Gender differences in the functional language networks at birth: a resting-state fNIRS study.

Numerous studies reported inconsistent results concerning gender influences on the functional organization of the brain for language in children and adults. However, data for the gender differences in the functional language networks at birth are sparse. Therefore, we investigated gender differences in resting-state functional connectivity in the language-related brain regions in newborns using functional near-infrared spectroscopy. The results revealed that female newborns demonstrated significantly stronger functional connectivities between the superior temporal gyri and middle temporal gyri, the superior temporal gyri and the Broca's area in the right hemisphere, as well as between the right superior temporal gyri and left Broca's area. Nevertheless, statistical analysis failed to reveal functional lateralization of the language-related brain areas in resting state in both groups. Together, these results suggest that the onset of language system might start earlier in females, because stronger functional connectivities in the right brain in female neonates were probably shaped by the processing of prosodic information, which mainly constitutes newborns' first experiences of speech in the womb. More exposure to segmental information after birth may lead to strengthened functional connectivities in the language system in both groups, resulting in a stronger leftward lateralization in males and a more balanced or leftward dominance in females.

High-power, ultra-broadband supercontinuum light generated in a single-mode fiber pumped with a nanosecond passively Q-switched microchip laser.

The compact, high-power, broadband continuum sources are extremely needed for developing portable instruments for various applications such as optical coherence tomography, high-resolution spectroscopy, and so on. Here, we develop a compact high-power, ultra-broadband supercontinuum (SC) light source in a single-mode fiber (SMF) pumped with a Yb:YAG/Cr4+:YAG passively Q-switched microchip laser oscillating at 1030 nm. The spectral bandwidth of the SC light is over 1150 nm covering from 600 to 1750 nm. The maximum average output power is 181.8 mW at an input pump power of 880 mW. The optical efficiency is 20.6%, and the net conversion efficiency is as high as 51.6% with respect to the pump power coupled into the fiber. The ultra-broadband spectrum of the SC generated in the SMF is caused by the intermodal four-wave mixing (IMFWM) and cascade stimulated Raman scattering effects. Various transverse modes have been experimentally observed in SC beam generated in the SMF. Wavelength-dependent transverse modes propagating in the SMF participating in the IMFWM process dramatically expand the spectral range in the visible region. The experimental results are basically consistent with the theoretical simulations of broadband SC generated in the SMF through the IMFWM process.

Circulating CD137+ CD8+ T cells accumulate along with increased functional regulatory T cells and thoracic tumour burden in lung cancer patients.

CD137 is a promising target for immunostimulation strategies against cancer. Previous studies showed that CD137+ CD8+ T cells are enriched in antitumour effector T cells in both preclinical tumour models and cancer patients, but to date, such T cells in the blood of lung cancer patients have not been sufficiently investigated. In this study, circulating antigen-activated CD8+ T cell subsets, identified as CD137+ CD8+ or PD-1+ (programmed cell death protein 1) CD8+ , and regulatory T cells (Treg), identified as CD4+ CD25+ CD127low/- , in 40 untreated lung cancer patients and in 49 age- and sex-matched healthy controls (HCs) were assessed by flow cytometry. Results were evaluated for associations with lung cancer patient clinical characteristics. Correlations between antigen-activated CD8+ T cells and effector Treg (CTLA-4+ [cytotoxic T-lymphocyte antigen 4] CD4+ CD25+ CD127low/- ) were also investigated. Higher percentages of PD-1+ , CD137+ and PD-1+ CD137+ amongst CD8+ T cells were observed in lung cancer patients compared with HCs. The percentages of CD137+ CD8+ and PD-1+ CD137+ CD8+ T cell subsets amongst CD8+ T cells were positively correlated with thoracic tumour burden and were strongly positively correlated with the percentage of effector Treg subset. Smoking patients harboured higher percentages of the PD-1+ CD8+ T cell subset compared with non-smoking patients. This study demonstrated that circulating antigen-activated CD8+ T cells accumulated in lung cancer patients along with increased effector Treg and thoracic tumour burden. These findings aid a better understanding of immune-host interactions in lung cancer patients using peripheral blood, and further support immunotherapeutic intervention strategies using combination therapy for differential control of Treg and activation of tumour-specific effector T cells.

Investigating the mechanism by which SMAD3 induces PAX6 transcription to promote the development of non-small cell lung cancer.

BACKGROUND: This study investigated the function of SMAD3 (SMAD family member 3) in regulating PAX6 (paired box 6) in non-small cell lung cancer. METHODS: First, qRT-PCR was employed to detect SMAD3 expression in cancer tissues along with normal tissues and four cell lines, including BEAS-2B, H125, HCC827 and A549 cells. SMAD3 was knocked down by small interference RNA (siRNA), and then its expression was determined via qRT-PCR and Western blot analysis. The correlation between SMAD3 and PAX6 was determined by double luciferase reporter experiments and chromatin immunoprecipitation (ChIP) assay. Cell viability was evaluated by CCK-8 and colony forming assays, while cell migration and invasion were detected by Transwell analysis. RESULTS: SMAD3 and PAX6 were upregulated in lung cancer tissues and cancer cells. Knocking down SMAD3 and PAX6 by transfection with siRNAs specifically suppressed the expression of SMAD3 and PAX6 mRNA and protein levels. SMAD3 could promote PAX6 transcriptional activity by binding to its promoter. Reduced expression of SMAD3 led to the downregulation of PAX6 mRNA and protein levels along with decreased cell migration, invasion, proliferation and viability in A549 and HCC827 cells. PAX6 overexpression altered the si-SMAD3-induced inhibition of cell migration, invasion, proliferation and viability in A549 and HCC827 cells. Additionally, PAX6 knockdown alone also repressed the cell migration, invasion, proliferation and viability of the cell lines. CONCLUSIONS: SMAD3 promotes the progression of non-small cell lung cancer by upregulating PAX6 expression.

Mechanism of TangGanJian on nonalcoholic fatty liver disease with type 2 diabetes mellitus.

CONTEXT: TangGanJian (TGJ) has a curative effect in the clinical treatment of nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes mellitus (T2DM), while the mechanism involved in the treatment process remains unclear. OBJECTIVE: This study details the mechanism of TGJ on the treatment of NAFLD with T2DM. MATERIALS AND METHODS: NAFLD was induced in T2DM rat model. Male Wistar rats were assigned into six groups: Group I (control), Group II (model), Group III (pioglitazone, 0.5 mg/kg), Group IV (high dose of TGJ, 24.8 g/kg), Group V (middle dose of TGJ, 12.4 g/kg) and Group VI (low dose of TGJ, 6.2 g/kg). All rats in each group were treated with the corresponding drugs by gavage for 8 weeks. Haematoxylin and eosin analysis was conducted. The indicators of inflammatory and oxidative stress were analysed utilizing one-way ANOVA. RESULTS: The contents of TNF-α (15.794 ± 3.302 pg/mL), IL-6 (76.801 ± 8.491 pg/mL), IL-1ß (100.101 ± 13.150 pg/mL), CRP (1.052 ± 0.079 pg/mL) and MDA (3.972 ± 0.159 pg/mL) were obviously elevated in NAFLD with T2DM rats compared to controls. Except for the IL-6, the levels of other markers declined in a dose-dependent manner after treatment with TGJ. The SOD (14.139 ± 1.479 U/mgprot) and GSH-PX (81.511 ± 5.276 U/mgprot) levels significantly decreased in NAFLD with T2DM rats, while the levels of these indicators increased after treatment with TGJ. CONCLUSIONS: TGJ may be a therapy for the NAFLD with T2DM rats by modulating the inflammatory response and the oxidative stress capacity.

Association of rs9340799 polymorphism in estrogen receptor alpha gene with the risk of osteoarthritis: evidence based on 8,792 subjects.

Osteoarthritis (OA) is one of the most common skeletal disease, which seriously affects the quality of life of patients, particularly in the middle-aged and elderly individuals. We aimed to explore whether rs9340799 [estrogen receptor alpha (ER-α) XbaI A/G] polymorphism was associated with OA using a meta-analysis. A literature search for eligible studies published before March 28, 2014 was conducted in the PubMed, Web of Science, Embase, Cochrane database, Current Controlled Trials, Clinicaltrials.gov, Chinese Clinical Trial Registry, CBMdisc, CNKI, Google Scholar and Baidu Library. The association between the rs9340799 polymorphism and OA risk was assessed by odds ratios (ORs) together with their 95 % confidence intervals (CIs). A total of 663 articles were found. After article review and quality assessment, 10 articles involving 2,924 OA cases and 5,868 controls were included in the final meta-analysis. The combined evidence suggested that rs9340799 polymorphism contributed significantly to an increased risk of OA (for G allele vs. A allele: OR = 1.21, 95 % CI 1.03-1.43, p = 0.02; for G/G vs. A/A: OR = 1.30, 95 % CI 1.07-1.57, p = 0.009). In the subgroup analyses, significant associations were found between the rs9340799 polymorphism and the OA risk in the European group, Asian group, and knee osteoarthritis group, respectively. These results suggested that the rs9340799 polymorphism might be associated with the risk of OA. However, the results should be interpreted with caution because of the publication bias.

The effect of music therapy on language communication and social skills in children with autism spectrum disorder: a systematic review and meta-analysis.

Background: Studies have shown that music therapy can be used as a therapeutic aid for clinical disorders. To evaluate the effects of music therapy (MT) on language communication and social skills in children with autism spectrum disorder (ASD), a meta-analysis was performed on eligible studies in this field. Methods: A systematic search was conducted in eight databases: PubMed, Embase, Web of Science, Cochrane Library databases, the China National Knowledge Infrastructure (CNKI), Wanfang Data, the Chinese Biomedical Literature (CBM) Database, and the VIP Chinese Science and Technology Periodicals Database. The standard mean difference (SMD) values were used to evaluate outcomes, and the pooled proportions and SMD with their 95% confidence intervals (CIs) were also calculated. Results: Eighteen randomized controlled trial (RCT) studies were included, with a total of 1,457 children with ASD. This meta-analysis revealed that music therapy improved their language communication [SMD = -1.20; 95%CI -1.45, -0.94; χ2 (17) = 84.17, I2 = 80%, p < 0.001] and social skills [SMD = -1. 13; 95%CI -1.49, -0.78; χ2 (17) = 162.53, I2 = 90%, p < 0.001]. In addition, behavior [SMD = -1.92; 94%CI -2.56, -1.28; χ2 (13) = 235.08, I2 = 95%, p < 0.001], sensory perception [SMD = -1.62; 95%CI -2.17, -1.08; χ2 (16) = 303.80, I2 = 95%, p < 0.001], self-help [SMD = -2. 14; 95%CI -3.17, -1.10; χ2 (6) = 173.07, I2 = 97%, p < 0.001] were all improved. Conclusion: Music therapy has a positive effect on the improvement of symptoms in children with ASD. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/.

The relations of psychotic-like experiences (PLEs) and depressive symptoms and the bias of depressive symptoms during the clustering among Chinese adolescents: Findings from the network perspective.

BACKGROUND: There are rare studies about the network structure of psychotic-like experiences (PLEs) and depressive symptoms among adolescents. Studies have widely acknowledged that PLEs in adolescents confer a higher risk of depressive symptoms, but the complex interactions remain inadequately understood. Our study aimed to examine the hierarchy and inter-associations of PLEs and depressive symptoms in a large adolescent sample from the network analysis perspective. METHODS: A total of 5008 Chinese adolescents were enrolled in our sample. Community Assessment of Psychic Experiences-42 (CAPE-42) was applied to build the network. Centrality indexes were calculated to represent the significance of nodes in the network. Community detection was conducted to figure out the specific clustering of nodes. Demographic information was collected for the sub-network comparisons. Accuracy and stability of the network were also tested. RESULTS: "Failure", "External control", and "Lack of activity" were the most central nodes. The main bridge nodes linking PLEs and depressive symptoms were "Failure", "Guilty", and "No future". Positive PLE "Odd looks" and negative PLE "Unable to terminate" are the two PLEs that were most relevant to depressive nodes. Community detection further demonstrated the bias of depressive nodes in the data-driven clustering. Comparative sub-network analysis suggested that age was the only demographic factor related to the current network. CONCLUSION: In this study of a large adolescent sample, we first demonstrated the network structure and specific clustering preference of PLEs and depressive symptoms. Our findings may enhance the understanding of the relationship between PLE and depressive symptoms.

Association between the interleukin-6 gene -572 C/G polymorphism and the risk of type 2 diabetes mellitus: a meta-analysis of 11,681 subjects.

The association between the interleukin-6 (IL-6) gene -572 C/G (rs1800796) polymorphism and type 2 diabetes mellitus (T2DM) risk remains controversial. Thus, we performed this meta-analysis by searching PubMed, Embase, Web of Science, CBMdisc and CNKI databases until January 30, 2012. In addition, hand searching of the references of identified articles was performed. A total of 10 case-control studies including 11,681 subjects were selected to evaluate the possible association. Our results showed evidence for significant association between the IL-6 gene -572 C/G polymorphism and T2DM risk (for G allele vs. C allele: odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.09-1.52, P = 0.002, P = 0.008 after Bonferroni testing; for G/G vs. C/C: OR = 1.89, 95% CI = 1.51-2.37, P < 0.00001, P < 0.00004 after Bonferroni testing; for GG vs. G/C + C/C: OR = 1.75, 95% CI = 1.20-2.56, P = 0.004, P = 0.016 after Bonferroni testing; for G/G + G/C vs. C/C: OR = 1.32, 95% CI = 1.11-1.57, P = 0.001, P = 0.004 after Bonferroni testing). In addition, similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta-analysis suggests a significant association between the IL-6 gene -572 G allele and increased risk of T2DM.

Association between interleukin 10 gene -1082 A/G polymorphism and the risk of type 2 diabetes mellitus: a meta-analysis of 4250 subjects.

Increasing evidence suggests that interleukin 10 (IL 10) gene -1082 A/G (rsl800896) polymorphism may be associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the results are inconsistent. The aim of this study is to analyze the association between this variant and the T2DM risk by meta-analysis. PubMed, Embase, Web of Science, and Google Scholar were searched from January 1, 1989 to February 17, 2012, as well as hand searching of the references of identified articles were performed. All the statistical tests were performed using Stata 11.0. Seven case-control studies were identified, covering a total of 1879 T2DM cases and 2371 controls. The results showed evidence of significant association between IL 10 gene -1082 A/G polymorphism and T2DM risk (for G/G+G/A vs. A/A: OR=1.21, 95% CI=1.05-1.40, p=0.010, p=0.040 after Bonferroni testing). In the subgroup analysis by ethnicity, no significant association was found between IL 10 gene -1082 A/G polymorphism and T2DM risk in Europeans. In summary, results from this meta-analysis provide evidence that IL 10 gene -1082 G allele is associated with increased risk of T2DM.

Influence of interleukin gene polymorphisms on development of acute pancreatitis: a systematic review and meta-analysis.

Several epidemiological studies have assessed the associations of interleukin (IL) gene polymorphisms with acute pancreatitis (AP) in different populations. However, the results were inconclusive. Therefore, we performed the present study to comprehensively evaluate the associations of IL gene polymorphisms and susceptibility to AP. Systematic searches of the PubMed, Web of Science, Embase, CNKI, CBMdisc and Google Scholar until February 27, 2013, as well as hand searching of the references of identified articles were performed. Data were extracted using standardized forms and odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. All statistical analyses were performed using Stata 11.0. Ten studies were included in our final combined analysis, covering a total of 1,220 AP cases and 1,351 controls. The results showed evidence for significant association between IL-8 -251 T/A (rs4073) polymorphism and AP risk, suggesting that IL-8 -251 A allele was associated with an increased risk of AP (for A allele vs. T allele: OR = 1.36, 95 % CI 1.05-1.76, p = 0.02; for A/A vs. T/T: OR = 2.28, 95 % CI 1.08-4.81, p = 0.03; for A/A+T/A vs. T/T: OR = 1.40, 95 % CI 1.11-1.77, p = 0.005). However, there were no significant associations between IL-1ß (IL-1ß +3954 C/T (rs1143634) and IL-1ß -511 C/T (rs16944)), IL-6 (IL-6 -174 G/C (rs1800795) and IL-6 -634 C/G (rs1800796)) and IL-10 (IL-10 -1082 A/G (rs1800896), IL-10 -819 C/T (rs1800871) and IL-10 -592 C/A (rs1800872)) gene polymorphisms and AP risk. In summary, the current study suggests that the IL-8 -251 T/A polymorphism is associated with an increased risk of AP. In addition, there were no significant associations between IL-1ß, IL-6 and IL-10 gene polymorphisms and AP risk.

Detection of malingering: psychometric evaluation of the Chinese version of the structured interview of reported symptoms-2.

BACKGROUND: Malingering detection has emerged as an important issue in clinical and forensic settings. The Structured Interview of Reported Symptoms-2 (SIRS-2) was designed to assess the feigned symptoms in both clinical and non-clinical subjects. The aim of the study was to examine the reliability and validity of the Chinese version of this scale. METHODS: Two studies were conducted to evaluate the reliability and validity of the Chinese Version of SIRS-2. In Study one, with a simulation design, the subjects included a. 40 students asked to simulate symptoms of mental illness; b. 40 general psychiatric inpatients and c. 40 students asked to reply to questions honestly. Scales scores for feigning symptoms among three groups were carried out for discriminant validity of the Chinese Version of SIRS-2. Minnesota Multiphasic Personality Inventory-2(MMPI-2) was administered in 80 undergraduate students. In Study two, with a known-groups comparison design, scales scores for feigning symptoms were compared between 20 suspected malingerers and 80 psychiatric outpatients from two forensic centers using the Chinese Version of SIRS-2. RESULTS: The Chinese Version of SIRS-2 demonstrated satisfactory internal consistency in both study one and two. In study one, criterion validity of this scale was supported by its significantly positive correlation with the MMPI-2 (r = 0.282 ~ 0.481 for Infrequency), and by its significantly negative correlation with the MMPI-2 (r = -0.255 ~ -0.519 for Lie and -0.205 ~ 0.391 for Correction). Scores of 10 out of 13 subscales of the Chinese Version of SIRS-2 for simulators were significantly higher than scores of honest students and general psychiatric patients. In study two, the mean scores of the Chinese Version of 13 subscales for suspected malingerers were significantly higher than those of psychiatric outpatients. For discriminant validity, it yielded a large effect size (d = 1.80) for the comparison of the participant groups in study one and two. Moreover, the sensitivity (proportion of malingerers accurately identified by the measure) and specificity (proportion of people accurately classified as responding honestly) of the Chinese version of SIRS-2 in the detection of malingering in these two studies are acceptable. CONCLUSIONS: The Chinese version of the SIRS-2 has good psychometric properties and is a valid and reliable tool for detection of malingering in Chinese populations.

Survival Analysis of 159 Patients With Advanced Non-Small-Cell Lung Cancer Resistant to First-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor.

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have limited or no response in some certain patients of non-small-cell lung cancer (NSCLC). However, real-world survival analyses comparing clinical data and EGFR-plasma mutation are still lacking. Methods: In total, 159 patients with advanced NSCLC resistant to first-generation EGFR-TKIs were included for consecutive blood sampling in this study. Super-amplification refractory mutation system (Super-ARMS) was used to detect EGFR-plasma mutations and correlations between survival and circulating tumor DNA (ctDNA) were analyzed. Results: Among 159 eligible patients, the T790M mutation was detected in 27.0% (43/159) of patients. The median progression-free survival (mPFS) was 10.7 months in all patients. Survival analysis revealed that patients with the T790M mutation had shorter progression-free survival (PFS) than those with the T790M wild-type (10.6 months vs 10.8 months, P = .038). Patients who cleared EGFR-plasma mutation had prolonged PFS compared with those with nonclearing EGFR-plasma mutation (11.6 months vs 9.0 months, P = .001). Cox multivariate analysis showed that the nonclearance of EGFR-plasma mutations was an independent risk factor for PFS (RR = 1.745, 95% CI: [1.184, 2.571], P = .005). The T790M mutation was associated with nonclearance of the EGFR-plasma mutation (χ2 = 10.407, P = .001). Conclusion: Patients with advanced NSCLC who were resistant to the first-generation EGFR-TKI had a prolonged PFS with clearance of EGFR-plasma mutation. Those nonclearers were more likely to harbor T790M mutations in plasma.

Structural and magnetic properties of Y3(GaAlFe)5O12 liquid-phase epitaxy films with low ferromagnetic resonance losses.

Ultra-thin rare earth iron garnet (RIG) films with a narrow ferromagnetic resonance (FMR) line width and a low damping factor have attracted a great deal of attention for microwave and spintronic applications. In this work, 200 nm Y3(GaAlFe)5O12 garnet (GaAl-YIG) films were prepared on gadolinium gallium garnet (GGG) substrates by liquid-phase epitaxy (LPE) with low saturation magnetization. The microstructural properties, chemical composition, and magnetostatic and dynamic magnetization characteristics of the films are discussed in detail. According to the structural analysis, these films exhibit a low surface roughness of less than 0.5 nm. The GaAl-YIG films show an obvious temperature dependence of lattice parameter and strain state, and the film's parameter is perfectly matched with that of the GGG substrate at 810°C. There is a clear variation in the Pb level, which brings about a gradual enhancement of the coercivity and a diminution of the squareness ratio of magnetic hysteresis loops as the growth temperature is reduced. Slight changes in surface roughness, strain condition and content of Pb induce the FMR line width and damping factor to vary on a small scale. The line width is less than 10.17 Oe at 12 GHz and the damping factor is of the order of 10-4. All these properties demonstrate that these ultra-thin GaAl-YIG films are of benefit for the development of devices operated at lower frequencies and in lower fields.

Association between tumor necrosis factor-alpha gene -308A/G polymorphism and the risk of acute pancreatitis: a meta-analysis.

BACKGROUND: Epidemiologic studies have evaluated the association between tumor necrosis factor-alpha (TNF-α) gene -308A/G polymorphism and the risk of acute pancreatitis (AP), but the results are inconsistent. In order to derive a more precise estimation of the associations, a meta-analysis was performed. MATERIALS AND METHODS: Systematic searches of electronic databases PubMed, Embase, and Web of Science, as well as hand searching of the references of identified articles, were performed. All case-control studies investigating the association between TNF-α gene -308A/G polymorphism and AP risk were included. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs). Publication bias was analyzed by Begg's funnel plot and Egger's regression test. RESULTS: The initial search revealed 818 potentially eligible studies. Having read the title, abstract, or full text, we included six relevant studies in the final meta-analysis, which contained 1,006 AP cases and 782 controls. Overall, no significant association was found between TNF-α gene -308A/G polymorphism and AP risk when all studies were pooled into the meta-analysis (for A/A+A/G versus G/G: OR = 1.03, 95% CI = 0.83-1.28, P = 0.79; for A/A versus A/G+G/G: OR = 0.97, 95% CI = 0.65-1.45, P = 0.87; for A/A versus G/G: OR = 1.23, 95% CI = 0.79-1.91, P = 0.37; for A allele versus G allele: OR = 0.99, 95% CI = 0.83-1.18, P = 0.90). In addition, the similar results were obtained in the subgroup analysis based on the ethnicity and subtype of AP. CONCLUSIONS: The present meta-analysis reveals that the TNF-α gene -308A/G polymorphism is not associated with AP risk. However, due to the small number of subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.

Associations between interleukin-6 gene -174 C/G and -572 C/G polymorphisms and the risk of gastric cancer: a meta-analysis.

BACKGROUND AND OBJECTIVES: Epidemiological studies have evaluated the associations between interleukin-6 (IL-6) gene -174 C/G (rs1800795) and -572 C/G (rs1800796) polymorphisms and gastric cancer (GC) risk, but results and conclusions remain controversial. In order to derive a more precise estimation of the associations, we performed this meta-analysis. METHODS: A meta-analysis was conducted to estimate the associations between IL-6 gene -174 C/G and -572 C/G polymorphisms and GC risk. RESULTS: Nine articles involving 13 studies were included in the final meta-analysis, covering a total of 1,581 GC cases and 2,563 controls. For IL-6 gene -174 C/G polymorphism, nine studies were combined showing no evidence for associations between IL-6 gene -174 C/G polymorphism and GC risk. For IL-6 gene -572 C/G polymorphism, four studies were combined. There was also lack of evidence for significant association between IL-6 gene -572 C/G polymorphism and GC risk. In addition, the similar results were obtained in the subgroup analyses and cumulative meta-analysis. CONCLUSIONS: The present meta-analysis suggests that IL-6 gene -174 C/G and -572 C/G polymorphisms are not associated with GC risk. However, due to the small subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.

Tangshen Decoction Enhances Podocytes Autophagy to Relieve Diabetic Nephropathy through Modulation of p-AMPK/p-ULK1 Signaling.

Traditional Chinese medicine has certain advantages in the prevention and treatment of diabetic nephropathy (DN); thus, Chinese medicine therapy is considered as a promising strategy for treating DN. Here, the diabetic nephropathy model was established and intervened with Tangshen Decoction to explore its repair effect on diabetic kidney injury and the mechanism of autophagy. Different doses (10, 20 g·kg-1) of Tangshen Decoction (so-called Tangshen Jian, TSJ) or metformin were used to intervene for 16 weeks. The body weight (BW) and fasting blood glucose (FBG) of rats in each group were regularly monitored; a urine protein test kit (CBB method) was used to detect changes in urine protein (UP) content. The serum biochemical indicators, including Cr (creatinine), BUN (blood urea nitrogen), TC (total cholesterol), and TG (triglyceride), were detected by an automatic biochemical analyzer. HE (hematoxylin-eosin) staining, PAS, and electron microscopy were used to observe the podocyte damage. We showed that administration of TSJ or metformin prevented the increases in FBG level, serum Cr, BUN, TC, and TG level, and urine protein excretion in diabetic nephropathy. Simultaneously, the foot process fusion and fall-off were partially reversed after TSJ treatment. TSJ or metformin markedly upregulated the level of nephrin and podocin, accompanied by evident enhancement of podocyte autophagy and activation of p-AMPK/p-ULK1 signaling in the diabetic nephropathy. Therefore, TSJ may enhance podocyte autophagy to relieve diabetic nephropathy through modulation of p-AMPK/p-ULK1 signaling, which has important application prospects in the clinical treatment of diabetic kidney damage in the future.

A Computational Framework to Identify Transcriptional and Network Differences between Hepatocellular Carcinoma and Normal Liver Tissue and Their Applications in Repositioning Drugs.

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide. Although there have been extensive studies on the molecular mechanisms of its carcinogenesis, FDA-approved drugs for HCC are rare. Side effects, development time, and cost of these drugs are the major bottlenecks, which can be partially overcome by drug repositioning. In this study, we developed a computational framework to study the mechanisms of HCC carcinogenesis, in which drug perturbation-induced gene expression signatures were utilized for repositioning of potential drugs. Specifically, we first performed differential expression analysis and coexpression network module analysis on the HCC dataset from The Cancer Genome Atlas database. Differential gene expression analysis identified 1,337 differentially expressed genes between HCC and adjacent normal tissues, which were significantly enriched in functions related to various pathways, including α-adrenergic receptor activity pathway and epinephrine binding pathway. Weighted gene correlation network analysis (WGCNA) suggested that the number of coexpression modules was higher in HCC tissues than in normal tissues. Finally, by correlating differentially expressed genes with drug perturbation-related signatures, we prioritized a few potential drugs, including nutlin and eribulin, for the treatment of hepatocellular carcinoma. The drugs have been reported by a few experimental studies to be effective in killing cancer cells.

Polymorphisms in CLDN1 are associated with age and differentiation of triple-negative breast cancer patients.

Purpose: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. It is very important to explore novel biomarkers to better clarify the characteristics of TNBC. It has been reported that polymorphisms in claudin 1 (CLDN1) are associated with risk of several cancers. But till now, there is no report about these polymorphisms and TNBC. Patients and methods: Between January 2004 and December 2013, 267 patients with stage I-III primary TNBC were included in our study. We investigated the association between polymorphisms in CLDN1 gene and clinicopathological characteristics or survival of these patients. We used Haploview 4.2 software to identify Tag single nucleotide polymorphisms (SNPs). MassARRAY MALDI-TOF System was used for genotyping. Results: We found that rs10513846 GA genotype was associated with older age [P=0.013, hazard ratios (HR) = 2.231, 95% confidence interval (CI): 1.186-4.195]. Rs10513846 AA genotype carriers were more likely to develop grade 3 tumors (P=0.005, HR = 2.889, 95% CI: 1.389-6.007). And rs9283658 genotypes were also related to grade, more patients with grade 3 tumors were rs9283658 CC genotype carriers (P=0.023, HR = 0.446, 95% CI: 0.222-0.894). There was no association between polymorphisms in CLDN1 and survival of TNBC patients. After multivariate analysis, tumor size (P=0.021, HR = 3.146, 95% CI: 1.185-8.354) and lymph node status (P<0.001, HR = 10.930, 95% CI: 3.276-36.470) were demonstrated to be independent prognostic factors. Conclusion: We first demonstrated that polymorphisms in CLDN1 gene were associated with age and differentiation of TNBC patients.