Evaluation of MALDI Biotyper Mycobacteria Library for Identification of Nontuberculous Mycobacteria.

The Bruker Biotyper matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) platform was assessed on its ability to accurately identify 314 nontuberculous mycobacteria (NTM) representing 73 species. All NTM isolates, representing 183 rapidly growing and 131 slowly growing organisms, were previously identified by Sanger DNA sequencing of the full-length 16S rRNA gene, and region V of the rpoB gene. An optimized version of the Bruker bead-beating procedure for protein extraction of NTM isolates was used to ensure high quality spectra for all NTM isolates, including less frequently encountered species. NTM spectra were analyzed using Bruker's research use only, Mycobacteria Library v6.0, supplemented by the MicrobeNet database. Identification of NTM by MALDI-TOF had an accuracy of 94% (296/314). The identification accuracy for rapidly growing mycobacteria was higher at 99% (182/183) than it was for slowly growing mycobacteria at 87% (114/131). While MALDI-TOF performed well against Sanger sequencing of the 16S rRNA gene alone, there were 11 species that required additional sequencing of rpoB. Most discrepancies between MALDI-TOF and sequencing results are likely due to underrepresentation of some species in the libraries used. Overall, the results of this study support Bruker's MALDI-TOF platform as an accurate and reliable method for the identification of NTM.

Identification of autophagy-related long non-coding RNA prognostic signature for breast cancer.

Autophagy-related long non-coding RNAs (lncRNAs) disorders are related to the occurrence and development of breast cancer. The purpose of this study is to explore whether autophagy-related lncRNA can predict the prognosis of breast cancer patients. The autophagy-related lncRNAs prognostic signature was constructed by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression. We identified five autophagy-related lncRNAs (MAPT-AS1, LINC01871, AL122010.1, AC090912.1, AC061992.1) associated with prognostic value, and they were used to construct an autophagy-related lncRNA prognostic signature (ALPS) model. ALPS model offered an independent prognostic value (HR = 1.664, 1.381-2.006), where this risk score of the model was significantly related to the TNM stage, ER, PR and HER2 status in breast cancer patients. Nomogram could be utilized to predict survival for patients with breast cancer. Principal component analysis and Sankey Diagram results indicated that the distribution of five lncRNAs from the ALPS model tends to be low-risk. Gene set enrichment analysis showed that the high-risk group was enriched in autophagy and cancer-related pathways, and the low-risk group was enriched in regulatory immune-related pathways. These results indicated that the ALPS model composed of five autophagy-related lncRNAs could predict the prognosis of breast cancer patients.

Multispecies Outbreak of Verona Integron-Encoded Metallo-ß-Lactamase-Producing Multidrug Resistant Bacteria Driven by a Promiscuous Incompatibility Group A/C2 Plasmid.

BACKGROUND: Antibiotic resistance is often spread through bacterial populations via conjugative plasmids. However, plasmid transfer is not well recognized in clinical settings because of technical limitations, and health care-associated infections are usually caused by clonal transmission of a single pathogen. In 2015, multiple species of carbapenem-resistant Enterobacteriaceae (CRE), all producing a rare carbapenemase, were identified among patients in an intensive care unit. This observation suggested a large, previously unrecognized plasmid transmission chain and prompted our investigation. METHODS: Electronic medical record reviews, infection control observations, and environmental sampling completed the epidemiologic outbreak investigation. A laboratory analysis, conducted on patient and environmental isolates, included long-read whole-genome sequencing to fully elucidate plasmid DNA structures. Bioinformatics analyses were applied to infer plasmid transmission chains and results were subsequently confirmed using plasmid conjugation experiments. RESULTS: We identified 14 Verona integron-encoded metallo-ß-lactamase (VIM)-producing CRE in 12 patients, and 1 additional isolate was obtained from a patient room sink drain. Whole-genome sequencing identified the horizontal transfer of blaVIM-1, a rare carbapenem resistance mechanism in the United States, via a promiscuous incompatibility group A/C2 plasmid that spread among 5 bacterial species isolated from patients and the environment. CONCLUSIONS: This investigation represents the largest known outbreak of VIM-producing CRE in the United States to date, which comprises numerous bacterial species and strains. We present evidence of in-hospital plasmid transmission, as well as environmental contamination. Our findings demonstrate the potential for 2 types of hospital-acquired infection outbreaks: those due to clonal expansion and those due to the spread of conjugative plasmids encoding antibiotic resistance across species.

Geographical influences on the iodine status in pregnant women, neonates, and school-age children in China.

BACKGROUND: Pregnant women, neonates, and school-age children are vulnerable to iodine deficiency. The iodine contents in the environment (drinking water and household salt for cooking) vary by geographical location in China. The aim of this study was to assess the iodine status in vulnerable groups from different geographical zones and analyze the iodine content in household salt and drinking water from these zones. METHODS: In coastal and inland regions of Zhejiang Province, China, samples of spot urine, drinking water, and household salt for cooking from both pregnant women and school-age children were determined for iodine concentration between 2017 and 2018. Thyroid-stimulating hormone (TSH) levels from neonates born between 2014 and 2015 were acquired from the Newborns Screening Information System. The iodine status of the vulnerable populations was assessed according to the criteria recommended by the World Health Organization. RESULTS: The median UIC of pregnant women was significantly lower in the coastal region (113.0 µg/L) than the inland region (134.9 µg/L; p < 0.001). The median UICs of pregnant women from these two regions were below the lower optimal iodine cutoff level of 150 µg/L. The percentage of neonates with elevated TSH (> 5 mIU/L) was significantly higher in the coastal region (15.8%) than the inland region (10.5%; p < 0.001). The percentage of neonates with elevated TSH from each region decreased within the range of mild iodine deficiency of 3-19.9%. The median UIC of the coastal school-age children was 156.0 µg/L, and the median UIC of inland children was 181.5 µg/L. Both medians fell within the recommended optimal iodine range of 100-299 µg/L. The iodine concentrations in drinking water varied from 1.0 µg/L in the inland region to 2.0 µg/L in the coastal region. The proportion of households that consumed iodized salt was lower in the coastal region (nearly 65%) than the inland region (approximately 95%). CONCLUSIONS: In these two regions with low iodine contents in drinking water, both pregnant women and neonates were iodine-deficient, although school-age children were iodine-sufficient. Urgent efforts are needed to improve the iodine status of pregnant women and neonates.

Conjugal Transfer, Whole-Genome Sequencing, and Plasmid Analysis of Four mcr-1-Bearing Isolates from U.S. Patients.

Four Enterobacteriaceae clinical isolates bearing mcr-1 gene-harboring plasmids were characterized. All isolates demonstrated the ability to transfer colistin resistance to Escherichia coli; plasmids were stable in conjugants after multiple passages on nonselective media. mcr-1 was located on an IncX4 (n = 3) or IncN (n = 1) plasmid. The IncN plasmid harbored 13 additional antimicrobial resistance genes. Results indicate that the mcr-1-bearing plasmids in this study were highly transferable in vitro and stable in the recipients.

Phenotypic and Genotypic Characterization of Enterobacteriaceae Producing Oxacillinase-48-Like Carbapenemases, United States.

Oxacillinase (OXA)-48-like carbapenemases remain relatively uncommon in the United States. We performed phenotypic and genotypic characterization of 30 Enterobacteriaceae producing OXA-48-like carbapenemases that were recovered from patients during 2010-2014. Isolates were collected from 12 states and not associated with outbreaks, although we could not exclude limited local transmission. The alleles ß-lactamase OXA-181 (blaOXA-181) (43%), blaOXA-232 (33%), and blaOXA-48 (23%) were found. All isolates were resistant to ertapenem and showed positive results for the ertapenem and meropenem modified Hodge test and the modified carbapenem inactivation method; 73% showed a positive result for the Carba Nordmann-Poirel test. Whole-genome sequencing identified extended-spectrum ß-lactamase genes in 93% of isolates. In all blaOXA-232 isolates, the gene was on a ColKP3 plasmid. A total of 12 of 13 isolates harboring blaOXA-181 contained the insertion sequence ΔISEcp1. In all isolates with blaOXA-48, the gene was located on a TN1999 transposon; these isolates also carried IncL/M plasmids.

Iodine deficiency in pregnant women after the adoption of the new provincial standard for salt iodization in Zhejiang Province, China.

BACKGROUND: Zhejiang has achieved the goal of elimination of iodine deficiency disorders (IDD) via the implementation of universal salt iodization (USI) since 2011. Iodine content in household table salt decreased from the national standard (35 ppm) to the Zhejiang provincial standard (25 ppm) in 2012. It is crucial to periodically monitor iodine status in pregnant women because IDD in pregnancy have adverse effects on fetal neurodevelopment. METHODS: We carried out a cross-sectional study between April 2014 and September 2015 in the eight sentinel surveillance counties across Zhejiang Province, where IDD was previously known to be endemic. A total of 1304 pregnant women participated and provided a random spot urine sample and a household table salt sample. Urinary iodine concentration (UIC) was determined using arsenic-cerium catalytic spectrophotometry. Iodine content in salt was measured using a titration method with sodium thiosulphate. RESULTS: Overall, the median UIC of the total study population of pregnant women was 129.3 µg/L, with a higher UIC in inland (152.54 µg/L) and a lower UIC in coastal counties (107.54 µg/L). Household coverage of iodized salt was 94.6% and the rate of adequately iodized salt was 89.9%. CONCLUSIONS: Our results indicate deficient iodine status in the pregnant population of Zhejiang, according to the lower cut-off value of optimal iodine nutrition (150 µg/L) recommended by the World Health Organization. In addition to sustaining USI, more efforts are urgently needed to improve iodine intake in women during pregnancy, especially those residing in the coastal counties.

Metal-free synthesis of isatin oximes via radical coupling reactions of oxindoles with t-BuONO in water.

A metal-free method for the synthesis of isatin oximes was developed through the radical coupling reactions of oxindoles with t-BuONO. This protocol provides a practical and environmentally benign method for the construction of C-N bonds in water at room temperature without using any other reagents. The advantages of this strategy are its mild reaction conditions and clean procedure.

[Effect factors of the prevalence of thyroid nodules in Zhejiang Province in 2010].

OBJECTIVE: To assess the prevalence of thyroid nodules and explore the risk factors for thyroid nodules among the community residents in Zhejiang Province. METHODS: The residents of twenty-two communities in Zhejiang Province were selectedwith stratified cluster sampling. The cross-sectional survey includes questionnaire, examination on thyroid. The prevalence and related factors of thyroid nodules was described, and the possible risk factors for thyroid nodules was analyzed with logistic regression. RESULTS: The prevalence of thyroid nodules in Zhejiang was 21. 78%, and the prevalence of a single nodule was 11. 75%, which was higher than that of multiple nodules( 10. 03%). The prevalence of thyroid nodules in men was less than women, urban residents higher than rural, and both increased gradually with age. The residents in coastal areas had the highest prevalence of thyroid nodules, followed by sub-coastal areas, inland minimum. High education level, consumption of seafood habits, high frequency of anger, the history of thyroid disease and iodine deficiency were potential risk factors for thyroid nodules in this surveyed population. CONCLUSION: The prevalence of thyroid nodules in Zhejiang Province was at the middle level, female prevalence was greater than male, and gradully increased with age, the elderly should be the focus of prevention. Although thyroid nodules of children was at the lower rate, it should be paid attention due to high risk to develop to malignancy. High education level, consumption of seafood habits, high frequency of anger, the history of thyroid disease and iodine deficiency were potential risk factors for thyroid nodules, which need to be confirmed by further epidemiologic study.

A study on the influencing factors of urinary iodine concentration and the relationship between iodised salt concentration and urinary iodine concentration.

The aim of the present study was to explore the influencing factors of urinary iodine concentration (UIC) and the relationship between iodised salt concentration and UIC in order to give suggestions for the surveillance of iodine nutrition status. For this purpose, a multi-stage cluster sampling technique was employed in the present cross-sectional study. Correlations between UIC and salt iodine concentration were evaluated by Spearmen's correlation analysis. Risk factors of having a lower UIC were identified by logistic regression analysis, and the equations of UIC and salt iodine concentration were fitted by curve regression analysis. The median UIC was found to be 162·0 (25th-75th percentile 98·2-248·6) µg/l. The UIC was correlated with salt iodine concentration (Spearman's ρ = 0·144, P< 0·05). The multiple logistic regression analysis found the following influencing factors for having a lower UIC: age (OR 0·98, 95% CI 0·98, 0·98, P< 0·05); sex (OR 0·81, 95% CI 0·71, 0·92, P< 0·05); education level (OR 0·87, 95% CI 0·83, 0·90, P< 0·05); status of occupation (OR 0·91, 95% CI 0·86, 0·96, P< 0·05); occupation (OR 1·03, 95% CI 1·00, 1·05, P< 0·05); pickled food (OR 1·24, 95% CI 1·08, 1·42, P< 0·05); salt iodine concentration (OR 1·03, 95% CI 1·02, 1·03, P< 0·05). The curve regression analysis found that UIC (y) and salt iodine concentration (x) could be expressed by the following equation: y= 1·5772x 1·4845. In conclusion, the median UIC of individuals in Zhejiang Province falls within optimal status as recommended by the WHO/UNICEF/International Council for Control of IDD. To maintain optimal iodine nutrition status, salt iodine concentration should be in the range of 16·4 to 34·3 mg/kg.

Report of the 13th vancomycin-resistant Staphylococcus aureus isolate from the United States.

Vancomycin-resistant Staphylococcus aureus (VRSA), an important multidrug-resistant organism of public health concern, has been infrequently identified in the United States since 2002. All previous VRSA isolates belonged to clonal complex 5, a lineage associated primarily with health care. This report describes the most recent (13th) U.S. VRSA isolate, the first to be community associated.

An assessment of iodine nutritional status and thyroid hormone levels in children aged 8-10 years living in Zhejiang Province, China: a cross-sectional study.

UNLABELLED: Iodine is an essential nutrient for the synthesis of thyroid hormones that are critical for brain development. Iodine deficiencies were prevalent in China until the introduction of universal salt iodization (USI) in 1995. USI has been considered as the world's best achievements. This study aims to assess children's iodine nutrition and goiter status in Zhejiang Province in order to provide reasonable suggestions to the government for policy-making under the USI period. A cross-sectional survey in Zhejiang Province was conducted to children aged 8-10 years by stage cluster random sampling method. Spot urine samples were collected and analyzed. Thyroid ultrasonography examination was performed by special trained technicians using a 7.5-MHz transducer. Fasting venous blood samples were collected and analyzed for thyroid functional status. The median urinary iodine concentration was found to be 173.3 µg/L. The percentage of urine samples with iodine concentration <100 µg/L, 100-300 µg/L, and >300 µg/L was 15.5, 42.0, and 13.3 %, respectively. Goiter prevalence rate with iodine concentration <100 µg/L, 100-300 µg/L, and >300 µg/L was 6.8, 10.0, and 14.9 %, respectively, with no significant difference. Children with goiter have lower serum FT3 and T3 concentrations compared to those without goiter (p < 0.05). CONCLUSIONS: The median urinary iodine concentration of children aged 8-10 years falls in optimal iodine status as recommended by WHO/UNICEF/ICCIDD. Maintaining USI at an appropriate level is an important part of preventing iodine deficiency disorders and should always be based on routine monitoring urinary iodine concentration by the province.

Iodine nutritional status after the implementation of the new iodized salt concentration standard in Zhejiang Province, China.

BACKGROUND: Iodine deficiencies were prevalent in China until the introduction of universal salt iodization (USI) in 1995. In 2012, the standard salt iodine concentration was adjusted to 20-30 mg/kg. The success of USI for the control of iodine deficiency disorders requires monitoring its effect at a population level. METHODS: Two cross sectional surveys of a representative sample of children aged 8-10 years in Zhejiang Province were carried out in 2011 and 2013. Data on participants' socio-demographic characteristics were collected from the children using a structured questionnaire. Spot urine samples were collected and delivered to local Center for Disease Control and Prevention laboratory for measuring urinary iodine concentration. In 2011, out of 420 selected children aged 8-10 years, 391 were recorded and provided urine samples. In 2013, out of 1560 selected children aged 8-10 years, 1556 were recorded and provided urine samples. RESULTS: The median urinary iodine concentration of subjects in the 2013 survey was 174.3 µg/L, significantly lower than that of 2011(p = 0.000). The median urinary iodine concentration of subjects living in urban and rural areas in the 2013 survey was 169.0 µg/L, and 186.1 µg/L respectively, significantly lower than that of 2011 only for subjects living in urban areas (p = 0.000). There were no significant differences for subjects living in rural areas in the survey in 2011 and in 2013 (p = 0.086). CONCLUSIONS: At the time the new local iodization policy put forward, iodine nutrition was generally adequate in both urban and rural areas, suggesting that the new policy for adjusting the standard salt iodine concentration is effective. Our data also indicate that the reason people living in urban areas had a lower urinary iodine concentration than people in rural areas may be due to their preference for using non-iodized salt in the last 2 or 3 years. Maintaining USI at an appropriate level is an important part of preventing iodine deficiency disorders and should always be based on regular monitoring and comparison of urinary iodine concentration by province.

New Delhi metallo-ß-lactamase-producing Enterobacteriaceae, United States.

We characterized 9 New Delhi metallo-ß-lactamase-producing Enterobacteriaceae (5 Klebsiella pneumoniae, 2 Escherichia coli, 1 Enterobacter cloacae, 1 Salmonella enterica serovar Senftenberg) isolates identified in the United States and cultured from 8 patients in 5 states during April 2009-March 2011. Isolates were resistant to ß-lactams, fluoroquinolones, and aminoglycosides, demonstrated MICs ≤1 µg/mL of colistin and polymyxin, and yielded positive metallo-ß-lactamase screening results. Eight isolates had blaNDM-1, and 1 isolate had a novel allele (blaNDM-6). All 8 patients had recently been in India or Pakistan, where 6 received inpatient health care. Plasmids carrying blaNDM frequently carried AmpC or extended spectrum ß-lactamase genes. Two K. pneumoniae isolates and a K. pneumoniae isolate from Sweden shared incompatibility group A/C plasmids with indistinguishable restriction patterns and a common blaNDM fragment; all 3 were multilocus sequence type 14. Restriction profiles of the remaining New Delhi metallo-ß-lactamase plasmids, including 2 from the same patient, were diverse.

pSK41-like plasmid is necessary for Inc18-like vanA plasmid transfer from Enterococcus faecalis to Staphylococcus aureus in vitro.

Vancomycin-resistant Staphylococcus aureus (VRSA) is thought to result from the in vivo conjugative transfer of a vanA plasmid from an Enterococcus sp. to S. aureus. We studied bacterial isolates from VRSA cases that occurred in the United States to identify microbiological factors which may contribute to this plasmid transfer. First, vancomycin-susceptible, methicillin-resistant S. aureus (MRSA) isolates from five VRSA cases were tested for their ability to accept foreign DNA by conjugation in mating experiments with Enterococcus faecalis JH2-2 containing pAM378, a pheromone-response conjugative plasmid. All of the MRSA isolates accepted the plasmid DNA with similar transfer efficiencies (∼10(-7)/donor CFU) except for one isolate, MRSA8, for which conjugation was not successful. The MRSA isolates were also tested as recipients in mating experiments between an E. faecalis isolate with an Inc18-like vanA plasmid that was isolated from a VRSA case patient. Conjugative transfer was successful for 3/5 MRSA isolates. Successful MRSA recipients carried a pSK41-like plasmid, a staphylococcal conjugative plasmid, whereas the two unsuccessful MRSA recipients did not carry pSK41. The transfer of a pSK41-like plasmid from a successful MRSA recipient to the two unsuccessful recipients resulted in conjugal transfer of the Inc18-like vanA plasmid from E. faecalis at a frequency of 10(-7)/recipient CFU. In addition, conjugal transfer could be achieved for pSK41-negative MRSA in the presence of a cell-free culture filtrate from S. aureus carrying a pSK41-like plasmid at a frequency of 10(-8)/recipient CFU. These results indicated that a pSK41-like plasmid can facilitate the transfer of an Inc18-like vanA plasmid from E. faecalis to S. aureus, possibly via an extracellular factor produced by pSK41-carrying isolates.

[Analysis of urine iodine level and its influencing factors in Zhejiang from 2009 to 2011].

OBJECTIVE: To evaluate the iodine nutrition level of population in Zhejiang province and to analyze the relevant influencing factors from 2009 to 2011. METHODS: From October 2009 to October 2011, a total of 19 517 subjects were recruited in this cross sectional survey, by multistage stratified cluster random sampling method. The subjects were all living over three years in Zhejiang province. The basic information and life styles were interviewed by questionnaires; and the samples of drinking water, edible salt and urines were separately collected from the subjects to test the content of iodine. In total, 16 228 subjects answered the questionnaire, and 265 samples of drinking water, 7811 samples of edible salt and 19 517 samples of urine were collected. Then, we analyzed the distribution of iodine in water, edible salt and urine samples, as well as the relevance. RESULTS: The median (25% - 75% percentile) of water iodine was 2.42 (1.17 - 6.28) µg/L in drinking water among Zhejiang residents; while separately 2.79 (1.60 - 6.87) µg/L in city and 2.04 (1.03 - 5.29) µg/L in country side (Z = 2.07, P < 0.05). The figures turned out to be 2.17 (1.22 - 5.73) µg/L, 2.77 (1.88 - 6.87) µg/L, and 1.40 (0.77 - 5.65) µg/L, respectively, in coastal areas, coastal periphery areas and inland areas (χ(2) = 11.16, P < 0.05). The median (25% - 75% percentile) of salt iodine was 28.80 (22.93 - 32.40) mg/kg; while separately 29.00 (24.50 - 32.60) mg/kg and 28.50 (13.90 - 32.29) mg/kg in city and country side (Z = 6.32, P < 0.05). The figures turned out to be 25.19 (0.00 - 30.20) mg/kg, 29.00 (26.60 - 31.70) mg/kg and 32.40 (28.94 - 36.30) mg/kg, respectively, in coastal areas, coastal periphery areas and inland areas (χ(2) = 1581.62, P < 0.05). The coverage rate of iodized salt was 79.54% (6213/7811) in all province. The urinary iodine median was 160.74(97.20 - 247.00) µg/L, while the urinary iodine median in pregnant women was 137.99 (82.40 - 215.30) µg/L, lower than the recommended optimal levels, which was 150 - 249 µg/L. The figures turned out to be 153.45(92.00 - 237.50) µg/L in city and 168.00 (102.18 - 257.00) µg/L in country side (Z = -9.25, P < 0.05); while in coastal, coastal periphery place and inland areas, the median were separately 156.00 (94.29 - 242.80) µg/L, 150.14 (94.70 - 227.00) µg/L and 187.70 (109.00 - 276.80) µg/L (χ(2) = 194.12, P < 0.05). The analysis of relevance between urine iodine, water iodine and iodized salt showed that the urine iodine would increase as long as the iodized salt increased; and the difference had statistical significance (χ(2) = 440.88, P < 0.01). And there were no relevance between urine iodine level and the water iodine level (χ(2)cmh = 0.57, P = 0.45). The analysis of the influencing factors showed that education background (χ(2) = 14.17, P < 0.05), different styles of career (χ(2) = 16.15, P < 0.01) and diet habits (χ(2) = 108.63, P < 0.01) could influence the level of urine iodine. CONCLUSION: Iodine was deficient in Zhejiang province. The nutrition level of iodine was fine in Zhejiang in 2009, however, the coverage rate of iodine was commonly low in coastal areas, especially the pregnant women suffered from iodine deficiency. In our study, the factors influencing the urine iodine level included iodized salt, age, education background and diet habits.

[Analysis of the prevalence and its influencing factors of diffuse goiter in Zhejiang].

OBJECTIVE: To evaluate the status of diffuse goiter of population in Zhejiang Province and to analyze the relevant influencing factors. METHODS: A total of 18 188 subjects were recruited in the cross sectional survey, by multistage stratified cluster random sampling method. B ultrasound measurement were carried among the subjects to detect the thyroid volume, and the basic information and life styles were interviewed by questionnaires. Then, we analyzed the distribution and its influencing factors of diffuse goiter. RESULTS: The ratio of diffuse goiter among the surveyed population was 2.2% (403/18 188), the difference showed statistical significance (χ(2) = 267.11, P < 0.05). The ratio among the group aged 6-7 years old and 8-10 years old was comparatively high, separately 10.3% (27/262) and 9.8% (51/519). The ratio among women (2.9%, 305/10 470) was higher than it among men (1.3%, 97/7672) (χ(2) = 55.55, P < 0.05). The residents from inland areas had the highest prevalence (3.2%, 138/4374), followed by residents from sub-coastal areas (2.0%, 131/6411), coastal areas minimum (1.8%, 138/4374) (χ(2) = 24.31, P < 0.05). The content of water iodine and salt iodine among people with symptoms of goiter had statistical difference with it among ordinary population (water iodine:χ(2) = 4.95, P = 0.026; salt iodine: χ(2) = 11.03, P < 0.01). The median(quartile) of water iodine in ordinary population was 2.41 (1.96-6.15) µg/L and among people with symptoms of goiter was 1.88 (1.49-5.15) µg/L. The median(quartile) of salt iodine in ordinary population was 30.18 (24.69-32.65) mg/kg and among people with symptoms of goiter was 29.1 (24.70-31.95) mg/kg. The influential factors of goiter were as follows: the family income, the education degree, the job and profession status, the diet character, the habitual sea food consumption, the alcohol intake status (χ(2) were separately 8.08, 37.85, 98.78, 68.69, 10.91, 12.21, 26.94, P < 0.05). Multi-factor analysis showed the results as follows: female (OR = 0.27 95%CI:0.18-0.39), school students (OR = 8.05, 95%CI:3.87-16.73), vegetarian (OR = 1.60, 95%CI:1.15-2.22) took a higher risk of getting pathogenic goiter; while the group of those who had university degree or above (OR = 0.84, 95%CI: 0.73-0.97), ate sea food frequently (OR = 0.62, 95%CI:0.44-0.88) took a lower risk. CONCLUSIONS: The ratio of diffuse goiter in the group aged among 6-7 years old and 8-10 years old was comparatively high. The ratio was influenced by many factors.

[Study on level of dietary iodine intake and its contribution rate of residents in Zhejiang].

OBJECTIVE: To assess the level of dietary iodine intake and its contribution in Zhejiang. METHODS: A total of 9798 subjects were recruited in this survey with multi-stage stratified cluster random sampling method in April, 2010, the 24-hours dietary recall method and the "food composition table" were used to obtain the dietary iodine intake, and edible salt and drinking water samples were collected to detect the content of iodine. RESULTS: A total of 9798 subjects were included in this survey. The mean intake of dietary iodine in Zhejiang residents per standard man-days was (395.13 ± 78.16) µg/d, which in between of Recommended Nutrient Intake (RNI) 150 µg/d and Tolerable Upper Intake Level (UL) 1000 µg/d; the iodine intake of 18.40% (1803/9798) subjects was lower than estimated average requirement of iodine (EAR), 4.68% (459/9798) subjects was higher than the UL. The means of dietary iodine intake in various areas were (498.85 ± 96.77) µg/d, (384.50 ± 88.76) µg/d and (326.33 ± 78.32)µg/d in inland areas, sub-coastal areas and coastal areas, successively (F = 27.17, P < 0.05); the proportions of dietary iodine intake lower than EAR were 34.89% (1239/3551), 10.48% (370/3530) and 7.14% (197/2717) in coastal areas, sub-coastal area and inland areas, successively (χ(2) = 62.87, P < 0.01) , while those higher than UL were 5.10% (180/3530), 4.86% (132/2717) and 4.14% (147/3551) in sub-coastal area, inland areas and coastal areas.In the condition of ignoring cooking loss, the mean contribution of dietary iodine intake in edible salt, all kinds of food and drinking water were 74.92% (296.03/395.13), 23.85% (94.24/395.13) and 1.23% (4.86/395.13), successively; the contributions of edible salt in inland areas, sub-coastal areas and coastal areas were 83.72% (417.64/498.85), 73.05% (280.88/384.50) and 66.83% (280.09/326.33), successively; the contributions of drinking water in sub-coastal areas, coastal areas and inland areas were 1.61% (6.19/384.50) , 1.44% (4.70/326.33) and 0.65% (3.24/498.85) , successively (χ(2) = 7.24, P = 0.032) ; the contribution of laver in coastal areas, sub-coastal areas and inland areas were 22.57% (73.65/326.33), 17.11% (65.79/384.50) and 8.09% (40.36/498.85), successively (χ(2) = 82.17, P < 0.01) ; the contribution of sea fish in coastal areas, sub-coastal areas and inland areas were 2.38% (7.77/326.33), 0.72% (2.77/384.50) and 0.68% (3.39/498.85) (χ(2) = 19.47, P = 0.012). CONCLUSIONS: The dietary iodine intake of Zhejiang residents was at recommended intake levels; the iodized salt turns out to be the main source, the iodine nutrition level was relatively low in coastal areas of Zhejiang, which the coverage of iodized salt should be improved.

Modular total syntheses of trans-clerodanes and sesquiterpene (hydro)quinones via tail-to-head cyclization and reductive coupling strategies.

The trans-clerodanes and sesquiterpene (hydro)quinones are a growing class of natural products that exhibit a wide range of biological activities. Although they are different types of natural products, some of them feature the same trans-decalin core structure. Here, we report the total syntheses of two members of trans-clerodanes, five members of sesquiterpene (hydro)quinones as well as the proposed structure of dysidavarone D via a modular synthetic route. A bioinspired tail-to-head cyclization strategy was developed to syntheses of the trans-decalin architectures by using two diastereochemically complementary radical polyene cyclization reactions catalyzed by Ti(III) and mediated by Mn(III), respectively. The different types of side chains were introduced by challenging nickel catalyzed reductive couplings of sterically hindered alkyl halides. The synthesis of the proposed dysidavarone D proved a wrong structural assignment of the natural product.

Epsin 3 potentiates the NF­κB signaling pathway to regulate apoptosis in breast cancer.

Endocrine drug resistance is common in some patients with estrogen receptor (ER)­positive breast cancer, so it is necessary to identify potential therapeutic targets. The aim of the present study was to investigate the regulatory effect and mechanism of epsin 3 (EPN3) expression level changes on the proliferation and apoptosis of ER­positive breast cancer. Online GEPIA was used to analyze the expression level of EPN3 in breast cancer. The online Kaplan­Meier plotter tool was used to analyze the relationship between EPN3 expression and the prognosis of patients with breast cancer. Reverse transcription­quantitative PCR, immunohistochemistry and western blotting were performed to detect the mRNA and protein expression levels of EPN3 in breast cancer tissues and cells. A lentiviral infection system was used to knockdown the expression of EPN3 in breast cancer cell lines. Cell Counting Kit­8 and flow cytometry assays were conducted to detect the effect of EPN3 knockdown on breast cancer cell proliferation and apoptosis. Western blotting was used to detect the regulation of EPN3 expression on NF­κB, and immunofluorescence was performed to detect the effect of EPN3 expression on NF­κB nuclear translocation. The results demonstrated that the expression level of EPN3 in breast cancer tissues was higher compared with that in adjacent tissues (P<0.05). The expression level of EPN3 in the ER­positive breast cancer cell line, MCF7, was higher compared with that in the other cell lines (MCF10A, ZR75­1, MDA­MB­231, BT549 and SK­BR­3). After knocking down the expression of EPN3 in MCF7 cells, the proliferative ability of the cells was decreased, and the apoptosis rate was increased (P<0.05). After EPN3 knockdown in MCF7 cells, the phosphorylation of NF­κB was decreased (P<0.05), and the nuclear translocation signal was weakened. Thus, it was suggested that EPN3 promoted cell proliferation and inhibited cell apoptosis by regulating the NF­κB signaling pathway in ER­positive breast cancer.