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Wetlands are one of the most critical resources in Inner Mongolia Plateau. However, the region has experienced severe wetland loss in the context of global change. To quantify the dynamic change and the related driving forces, we extracted wetland information using multi-temporal Landsat images between 1993 and 2013 using ArcGIS platform and man-machine interactive interpretation. Dynamically changing characteristics for the past 20 years were analyzed, including wetland types and spatial distribution patterns of the wetlands in Inner Mongolia. We also performed correlation analysis and generalized linear models to quantify the contribution of natural and human factors to the changes in natural wetland area. Our results indicated that the total area of wetlands was 42421.2 km2 in 1993, and decreased to 38912.4 km2 in 2013, a decline ratio of 8.3%. Meanwhile, all types of wetlands showed a trend of transformation into non-wetlands. Anthropogenic factors led to the loss of natural wetlands in Inner Mongolia. In grasslands, mining coal was the dominant driver for natural wetland loss, while in arable lands, agricultural encroachment and irrigation were the primary driving forces. These findings can provide meaningful information for improving sustainable wetlands management strategies according to local conditions in different sub-regions. [ABSTRACT FROM AUTHOR]

Antibody-based technology is the main method for diagnosis and treatment of snake bite envenoming currently. However, the development of an antibody, polyclonal or monoclonal, is a complicated and costly procedure. Aptamers are single stranded oligonucleotides that recognize specific targets such as proteins and have shown great potential over the years as diagnostic and therapeutic agents. In contrast to antibodies, aptamers can be selected in vitro without immunization of animals, and synthesized chemically with extreme accuracy, low cost and high degree of purity. In this study we firstly report on the identification of DNA aptamers that bind to β-bungarotoxin (β-BuTx), a neurotoxin from the venom of Bungarus multicinctus. A plate-SELEX method was used for the selection of β-BuTx specific aptamers. After 10 rounds of selection, four aptamer candidates were obtained, with the dissociation constant ranged from 65.9 nM to 995 nM measured by fluorescence spectroscopy. Competitive binding assays using both the fluorescently labeled and unlabeled aptamers revealed that the four aptamers bound to the same binding site of β-BuTx. The best binder, βB-1, bound specifically to β-BuTx, but not to BSA, casein or α-Bungarotoxin. Moreover, electrophoretic mobility shift assay and enzyme-linked aptamer assay demonstrated that βB-1 could discriminate B. multicinctus venom from other snake venoms tested. The results suggest that aptamer βB-1 can serve as a useful tool for the design and development of drugs and diagnostic tests for β-BuTx poisoning and B. multicinctus bites. [ABSTRACT FROM AUTHOR]

The breakdown in tolerance of autoreactive B cells in the lupus-prone NZM2410-derived B6.Sle1.Sle2.Sle3 (TC) mice results in the secretion of autoantibodies. TC dendritic cells (DCs) enhance B cell proliferation and antibody secretion in a cytokine-dependent manner. However, the specific cytokine milieu by which TC DCs activate B cells was not known. In this study, we compared TC and C57BL/6 (B6) control for the distribution of DC subsets and for their production of cytokines affecting B cell responses. We show that TC DCs enhanced B cell proliferation through the production of IL-6 and IFN-γ, while antibody secretion was only dependent on IL-6. Pre-disease TC mice showed an expanded PDCA1+ cells prior to disease onset that was localized to the marginal zone and further expanded with age. The presence of PDCA1+ cells in the marginal zone correlated with a Type I Interferon (IFN) signature in marginal zone B cells, and this response was higher in TC than B6 mice. In vivo administration of anti-chromatin immune complexes upregulated IL-6 and IFN-γ production by splenic DCs from TC but not B6 mice. The production of BAFF and APRIL was decreased upon TC DC stimulation both in vitro and in vivo, indicating that these B cell survival factors do not play a role in B cell modulation by TC DCs. Finally, TC B cells were defective at downregulating IL-6 expression in response to anti-inflammatory apoptotic cell exposure. Overall, these results show that the TC autoimmune genetic background induces the production of B cell-modulating inflammatory cytokines by DCs, which are regulated by the microenvironment as well as the interplay between DC. [ABSTRACT FROM AUTHOR]

Nonresolving inflammatory processes affect all stages of carcinogenesis. Lactoferrin, a member of the transferrin family, is involved in the innate immune response and anti-inflammatory, anti-microbial, and anti-tumor activities. We previously found that lactoferrin is significantly down-regulated in specimens of nasopharyngeal carcinoma (NPC) and negatively associated with tumor progression, metastasis, and prognosis of patients with NPC. Additionally, lactoferrin expression levels are decreased in colorectal cancer as compared with normal tissue. Lactoferrin levels are also increased in the various phases of inflammation and dysplasia in an azoxymethane–dextran sulfate sodium (AOM-DSS) model of colitis-associated colon cancer (CAC). We thus hypothesized that the anti-inflammatory function of lactoferrin may contribute to its anti-tumor activity. Here we generated a new Lactoferrin knockout mouse model in which the mice are fertile, develop normally, and display no gross morphological abnormalities. We then challenged these mice with chemically induced intestinal inflammation to investigate the role of lactoferrin in inflammation and cancer development. Lactoferrin knockout mice demonstrated a great susceptibility to inflammation-induced colorectal dysplasia, and this characteristic may be related to inhibition of NF-κB and AKT/mTOR signaling as well as regulation of cell apoptosis and proliferation. Our results suggest that the protective roles of lactoferrin in colorectal mucosal immunity and inflammation-related malignant transformation, along with a deficiency in certain components of the innate immune system, may lead to serious consequences under conditions of inflammatory insult. [ABSTRACT FROM AUTHOR]

Background:Pulmonary tuberculosis (TB) patients often suffer from anorexia and poor nutrition, causing weight loss. The peptide hormones leptin and its counterpart ghrelin, acting in the regulation of food intake and fat utilization, play an important role in nutritional balance. This study aimed to investigate the association of blood concentrations of leptin, ghrelin and inflammatory cytokines with body mass index (BMI) in TB patients with and without type 2 diabetes mellitus (T2DM). Methods:BMI, biochemical parameters and plasma levels of leptin, ghrelin and inflammatory cytokines were measured before the start of treatment in 27 incident TB patients with T2DM, 21 TB patients and 23 healthy subjects enrolled in this study. Results:The levels of leptin were significantly higher in TB patients (35.2±19.1 ng/ml) than TB+T2DM (12.6±6.1 ng/ml) and control (16.1±11.1 ng/ml) groups. The level of ghrelin was significantly lower in TB (119.9±46.1 pg/ml) and non-significantly lower in TB+T2DM (127.7±38.6 pg/ml) groups than control (191.6±86.5 pg/ml) group. The levels of TNF-α were higher, while IFN-γ and IL-6 levels were lower in patients than in the control group. Leptin showed a negative correlation with BMI in TB (r=-0.622, p<0.05) and TB+T2DM (r= -0.654, p<0.05) groups, but a positive correlation with BMI in the control group (r=0.521, p<0.05). Contrary ghrelin showed a positive correlation with BMI in TB (r=0.695, p<0.05) and TB+T2DM (r= 0.199, p>0.05) groups, but negative correlation with BMI in the control (r=-0.693, p<0.05) group. Inflammatory cytokines were poorly correlated with BMI in this study. Only IFN-γ showed a significant negative correlation with BMI in the control group (r=-0.545, p<0.05). Conclusions:This study may suggest that possible abnormalities in ghrelin and leptin regulation (high levels of leptin and low levels of ghrelin) may be associated with low BMI and may account for the poor nutrition associated with TB and TB+T2DM. [ABSTRACT FROM AUTHOR]

Background: Natural drug resistance is a major cause of antiviral treatment failure. The characteristics of HIV-1 natural drug resistance-associated mutations in former paid blood donors in Henan Province remain unclear. Methods: One hundred and fifty HIV-1-positive plasma samples were collected. Plasma viral RNA was extracted for pol gene amplification and sequencing. The sequencing results were submitted to the HIV-1 drug resistance database for drug-resistance analysis. Results: The rates of natural drug resistance and resistance-associated mutations were 17.7% (19/107) and 40.2% (43/107), respectively. The rates of PI major, PI minor, NRTI, and NNRTI mutations were: 0, 30.8% (33/107), 10.3% (11/107), and 18.7% (20/107), respectively. Nine cases (8.4%) had both NRTI and NNRTI resistance-associated mutations. Seven cases (6.5%) had PI minor, NRTI and NNRTI resistance-associated mutations. NNRTI resistance was the most serious, followed by NRTI resistance and PI resistance. Polymorphism mutation sites with mutation rates in the protease region higher than 60.0% were: L63A/P/S/T 89.7%, V77I 82.2%, I72E/M/K/T/V 80.4%, I93L 75.7%, and E35D 72.9%. Polymorphism mutation sites with mutation rates in the RT region higher than 60.0% were: I135A/L/M/R/T/V 93.5%, T200A/E/I/P/V 89.7%, Q278E/K/N/T 88.8%, S162C/Y 82.2%, and K277R/S 66.4%. The distribution of 107 gene sequences was scattered, with some drug-resistant strains grouped in the same cluster. Conclusion: The natural drug resistance mutation rate of HIV-1 in former paid blood donors in Henan Province was 17.7%, with NNRTI resistance the most serious. The distribution of drug-resistant strains was scattered, with some correlations found in certain resistance loci. [ABSTRACT FROM AUTHOR]

Vasculature is an interface between the circulation and the hematopoietic tissue providing the means for hundreds of billions of blood cells to enter the circulation every day in a regulated fashion. The precise mechanisms that control the interactions of hematopoietic cells with the vessel wall are largely undefined. Here, we report on the development of an in vitro 3D human marrow vascular microenvironment (VME) to study hematopoietic trafficking and the release of blood cells, specifically platelets. We show that mature megakaryocytes from aspirated marrow as well as megakaryocytes differentiated in culture from CD34+ cells can be embedded in a collagen matrix containing engineered microvessels to create a thrombopoietic VME. These megakaryocytes continue to mature, penetrate the vessel wall, and release platelets into the vessel lumen. This process can be blocked with the addition of antibodies specific for CXCR4, indicating that CXCR4 is required for megakaryocyte migration, though whether it is sufficient is unclear. The 3D marrow VME system shows considerable potential for mechanistic studies defining the role of marrow vasculature in thrombopoiesis. Through a stepwise addition or removal of individual marrow components, this model provides potential to define key pathways responsible for the release of platelets and other blood cells. [ABSTRACT FROM AUTHOR]

To understand the mechanisms underlying the discordance between normal serum alanine aminotransferase (ALT) levels and significant alterations in liver histology of chronic hepatitis B virus (HBV) infection with persistent normal ALT (PNALT) or minimally elevated ALT. A total of 300 treatment-naive chronic HBV-infected patients with PNALT (ALT ≤ upper limit of normal [ULN, 40 U/ml]) or minimally elevated ALT (1-2×ULN) were retrospectively enrolled. All patients underwent liver biopsy and histological changes were analyzed along with biochemical and HBV markers. Among 300 participants, 177 were HBeAg-positive and 123 HBeAg-negative. Significant histologic abnormalities were found in 42.9% (76/177) and 52.8% (65/123) of HBeAg-positive and HBeAg-negative patients, respectively. Significant fibrosis, which is a marker of prior injury, was more frequently detected than significant necroinflammation (suggesting active liver injury) in both HBeAg-positive and -negative groups, suggesting that liver injury occurred intermittently in our cohort. No significant differences were noticed in the percentage of patients with severe fibrosis between HBeAg-positive and negative phases or between ages 30 and 40 and over 40, suggesting that the fibrosis was possibly carried over from an early phase. Finally, lowering ALT ULN (30 U/L for men, 19 U/L for women) alone was not adequate to increase the sensitivity of ALT detection of liver injury. However, the study was limited to a small sample size of 13 HBeAg-positive patients with ALT in the revised normal range. We detected significant liver pathology in almost 50% of chronic HBV infected patients with PNALT (ALT ≤ 40 U/ml) or minimally elevated ALT. We postulated that small-scale intermittent liver injury was possibly responsible for the discordance between normal serum ALT and significant liver changes in our cohort. [ABSTRACT FROM AUTHOR]

This research was intended to investigate the fetal origins of changed birth weight of the offspring born through assisted reproductive technology (ART). The association between hormone and lipid metabolism or body weight has been generally accepted, and as the basic and specific treatment in ART procedure, gonadotropin stimulation might have potential effects on intrauterine lipid metabolism. In our studies, the mice were superovulated with two doses of gonadotropin. The cholesterol metabolism in ovaries and the triglyceride metabolism in embryos were analyzed. The results showed gonadotropin probably accelerated luteinization and induced a longer time follicle development and ovulation, which resulted in histological and morphological alteration of ovary, and increased the cholesterol content and the expressions of steroidogenesis-related genes. In embryos, gonadotropin increased lipid accumulation and decreased fatty acid synthesis in a dose-dependent manner. Moreover, the changes of fatty acid composition were also shown in superovulation groups. Our studies firstly provided the evidence that the superovulation might affect the maternal and fetal lipid metabolism. These variations of lipid metabolism in our results may be associated with birth weight of ART infants. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether the genetic susceptibility of T2D was associated with overall survival (OS) and disease-free survival (DFS) outcomes for breast cancer (BC). Methods: Included in the study were 6346 BC patients who participated in three population-based epidemiological studies of BC and were genotyped with either GWAS or Exome-chip. We constructed a genetic risk score (GRS) for diabetes using risk variants identified from the GWAS catalog () that were associated with T2D risk at a minimum significance level of P ≤ 5.0E-8 among Asian population and evaluated its associations with BC outcomes with Cox proportional hazards models. Results: During a median follow-up of 8.08 years (range, 0.01–16.95 years), 1208 deaths were documented in 6346 BC patients. Overall, the diabetes GRS was not associated with OS and DFS. Analyses stratified by estrogen receptor status (ER) showed that the diabetes GRS was inversely associated with OS among women with ER- but not in women with ER+ breast cancer; the multivariable adjusted HR was 1.38 (95% CI: 1.05–1.82) when comparing the highest to the lowest GRS quartiles. The association of diabetes GRS with OS varied by diabetes status (P for interaction <0.01). In women with history of diabetes, higher diabetes GRS was significantly associated with worse OS, with HR of 2.22 (95% CI: 1.28–3.88) for the highest vs. lowest quartile, particularly among women with an ER- breast cancer, with corresponding HR being 4.59 (95% CI: 1.04–20.28). No significant association between the diabetes GRS and OS was observed across different BMI and PR groups. Conclusions: Our study suggested that genetic susceptibility of T2D was positively associated with total mortality among women with ER- breast cancer, particularly among subjects with a history of diabetes. Additional studies are warranted to verify the associations and elucidate the underlying biological mechanism. [ABSTRACT FROM AUTHOR]

Objective: The objective of this biomechanical study was to evaluate the stability provided by a newly developed shape memory alloy hook (SMAH) in a cadaveric transforaminal lumbar interbody fusion (TLIF) model. Methods: Six human cadaveric spines (L1-S2) were tested in an in vitro flexibility experiment by applying pure moments of ±8 Nm in flexion/extension, left/right lateral bending, and left/right axial rotation. After intact testing, a TLIF was performed at L4-5. Each specimen was tested for the following constructs: unilateral SMAH (USMAH); bilateral SMAH (BSMAH); unilateral pedicle screws and rods (UPS); and bilateral pedicle screws and rods (BPS). The L3–L4, L4–L5, and L5-S1 range of motion (ROM) were recorded by a Motion Analysis System. Results: Compared to the other constructs, the BPS provided the most stability. The UPS significantly reduced the ROM in extension/flexion and lateral bending; the BSMAH significantly reduced the ROM in extension/flexion, lateral bending, and axial rotation; and the USMAH significantly reduced the ROM in flexion and left lateral bending compared with the intact spine (p<0.05). The USMAH slightly reduced the ROM in extension, right lateral bending and axial rotation (p>0.05). Stability provided by the USMAH compared with the UPS was not significantly different. ROMs of adjacent segments increased in all fixed constructs (p>0.05). Conclusions: Bilateral SMAH fixation can achieve immediate stability after L4–5 TLIF in vitro. Further studies are required to determine whether the SMAH can achieve fusion in vivo and alleviate adjacent segment degeneration. [ABSTRACT FROM AUTHOR]

Background: A 7.0-magnitude earthquake hit Lushan County in China’s Sichuan province on April 20, 2013, resulting in 196 deaths and 11,470 injured. This study was designed to analyze the characteristics of the injuries and the treatment of the seismic victims. Methods: After the earthquake, an epidemiological survey of injured patients was conducted by the Health Department of Sichuan Province. Epidemiological survey tools included paper-and-pencil questionnaires and a data management system based on the Access Database. Questionnaires were completed based on the medical records of inpatients with earthquake-related injuries. Outpatients or non-seismic injured inpatients were excluded. A total of 2010 patients from 140 hospitals were included. Results: The most common type of injuries involved bone fractures (58.3%). Children younger than 10 years of age suffered fewer fractures and chest injuries, but more skin and soft -tissue injuries. Patients older than 80 years were more likely to suffer hip and thigh fractures, pelvis fractures, and chest injuries, whereas adult patients suffered more ankle and foot fractures. A total of 207 cases of calcaneal fracture were due to high falling injuries related to extreme panic. The most common type of infection in hospitalized patients was pulmonary infections. A total of 70.5% patients had limb dysfunction, and 60.1% of this group received rehabilitation. Most patients received rehabilitation within 1 week, and the median duration of rehabilitation was 3 weeks. The cause of death of all seven hospitalized patients who died was severe traumatic brain injuries; five of this group died within 24 h after the earthquake. Conclusions: Injuries varied as a function of the age of the victim. As more injuries were indirectly caused by the Lushan earthquake, disaster education is urgently needed to avoid secondary injuries. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated vitamin D status in association with modifiable lifestyle factors and clinical characteristics among breast cancer patients, with no studies among Chinese women, who may be at higher risk of vitamin D deficiency. We aimed to evaluate circulating 25-hydroxyvitamin D (25(OH)D) levels in association with clinical and lifestyle factors among 1,940 Chinese breast cancer patients. Methods: Participants included breast cancer cases aged 22–77 from a population-based case-control study conducted in Shanghai, China during 1996–1998 (n = 1,044) and 2002–2005 (n = 896). Circulating 25(OH)D levels were measured in plasma samples (95% collected ≤6 months post-diagnosis). Prevalence ORs and 95% CIs were derived from multinomial logistic regression models, adjusting for age, season, and other factors. Results: About 23% and 48% of women were vitamin D deficient (<30 nmol/L) or insufficient (30–50 nmol/L), respectively. Tumor characteristics were not associated with vitamin D status. Higher BMI was associated with increased odds of vitamin D deficiency (ORs (95% CIs): 1 (reference), 1.12 (0.85,1.47), and 1.57 (1.02,2.42), for <23, 23–<27.5, and ≥27.5 kg/m2, respectively, Ptrend <0.06). Total physical activity was associated with reduced odds of vitamin D deficiency (ORs (95% CIs):1 (reference), 0.84 (0.59,1.20), 0.65 (0.45,0.93), and 0.69 (0.48,1.00), for <7.65, 7.65–<10.6, 10.6–<13.5, ≥13.5 MET-hours/day, respectively, Ptrend <0.02). Smoking was associated with vitamin D insufficiency and deficiency (ORs (95% CIs): 2.50 (1.07,5.84) and 2.78 (1.11,6.95), respectively). Conclusions: In the largest study to date, the prevalence of low vitamin D status was high among Chinese breast cancer patients and associated with higher BMI, smoking, and lower physical activity. Our findings support careful monitoring of vitamin D status and recommendations for supplementation and other lifestyle modifications that may improve vitamin D status in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: To examine the characteristics of oxidative stress in patients with acute kidney injury (AKI) and investigate the association between plasma nitrotyrosine levels and 90-day mortality in patients with AKI. Methodology/Principal Findings: 158 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. Twelve critically ill patients without AKI and 15 age and gender-matched healthy subjects served as control. Plasma 3-nitrotyrosine was analyzed in relation to 90-day all cause mortality of patients with AKI. The patients with AKI were followed up for 90 days and grouped according to median plasma 3-nitrotyrosine concentrations. Highest 3-NT/Tyr was detected in patients with AKI compared with healthy subjects, and critically ill patients without AKI (ANOVA p<0.001). The 90-day survival curves of patients with high 3-NT/Tyr showed significant differences compared with the curves of individuals with low 3-NT/Tyr (p = 0.001 by log rank test). Multivariate analysis (Cox regression) revealed that 3-NT/Tyr (p = 0.025) was independently associated with mortality after adjustment for age, gender, sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Conclusions/Significance: There is excess plasma protein oxidation in patients with AKI, as evidenced by increased nitrotyrosine content. 3-NT/Tyr level was associated with mortality of AKI patients independent of the severity of illness. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is a devastating disease with dismal prognosis. Large population-based evidence on its survival rate and influence factors is lacking in China. Objective: This study aimed to depict the demographic factors, tumor characteristics, incidence rate and survival rate of pancreatic cancer cases in urban China. Methods: The demographic factors, tumor characteristics were collected for all the pancreatic cancer cases identified during 2004 to 2009 from the Shanghai Cancer Registry. The survival time was ascertained through linkage of the Shanghai Cancer Registry and the Shanghai Vital Statistics Registry. The deadline of death certificates was the end of December 2012. Kaplan-Meier method and Cox proportional-hazards regression model were used to explore the survival rate and influence factors. Results: 11,672 new pancreatic cancer cases were identified among Shanghai residency during 2004 to 2009. The crude incidence rate of pancreatic cancer was increasing from 12.80/100,000 in 2004 to 15.66/100,000 in 2009, while the standardized incidence rate was about 6.70/100,000 and didn't change a lot. The overall 5-year survival rate was 4.1% and the median survival time was 3.9 (95% Confidence Interval (CI) 3.8–4.0) months. Subjects had received surgical resection had improved survival (HR  = 0.742, 95% CI: 0.634–0.868) than its counterparts. In adjusted multivariable Cox proportional-hazard models, factors associated with poor survival included older age at diagnosis (age > = 70 years: hazard ratio (HR)  = 1.827, 95% CI: 1.614–2.067), male sex (HR  = 1.155, 95% CI: 1.041–1.281), distant disease at diagnosis (HR =  1.257, 95% CI: 1.061–1.488), positive lymph node (HR  = 1.236, 95% CI: 1.085–1.408), tumor stage (Stage IV HR  = 2.817, 95% CI: 2.029–3.909). Conclusion: The age-adjusted incidence rate was stable and overall survival rate was low among pancreatic cancer patients of Shanghai residency. Early detection and improved treatment strategies are needed to improve prognosis for this deadly disease. [ABSTRACT FROM AUTHOR]

The brain activity induced by heroin-related cues may play a role in the maintenance of heroin dependence. Whether the reinforcement or processing biases construct an everlasting feature of heroin addiction remains to be resolved. We used an event-related fMRI paradigm to measure brain activation in response to heroin cue-related pictures versus neutral pictures as the control condition in heroin-dependent patients undergoing short-term and long-term abstinence. The self-reported craving scores were significantly increased after cue exposure in the short-term abstinent patients (t = 3.000, P = 0.008), but no increase was found in the long-term abstinent patients (t = 1.510, P = 0.149). However, no significant differences in cue-induced craving changes were found between the two groups (t = 1.193, P = 0.850). Comparing between the long-term abstinence and short-term abstinence groups, significant decreases in brain activation were detected in the bilateral anterior cingulated cortex, left medial prefrontal cortex, caudate, middle occipital gyrus, inferior parietal lobule and right precuneus. Among all of the heroin dependent patients, the abstinence duration was negatively correlated with brain activation in the left medial prefrontal cortex and left inferior parietal lobule. These findings suggest that long-term abstinence may be useful for heroin-dependent patients to diminish their saliency value of heroin-related cues and possibly lower the relapse vulnerability to some extent. [ABSTRACT FROM AUTHOR]

Background: Several studies have indicated that CYP2C19 loss-of-function polymorphisms have a higher risk of stent thrombosis (ST) after percutaneous coronary interventions (PCIs). However, this association has not been investigated thoroughly in a Chinese population. In this study, we aimed to determine the effect of CYP2C19*2 and CYP2C19*3 loss-of-function polymorphisms on the occurrence of ST and other adverse clinical events in a Chinese population. Methods: We designed a cohort study among 1068 consecutive patients undergoing intracoronary stent implantation after preloading with 600 mg of clopidogrel. CYP2C19*2 and CYP2C19*3 were genotyped by using polymerase chain reaction-restriction fragment length polymorphism analysis. The adverse clinical events recorded were ST, death, myocardial infarction (MI), and bleeding events. The primary end point of the study was the incidence of cumulative ST within 1 year after PCI. The secondary end point was other adverse clinical outcomes 1 year after the procedure. Results: The cumulative 1-year incidence of ST was 0.88% in patients with extensive metabolizers (EMs) (CYP2C19*1/*1 genotype), 4.67% in patients with intermediate metabolizers (IMs) (CYP2C19*1/*2 or *1/*3 genotype), and 10.0% in patients with poor metabolizers (PMs) (CYP2C19*2/*2, *2/*3, or *3/*3 genotype) (P<0.001). The one-year event-free survival was 97.8% in patients with EMs, 96.5% in patients with IMs, and 92.0% in patients with PMs (P = 0.014). Multivariate analysis confirmed the independent association of CYP2C19 loss-of-function allele carriage with ST (P = 0.009) and total mortality (P<0.05). Conclusion: PM patients had an increased risk of ST, death, and MI after coronary stent placement in a Chinese population. [ABSTRACT FROM AUTHOR]

Background: Age at natural menopause (ANM) is a complex trait with high heritability and is associated with several major hormonal-related diseases. Recently, several genome-wide association studies (GWAS), conducted exclusively among women of European ancestry, have discovered dozens of genetic loci influencing ANM. No study has been conducted to evaluate whether these findings can be generalized to Chinese women. Methodology/Principal Findings: We evaluated the index single nucleotide polymorphisms (SNPs) in 19 GWAS-identified genetic susceptibility loci for ANM among 3,533 Chinese women who had natural menopause. We also investigated 3 additional SNPs which were in LD with the index SNP in European-ancestry but not in Asian-ancestry populations. Two genetic risk scores (GRS) were calculated to summarize SNPs across multiple loci one for all SNPs tested (GRSall), and one for SNPs which showed association in our study (GRSsel). All 22 SNPs showed the same association direction as previously reported. Eight SNPs were nominally statistically significant with P≤0.05: rs4246511 (RHBDL2), rs12461110 (NLRP11), rs2307449 (POLG), rs12611091 (BRSK1), rs1172822 (BRSK1), rs365132 (UIMC1), rs2720044 (ASH2L), and rs7246479 (TMEM150B). Especially, SNPs rs4246511, rs365132, rs1172822, and rs7246479 remained significant even after Bonferroni correction. Significant associations were observed for GRS. Women in the highest quartile began menopause 0.7 years (P = 3.24×10−9) and 0.9 years (P = 4.61×10−11) later than those in the lowest quartile for GRSsel and GRSall, respectively. Conclusions: Among the 22 investigated SNPs, eight showed associations with ANM (P<0.05) in our Chinese population. Results from this study extend some recent GWAS findings to the Asian-ancestry population and may guide future efforts to identify genetic determination of menopause. [ABSTRACT FROM AUTHOR]

Background: The formation of compulsive pattern of drug use is related to abnormal regional neural activity and functional reorganization in the heroin addicts’ brain, but the relationship between heroin-use-induced disrupted local neural activity and its functional organization pattern in resting-state is unknown. Methodology/Principal Findings: With fMRI data acquired during resting state from 17 male heroin dependent individuals (HD) and 15 matched normal controls (NC), we analyzed the changes of amplitude of low frequency fluctuation (ALFF) in brain areas, and its relationship with history of heroin use. Then we investigated the addiction related alteration in functional connectivity of the brain regions with changed ALFF using seed-based correlation analysis. Compared with NC, the ALFF of HD was obviously decreased in the right caudate, right dorsal anterior cingulate cortex (dACC), right superior medial frontal cortex and increased in the bilateral cerebellum, left superior temporal gyrus and left superior occipital gyrus. Of the six regions, only the ALFF value of right caudate had a negative correlation with heroin use. Setting the six regions as “seeds”, we found the functional connectivity between the right caudate and dorsolateral prefrontal cortex (dlPFC) was reduced but that between the right caudate and cerebellum was enhanced. Besides, an abnormal lateral PFC-dACC connection was also observed in HD. Conclusions: The observations of dysfunction of fronto-striatal and fronto-cerebellar circuit in HD implicate an altered balance between local neuronal assemblies activity and their integrated network organization pattern which may be involved in the process from voluntary to habitual and compulsive drug use. [ABSTRACT FROM AUTHOR]

Optical microangiography (OMAG) and Doppler optical microangiography (DOMAG) are two non-invasive techniques capable of determining the tissue microstructural content, microvasculature angiography, and blood flow velocity and direction. These techniques were used to visualize the acute and chronic microvascular and tissue responses upon an injury in vivo. A tissue wound was induced using a 0.5 mm biopsy punch on a mouse pinna. The changes in the microangiography, blood flow velocity and direction were quantified for the acute (<30 min) wound response and the changes in the tissue structure and microangiography were determined for the chronic wound response (30 min–60 days). The initial wound triggered recruitment of peripheral capillaries, as well as redirection of main arterial and venous blood flow within 3 min. The complex vascular networks and new vessel formation were quantified during the chronic response using fractal dimension. The highest rate of wound closure occurred between days 8 and 22. The vessel tortuosity increased during this time suggesting angiogenesis. Taken together, these data signify that OMAG has the capability to track acute and chronic changes in blood flow, microangiography and structure during wound healing. The use of OMAG has great potential to improve our understanding of vascular and tissue responses to injury in order to develop more effective therapeutics. [ABSTRACT FROM AUTHOR]

Menopausal symptoms have been suggested to be an indicator of better prognosis among patients treated for breast cancer, because women who experience these symptoms usually have a lower level of estrogen. We tested this hypothesis in a population-based, prospective cohort study involving 4,842 women with stage 0 to III primary breast cancer who were enrolled in the Shanghai Breast Cancer Survival Study between March 2002 and April 2006, were aged 20 to 75 years, and were recruited 6 months post-diagnosis. They were followed-up by in-person surveys and record linkages with the vital statistics registry. Cox regression analysis was used to evaluate the association of menopausal symptoms at baseline with breast cancer recurrence. Approximately 56% of patients experienced at least one menopausal symptom, including hot flashes, night sweats, and/or vaginal dryness at baseline. During a median follow-up period of 5.3 years, 720 women had a recurrence. Experiencing hot flashes or having ≥2 menopausal symptoms was associated with lower risk of recurrence among premenopausal women (hazard ratio [HR]=0.77, 95% confidence interval [CI]: 0.62-0.96 for hot flashes; 0.73, 0.56-0.96 for ≥2 menopausal symptoms). Lower recurrence risk in relation to hot flashes was also observed among women who were not overweight/obese (HR=0.78, 95% CI: 0.64-0.99), those with relatively low waist-to-hip ratio (WHR) (HR=0.77, 95% CI: 0.61-0.97), and those who used tamoxifen (HR=0.75, 95% CI: 0.58-0.98). Consistently experiencing multiple menopausal symptoms was associated with lower recurrence risk among women with low WHR or who used tamoxifen. This large, population-based cohort study of women with breast cancer confirms that experiencing menopausal symptoms is an indicator of favorable breast cancer prognosis. [ABSTRACT FROM AUTHOR]