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Objective: Intrahepatic cholestasis of pregnancy (ICP) is a special complication of pregnancy characterized by skin pruritus, abnormal liver function tests and bile acids. To compare the efficacy of ursodeoxycholic acid (UDCA) and S-adenosylmethionine (SAMe) monotherapy with their combined effect on intrahepatic cholestasis of pregnancy (ICP)., Patients and Methods: Singleton pregnancies with ICP in five tertiary medical centers were randomly divided into three treatment groups: oral UDCA 4×250 mg daily (Group 1, n = 41), intravenous SAMe 1000 mg daily (Group 2, n = 38), and a combination of both drugs (Group 3, n = 41) until delivery. Paired t test, analysis of covariance and non-parametric test were used., Results: All therapies significantly and equally improved pruritus. The serum levels of total bile acids (TBA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TB) in each group significantly decreased after treatment (p < 0.05). Group 1 was more effective than Group 2 in reducing TBA concentration (p < 0.05), Group 1 and Group 3 showed more effective than Group 2 in reducing AST and TB concentrations (p < 0.05), and Group 1 facilitated deliveries at term. No perinatal death or adverse drug reactions were observed., Conclusions: UDCA and SAMe are both effective and safe in the treatment of ICP. UDCA monotherapy should be used as the first line therapy for ICP because it is more efficacious, cost-effective and convenient.

We established a rat model of hyperphosphatemia and investigated the systemic effects of high phosphorus (P). Sprague Dawley rats were randomly divided into high (HP), low (LP), and normal (NP) P groups (N = 12 each), which received injections of fructose diphosphate sodium, or were fed self-manufactured low phosphorus or normal diets, respectively. In each group, 4 rats were sacrificed at the first, third, and sixth week to detect the serum (Scr) and urinary creatinine and P, and calcium (Ca) levels. The HP group's serum P and intact parathyroid hormone (iPTH) were significantly higher than those in the other groups at the first, third, and sixth weeks, (P < 0.05); the LP group's serum P was lower than the NP group's at the third week (P < 0.05), while at the sixth week, the serum P and iPTH were lower (P < 0.05). No significant differences were detected for blood Ca+ (P > 0.05). The HP group's Scr increased (P < 0.01), whereas the fractional excretion decreased (P < 0.05) significantly. Thighbone and lumbar spine bone densities differed significantly between groups in the third week (P < 0.05); LP group densities were lower than NP group measures (P < 0.05). Crystallized stones were not observed microscopically following hematoxylin and eosin staining of the kidney. We successfully established a hyperphosphatemia rat model, and high blood P was found to significantly influence renal function and bone density. These results might provide a foundation to study the effects of hyperphosphatemia in rats.

Aims: To determine the varieties and concentrations of pesticides by detecting the changes of microalgae components using Raman microspectroscopy technology., Methods and Results: Raman microspectroscopy technology was used to detect the internal elements and characteristics of Chlorella pyrenoidosa. Partial least squares (PLS) was used to build the model between Raman signals of C. pyrenoidosa and different varieties or concentrations of pesticides. The PLS models were built with different preprocessing methods and the most optimized preprocessing method was found. Linear discriminant analysis (LDA) was also used to build the models to identify different pesticide varieties or concentrations. Sensitive wavelengths (SWs) corresponding to pigments of microalgae were selected, and the SWs-LDA models were built with the classification accuracy rate up to 96·7 and 90% respectively for pesticide varieties and concentrations identification., Conclusions: Measuring changes of microalgae components by Raman microspectroscopy techniques could be used to identify the varieties and concentrations of pesticides in water., Significance and Impact of the Study: Although the low concentration level of pesticides does not have significant impact on the overall water environment, water would become worse due to the pollution accumulation in long-term. The method disclosed in this study can be used as a good example for pesticide detection with the help of microalgae. Raman microspectroscopy technology is a convenient and rapid tool to detect the characteristics of microalgae and contribute for pesticide detection., (© 2015 The Society for Applied Microbiology.)

Previous studies that utilized task-based approaches have demonstrated that the chronic use of heroin is associated with altered activity of the anterior cingulate cortex (ACC). However, few studies have focused on examining the variation in resting-state functional connectivity in heroin-dependent individuals, which might help further understanding the mechanisms underlying heroin addiction. Due to the structural and functional heterogeneity of the ACC, we systematically mapped the resting-state functional connectivity patterns of three sub-regions of the ACC in heroin-dependent individuals, wondered whether the partition of three sub-regions of the ACC is feasible in heroin-dependent individuals, and identified how heroin affected the correlated activities among three sub-regions of the ACC using resting-state functional magnetic resonance imaging (fMRI). In the present study, fMRI data were acquired from 21 heroin-dependent individuals (Her group) and 15 non-addicted controls (CN group). Compared to controls, there were reduced functional connectivities in the dorsal ACC (dACC) and rostral ACC (rACC) networks with different areas of the dorsal striatum (the caudate and the putamen) in the Her group. Meanwhile, there exhibited an inverted alteration of pattern for orbital frontal cortex (OFC) and superior frontal gyrus (SFG) in the functional connectivity network with the dACC and subcallosal ACC (sACC), and a different alteration of the cerebellum and the amygdala in the functional connectivity network with the rACC and the sACC. In addition, we also found reduced connectivities between dACC and rACC, as well as reduced connectivities between sACC and dACC. Our findings of variations of functional connectivities in three sub-regions of ACC in Her group implied that these sub-regions of the ACC together with other key brain areas (such as dorsal striatum, OFC, SFG, cerebellum, amygdale, etc.) might potentially play independent and/or overlapping roles in heroin addiction, which might indicate the potential direction of future research., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Lipoprotein lipase (LPL) is a candidate gene for obesity based on its role in triglyceride hydrolysis and the partitioning of fatty acids towards storage or oxidation. Whether dietary fatty acids modify LPL associated obesity risk is unknown., Methods and Results: We examined five single nucleotide polymorphisms (SNPs) (rs320, rs2083637, rs17411031, rs13702, rs2197089) for potential interaction with dietary fatty acids for obesity traits in 1171 participants (333 men and 838 women, aged 45-75 y) of the Boston Puerto Rican Health Study (BPRHS). In women, SNP rs320 interacted with dietary polyunsaturated fatty acids (PUFA) for body mass index (BMI) (P = 0.002) and waist circumference (WC) (P = 0.001) respectively. Higher intake of PUFA was associated with lower BMI and WC in homozygotes of the major allele (TT) (P = 0.01 and 0.005) but not in minor allele carriers (TG and GG). These interactions were replicated in an independent population, African American women of the Atherosclerosis Risk in Communities (ARIC) study (n = 1334)., Conclusion: Dietary PUFA modulated the association of LPL rs320 with obesity traits in two independent populations. These interactions may be relevant to the dietary management of obesity, particularly in women., (Copyright © 2014. Published by Elsevier B.V.)

Background: Rapid molecular methods have been recommended for early detection of drug-resistant tuberculosis (TB)., Objective: To evaluate the performance of the GenoType(®) MTBDRplus assay in routine settings in China., Methods: Sputum-positive samples were collected consecutively from 1 April to 31 December 2010. MTBDRplus results were compared to those of conventional drug susceptibility testing (DST). The McNemar χ(2) test and κ coefficient were used to assess performance., Results: Of 427 smear-positive sputum samples collected, conventional DST and MTBDTplus confirmed drug resistance in 326. The sensitivities and specificities for MTBDRplus in detecting isoniazid (INH) and rifampicin (RMP) resistance were respectively 76.47%, 95.44%, 85.94% and 93.13%. The McNemar χ(2) test indicated no significant difference between the two methods (P = 0.106 for INH and P = 0.083 for RMP). The κ values for INH, RMP and multidrug resistance were respectively 0.75, 0.75 and 0.70., Conclusions: Although the MTBDRplus assay was moderately concordant with conventional DST in detecting INH and RMP resistance, as a prospective rapid molecular method for MDR-TB detection, potential resistant mutations need to be incorporated to improve the accuracy of detection.

What Is Known and Objective: Gabapentin has been used for the management of post-herpetic neuralgia (PHN). However, inconsistent results have been reported. This meta-analysis was performed to assess the efficacy and safety of gabapentin 1800 mg/day in PHN patients by conducting a meta-analysis., Methods: Electronic databases were searched for relevant randomized controlled trials (RCTs) that compared gabapentin 1800 mg/day to placebo for PHN. The primary outcomes were reduction in 24-h average pain intensity scores, 50% and 30% pain intensity reduction and gabapentin-related side effects. The secondary outcomes were reduction in sleep rating scores and improvement in Patient Global Impression of Change (PGIC) or Clinician Global Impression of Change (CGIC)., Results and Discussion: Six RCTs were included. Gabapentin 1800 mg/day reduced the 24-h average pain intensity scores [standard mean differences (SMD) -0·50; 95% confidence interval (CI) -0·88, -0·13; I(2)  = 86·3%] and average daily sleep rating scores [weighted mean differences (WMD) -0·71; 95% CI -1·11, -0·32; I(2)  = 0%]. Gabapentin treatment yielded an improvement in pain intensity (risk ratio (RR) 1·88; 95% CI 1·35, 2·29; I(2)  = 64·8%; for 50% reduction and RR 1·43; 95% CI 1·12, 1·83; I(2)  = 0% for 30% reduction, respectively), PGIC (RR 1·49; 95% CI 1·28, 1·74; I(2)  = 0%), and CGIC (RR 1·58; 95% CI 1·29, 1·92; I(2)  = 30·9%). However, gabapentin increased the somnolence (RR 2·03; 95% CI 1·39, 2·98; I(2)  = 2%), dizziness (RR 2·68; 95% CI 1·95, 3·69; I(2)  = 15%), peripheral oedema (RR 9·10; 95% CI 3·23, 25·60; I(2)  = 2%), total adverse effects (RR 1·28; 95% CI 1·16, 1·42; I(2)  = 0%) and withdrawal due to adverse events (RR 1·51; 95% CI 1·06, 2·16; I(2)  = 6%), but these adverse effects were often mild to moderate., What Is New and Conclusion: Treatment with gabapentin 1800 mg/day yielded a significant reduction in PHN up to 14 weeks. Gabapentin 1800 mg appeared safe in treating PHN for up to 24 weeks., (© 2014 John Wiley & Sons Ltd.)

Introduction: To determine if the upper part of the lower segment of the uterus is a better site for cesarean incision then the traditionally used lower end., Methods: This is a case-control study (1:1 ratio) conducted from 1(st) October 2012- 30(th) September 2013 observed between transverse incision at the upper part of the lower segment versus traditional lower segment of the uterus. Two hundred caesarean sections were performed via a transverse uterine incision at the upper part of the lower segment and equal numbers of uterine incision was performed at traditional lower segment. To obtain less intraoperative bleeding high incision made at thicker wider muscular part at of the upper part of lower segment about 2-3 cm distances from vesico-uterine serosa., Results: The estimated volume of blood loss in high incision 188±60.1 ml was significantly less compared to traditional incision 330.1± 86.5 ml (p<0.05). Duration of operation 30.5± 6.6 minute versus 45.3±7.2 minute and tearing the uterine incision was significantly less with the high incision versus traditional incision. Other procedural and patient benefits are noted., Conclusions: An incision at the upper part of the lower segment reduces blood loss, enhances uterine retraction, predisposes to fewer complications, is easier to repair, precludes bladder adhesion to the suture line and reduces operation time.

By utilizing a simple and low-cost arc-discharge method in either liquid nitrogen or ethanol at ambient temperature and pressure, carbon-coated cementite (Fe3C) nanocapsules, with size ranges of 10–60 nm and 10–20 nm, respectively, have been synthesized on a large scale. The Fe3C/C nanocapsules synthesized in different media possess similar permeability but different permittivity, which results from the different defect amounts within the carbon shell. It has been found that the as-prepared products exhibit different electromagnetic wave absorption abilities: for the ones prepared in liquid nitrogen, the optimal reflection loss is above -10 dB in the range of 1-18 GHz with the thickness ranging from 1 to 10 mm; meanwhile, for those fabricated in ethanol, the reflection loss could be below -20 dB within the thickness range of 1.5-2.4 mm in the frequency range of 10-15 GHz, and reach -38 dB at a thickness of 1.9 mm with a matching frequency of 12.9 GHz. This indicates that the nanocapsules prepared in ethanol exhibit good electromagnetic wave absorption properties. These results provide a new way to fabricate carbon-coated Fe3C nanocapsules with the ability of electromagnetic wave absorption.

Loss of the cell polarity gene could cooperate with oncogenic Ras to drive tumor growth and invasion, which critically depends on the c-Jun N-terminal Kinase (JNK) signaling pathway in Drosophila. By performing a genetic screen, we have identified Src42A, the ortholog of mammalian Src, as a key modulator of both Ras(V12)/lgl(-/-) triggered tumor invasion and loss of cell polarity gene-induced cell migration. Our genetic study further demonstrated that the Bendless (Ben)/dUev1a ubiquitin E2 complex is an essential regulator of Src42A-induced, JNK-mediated cell migration. Furthermore, we showed that ectopic Ben/dUev1a expression induced invasive cell migration along with increased MMP1 production in wing disc epithelia. Moreover, Ben/dUev1a could cooperate with Ras(V12) to promote tumor overgrowth and invasion. In addition, we found that the Ben/dUev1a complex is required for ectopic Src42A-triggered cell death and endogenous Src42A-dependent thorax closure. Our data not only provide a mechanistic insight into the role of Src in development and disease but also propose a potential oncogenic function for Ubc13 and Uev1a, the mammalian homologs of Ben and dUev1a.

The study evaluated the comparability of two branded computer-aided sperm analysis (CASA) systems commonly used in andrology laboratories in China. The same semen sample was analysed using two branded CASA systems (WLJY-9000 and CFT-9200) by one well-trained technician. Results of semen analysis obtained from two branded CASA systems were then compared. The accuracy of counting results of CASA systems was evaluated using latex bead solutions with known concentrations of (35 ± 5) × 10⁶ ml⁻¹ and (18 ± 2.5) × 10⁶ ml⁻¹. There were significant differences in all parameters (P < 0.01) except for LIN and WOB. The counting results of CFT-9200 were close to the standard solutions [(38.86 ± 3.79) × 10⁶ ml⁻¹ and (19.03 ± 1.99) × 10⁶ ml⁻¹], while those of WLJY-9000 were underestimated [(28.53 ± 2.06) × 10⁶ ml⁻¹ and (14.62 ± 0.95) × 10⁶ ml⁻¹]. But the coefficient of variation of WLJY-9000 was lower than that of CFT-9200 (7.22%, 6.50% vs. 9.82%, 10.46%). It is concluded that factors such as parameter settings and evaluation algorithms could significantly affect the results obtained from these two branded CASA systems. Great attention should also be paid to the quality control in semen analysis with CASA., (© 2012 Blackwell Verlag GmbH.)

In oromaxillofacial surgery patients, the incidence of difficult airways is up to 15.4-16.9%. Blind nasal intubation remains a safe technique for difficult airway management in some remote areas where a fibreoptic bronchoscope is not always available. The lightwand is an easy-to-use, highly economical device, and can facilitate endotracheal intubation through illumination in the neck. The study aims to evaluate the efficacy of nasotracheal intubation using lightwand in oromaxillofacial surgery patients with difficult airways. One hundred and sixteen patients with difficult airways requiring nasotracheal intubation were randomly divided into a lightwand group and a blind group, with 58 cases in each group. The first attempt and overall success rates of lightwand intubation were 84.5% and 93.1%, respectively, which were higher than those of blind intubation (65.5% and 75.9%, respectively; P<0.05). The total intubation time was 91.4±27.7s in the lightwand group and 130.7±33.4s in the blind group (P<0.001). Patients in the lightwand group also experienced more stable haemodynamic responses and less pharyngalgia. In conclusion, lightwand-guided nasotracheal intubation is superior to blind intubation in patients with difficult airways, with a higher success rate, more stable haemodynamic responses, and fewer postoperative complications., (Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

A novel Ti3Sn/NiTi shape memory alloy anode with a sandwich structure was fabricated by arc melting. In order to characterize in situ the Ti3Sn/NiTi anode microstructure changes and phase transformations during cycling, a nanoscale lithium battery was set up inside a transmission electron microscope, which consists of Li metal as the cathode, the native Li2O layer on the surface of Li metal as the solid electrolyte, and the Ti3Sn/NiTi as the anode. Only the Ti3Sn intermetallic compound experienced the electrochemical reaction, while the NiTi alloy (inactive with Li(+)) was applied for buffering the Ti3Sn volume change during cycling. An obvious reaction front of Ti3Sn migrated from one end to the other during lithiation, which can also return after delithiation. It provides direct evidence that the NiTi alloy can effectively accommodate the anode volume change during electrochemical lithiation and delithiation.

Acid ceramidase (AC) is overexpressed in most prostate tumors and confers oncogenic phenotypes to prostate cancer cells. AC modulates the cellular balance between ceramide, sphingosine and sphingosine 1-phosphate (S1P). These bioactive sphingolipids have diverse, powerful and often oppositional impacts on cell signaling, including the activation status of the oncogenic kinase Akt. Our studies show that AC expression correlates with phosphorylation of Akt in human prostate tumors, and elevation of phosphorylated Akt in tumor versus patient-matched benign tissue is contingent upon AC elevation. Investigation of the mechanism for AC-induced Akt activation revealed that AC activates Akt through sphingosine kinase 1 (SphK1)-derived generation of S1P. This signaling pathway proceeds through S1P receptor 2 (S1PR2)-dependent stimulation of PI3K. Functionally, AC-overexpressing cells are insensitive to cytotoxic chemotherapy, however, these cells are more susceptible to targeted inhibition of Akt. AC-overexpressing cells proliferate more rapidly than control cells and form more colonies in soft agar; however, these effects are profoundly sensitive to Akt inhibition, demonstrating increased dependence on Akt signaling for the oncogenic phenotypes of AC-overexpressing cells. These observations may have clinical implications for targeted therapy as PI3K and Akt inhibitors emerge from clinical trials.

Materials with very low thermal conductivity are of great interest for both thermoelectric and optical phase-change applications. Synthetic nanostructuring is most promising for suppressing thermal conductivity through phonon scattering, but challenges remain in producing bulk samples. In crystalline AgSbTe2 we show that a spontaneously forming nanostructure leads to a suppression of thermal conductivity to a glass-like level. Our mapping of the phonon mean free paths provides a novel bottom-up microscopic account of thermal conductivity and also reveals intrinsic anisotropies associated with the nanostructure. Ground-state degeneracy in AgSbTe2 leads to the natural formation of nanoscale domains with different orderings on the cation sublattice, and correlated atomic displacements, which efficiently scatter phonons. This mechanism is general and suggests a new avenue for the nanoscale engineering of materials to achieve low thermal conductivities for efficient thermoelectric converters and phase-change memory devices.

Aim: This study examined clinical features and neuroimaging characteristics of severe brain damage in premature infants with postnatal infection., Methods: We retrospectively analyzed clinical data of two preterm infants who developed extensive encephalomalacia secondary to postnatal infection., Results: Two premature boys experienced serious postnatal infection at about 3 weeks after birth; the infection was characterized by lethargy, apnea, increased CRP, severe bilateral pneumonia, positive sputum culture for multidrug-resistant bacteria, and mild changes of cerebrospinal fluid. Both infants required ventilation and antibiotic therapy. While both infants survived, a very extensive encephalomalacia was documented by serial cranial ultrasound, MRI and CT scans 3 to 4 weeks after postnatal infection. Their mothers had no premature ruptures of membranes and no signs of antenatal infection, suggesting potential postnatal infection in the infants., Conclusion: More studies are needed to better understand the underlying mechanism of encephalomalacia associated with postnatal infection. To facilitate early diagnosis and effective treatment, cranial ultrasound scans should be done routinely in premature infants with serious postnatal infection.

We present a new multifocal multiphoton microscope that employs a programmable spatial light modulator to generate dynamic multifocus arrays which can be rapidly scanned by changing the incident angle of the laser beam using a pair of galvo scanners. Using this microscope, we can rapidly select the number and the spatial density of focal points in a multifocus array, as well as the locations and shapes of arrays according to the features of the areas of interest in the field of view without any change to the hardware.

Background: Atopic dermatitis (AD) is a chronic, relapsing allergic skin disease. The histamine H4 receptor (HRH4) has been shown to be associated with a number of autoimmune disorders, including AD., Aim: To explore a possible association between copy-number variations (CNVs) of the HRH4 gene and the risk of AD in a Chinese population., Methods: Genomic DNA and RNA were collected from 541 patients with AD and 613 healthy controls, and the CNVs and mRNA levels of HRH4 were examined. ELISA was used to measure the levels of IgE in all participants., Results: Amplifications of HRH4 copy numbers were associated with the risk of developing AD (P < 0.05, OR = 1.85, 95% CI 1.30-2.63), whereas deletions of HRH4 copy numbers were not associated with disease risk for AD (P = 0.30, OR = 0.82, 95% CI 0.57-1.19). HRH4 mRNA levels were much higher in samples with HRH4 copy-number amplifications than in those without such amplifications (P < 0.05). IgE levels were associated with amplifications (P < 0.05, OR = 1.96, 95% CI 1.19-3.25), but not with deletions (P = 0.63, OR = 0.87, 95% CI 0.49-1.54) of HRH4 copy numbers., Conclusions: CNVs of the HRH4 gene are associated with AD in a Chinese population., (© The Author(s) CED © 2013 British Association of Dermatologists.)

Background: The standard treatment for brain metastases is whole brain radiation, but the medium survival is about 3-10 months and hadn't be improved for years., Aim: This study was to evaluate the effect of antineoplastic therapy combined with whole brain radiation for brain metastases., Materials and Methods: We searched PubMed, EMBASE, Cochrane Library, Chinese Biomedical Literature Database, China Journal Full Text Database and references of the included studies up to May 2011. Randomized controlled trials involving antineoplastic combined with whole brain radiation compare with whole brain radiation alone for brain metastases were analysed. Study selection, data collection and quality assessment of studies were performed by two individual reviewers according to the Cochrane Handbook for systematic reviews of interventions 5.0.2. Statistic analyses were calculated using RevMan5.0.17 software. 9 randomized controlled trails, a total of 1582 patients were included., Results: There were no significant differences in overall survival, six to twenty-four months survival rate and death from central nervous system (CNS) cause, only the objective response rate was statistically higher in the combined group. (RR = 1.47, 95% CI: 1.10, 1.97; p = 0.009) Subgroup analysis of lung cancer got the same result, except that death from central nervous system (CNS) cause was higher in the combined therapy group, it was statistical significant (RR = 0.70, 95% CI: 0.53, 0.93; p = 0.01)., Conclusions: The benefit of antineoplastic combined with whole brain radiation for brain metastases was not concerned, either in the brain metastases from unselected primary tumors or lung cancer.

During the onset of lactation, there is a dramatic increase in the expression of glucose transporters (GLUT) and a group of enzymes involved in milk fat synthesis in the bovine mammary gland. The objective of this study was to investigate whether the lactogenic hormones mediate both of these increases. Bovine mammary explants were cultured for 48, 72, or 96 h with the following hormone treatments: no hormone (control), IGF-I, insulin (Ins), Ins + hydrocortisone + ovine prolactin (InsHPrl), or Ins + hydrocortisone + prolactin + 17β-estradiol (InsHPrlE). The relative expression of β-casein, α-lactalbumin, sterol regulatory element binding factor 1 (SREBF1), fatty acid synthase (FASN), acetyl-CoA carboxylase α (ACACA), stearyol-CoA desaturase (SCD), GLUT1, GLUT8, and GLUT12 were measured by real-time PCR. Exposure to the lactogenic hormone combinations InsHPrl and InsHPrlE for 96 h stimulated expression of β-casein and α-lactalbumin mRNA by several hundred-fold and also increased the expression of SREBF1, FASN, ACACA, and SCD genes in mammary explants (P < 0.01). However, those hormone combinations had no effect on GLUT1 or GLUT8 expression and inhibited GLUT12 expression by 50% after 72 h of treatment (P < 0.05). In separate experiments, the expression of GLUTs in the mouse mammary epithelial cell line HC11 or in bovine primary mammary epithelial cells was not increased by lactogenic hormone treatments. Moreover, treatment of dairy cows with bovine prolactin had no effect on GLUT expression in the mammary gland. In conclusion, lactogenic hormones clearly stimulate expression of milk protein and lipogenic genes, but they do not appear to mediate the marked up-regulation of GLUT expression in the mammary gland during the onset of lactation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This study evaluates the correlation between natural killer (NK) cell function and human immunodeficiency virus (HIV)-1 disease progression in 133 untreated HIV-1 positive Chinese subjects, including 41 former plasma donors (FPDs) and 92 men who have sex with men, and 35 HIV-negative controls. Flow cytometry was used to determine the abundance of NK cell subsets, the expression levels of receptor species, human leucocyte antigen (HLA) genotyping and the antibody-dependent cell-mediated cytotoxicity (ADCC) responses of NK cells. We observed a decreased expression of CD56(dim) CD16(+) NK cell subsets and an increased expression of CD56(-) CD16(+) with HIV-1 infection. As well, the expression of activating and inhibitory receptors increased significantly in NK cells, but CD16 receptor levels and the NKG2A/NKG2C ratio were down-regulated with HIV-1 infection. ADCC responses were higher in elite controllers than in all other groups, and were correlated inversely with HIV-1 viral load but correlated positively with CD4 count only in FPDs. Furthermore, individuals infected for < 1 year have lower ADCC responses than those infected for > 1 year. We also observed a negative association between ADCC responses and viral load in those who carry the HLA-A*30/B*13/Cw*06 haplotype. The positive correlation between CD16 expression and ADCC responses and a negative correlation trend between CD158a and ADCC responses were also observed (P = 0·058). Our results showed that the ADCC response is associated with patients' disease status, receptor expression levels, infection time and specific HLA alleles, which indicates that ADCC may offer protective effects against HIV-1 infection., (© 2012 The Authors Clinical and Experimental Immunology © 2012 British Society for Immunology.)

IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Colorectal carcinoma is one of the most frequent cancer diseases. For patients with this type of cancer, liver metastases are the main cause of death. Therefore, new therapeutic approaches are urgently needed to improve the outcomes. We found that both mRNA and protein levels of tissue inhibitor of metalloproteinase-3 (TIMP3) were decreased significantly in colorectal cancer tissue when compared with normal mucosa, suggesting that decrease of TIMP3 expression was correlated with malignant behavior of colorectal cancer. We evaluated the power of TIMP3, a new potent multiple functional molecule, as a biotheropeutic tool to treat cancer. Adenovirus-mediated TIMP3 transduction in CT26 colon cancer model demonstrated multiple effects to arrest cancer cell growth and induced massive apoptosis. Also, adenovirally transferred TIMP3 reduced adhesion, migration and invasion behaviors of CT26 cells in vitro. In vivo data showed that TIMP3 suppressed in vivo tumor growth and that liver metastasis was significantly reduced by TIMP3 transduction. This is the first systematic preclinical study to show that TIMP3 may be a potential molecular tool for colon cancer biological therapy.

B-RAF is mutated to a constitutively active form in 8% of human cancers including 50% of melanomas. In clinical trials, the RAF inhibitor, PLX4032 (vemurafenib), caused partial or complete responses in 48-81% of mutant B-RAF harboring melanoma patients. However, the average duration of response was 6-7 months before tumor regrowth, indicating the acquisition of resistance to PLX4032. To understand the mechanisms of resistance, we developed mutant B-RAF melanoma cells that displayed resistance to RAF inhibition through continuous culture with PLX4720 (the tool compound for PLX4032). Resistance was associated with a partial reactivation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, recovery of G1/S cell-cycle events, and suppression of the pro-apoptotic B-cell leukemia/lymphoma 2 (Bcl-2) homology domain 3 (BH3)-only proteins, Bcl-2-interacting mediator of cell death-extra large (Bim-EL) and Bcl-2 modifying factor (Bmf). Preventing ERK1/2 reactivation with MEK (mitogen-activated protein/extracellular signal-regulated kinase kinase) inhibitors blocked G1-S cell-cycle progression but failed to induce apoptosis or upregulate Bim-EL and Bmf. Treatment with the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid, led to de-repression of Bim-EL and enhanced cell death in the presence of PLX4720 or AZD6244 in resistant cells. These data indicate that acquired resistance to PLX4032/4720 likely involves ERK1/2 pathway reactivation as well as ERK1/2-independent silencing of BH3-only proteins. Furthermore, combined treatment of HDAC inhibitors and MEK inhibitors may contribute to overcoming PLX4032 resistance.

Background: Circulating asymmetric dimethylarginine (ADMA) concentration is elevated in patients with Type 2 diabetes mellitus (T2DM)., Aim: To assess the relationship between plasma ADMA concentration and carotid atherosclerosis in patients with T2DM., Subjects and Methods: A total of 72 newly diagnosed and untreated T2DM individuals and 72 healthy controls were studied. Carotid atherosclerosis was determined by ultrasonographically evaluated intima- media thickness (IMT) and plaque score. Plasma concentration of ADMA was measured by high-performance liquid chromatography., Results: Plasma ADMA, mean IMT, and plaque score were higher in diabetic patients compared with controls. Univariate and multivariate analyses demonstrated an independent association between ADMA and mean IMT in diabetic patients. On a multiple logistic regression analysis, ADMA was the sole predictor of carotid plaque formation (plaque score ≥1.1) (odds ratio 2.43, 95% confidence interval 1.19 to 4.94, p<0.05)., Conclusion: Our results suggest that increased levels of ADMA might be involved in the development of carotid atherosclerosis in T2DM.

Systemic lupus erythematosus (SLE) is a complex immune disease. The genetic variation in the B lymphoid tyrosine kinase (BLK) gene was found to associate with SLE in Caucasian population. However, the association of rs13277113 and rs4840568 with SLE was not extensively studied in Chinese population. In this study, we aim to test the association of SNP rs13277113 and rs4840568 with the disease risk of SLE in Chinese mainland population. A total of 532 patients with SLE and 576 controls were recruited. Unlabelled probe-based high-resolution melting analysis (HRMA) was used in genotyping. HRMA with unlabelled probe successfully distinguished all genotypes. Significant differences were observed in both genotype and allele frequencies for rs13277113 and rs4840568. Minor alleles of rs13277113 (P = 4.2E-05, odds ratio [OR] 0.66, [95% CI 0.54-0.81]) and rs4840568 (P = 7.1E-05, OR 0.67, [95% CI 0.55-0.82]) were found to be protective against SLE. Polymorphisms of rs13277113 and rs4840568 in BLK gene were associated with SLE in Chinese population., (© 2012 Blackwell Publishing Ltd.)

Purpose: A prototype small animal PET is developed with several novel technologies to measure 3D gamma-interaction positions and to substantially improve imaging performance., Methods: Each new detector has an 8×8 array of 1.95×1.95×30 mm̂3 LYSO scintillators, with each end optically connected to a solid-state photo multiplier (SSPM) array through a light guide. This dual-ended-readout enables the depth-of-interaction (DOI) measurement. Each SSPM array has 16 SSPMs arranged in a 4×4 matrix. Each SSPM has active area about 3×3 mm̂2, with its output read by an ASIC electronics that directly converts analog signals to digital timing pulses which encode the interaction information for energy, timing, crystal of interaction, and DOI calculations. These digital pulses are transferred to and decoded by FPGA-based TDC for coincident event selection and data acquisition. This independent readout of each SSPM and parallel signal process significantly improve signal-to-noise ratio and permit applying flexible data processing algorithms. The current prototype system consists of two rotating detector panels on a portable gantry, with 4 detectors linearly packed together in each panel to provide ∼16 mm axial and variable trans- axial FOV with adjustable panel-to-panel distance. List-mode OSEM-based image reconstruction with resolution modeling was implemented. Both Na- 22 point source and phantom were used to evaluate the system performance., Results: The measured energy, timing, spatial and DOI resolutions for each crystal were around 16%, 2.6 ns, 2.0 mm and 5.0 mm, respectively. The measured spatial resolutions with DOI were ∼1.7 mm across the entire FOV in all direction, while those without DOI were much worse and non-uniform across the FOV, in the range predominately around 3.0 to 4.0 mm. In addition, images from a F-18 hot-rod phantom with DOI show significantly improved quality compared to those without DOI., Conclusions: DOI- measurable PET shows substantially improved image performance for a compact system. National Institute of Health. University of Texas MD Anderson Cancer Center., (© 2012 American Association of Physicists in Medicine.)

Accurate identification of sparse heterozygous single-nucleotide variants (SNVs) is a critical challenge for identifying the causative mutations in mouse genetic screens, human genetic diseases and cancer. When seeking to identify causal DNA variants that occur at such low rates, they are overwhelmed by false-positive calls that arise from a range of technical and biological sources. We describe a strategy using whole-exome capture, massively parallel DNA sequencing and computational analysis, which identifies with a low false-positive rate the majority of heterozygous and homozygous SNVs arising de novo with a frequency of one nucleotide substitution per megabase in progeny of N-ethyl-N-nitrosourea (ENU)-mutated C57BL/6j mice. We found that by applying a strategy of filtering raw SNV calls against known and platform-specific variants we could call true SNVs with a false-positive rate of 19.4 per cent and an estimated false-negative rate of 21.3 per cent. These error rates are small enough to enable calling a causative mutation from both homozygous and heterozygous candidate mutation lists with little or no further experimental validation. The efficacy of this approach is demonstrated by identifying the causative mutation in the Ptprc gene in a lymphocyte-deficient strain and in 11 other strains with immune disorders or obesity, without the need for meiotic mapping. Exome sequencing of first-generation mutant mice revealed hundreds of unphenotyped protein-changing mutations, 52 per cent of which are predicted to be deleterious, which now become available for breeding and experimental analysis. We show that exome sequencing data alone are sufficient to identify induced mutations. This approach transforms genetic screens in mice, establishes a general strategy for analysing rare DNA variants and opens up a large new source for experimental models of human disease.

To control anal incontinence, we have developed an artificial anal sphincter system with sensor feedback. The artificial anal sphincter system is a novel hydraulic-electric muscle which mainly comprises an artificial anal sphincter, a wireless power supply subsystem, and a rectal sensation reconstruction subsystem. To investigate the features of the patients' rectal sensation, we have developed an in vitro experimental platform of artificial anal sphincter. In vitro experiments have been performed, and demonstrate that the traditional threshold method is not suitable for predicting the time for defecation. The traditional threshold method only uses single-dimensional pressure time series which may contain a few interdependent components simultaneously. A wavelet packet analysis algorithm is employed to extract the feature vector of the rectal pressure signal, then the rectal sensation prediction model is constructed based on a support vector machine for defecation pattern recognition. The results show that the proposed method is an effective approach for the reconstruction of patients' rectal sensation.

Glucose is an essential substrate for lactose synthesis and an important energy source in milk production. Glucose uptake in the mammary gland, therefore, plays a critical role in milk synthesis. Facilitative glucose transporters (GLUT) mediate glucose uptake in the mammary gland. Glucose transporter 1 (GLUT1) is the major facilitative glucose transporter expressed in the bovine mammary gland and has been shown to localize to the basolateral membrane of mammary epithelial cells. Glucose transporter 1 is, therefore, thought to play a major role in glucose uptake during lactation. The objective of this study was to determine the transport kinetic properties and substrate specificity of bovine GLUT1 using the Xenopus oocyte model. Bovine GLUT1 (bGLUT1) was expressed in Xenopus oocytes by microinjection of in vitro transcribed cRNA and was found to be localized to the plasma membrane, which resulted in increased glucose uptake. This bGLUT1-mediated glucose uptake was dramatically inhibited by specific facilitative glucose transport inhibitors, cytochalasin B, and phloretin. Kinetic analysis of bovine and human GLUT1 was conducted under zero-trans conditions using radio-labeled 2-deoxy-D-glucose and the principles of Michaelis-Menten kinetics. Bovine GLUT1 exhibited a Michaelis constant (K(m)) of 9.8 ± 3.0mM for 2-deoxy-d-glucose, similar to 11.7 ± 3.7 mM for human GLUT1. Transport by bGLUT1 was inhibited by mannose and galactose, but not fructose, indicating that bGLUT1 may also be able to transport mannose and galactose. Our data provides functional insight into the transport properties of bGLUT1 in taking up glucose across mammary epithelial cells for milk synthesis., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

B-cell lymphoma 2 (Bcl-2) homology 3 (BH3)-only proteins represent a class of pro-apoptotic factors that neutralize pro-survival Bcl-2 proteins, and, in some cases, directly activate Bax. The mechanisms of control and the role of BH3-only proteins, such as Bcl-2 like protein 11 extra large and Bad are well studied. By contrast, relatively little is known about the regulation and role of Bcl-2 modifying factor (Bmf). The B-RAF oncogene is mutated in ∼8% of human tumors. We have previously shown that Bmf is upregulated at the transcript level and is required for apoptosis induced by targeting B-RAF signaling in tumor cells harboring mutant B-RAF. In this study, we show that Bmf is regulated at the post-translational level by mutant B-RAF-MEK-ERK2 signaling. Extracellular signal-regulated kinase (ERK2) directly phosphorylates Bmf on serine 74 and serine 77 residues with serine 77 being the predominant site. In addition, serine 77 phosphorylation reduces Bmf pro-apoptotic activity likely through a mechanism independent of altering Bmf localization to the mitochondria and/or interactions with dynein light chain 2 and the pro-survival proteins, B-cell lymphoma extra large, Bcl-2 and Mcl-1. These data identify a novel mode of regulation in Bmf that modulates its pro-apoptotic activity in mutant B-RAF tumor cells.

Introduction: While quizzing during informed consent for research to ensure understanding has become commonplace, it is unclear whether the quizzing itself is problematic for potential participants. In this study, we address this issue in a multinational HIV prevention research trial enrolling injection drug users in China and Thailand., Methods: Enrolment procedures included an informed consent comprehension quiz. An informed consent survey followed., Results: 525 participants completed the informed consent survey (Heng County, China¼255, Xinjiang, China¼229, Chiang Mai, Thailand¼41). Mean age was 33 and mean educational level was 8 yrs. While quizzing was felt to be a good way to determine if a person understands the nature of clinical trial participation (97%) and participants did not generally find the quiz to be problematic, minorities of respondents felt pressured (6%); anxious (5%); bored (5%); minded (5%); and did not find the questions easy (13%). In multivariate analysis, lower educational level was associated with not minding the quizzing (6e10 yrs vs 0e5 yrs: OR¼0.27, p¼0.03; more than 11 yrs vs 0e5 yrs: OR¼0.18, p¼0.03). There were also site differences (Heng County vs Xinjiang) in feeling anxious (OR¼0.07; p¼<0.01), not minding (OR¼0.26; p¼0.03), being bored (OR¼0.25; p¼0.01) and not finding the questions easy (OR¼0.10; p¼<0.01)., Conclusions: Quizzing during the informed consent process can be problematic for a minority of participants. These problems may be associated with the setting in which research takes place and educational level. Further research is needed to develop, test and implement alternative methods of ensuring comprehension of informed consent., Trial Registration: clinicaltrials.gov number NCT00270257.

Seven novel MhcMamu-DQB1 alleles were observed in a population of rhesus macaques of Chinese origin., (© 2011 John Wiley & Sons A/S.)

The aim of this study is to characterize the changes of CD4(+) CD25(high) forkhead box P3 (FoxP3(+) ) regulatory T cells (T(reg) ), interleukin (IL)-17 secreting T helper type 17 (Th17) cell frequencies and the balance of these two subsets in a cohort of chronic human immunodeficiency virus type 1 (HIV-1)-infected patients in China. A total of 115 untreated chronic HIV-infected individuals and 32 healthy donors were recruited in this study. Peripheral blood mononuclear cells were isolated from ethylenediamine tetracetic acid (EDTA) anti-coagulated fresh whole blood and stained to characterize the frequencies of T(reg) and Th17. Of a total 115 patients, 42 individuals including 10 elite controllers were followed-up for more than 1 year, and changes of T(reg) and Th17 frequencies were analysed over time. The continuous loss of Th17 cells was accompanied by a concomitant rise in the frequency of T(reg) cells, resulting in a loss of Th17/T(reg) balance during the progressive HIV infection. Meanwhile, the T(reg) levels, Th17 levels and Th17/T(reg) ratios of the elite controller group were comparable to those of the HIV-1 negative controls in the follow-up study. Additionally, we demonstrated that loss of balance between Th17 and T(reg) is associated with an earlier CD4 T cell decline during the course of HIV infection. Our results indicate that a loss of immune-balance of Th17 to T(reg) during HIV-1 disease progression and the persistence of such an immune-balance in the elite controllers may have a critical role in HIV-1 infection and further shed new light into understanding the pathogenesis of HIV-1., (© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.)

Background: A kinase anchor protein 12 (AKAP12/gravin) belongs to a family of scaffold proteins and organizes protein kinase (PK)A and PKC. DNA hypermethylation in the AKAP12 promoter region has been reported in a variety of human cancers with the exception of skin cancer. Methylation-specific high-resolution melting (MS-HRM) analysis is a novel tool for analysis of promoter methylation., Aim: To use MS-HRM analysis to detect the methylation levels of the AKAP12 gene in skin samples., Methods: In total, 195 samples, including basal cell carcinoma, squamous cell carcinoma and actinic keratosis were examined. MS-HRM analysis was used to detect methylation levels of the AKAP12 gene in these samples., Results: MS-HRM analysis successfully detected the methylation of AKAP12 in skin samples. The frequencies of AKAP12 methylation in all three types of skin abnormalities were significantly higher than in normal tissues., Conclusions: Application of MS-HRM analysis proved to be a fast and high-throughput method to investigate the epigenetic status of AKAP12. Methylation of AKAP12 can be detected in different skin abnormalities., (© The Author(s). CED © 2010 British Association of Dermatologists.)

The HIV epidemic in China started among intravenous drug users in the late 1980s. The second wave of the epidemic was caused by an outbreak in the paid plasma donors in central China in the mid-1990s. Sexually transmitted HIV cases have steadily increased and comprised more than half the reported HIV/AIDS infections since 2007. In the last 5 years, there has been a sharp increase of HIV infection in men who have sex with men. The HIV epidemic in China has expanded from high-risk groups to the general population and from rural regions to urban areas. This brief article discusses the history of HIV epidemics in China and the challenges facing the current AIDS control efforts in the country. It explains that only scientific approaches can sustain the national AIDS control programs and introduce the type of research needed to address those challenges. The selected research areas include molecular epidemiology, drug resistance surveillance, and the Chinese HIV vaccine research.

Background: The laparoscopically assisted ventriculoperitoneal (VP) shunt has been widely used in the clinical treatment of hydrocephalus for its simplicity and reliability. Despite significant improvements in shunt procedures, shunt complications remain common. Our clinical experiences suggest that the fixation of the distal (peritoneal) shunt catheter using threads and hemoclips may partially contribute to complications of the distal shunt including obstruction of the shunt and infection. In this study, we explored a novel fixation method in the laparoscopically assisted VP shunt with use of the liver falciform ligament as a natural support for fixation of the distal shunt catheter., Methods: 10 patients with hydrocephalus underwent laparoscopically assisted VP shunt and the distal shunt catheter was placed into the hepatodiaphragmatic space and the catheter was traversed through 2-3 drilled holes in the liver falciform ligament without using any artificial material for fixation., Results: In all the patients who received surgery with the adopted new procedure the clinical symptoms were alleviated. The size of cerebral ventricles returned to normal after 1 week. The distal catheters were in the hepatodiaphragmatic space in 9 of 10 patients, while in 1 patient it migrated to the peritoneal cavity underneath the liver. All the 9 patients were followed up for 1 year and no surgery-related catheter obstructions and infections were observed., Conclusions: The modified laparoscopically assisted VP shunt in the treatment of hydrocephalus with fixation of the distal shunt catheter to a natural anatomic structure could potentially reduce the necessity of repeat surgery for addressing the complications caused by catheter obstruction and infections, reduce the chance of adhesions, and would be of benefit to those patients who need future revisions., (© Georg Thieme Verlag KG Stuttgart · New York.)

Activating mutations in B-RAF and N-RAS occur in ∼60 and ∼15% of melanomas, respectively. The most common mutation in B-RAF is V600E, which activates B-RAF and the downstream MEK-ERK1/2 pathway. Thus, B-RAF(V600E) is a viable therapeutic target. PLX4720 is a selective inhibitor of mutant B-RAF and its analog, PLX4032, is currently undergoing clinical trials in melanoma. However, the effects of PLX4720 across the genotypic spectrum in melanoma remain unclear. Here, we describe that PLX4720 treatment rapidly induces hyperactivation of the MEK-ERK1/2 pathway in mutant N-RAS melanoma cells. Furthermore, we demonstrate that C-RAF is the major RAF isoform involved in this process. Importantly, PLX4720-induced hyperactivation of the MEK-ERK1/2 pathway promotes resistance to apoptosis in both non-invasive and invasive mutant N-RAS melanoma cells but does not enhance cell cycle properties. These findings underscore the need to genotypically stratify melanoma patients before enrollment on a mutant B-RAF inhibitor trial.

Systemic lupus erythematosus (SLE) is a complex immune disease. The genetic variation in the PXK gene was found to associate with SLE in Caucasian populations. However, the association of rs6445975 with SLE has not been extensively studied in a Chinese mainland population. A total of 288 SLE patients and 357 controls were recruited. Unlabeled probe-based high-resolution melting analysis (HRMA) was used in genotyping. HRMA with unlabeled probe successfully distinguished all genotypes. Neither genotype nor allele frequencies of SNP rs6445975 showed statistically significant differences between SLE patients and controls. The association of SNP rs6445975 with the diagnostic criteria of SLE was also examined. No obvious association was observed between rs6445975 and the incidence of clinical symptoms. However, the minor allele (G) of rs6445975 was found to significantly associate with increased abnormalities of anti-Smith (p = 0.004, odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.22-3.09), anti-Ro (p = 0.015, OR = 1.69, 95% CI = 1.10-2.58), anti-La (p = 0.008, OR = 1.86, 95% CI = 1.17-2.93) and C3C4 (p = 0.007, OR = 1.79, 95% CI = 1.17-2.74). Polymorphisms of rs6445975 in the PXK gene were associated with autoantibody production, but not disease risk, of systemic lupus erythematosus in a Chinese population.

The development of malignant prostate cancer involves multiple genetic alterations. For example, alterations in both survivin and p53 are reported to have crucial roles in prostate cancer progression. However, little is known regarding the interrelationships between p53 and survivin in prostate cancer. Our data demonstrate that the expression of survivin is inversely correlated with that of wtp53 protein (r(s)=0.548) in prostate cancer and in normal prostate tissues. We have developed a therapeutic strategy, in which two antitumor factors, small interfering RNA-survivin and p53 protein, are co-expressed from the same plasmid, and have examined their effects on the growth of PC3, an androgen-independent prostate cancer cell line. When p53 was expressed along with a survivin-specific short hairpin RNA (shRNA), tumor cell proliferation was significantly suppressed and apoptosis occurred. In addition, this combination also abrogated the expression of downstream target molecules such as cyclin-dependent kinase 4 and c-Myc, while enhancing the expression of GRIM19. These changes in gene expression occurred distinctly in the presence of survivin-shRNA/wtp53 compared with control or single treatment groups. Intratumoral injection of the co-expressed construct inhibited the growth and survival of tumor xenografts in a nude mouse model. These studies revealed evidence of an interaction between p53 and survivin proteins plus a complex signaling network operating downstream of the wtp53-survivin pathway that actively controls tumor cell proliferation, survival and apoptosis.

Background: Systemic lupus erythematosus (SLE) is a complex genetic disease; the histamine H4 receptor (HRH4) has been shown to be related to different kinds of autoimmune disorders; and copy number variations (CNVs) have been found to be associated with various types of diseases., Objectives: To explore a possible association between HRH4 (formerly H4R) CNVs and the risk of SLE., Methods: Genomic DNA and RNA from 340 patients with SLE and 392 healthy controls were extracted, and CNVs and mRNA levels of HRH4 were examined., Results: The expression of HRH4 mRNA was significantly increased in patients with SLE compared with controls. Amplification of HRH4 copy numbers significantly increased the risk of SLE [P < 0·001, odds ratio (OR) 2·26, 95% confidence interval (CI) 1·50-3·40]. HRH4 amplifications also positively correlated with the incidence of arthritis (P = 0·019, OR 1·96, 95% CI 1·11-3·47), and proteinuria (P < 0·001, OR 2·95, 95% CI 1·73-5·00) and antinuclear antibody abnormalities (P < 0·001, OR 2·97, 95% CI 1·66-5·33). Deletions of HRH4 copy numbers were protective against proteinuria (P = 0·03, OR 0·50, 95% CI 0·26-0·94)., Conclusion: CNVs of the HRH4 gene are associated with SLE., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists.)

This paper discusses a novel artificial anal sphincter with sensor feedback for controlling anal incontinence. The artificial anal sphincter system is a novel hydraulic-electric muscle which mainly comprises an artificial anal sphincter, a wireless power supply subsystem, and a communication subsystem. High integration of all functional components and no wire linking to the outer device make surgical implantation easier and lower risk. The wireless power supply subsystem employs a Class-E power amplifier based on adaptive control technique, and the electromagnetic compatibility in biological tissue is analysed. With the goal of designing a reliable and safe instrument, the models of human colonic blood flow and rectum motion are developed, the biomechanical material properties of human rectum and tissue ischaemia are analysed. The results show that the deformation of the artificial anal sphincter can be controlled by the press of reservoir below the upper limit of human tissue ischaemia. In vitro experiments demonstrate the artificial anal sphincter system is a good cure for human anal incontinence problems.

Background: Atopic dermatitis (AD) is a chronic skin disease affecting more than 15% of children and 2% of adults. A strong connection between genetic factors and AD has been described for a long time. Histamine receptor H4 (HRH4) has been shown to be related to different kinds of allergic and autoimmune disorders. However, an association between HRH4 and AD has not yet been reported., Objectives: To examine a possible association between HRH4 and AD., Methods: Genomic DNA from 301 patients with AD and 313 healthy controls was extracted and three exons of HRH4 were sequenced., Results: We found three new single nucleotide polymorphisms (SNPs) in HRH4 which were significantly associated with AD: ss142022671 [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.24-2.81; P = 0.002], ss142022677 (OR 4.40, 95% CI 2.42-8.00; P = 1.5 x 10(-7)) and ss142022679 (OR 4.26, 95% CI 2.38-7.61; P = 1.3 x 10(-7)). The SNPs ss142022677 and ss142022679 were found to be in strong linkage disequilibrium (D' = 0.98; r(2) = 0.92). Two-SNP haplotype analysis (ss142022677 and ss142022679) showed that the major AA haplotype was protective against AD (OR 0.22, 95% CI 0.12-0.40; P = 3.1 x 10(-8)) and the minor TT haplotype was significantly associated with AD (OR 4.13, 95% CI 2.27-7.54; P = 6.6 x 10(-7)). In addition, in a three-SNP haplotype analysis (ss142022671, ss142022677 and ss142022679), the major TAA haplotype was protective against AD (OR 0.46, 95% CI 0.31-0.69; P = 0.0001), while the complementary ATT haplotype was found to be significantly associated with AD (OR 3.81, 95% CI 2.03-7.14; P = 8.3 x 10(-6))., Conclusions: Polymorphisms of ss142022671, ss142022677 and ss142022679 in HRH4 are associated with AD.

An aberration-corrected JEOL 2200FS scanning-transmission electron microscope (STEM), equipped with a high-angle annular dark-field detector (HAADF), is used to monitor the coalescence and sintering of Pt nanoparticles with an average diameter of 2.8 nm. This in situ STEM capability is combined with an analysis methodology that together allows direct measurements of mass transport phenomena that are important in understanding how particle size influences coalescence and sintering at the nanoscale. To demonstrate the feasibility of this methodology, the surface diffusivity is determined from measurements obtained from STEM images acquired during the initial stages of sintering. The measured surface diffusivities are in reasonable agreement with measurements made on the surface of nanoparticles, using other techniques. In addition, the grain boundary mobility is determined from measurements made during the latter stages of sintering.

Herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcerative disease in the developed world. Keratinocytes are the primary cells involved in clinical lesions caused by HSV-2. In our study, we intensively examined cytokine expression in the HSV-2-infected keratinocytes. We observed upregulation of a series of cytokines including early-induced antiviral cytokines as interferons α, β (IFN-α, β), tumor necrosis factor α (TNF-α), colony stimulating factors (CSFs) as G-CSF, GM-CSF, interleukin 3 (IL-3), growth factors (EGF, KGF, and IGF-β1), defensins, selectins, leukocyte function-associated antigens (LFAs,) and toll-like receptors (TLR-2, 3, 4, and 9). More importantly, we found that HSV-2-infected keratinocytes stimulated the proliferation of lymphocytes in co-cultivation system. These data suggest that keratinocytes participate in the immune response to HSV-2 infection in two ways. They secrete inflammatory cytokines to resist the HSV-2 infection directly and recruit the immune cells to eliminate the primary infection indirectly and enhance the adaptive immunity to prevent subsequent infections.

We implemented a portable smart pen system capable of detecting lapses in concentration during reading. An accelerometer and a microcontroller are embedded within a pen casing to record data as a user reads sections of text using the pen as a pointer. When a substantial pause in reading is detected, the system generates an appropriate warning or alarm. An accompanying software program can communicate with the pen through a USB interface to customize system parameters, record relevant data, and graph collected data over time. The overall effectiveness of a prototype system was tested on 11 normal volunteers and 3 persons with attention deficit disorder (ADD). The prototype system had probability of false alarm of 19%, and sensitivity of 82%. With further refinement, this system could enable patients with attention deficit/hyperactivity disorder maintain concentration during reading in a variety of environments.

Protocadherins are celladhesion molecules with 6 or 7 cadherin motifs in their extracellular domain and various cyotoplasmic domains. PCDH10 was characterized a novel tumor suppressive gene in and was epigenetically silenced in multiple haematologic malignancies as well as some solid tumors such as gastric cancer, nasopharyngeal carcinoma and esophageal carcinoma. High-resolution melting (HRM) analysis has been used as a novel tool for analysis of promoter methylation. In our study, we used HRM analysis to detect the methylation levels of PCDH10 gene in 100 gastric cancers, 100 colorectal cancers, 70 pancreatic cancers and equal number of adjacent normal tissues. The frequency of PCDH10 methylation in all three types of cancers was significantly higher than that in normal tissues. Consistent with previous reports, expression levels of PCDH10 were inversely correlated with methylation levels. But we didn't find significant association between PCDH10 methylation status and TNM staging in all three types of cancers. In summary, application of HRM analysis to large amount of clinical samples proves to be a fast and high-throughput way to investigate the epigenetic status of PCDH10. And this is the first study to evaluate the prevalence of PCDH10 methylation based on large amount of tumor samples, showing that epigenetic regulation of PCDH10 was associated with carcinogenesis.