of TNFAIP8 rs1045241C>T may contribute to NHL susceptibility in a Chinese population. Further large-scale and well-designed studies are needed to confirm these results.

BackgroundLittle has been known about the demographic and clinical features of the melancholic subtype of major depressive disorder (MDD) in Chinese patients. This study examined the frequency of melancholia in Chinese MDD patients and explored its demographic and clinical correlates and prescribing patterns of psychotropic drugs.MethodsA consecutively collected sample of 1,178 patients with MDD were examined in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The diagnosis of the melancholic subtype was established using the Mini International Neuropsychiatric Interview (MINI). Medications ascertained included antidepressants, mood stabilizers, antipsychotics and benzodiazepines.ResultsSix hundred and twenty nine (53.4%) of the 1,178 patients fulfilled criteria for melancholia. In multiple logistic regression analyses, compared to non-melancholic counterparts, melancholic MDD patients were more likely to be male and receive benzodiazepines, had more frequent suicide ideations and attempts and seasonal depressive episodes, while they were less likely to be employed and receive antidepressants and had less family history of psychiatric disorders and lifetime depressive episodes.ConclusionsThe demographic and clinical features of melancholic MDD in Chinese patients were not entirely consistent with those found in Western populations. Compared to non-melancholic MDD patients, melancholic patients presented with different demographic and clinical features, which have implications for treatment decisions.

Aimed at the network teaching system to provide recommendation services for learners that there are some shortage. By analyzing the characteristics of personalized teaching, it designed a personalized teaching resources recommendation model which based on association rules. Teaching resources in this paper are organized by the relationship of curriculum knowledge points, the learners are clustered by the similar characteristics, thus to obtain learners - knowledge points two-dimensional table. This paper presents an improved Apriori algorithm. Association rules are obtained through looking up frequent item sets in the two-dimensional table, to recommend the knowledge, thus to achieve the objective of personalized recommendation.

Glutathione S-transferase M1 (GSTM1), which plays an important role in detoxification pathways to protect against damage caused by reactive metabolites of chemicals, has been considered as potential gastric cancer susceptibility genes. However, the published data on the association between GSTM1 present/null polymorphism and gastric cancer risk are still inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Totally, 44 studies including 5440 cases and 11607 controls were involved in the analysis. When all studies were pooled into the meta-analysis, obviously increased gastric cancer risk was found in null genotype carriers (OR = 1.19, 95% CI: 1.08–1.33). When stratified by ethnicity, obviously evaluated risk was found in Asians (OR = 1.31, 95% CI: 1.11–1.54) but not reached to statistically significance in Caucasians (OR = 1.11, 95% CI: 0.96–1.28). In the subgroup analysis by hospital-based studies or population-based studies, statistically significantly elevated risk was found in hospital-based studies (OR = 1.34, 95% CI: 1.07–1.67) but not reached to statistically significance in population-based studies (OR = 1.11, 95% CI: 0.99–1.25). In summary, this meta-analysis result indicates that the GSTM1 null genotype is a low-penetrant risk factor for gastric cancer development in Asians.

This study tested the potential of small interfering RNAs (siRNA) targeting human peroxisome proliferator activated receptor gamma (PPARγ) to repress the adipogenic effect of alcohol on human bone marrow-derived mesenchymal cells (hBMSCs). hBMSCs were cultured from hip replacement surgery patients (n = 10). PPARγ-siRNA was transiently transfected into hBMSCs cultured in ostogenic media containing 50 mM alcohol by using a liposome-based strategy. Oil red O staining was used to test the development of differentiated adipocytes, and Alizarin red staining was used to test mineral deposition. Marker genes of adipogenesis (PPARγ2 and aP2) and osteogenesis (Osf2/Cbfa1) were examined through real time RT-PCR and Western blot, respectively. Collagen type I, alkaline phosphatase and osteocalcin protein synthesis of cultures were also assayed. Data were presented as mean ± SD. Differences between the means of the treatment groups were determined with ANOVA. PPARγ-siRNA transfection resulted in significantly lower adipocyte number, increased matrix mineralisation, repressed adipogenic gene markers, up-regulated osteogenic gene marker and bone matrix protein synthesis in the PPARγ-siRNA group compared to controls (P < 0.05). PPARγ-siRNA is a useful strategy to inhibit the adipogenic effect and the osteogenic repression of alcohol on hBMSCs. This may be a novel therapeutic intervention for osteopenic disorders in alcoholism and other conditions.

To explore the feasibility of semi-nested PCR technique for detection of immunoglobulin heavy chain (IgH) clonal rearrangement in bone marrow of B-cell lymphoma patient and to further evaluate its clinicopathological value.Gene clonal rearrangement of IgH was detected by semi-nested PCR using primers of FR2FR3A in 105 bone marrow samples of patients with B-cell lymphoma. The PCR detection results were compared with the cytomorphology of bone marrow aspiration biopsy. The correlation between PCR detection results and clinicopathological factors were evaluated.Among 105 cases of B-cell lymphoma, bone marrow involvement was detected by PCR technique in 48 cases (45.7%), while only 22 cases (21.0%) were detected by bone marrow cytological analysis. There was a significant difference between two methods (P0.05), and the concordance rate was 71.4%. The incidence of bone marrow involvement at the time of initial diagnosis detected by PCR technique was 30.8% for diffuse large B cell lymphoma (DLBCL), 25.0% for follicular lymphoma (FL), and 100.0% for small lymphocytic lymphoma (SLL), respectively. Bone marrow involvement detected by PCR detection correlated with Ann Arbor stage. Rate of clonal IgH gene rearrangement by PCR in early B-cell lymphoma was lower than that in advanced stage B-cell lymphoma patients (P = 0.02). There was no statistically significant difference in efficacy between patients with positive and negative results detected by PCR (P0.05). But difference in complete response (CR) rate (23.3% and 46.3%) had significant difference (P = 0.019).Semi-nested PCR analysis may be an effective method for detection of abnormalities in bone marrow in patients with B-cell lymphoma and is superior to cytomorphology. The positive rate in patients with advanced Ann Arbor stage is higher than that in patients with early Ann Arbor stage, and patients with PCR negative result have more chances to achieved CR after treatment.

Interaction of cancer cells with stroma cells facilitates tumor progression by rebuilding the existing extracellular matrix (ECM) microenvironment. In the tumor, upregulation of Tenascin-C (Tn-C) expression potentially can alter tumor behavior. However, the molecular mechanisms by which tumor-stroma interactions affect the tumor microenvironment have not been well characterized. In this study, we analyzed the expression of fibrillar Tn-C (fTn-C) in human metastatic pancreatic cancers. After co-culturing two pancreatic cancer cell lines, highly metastatic BxPc3 cells and non-metastatic PaCa2 cells, with stromal fibroblasts (SF), we evaluated the roles of matrix metalloproteinase 2 (MMP-2) activation and SF in promoting Tn-C organization. Next, we evaluated whether fibrillar Tn-C promotes pancreatic cancer cell movement using cell adhesion and migration assays. Finally, we observed the relationship between MMP-2 activation and fTn-C formation in vivo by injecting the BxPc3 and PaCa2 cells into nude mice. We found that fTn-C was increased in metastatic pancreatic cancer. The fTn-C expression correlated with MMP-2 activity. In the in vitro co-culture, fTn-C organization was found only in BxPc3/SF co-cultures, and required the participation of active MMP-2. The fTn-C reduced cell adhesion and promote pancreatic cancer cell migration by decreasing the adhesive interactions between integrin alpha6beta1 and the ECM. The in vivo tumorigenesis analysis showed that the fTn-C formation and active MMP-2 were significantly increased in the BxPc3 tumors, compared to the PaCa2 tumors. These results demonstrate that Tn-C deposition into the ECM requires participation of active MMP-2 and SF. The deposited Tn-C could promote pancreatic cancer progression.

Burkitt’s lymphoma is an aggressive B-cell lymphoma with rapid proliferative index, which makes it disseminate easily to distal sites, especially to bone marrow and the central nerve system. We report here a 22-year-old woman with Burkitt’s lymphoma involving multiple organs, including kidneys, breasts, left ovary, and bone marrow at the time of diagnosis. The patient responded well to intensive chemotherapy before the onset of retro-orbital pain, vomiting, and photophobia. The contrast-enhanced T1-weighted image in a second magnetic resonance image (MRI) showed a 2 × 1.9 cm mass in her left cavernous sinus that was not found in her initial MRI. Central nervous system (CNS)-directed high-dose chemotherapy and whole-brain radiation could not change the final failed treatment outcome caused by the cavernous sinus involvement disseminating to her entire CNS. Further study should provide well-designed therapeutic strategies to Burkitt’s patients with cavernous sinus involvement.

To investigate the clinical manifestations and risk factors of the patients from developmental dysplasia of the hip(DDH) family.Detailed epidemiology investigation, physical examination, functional movement assessment, lab test and X-ray examination were applied to the whole members of a DDH family.In the family with 9 generations and 218 persons, the incidence of DDH was 31.03% in 145 survivors. Patients mainly manifested bilateral knee and hip joint pain, flexion contracture of hip, limitation in internal and external rotation of hip; a few had arthritic functional disorder, deformation, and limp. The radiography illustrated shallow acetabulum with increased inclination, which encompassed the femoral head badly. Deformation of the femoral head, narrow joint space and osteophyte were also found by X-ray examination. The main risk factors of DDH were genetic factors, gender, birth season etc. The son or daughter with one or two DDH parents had a higher risk for developing DDH than those with no DDH parents. Furthermore, first-degree relatives of the DDH patients also had a greater chance to develop DDH than second-degree relatives and third-degree relatives. The incidence among females was higher than males, and the family member who was given birth in winter had a highest risk for developing DDH. However, there was no difference between incidence of DDH in children and youths and in adults; the incidence of DDH in the immigrants with no blood relationship also did not differ from the incidence of DDH in the family member.The genetic factors play an important role in the development of DDH, so do the environmental factors.

Nanometer size titanium dioxide modified with 3,5-dinitrosalicylic acid (3,5-DA) was prepared using chemical adsorption method. The influences of surface modification on the adsorption of p-nitrophenol (PNP) and the dispersion in solvent such as water, benzene and ethanol were studied. The 3,5-dinitrosalicylic acid is bonded to the surface hydroxyl from TiO2 nanoparticles, results in the formation of a stable, six-ring complex which color is buff. The 3, 5-DA-modified TiO2 nanoparticles have good dispersive capacity in water, benzene and ethanol. Under the optimum conditions such as pH value 3, adsorption time 10 min, the adsorption ratio of PNP by TiO2 is improved from 43% to 99.9% through surface modification. A new method could be used to remove directly 3 approximately 10mg/L PNP, and the residual concentrations is below the integrated wastewater discharge standard (GB 8978-1996).

We present autofluorescence modeling of different cervix tissue dysplasia for clinical diagnosis. We used double integrating sphere system and inverse adding-doubling (IAD) method to evaluate tissue optical parameters (absorption coefficient, /spl mu//sub a/, scattering coefficient, /spl mu//sub s/) of different cervix dysplasia. We used fluorescence Monte Carlo model included absorption coefficient and scattering coefficient from IAD and integrate sphere, to simulate autofluorescence spectra. The results show the increasing thickness of abnormal tissue on the cervical epithelium accompanied with the decreasing in autofluorescence intensity, in collagen peak (390 nm) and in NADH peak (460 nm), along with the lesion developments.

This paper is deals with the implementation of autofluorescent excitation-emission matrices for the differentiation of cervical tissue. Autofluorescence diagnosis is characterized by the stimulation of endogenous fluorophores, such as, collage, NADH, and FAD in normal and abnormal tissue. !t has minimum invasion and it is in real time. In this research, we developed a small autofluorescence spectra measurement system. It consists of a sensitive PMT with a double gratings spectrometer, a Y type fiber including 18-excitation to 19-emission fibers, and xenon lamp with monochromate as multi-wavelength light source. We utilized this autofluorescence spectra and excitation-emission matrices (EEM) in cervical cancer study and measured normal and abnormal tissues (cervical intraepithelial neoplasia, CIN squamous cell carcinoma: SCC). EEM represented multi-excited wavelengths induced by different range wavelength of the emission. It allows us to get more information about tissues' characteristic. We used partial least squares (PLS) to analyze these data of the spectra and EEM. The result shows that the diagnostic ability by autofluorescence technology can be applied to ClN and using PLS analyzed pathological changes of the cervical tissue has a discriminative property. We also got high sensitivity and specificity to distinguish between normal endo and exo cervix by combining EEM and PLS . In the future, we will build autofluorescence EEM database for clinic diagnosis information.

Water-alternating gas (WAG) displacement is a pronounced technique to improve gas or/and water injection in heterogeneous reservoirs. For the last half century it has been successfully applied to more than 60 oilfields worldwide. However, its mechanism still deserves further investigation. In this work, a series of water, gas, and WAG displacement studies were conducted with a sets of glass micro-models which were reproduced from a target reservoir rock by copying the pore structure images into the glass media. The pore size and geometry structure of the glass micro-model are very similar to the original. The proceeding of WAG displacement was video tape recorded versus time so that the kinetic saturation to each phase in the porous media can be obtained though a PC based image analyzer. Corroborated with the measured pressure drop across the model, the effect of WAG on mobility control is systematically studied. The results show that the mechanism of WAG flow in porous media is much different from two phase (gas-oil and water-oil) flow. For water displacing oil, a piston-like displacement mainly occurred in the small pores (assisted with capillary pressure) and a non piston-like displacement mainly occurred in large pores. For gas displacing oil, the piston-like displacement occurred in both large and small pores as long as the viscous forces can overcome the capillary force. In general, the piston-like displacement gives a higher displacement efficiency than non piston-like displacement. Channeling of displacing phase (water or gas) caused by heterogeneous feature of the pore media was observed. However, when three phase (water-gas-oil) flow is involved, the mechanism of displacement is changed. The oil phase becomes intermediate wetting, and the gas becomes non-wetting phase and water phase remains a wetting phase. Water phase prefer to occupying the small pores due to capillary effect, while the gas prefer to occupying the large pores. The oil phase presents in the porous media in a discontinuous status; the feature of oil flow is mainly in the form of oil slug or oil film at the interfaces between water and gas phases. Accumulation and expansion of gas phase from the large pores expel the oil phase into down stream. With the proceeding of WAG displacement, the oil slug becomes smaller and finally turns into oil film; the residual oil saturation in average after WAG displacement is less than 20% OOIP, benefited from a reduced size of oil drop. It is found that pore geometry has a significant effect on residual oil saturation. "Snap off " effect plays a very important role to cut off the oil slug into oil blobs and form gas bubbles during WAG displacement. Increase in cycles of WAG tends to reduce residual oil saturation. Oil blobs trapped in very tiny pores, pore corners, and dead pores are the main type of the residual oils. At the last, an optimal WAG project to the target reservoir will be presented.

We have carried out flooding test with cores, sandpack, pore level model by microbe NG80, special metabolic products (G01, G02, G03) under reservoir temperature. The results are: Microbes migrated through core pore and fermented in it; microbial concentration has an increasing trend, part of cells were absorbed on sand surface. Oil recovery that flooded by bacteria with concentration 10% is over 6% higher than in water. The highest recovery is 13.8%, flooded at best flooding mode, NG80 products and its constitute; The earlier the time of injecting fermented broth, the better the result obtained; Metabolites bear effect of denudation on oil films; and metabolisms result in alteration of wettability, in witch a special biochemical process and "in situ growth" effects characterized by bacteria take place; Mechanisms observed in the pore level model during microbial flooding are: starting residual oil re-flowing by emulsification-carrying, changing the wettability, denuding oil films and producing "Jamin Effect" in the pores while flooding. We performed microbial flooding program in G69 block, which has 5 injections wells and 7 drainage points. Mixed original, NG80, 80 and DG2, fermented broth 720m3 was injected in with three slugs during March to July,2001. Monitored preliminary results show that the decline trend of the block oil production was controlled and some wells' production began to increase. That the mechanism of microbial flooding in the oilfield improves poducibility.

For the last decade, some specifically selected microbes have been successfully used to improve oil recovery in some waxy or heavy oil reservoirs. The main feature of this new technology is that the applied microbes can degradate heavy oil components to improve oil properties, for example, reduction in oil viscosity or cloud pour point. However, successful application of microbial technology in high temperature reservoirs has been remaining a challenge due to quick disactivate of microbes at elevated temperature. In this work, we present the result of application of self-incubated thermophilic microorganisms that are growing at a reservoir temperature of 73°C.This microbes can self-colony and quickly grow up at the reservoir conditions. The analysis of the crude oil on samples before and after treated with microorganisms showed that (1) oil viscosity decreased by 34%, (2) pour point decreased 3°C, (3) the weigh of heavy oil components decreased significantly, and (4) the interfacial tension between oil and formation water decreased about 31%. In addition, the pH value of the crude oil samples decreased from 7.3 to 5.5. The results from coreflooding tests showed that the oil recovery could be improved by 6.6%(OOIP) by injection the microbes. We also performed a‘ huff and puff pilot test in a production well that having 91% of water cut before the test. The results showed that after the well was stimulated with the microbes, the oil production rate increased from 20 to 40 barrels per day, and the water cut decreased from 91% to 87.8%. The effect of the stimulation with the microbes continued more than 6 months and the total oil incremental was than 2400 barrels.

The solvent properties, especially the polarity, of room-temperature ionic liquids (RTILs) of the general type [Cnmim]X, where [Cnmim] is the 1-CnH2n+1-3-methylimidazolium cation and X is [BF4]−, [PF6]−, [NO3]−, [SCN]−, or [NTf2]− (Tf = CF3SO2), have been investigated using Fourier-transform infrared (FTIR) spectroscopy. Comparing the experimental shifts in the νC=O stretching frequencies of acetone and N,N-dimethylformamide (DMF) as probe molecules suggests that the polarities of most common RTILs are between that of DMF and methanol. A more sensitive probe, Fe(CO)5, can distinguish small polarity differences between RTILs with similar structures. The effects of varying the structure of RTILs by introducing functional groups and different anions on their polarity are also compared.