Associations between whole grains intake and new-onset hypertension: a prospective cohort study.

IMPORTANCE: Epidemiological evidences regarding the association between whole grain intake and the risk of new-onset hypertension are still controversial. OBJECTIVE: We aimed to investigate the relationship between whole grain intake and new-onset hypertension and examine possible effect modifiers in the general population. METHODS: A total of 10,973 participants without hypertension from the China Health and Nutrition Survey were enrolled, with follow-up beginning in 1997 and ending in 2015. Whole grain intake was assessed by 3 consecutive 24-h dietary recalls combined with a household food inventory. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression model after adjusting for potential risk factors. RESULTS: During a median follow-up of 7.0 years, 3,733 participants developed new-onset hypertension. The adjusted HRs (95% CIs) were as follows: for quartile 2 (HR: 0.52; 95% CI: 0.47-0.57), quartile 3 (HR: 0.46; 95% CI: 0.42-0.51), and quartile 4 (HR: 0.35; 95% CI: 0.31-0.38), compared with quartile 1. Different types of whole grain types, including wheat (adjusted HR, 0.35; 95% CI, 0.32-0.39), maize (adjusted HR, 0.50; 95% CI, 0.42-0.59), and millet (adjusted HR, 0.38; 95% CI, 0.30-0.48), showed significant associations with a reduced risk of hypertension. The association between whole grain intake and new-onset hypertension was stronger in individuals with older age (P for interaction < 0.001) and higher BMI (P for interaction < 0.001). CONCLUSION: Higher consumption of whole grains was significantly associated with a lower risk of new-onset hypertension. This study provides further evidence supporting the importance of increasing whole grain intake for hypertension prevention among Chinese adults.

Long-term air pollutants exposure and respiratory mortality: A large prospective cohort study.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Association between Whole Grain Intake and Chronic Kidney Disease.

BACKGROUND: The relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. OBJECTIVE: This study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. METHODS: The present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the dose‒response relationship between whole grain and risk of CKD. RESULTS: A total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. CONCLUSIONS: Increased whole grain intake was associated with a decreased risk of CKD in Chinese adults.

Long-term air pollution exposure, habitual physical activity, and incident chronic kidney disease.

Both air pollution and physical inactivity contribute to the increased risk of incident chronic kidney disease (CKD). However, the detrimental effects of air pollution exposure could be augmented by an elevated intake of air pollutants during exercise. In the present study, we analyzed 367,978 participants who were CKD-free at baseline (2006-2010) based on the UK Biobank. Air pollutants included fine particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX). Physical activity (PA) was obtained by the self-reported questionnaire. Using Cox proportional hazards models, hazard ratios (HRs) for incident CKD related to air pollution, PA, and incident CKD were evaluated. During a median of 12.4 years of follow-up, 14,191 incident CKD events were documented. High PM2.5, PM10, NO2, and NOX increased CKD risks by 11 %, 15 %, 14 %, and 12 %, respectively, while moderate and high PA reduced CKD risks by 18 % and 22 %, respectively. Participants with high PA and low air pollution exposure had 29 %, 31 %, 30 %, and 30 % risks of incident CKD than those with low PA and high air pollution exposure for the four air pollutants, with multivariable-adjusted HRs of 0.71 (95 % confidence intervals [CI]: 0.65-0.76) for PM2.5, 0.69 (95 % CI: 0.64-0.75) for PM10, 0.70 (95 % CI: 0.64-0.75) for NO2, and 0.70 (95 % CI: 0.64-0.75) for NOX. No clear interactions were observed between each air pollutant exposure and PA (all P for interaction > 0.05). The findings that reducing air pollution exposure and increasing PA were both independently correlated with a diminished risk of incident CKD suggest that PA could be targeted to prevent CKD generally regardless of air pollution levels. Further research is needed in areas polluted moderately and severely to examine our findings.

[Distribution and Risk Assessment of OCPs in Surface Water, Sediments, and Fish from Lake Gucheng and Inflow and Outflow Rivers].

To investigate the distribution, source, and ecological risk of organochlorine pesticides (OCPs) residues in Lake Gucheng, surface water, sediment, and biological samples were collected from 12 sampling sites of Lake Gucheng and its inlets and outlets during summer and winter, and the concentrations of 19 OCPs were analyzed. The results showed that the concentration (dry weight) of OCPs in Lake Gucheng ranged from 26.74 to 48.12 ng·L-1 in surface water, 9.01 to 35.34 ng·g-1 in sediment, and 13.39 to 124.29 ng·g-1 in organisms. The pollution characteristics of OCPs in surface water showed that the concentration was much higher in summer than in winter, and much higher at inflow and outflow rivers than in farming ponds and the central region of Lake Gucheng; the seasonal pollution characteristics in sediment were not obvious. All 19 kinds of OCPs in water, sediment, and organisms were detected in different degrees, and the dominant contaminants were HCHs and DDTs. α-HCH was the main pollutant at all sites in both surface water and sediment, with 21% to 42% of total HCHs in two seasons. p,p'-DDD was the main pollutant in surface water with 30% to 76% of total DDTs, whereas p,p'-DDT was the main pollutant in sediment with 68% to 93% of total DDTs in two seasons. Source analysis based on ratios of HCHs isomers and DDTs isomers indicated that there was a new input of OCPs under anaerobic conditions in the study area. The ecological risk assessment showed that the OCPs in surface water did not lead to significant health risks, but the OCPs in sediments might pose ecological risks to the Lake Gucheng ecosystem. The organisms were within the acceptable potential carcinogenic risk range.

MG-132 treatment promotes TRAIL-mediated apoptosis in SEB-1 sebocytes.

AIMS: This study aimed to identify the mechanism of how MG-132 stimulates cell death in SEB-1 sebocytes. MATERIALS AND METHODS: TUNEL staining and annexin-FITC/PI flow cytometry were utilized to examine the apoptotic cell number of SEB-1 sebocytes and HaCaT keratinocytes upon MG-132 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment. MTT assay and CCK-8 assay monitored the proliferative rate and viability of both cell lines with different treatment. Western blotting (WB) and qPCR were performed to detect the expression of TRAIL and members of Bcl-2 family at protein and gene level. Additionally, RNA interfering was used to knockdown the mRNA transcription of TRAIL and BIK gene. KEY FINDINGS: MG-132 treatment enhanced cell death in SEB-1 sebocytes but not in HaCaT keratinocytes. Meanwhile, TRAIL concentrations in SEB-1 sebocytes treated with MG-132 were markedly elevated. Furthermore, treatment with TRAIL or the TRAIL receptor-specific monoclonal antibody AY4 at various doses stimulated cell death in SEB-1 sebocytes in a time- and dose-dependent manner. Silencing of TRAIL restored the cell viability of SEB-1 cells to a normal level after MG-132 treatment. Combined treatment of SEB-1 sebocytes with TRAIL and MG-132 synergistically triggered cell death, suppressed cell proliferation and survival, and promoted BIK expression. Furthermore, BCL2 Interacting Killer (BIK) knockdown via RNA interference participated in the recovery of cell survival reduced by treatment with TRAIL and MG-132. SIGNIFICANCE: These findings suggest that treatment with the selective proteasome suppressor MG-132 and TRAIL induces cell death in sebocytes through upregulation of BIK, a member of the Bcl-2 family.

miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2).

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. MicroRNAs (miRNAs) have been indicated as crucial actors in cancer biology. Accumulating evidence suggests that miRNAs can be used as diagnostic and prognostic markers for NSCLC. METHODS: The purpose of this study was to characterize and identify the novel biomarker miR-4317 and its targets in NSCLC. The expression of miR-4317 was analyzed by in situ hybridization (ISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of miR-4317 on proliferation was evaluated through 3-4,5-dimethylthiazol-2-yl-5-3-carboxymethoxyphenyl-2-4-sulfophenyl-2H-tetrazolium (MTS) and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by qRT-PCR and western blot. Dual-luciferase reporter assay was used to assess the target genes of miR4317 in NSCLC cells. RESULTS: Our results demonstrated that miR-4317 was downregulated in NSCLC tissues and serum, particularly in lymph node metastasis and advanced clinical stage tissues. Kaplan-Meier survival analysis showed that NSCLC patients with high expression of miR-4317 exhibited better overall survival (OS). Enhanced expression of miR-4317 significantly inhibited proliferation, colony formation, migration and invasion, and hampered cycles of NSCLC cell lines in vitro. Our results suggested that miR-4317 functions by directly targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2). In concordance with in vitro studies, mouse xenograft, lung, and brain metastatic studies validated that miR-4317 functions as a potent suppressor miRNA of NSCLC in vivo. Systemically delivered agomiR-4317 reduced tumor growth and inhibited FGF9 and CCND2 protein expression. Reintroduction of FGF9 and CCND2 attenuated miR-4317-mediated suppression of migration and invasion in NSCLC. CONCLUSIONS: Our results indicate that miR-4317 can reduce NSCLC cell growth and metastasis by targeting FGF9 and CCND2. These findings provide new evidence of miR-4317 as a potential non-invasive biomarker and therapeutic target for NSCLC.

Cytokine and soluble adhesion molecule profiles and biomarkers for treatment monitoring in Re-treated smear-positive patients with pulmonary tuberculosis.

Relapse of pulmonary tuberculosis (PTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis. Severe immunodeficiency or immune disorders may be the main reason for TB recurrence. This study aimed to quantify serum inflammatory cytokine and soluble adhesion molecule levels in Re-treated smear-positive PTB patients before and after re-anti-TB drug therapy. Serum samples were collected from 30 healthy controls and 215 Treated active PTB patients at baseline and 2, 4, and 6 months post-re-treatment. Levels of 18 serum cytokines and soluble adhesion molecules were measured by a high-throughput Cytometric Bead Array. At baseline, IL-1, IL-2, IL-12P70, and soluble CD62E levels were significantly higher in PTB patients than those in the healthy controls (p < 0.05); IL-4, IL-5, IL-7, IL-8, IL-10, IL-17, IL-21, soluble CD54, MIG, and TGF-ß levels in PTB patients were significantly lower than those in the healthy controls (p < 0.05), of which TGF-ß, IL-7, IL-8, IL-10, soluble CD54, and MIG were most notably (p < 0.0005). After re-treatment, IFN-γ, IL-2, IL-7, and soluble CD54 levels and IL-2/IL-10 and IFN-γ/IL-10 ratios showed an upward trend during the re-treatment period. They were more sensitive than other cytokines and adhesion molecules and could be effective as serum indicators for re-treatment response. The immune response was imbalance in treated smear-positive PTB patients: Th1 response was elevated, but Th2 and Th17 responses were reduced. Systematic and comprehensive understanding of the cytokine and soluble adhesion molecule profiles provides a theoretical basis for immuno-diagnosis, immunotherapy, and immuno-monitoring of Re-treated PTB patients.

miR-339-5p downregulation contributes to Taxol resistance in small-cell lung cancer by targeting α1,2-fucosyltransferase 1.

Lung cancer is a leading cause of cancer-related mortality, and non-small-cell lung carcinoma is responsible for almost 80% of lung cancer-related deaths. In recent years, lung cancer has shown increasing incidence but poor prognosis, and many studies have demonstrated that microRNAs play crucial roles in the development of lung carcinoma and chemoresistance. This study investigated the role of miR-339-5p involvement in lung carcinoma cell lines and chemoresistance to Taxol. We observed that miR-339-5p was significantly downregulated in Taxol-A549 cells compared with A549 cells. In vitro studies further indicated that miR-339-5p could promote colony formation and attenuate apoptosis of lung carcinoma cell lines through targeting α1,2-fucosyltransferase 1 and regulation of the downstream protein Lewis y. Furthermore, miR-339-5p was found to enhance the proliferation inhibition ability of Taxol in lung carcinoma cell lines as well as in the Taxol-A549 subclone. An in vivo study indicated that both miR-339-5p and Taxol could attenuate the growth of lung carcinoma; moreover, miR-339-5p could synergistically promote this inhibitory function of Taxol. In summary, our results suggest a miR-339-5p molecular network that is involved in controlling lung carcinoma progression. © 2017 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 69(11):841-849, 2017.

Overexpressing IbCBF3 increases low temperature and drought stress tolerance in transgenic sweetpotato.

Dehydration-responsive element-binding/C-repeat-binding factor (DREB/CBF) proteins regulate the transcription of genes involved in cold acclimation in several species. However, little is known about the physiological functions of CBF proteins in the low temperature-sensitive crop sweetpotato. We previously reported that the DREB1/CBF-like sweetpotato gene SwDREB1/IbCBF3 is involved in responses to diverse abiotic stresses. In this study, we confirmed that IbCBF3 is localized to the nucleus and binds to the C-repeat/dehydration-responsive elements (CRT/DRE) in the promoters of cold-regulated (COR) genes. We generated transgenic sweetpotato plants overexpressing IbCBF3 under the control of the CaMV 35S promoter (referred to as SC plants) and evaluated their responses to various abiotic stresses. IbCBF3 expression was dramatically induced by cold and drought but much less strongly induced by high salinity and ABA. We further characterized two SC lines (SC3 and SC6) with high levels of IbCBF3 transcript. The SC plants displayed enhanced tolerance to cold, drought, and oxidative stress on the whole-plant level. Under cold stress treatment (4 °C for 48 h), severe wilting and chilling injury were observed in the leaves of wild-type (WT) plants, whereas SC plants were not affected by cold stress. In addition, the COR genes were significantly upregulated in SC plants compared with the WT. The SC plants also showed significantly higher tolerance to drought stress than the WT, which was associated with higher photosynthesis efficiency and lower hydrogen peroxide levels. These results indicate that IbCBF3 is a functional transcription factor involved in the responses to various abiotic stresses in sweetpotato.

[Efficacy Comparison of Different Salvage Treatment Regimens for Patients with Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively. According to the treatment regimens, 156 patients were divided into MAC group (n=60), FLAG group (n=45) and CAG group (n=51). The complete remission(CR), partial remissison(PR), overall survival(OS), disease-free survival(DFS) and adverse events during the treatment were analyzed, so as to compare and evaluate the efficacy and safety of the 3 different regimens. RESULTS: After 1 course of re-induction chemotherapy, CR in MAC group was significantly higher than that in FLAG and CAG group (55.4% vs 34.1% vs 34.0%)(P<0.05). The OS was not statistically significantly different among 3 groups (P>0.05) with a median OS of 11 months, 5.46 months and 10.2 months, respectively. The myelosuppression was the main adverse event with no significant difference among the groups(P>0.05). More patients treated with MAC regimen underwent febrile neutropenia (93.3% vs 86.7% vs 64.7%)(P<0.001). However, the incidence of fatal infections was not signicantly different among 3 groups(5% vs 8.9% vs 5.9%)(P>0.05). CONCLUSION: Compared with FLAG and CAG regimen, the MAC regimen can enable more AML patients with primary induction failure and refractory to achieve CR without increasing severe adverse events,therefore,this regimen may provide a opportunity for patients to recieve hematopoietic stem cell transplantation.

[Effects of long-term fertilization on soil fertility in yellow fluvo-aquic soil]. / 长期不同施肥方式对黄潮土肥力特征的影响.

Based on the long-term field fertilization experiment in yellow fluvo-aquic soil, this study selected 2 types of soil physical, 8 items of soil chemical, and 5 soil biological properties for principal component-cluster analysis to valuate comprehensively effects of long-term fertilization on soil fertility. Results showed that significant differences of soil properties were found among the fertilization treatments. Compared with no organic manure treatment (NPK), all treatments of organic manure (M) or its combination with inorganic fertilizers (MN, MNP, MNPK) significantly reduced soil bulk density, and increased soil total porosity, the contents of soil organic carbon, total nitrogen, alkali-hydrolyzable nitrogen, available phosphorus, microbial biomass, and activities of catalase, urease, alkaline phosphatase and invertase. Two principal components that could reflect 85.5% of the original information quantity without losing any original variables were extracted from the initial 15 indices. Within the primary group of principal components, bulk density, total porosity, organic matter, total nitrogen, alkali-hydrolyzable nitrogen, total phosphorous, available phosphorus, available potassium,microbial biomass, catalase, urease, alkaline phosphatase and inver-tase were the major contributors, while among the secondary group of principal components, total potassium and pH were the major ones. Hierarchical cluster analysis of the new indices extracted based on scores of the two principal components revealed the effects of different patterns of long-term fertilization displayed an order of MNPK＞MNP＞M, MN＞NPK＞N, NP＞CK. In conclusion, organic fertilizer has the positive effect on improving soil fertility, and combined application of organic and N, P, K fertilizer is the best fertilizing model.

Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study.

BACKGROUND: Extranodal natural killer T-cell lymphoma (NKTCL), nasal type, is a rare and aggressive malignancy that occurs predominantly in Asian and Latin American populations. Although Epstein-Barr virus infection is a known risk factor, other risk factors and the pathogenesis of NKTCL are not well understood. We aimed to identify common genetic variants affecting individual risk of NKTCL. METHODS: We did a genome-wide association study of 189 patients with extranodal NKTCL, nasal type (WHO classification criteria; cases) and 957 controls from Guangdong province, southern China. We validated our findings in four independent case-control series, including 75 cases from Guangdong province and 296 controls from Hong Kong, 65 cases and 983 controls from Guangdong province, 125 cases and 1110 controls from Beijing (northern China), and 60 cases and 2476 controls from Singapore. We used imputation and conditional logistic regression analyses to fine-map the associations. We also did a meta-analysis of the replication series and of the entire dataset. FINDINGS: Associations exceeding the genome-wide significance threshold (p<5 × 10(-8)) were seen at 51 single-nucleotide polymorphisms (SNPs) mapping to the class II MHC region on chromosome 6, with rs9277378 (located in HLA-DPB1) having the strongest association with NKTCL susceptibility (p=4·21 × 10(-19), odds ratio [OR] 1·84 [95% CI 1·61-2·11] in meta-analysis of entire dataset). Imputation-based fine-mapping across the class II MHC region suggests that four aminoacid residues (Gly84-Gly85-Pro86-Met87) in near-complete linkage disequilibrium at the edge of the peptide-binding groove of HLA-DPB1 could account for most of the association between the rs9277378*A risk allele and NKTCL susceptibility (OR 2·38, p value for haplotype 2·32 × 10(-14)). This association is distinct from MHC associations with Epstein-Barr virus infection. INTERPRETATION: To our knowledge, this is the first time that a genetic variant conferring an NKTCL risk is noted at genome-wide significance. This finding underlines the importance of HLA-DP antigen presentation in the pathogenesis of NKTCL. FUNDING: Top-Notch Young Talents Program of China, Special Support Program of Guangdong, Specialized Research Fund for the Doctoral Program of Higher Education (20110171120099), Program for New Century Excellent Talents in University (NCET-11-0529), National Medical Research Council of Singapore (TCR12DEC005), Tanoto Foundation Professorship in Medical Oncology, New Century Foundation Limited, Ling Foundation, Singapore National Cancer Centre Research Fund, and the US National Institutes of Health (1R01AR062886, 5U01GM092691-04, and 1R01AR063759-01A1).

[Preliminary Clinical Efficiency of Autologous Peripheral Blood Mononuclear Cells for Treating Critical Limb Ischemia of Thromboangiitis Obliterans].

OBJECTIVE: To evaluate the long-term clinical effect of autologous peripheral blood mononuclear cells (PB-MNC) on critical limb ischemia (CLI) in patients with thromboangiitis obliterans (TAO) patients. METHODS: The clinical data of 22 patients with CLI caused by TAO from July 2004 to May 2013 were analyzed retrospectively, 22 patients were divided into 2 groups; out of them 12 cases in one group were treated with granulocyte colony-stimulating factor (G-CSF)-mobilized autologous peripheral blood mononuclear cells (auto-PBMNC group), 10 cases in another group received conservative treatment (CT group). The log-rank test was used to compare the long-term outcomes in auto-PBMNC group and CT group. RESULTS: The wound healing rate (P=0.016) and CLI-free rate (P=0.013) were significantly higher in PB-MNC group compared with that in CT group. No difference was found in amputation rates between the 2 groups (major amputation: P=0.361, minor and major amputation: P=0.867). No patients died or no serious adverse events occurred during the follow-up period. CONCLUSION: The auto-PBMNC therapy can significantly promote the wound healing, and protect against CLI in TAO patients, but the risk of amputation is not low in comparison with conservative treatment.

Testin on Atherosclerosis in Rabbits.

BACKGROUND: The expression of TES, a novel tumor suppressor gene, is found to be down-regulated in the left anterior descending aorta of patients with coronary artery disease (CAD) compared with non-CAD subjects. This study aimed to investigate the expression of TES during the development of atherosclerosis in rabbits. METHODS: Thirty-two New Zealand rabbits were randomly divided into a normal diet (ND) and high-fat diet (HFD) groups. Body weight and serum lipid levels were measured at 0, 4, and 12 weeks after diet treatment. The degree of atherosclerosis in thoracic aortas was analyzed by histological examinations. The expression of Testin in the tissue samples was inspected via immunohistochemical and immunofluorescence confocal microscopy. Real time-polymerase chain reaction and Western blot analysis were performed to evaluate the expression of TES/Testin at mRNA and protein levels in the aortic tissues. RESULTS: After 12 weeks postenrollment, rabbits in HFD group had a higher level of serum lipids and atherosclerotic plaque compared to ND group (P < 0.05). Testin expression was detected at high levels in the endothelium and a weak expression on the subendothelium area. The expression of TES mRNA was markedly reduced by 10-fold in the aortic tissues in the HFD group compared with the ND group (P = 0.015), and the protein level was also significantly decreased in the HFD group (P < 0.05). CONCLUSIONS: Reduced TES/Testin expression is associated with the development of atherosclerosis, implicating a potentially important role in the pathogenesis of atherosclerosis.

Molecular epidemiology and clinical characteristics of drug-resistant Mycobacterium tuberculosis in a tuberculosis referral hospital in China.

BACKGROUND: Despite the large number of drug-resistant tuberculosis (TB) cases in China, few studies have comprehensively analyzed the drug resistance-associated gene mutations and genotypes in relation to the clinical characteristics of M. tuberculosis (Mtb) isolates. METHODOLOGY/PRINCIPAL FINDINGS: We thus analyzed the phenotypic and genotypic drug resistance profiles of 115 Mtb clinical isolates recovered from a tuberculosis referral hospital in Beijing, China. We also performed genotyping by 28 loci MIRU-VNTR analysis. Socio-demographic and clinical data were retrieved from medical records and analyzed. In total, 78 types of mutations (including 42 previously reported and 36 newly identified ones) were identified in 115 Mtb clinical isolates. There was significant correlation between phenotypic and genotypic drug resistance rates for first-line anti-TB drugs (P<0.001). Genotyping revealed 101 MIRU-VNTR types, with 20 isolates (17.4%) being clustered and 95 isolates (82.6%) having unique genotypes. Higher proportion of re-treatment cases was observed among patients with clustered isolates than those with unique MIRU-VNTR genotypes (75.0% vs. 41.1%). Moreover, clinical epidemiological links were identified among patients infected by Mtb strains belonging to the same clusters, suggesting a potential of transmission among patients. CONCLUSIONS/SIGNIFICANCE: Our study provided information on novel potential drug resistance-associated mutations in Mtb. In addition, the genotyping data from our study suggested that enforcement of the implementation of genotyping in diagnostic routines would provide important information for better monitor and control of TB transmission.

Secretory breast carcinoma in a 12-year-old girl: A case report.

Secretory breast carcinoma (SBC) is a rare tumor that was originally described in children and adolescent women, with a characteristic morphology and controversy regarding the choice of treatment. This unusual breast cancer subtype generally has a favorable prognosis, although several cases have been described in adults with increased tumor aggressiveness and a risk of metastases. Surgery is considered the most appropriate treatment for this pathology. The present study describes the case of a 12-year-old female who presented with a painless lump in the left breast, and subsequently underwent a biopsy of the sentinel lymph node and a partial resection of the left breast (breast-conserving therapy). Periodic follow-up examinations after completion of the surgical and chemotherapeutic treatment have shown no evidence of either local regression or distant metastases and, one year later, the patient remains free of the disease. This study suggests that local excision with sentinel lymph node mapping may be a suitable therapeutic approach for children with SBC.

A comparison of loop-mediated isothermal amplification (LAMP) with other surveillance tools for Echinococcus granulosus diagnosis in canine definitive hosts.

BACKGROUND: Cystic echinococcosis is highly prevalent in northwest China. A cost-effective, easy to operate diagnostic tool with high sensitivity and specificity would greatly facilitate the monitoring of Echinococcus infections in canine definitive hosts. METHODS: The primers used in the LAMP assay were based on the mitochondrial nad5 gene of E. granulosus sensu stricto (E. granulosus s.s., or E.g.s.s.) and were designed using Primer Explorer V4 software. The developed LAMP assay was compared with a conventional PCR method, copro-ELISA and microscopy, using the faeces of dogs experimentally infected with E.g.s.s., and field-collected faeces of domestic dogs including 190 from Qinghai province highly endemic for E.g.s.s. and 30 controls from an area in Gansu, where a domestic dog de-worming program was in operation. RESULTS: The positivity rates obtained for the field-collected faecal samples were 12.6%, 1.6% and 2.1% by the LAMP, PCR and copro-ELISA assays, respectively. All samples obtained from the control dogs were negative. Compared with the conventional PCR, the LAMP assay provided 88.8% specificity and 100% sensitivity. The higher sensitivity of the LAMP method was also shown by the fact that it could detect the presence of laboratory challenge dog infections of E. granulsous s.s. four days earlier than the PCR method. Three copro-samples shown positive by the commercial copro-ELISA were all negative by LAMP, PCR and microscopy, which suggests these samples may have originated from another infection rather than E. granulsous s.s., possibly E. shiquicus or E. Canadensis, which is also present in China. CONCLUSIONS: We have developed a potentially useful surveillance tool for determining the prevalence of canine E. granulosus s.s. infections in the field. The LAMP assay may lead to a more cost-effective and practicable way of tracking Echinococcus infections in canids, especially when combined with the copro-ELISA.

Comparative genomic analysis of Mycobacterium tuberculosis clinical isolates.

BACKGROUND: Due to excessive antibiotic use, drug-resistant Mycobacterium tuberculosis has become a serious public health threat and a major obstacle to disease control in many countries. To better understand the evolution of drug-resistant M. tuberculosis strains, we performed whole genome sequencing for 7 M. tuberculosis clinical isolates with different antibiotic resistance profiles and conducted comparative genomic analysis of gene variations among them. RESULTS: We observed that all 7 M. tuberculosis clinical isolates with different levels of drug resistance harbored similar numbers of SNPs, ranging from 1409-1464. The numbers of insertion/deletions (Indels) identified in the 7 isolates were also similar, ranging from 56 to 101. A total of 39 types of mutations were identified in drug resistance-associated loci, including 14 previously reported ones and 25 newly identified ones. Sixteen of the identified large Indels spanned PE-PPE-PGRS genes, which represents a major source of antigenic variability. Aside from SNPs and Indels, a CRISPR locus with varied spacers was observed in all 7 clinical isolates, suggesting that they might play an important role in plasticity of the M. tuberculosis genome. The nucleotide diversity (Л value) and selection intensity (dN/dS value) of the whole genome sequences of the 7 isolates were similar. The dN/dS values were less than 1 for all 7 isolates (range from 0.608885 to 0.637365), supporting the notion that M. tuberculosis genomes undergo purifying selection. The Л values and dN/dS values were comparable between drug-susceptible and drug-resistant strains. CONCLUSIONS: In this study, we show that clinical M. tuberculosis isolates exhibit distinct variations in terms of the distribution of SNP, Indels, CRISPR-cas locus, as well as the nucleotide diversity and selection intensity, but there are no generalizable differences between drug-susceptible and drug-resistant isolates on the genomic scale. Our study provides evidence strengthening the notion that the evolution of drug resistance among clinical M. tuberculosis isolates is clearly a complex and diversified process.

Overexpression of inducible nitric oxide synthase impairs the survival of bone marrow stem cells transplanted into rat infarcted myocardium.

AIMS: Inducible nitric oxide synthase (iNOS) over-expression is considered critical to the death of transplanted cells in infarcted myocardium. The present study was to investigate the effect of iNOS on the survival of transplanted bone marrow mesenchymal stem cells (BMSCs) in infarcted myocardium. MAIN METHODS AND KEY FINDINGS: Male rat BMSCs were injected into the infarct region of female rat hearts at 1 hour (H1, group A), day 3 (D3, group B), and day 7 (D7, group C) after coronary artery ligation, and harvested on D7 after transplantation. Myocardial iNOS expression was significantly increased shortly after coronary ligation with its peak on D3, and returned to baseline at D7. The cell survival rates were 6.2%, 2.1%, and 8.3% in group A, B, and C, respectively, one week after transplantation as assessed by detecting the Y-chromosome sry sequence in the infarct region. There was no significant difference in the survival rates between D7 and week 6 after cell transplantation in group A. Treating the animals in group B with the selective iNOS inhibitor 1400 W significantly increased the survival rate (from 1.8% to 4.2%). Apoptosis level of the transplanted cells was also significantly reduced with 1400 W treatment in group B. SIGNIFICANCE: BMSC transplantation on H1 and D7 after coronary ligation might be the optimal time for cell survival. The loss of transplanted BMSCs in the infarcted myocardium was partially due to increased apoptosis and iNOS overexpression. Selective iNOS inhibition early in myocardial infarction may increase the cell viability.