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Objective We evaluated the intraday changes of thyroid function biomarkers in healthy subjects to help clinicians diagnose thyroid diseases in appropriate timing. Methods Blood samples were collected from 31 subjects at 0:00, 4:00, 8:00, 12:00, 16:00 and 20:00 on the sampling day and analyzed for thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), and free T4 (FT4). The intraday concentration changes were analyzed using Friedman’s 2-way analysis of variance by ranks. Results The concentrations of TSH, T3, T4, FT3, and FT4 in males were significantly higher than those in females (P Conclusion Sex differences should be considered in interpreting thyroid function tests. It is important to select the sampling time according to the clinician’s diagnostic needs, especially at night when TSH secretion peaks.

Supplementary Table S1. GFP-NAT10s, construction and subcellular localization; Supplementary Table S2. Primers used in PCR-direct sequencing for the 28 exons of NAT10gene (Gene ID: 55226); Supplementary Table 3: Correlations between cytoplasmic/membranous staining of NAT10 and nuclear translocation of β-catenin in CRCs; Supplementary Table S4. Correlations between cytoplasmic/membranous staining of NAT10 and staining of E-cadherin and GSK-3β; TableS5. Correlations between NAT10 membranous staining and clinicopathologic parameters in CRCs.

Purpose: NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution.Experimental Design: The expression and subcellular redistribution of NAT10, β-catenin, E-cadherin, and GSK-3β were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3β, transfection of wild-type or kinase-inactivated GSK-3β, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays.Results: NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive “leading edge” of the tumor. This correlated well with nuclear accumulation of β-catenin (P < 0.001; χ2 = 68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values < 0.001), and was associated with a poorer prognosis (P = 0.023; χ2 = 5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3β. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility.Conclusion: The subcellular redistribution of NAT10 can be induced by decreases in GSK-3β activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma. Clin Cancer Res; 20(17); 4717–29. ©2014 AACR.

To explore the value of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) for differential diagnosis of fibroadenomas and malignant breast tumors.This prospective study enrolled 56 patients with suspected breast tumors and performed APTw imaging. Based on the histopathology results, patients were divided into group 1 with malignant breast tumors (n = 41) and group 2 with fibroadenomas (n = 15). The measured image parameters (APTw value, ADC value, type of Time of Intensity Curve, maximum tumor diameter in image) and the maximal diameter of the tumors measured from surgical resection were compared between the two groups, and the diagnostic performance based on these parameters was quantified with ROC curve. Spearman's correlation coefficient was used to analyze the association between APTw or ADC values and ER, PR, HER2, and Ki-67 expressions.The intraclass correlation coefficients (ICC = 0.87 and 0.91) indicated a good inter-observer agreement of the measured APTw values. APTw values of malignant lesions were significantly higher than those of fibroadenomas (3.21 ± 1.04% vs 1.50 ± 0.54%, p 0.001). Area under the curve (AUC) obtained from APTw imaging, DWI, DCE, APTw imaging+DWI, APTw imaging+DWI, and APTw imaging+DWI + DCE was 0.959, 0.897, 0.976, 0.997, and 1 respectively. The APTw value showed a negative correlation with ER expression (r = -0.357).APTw imaging yielded similar diagnosis performance in discriminating fibroadenomas and malignant breast tumors when compared to the DCE and better than DWI imaging, and provided supplement information on tumor cell activity to DWI images. The APTw value showed correlations with some prognostic factors for breast cancer.

BACKGROUND Primary soft tissue giant cell tumor (GCT-ST) is rare and has relatively low malignant potential. Most reports are pathological and clinical studies, while imaging studies have only been reported in cases of adjacent bone or with atypical cystic degeneration. With regard to the findings on magnetic resonance imaging (MRI) or ultrasonography, superficial masses can be further identified based on facial edema, skin thickening, skin contact, internal hemorrhage or necrosis and lobulation of the mass. Unlike deep-seated masses, MRI features do not always provide an accurate diagnosis for benign and malignant patients with superficial soft-tissue lesions. Thus, the application of diffusion-weighted imaging (DWI) to evaluate superficial soft tissue tumors is necessary. CASE SUMMARY A 36-year-old woman who had a suspected malignant tumor in the upper limb on ultrasound and computed tomography is reported. The signal intensity of the suspected tumor was heterogeneous on plain MRI; nodular and heterogeneous enhancement was observed in the tumor with irregular shapes and blurred margins on dynamic contrast-enhanced MRI. The lesion on DWI was hyperintense with a higher mean apparent diffusion coefficient (ADC) value. Finally, a GCT-ST was confirmed by pathology. This case suggests that GCT-ST should be distinguished as a benign soft tissue mass from giant cell-rich soft tissue neoplasms or malignant tumors. CONCLUSION The MRI features of the superficial GCT-ST in the upper limb included heterogeneous signal intensity within the lesion on T2-weighted image (T2WI) and T1-weighted fat-saturation spoiled gradient recalled echo (T1 FSPGR), nodular enhancement with blurred margins, irregular shapes, and a slow-increased enhancement. DWI could be used to differentiate a benign soft tissue mass from a malignant mass by the mean ADC value and provide more radiologic-pathologic information for the diagnosis of GCT-ST. Comprehensive imaging of primary GCT-ST could help complete tumor resection, and in turn likely prolong survival after surgery.

While a number of population preventive measures for COVID-19 exist that help to decrease the spread of the virus in the community, there are still many areas in preventative efforts that need improvement or refinement, particularly as new strains of the virus develop. Some of the key issues currently include incorrect and/or inconsistent use of face masks, low acceptance of early screening or vaccination for COVID-19, vaccine hesitance, and misinformation. This is particularly the case in some vulnerable populations, such as older people with chronic illnesses, ethnic minorities who may not speak the mainstream language well and children. The current protocol introduces a large programme of research through five interrelated studies that all focus on social and behavioural interventions to improve different aspects of community-related preventative indicators. Hence, the specific objectives of the overall programme are to (1) increase early testing for COVID-19 and promote the uptake of COVID-19 vaccines in the community (Study 1); (2) increase COVID-19-related health literacy and vaccine literacy and promote improved preventative measures in minority ethnic groups, chronically ill populations and caregivers (Study 2); (3) strengthen the public's motivation to stay at home and avoid nonessential high-risk activities (Study 3); (4) decrease COVID-19 vaccine hesitancy (Study 4); and (5) enhance the adherence to COVID-19-related hygiene practices and the uptake of early testing in school children (Study 5).We will utilise a community-based participatory research (CBPR) approach in the proposed studies. All studies will incorporate an intervention development phase in conjunction with key community stakeholders, a feasibility study and an execution stage. A variety of self-reported and objective-based measures will be used to assess various outcomes, based on the focus of each study, in both the short- and long-term, including, for example, the 8-item self-reported eHealth Literacy Scale (eHEAL) and objective measures such as vaccine uptake.Theory-driven interventions will address each study's focus (e.g., social distancing, promotion of vaccine uptake, eHealth education, preventive measures and early detection). Improvements are expected to be seen in the outcomes of vulnerable and high-risk groups. Decreased infection rates are expected due to improved preventative behaviours and increased vaccine uptake. Long-term sustainability of the approach will be achieved through the CBPR model. The publication of this protocol can assist not only in sharing a large-scale and complex community-based design, but will also allow all to learn from this, so that we will have better insight in the future whether sharing of study designs can elicit timely research initiatives.

Solar-driven evaporation is an emerging process to acquire freshwater from saline water or wastewater, in which photothermal materials play a crucial role. Significant effort has been devoted to promoting energy conversion efficiency by material and device design. In the current review, we discuss the major factors affecting evaporator efficiency and long-term performance, including selection of photothermal materials, promotion of evaporation efficiency, and solutions to the problem of scaling. Both the material components and structure will affect the absorption and reflection of the incident light, and the evaporation efficiency can be enhanced by reducing heat loss, enlarging surface area, and recycling latent heat. Scaling can be addressed by tailoring surface properties and structure.

Background Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), and free T4 (FT4) are used to diagnose thyroid diseases and monitor treatment effects. Reliable biological variation (BV) data is required to ensure accurate clinical decisions. Methods Blood samples were collected from 31 healthy subjects at 00:00, 04:00, 08:00, 12:00, 16:00, and 20:00; each sample was analyzed twice for TSH, T3, T4, FT3, and FT4. After outlier exclusion, normality assessment, and variance homogeneity, sex-stratified BV, including within-subject (CVI) and between-subject (CVG), was defined using nested ANOVA. Results Concentrations of five biomarkers were significantly different between sexes. The CVI and CVG estimates were 34.54% and 34.43% for TSH, 5.89% and 14.18% for T3, 4.48% and 14.96% for T4, 5.37% and 11.23% for FT3, and 3.57% and 8.03% for FT4, respectively. The individual indexes (IIs) of all the biomarkers (except TSH) were ≤ 0.63. Males had lower CVIs and IIs than females. Conclusion CVI estimates of all hormones, except TSH, were lower than those reported on the BV website, showing low IIs and differences between sexes. We provide updated data on the short-term BV of thyroid function biomarkers according to sex and complement BV data of thyroid function biomarkers.

Objective: To observe the effect of interferon α-2b treatment on liver function, liver fibrosis, complement protein and oxidative stress in patients with hepatitis B. Methods: A total of 100 patients with hepatitis B in our hospital were randomly divided into the control group and the observation group, with 50 cases in each group. After admission, patients in the control group were treated with entecavir, while patients in the observation group were treated with interferon α-2b combined with entecavir. The levels of serum total bilirubin (TBil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), type III procollagen (PCIII), type IV collagen (CIV), complement C3 protein (C3), complement C4 protein (C4), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were compared between the two groups before and after treatment. Results: After treatment, the levels of TBil, AST, ALT, PCIII, CIV, MDA and NO in serum of patients with hepatitis B in both groups were significantly lower than those before treatment, and the levels of C3, C4 and SOD were significantly higher than those before treatment (P

Human sirtuin 5 (SIRT5) plays pivotal roles in metabolic pathways and other biological processes, and is involved in several human diseases including cancer. Development of new potent and selective SIRT5 inhibitors is currently desirable to provide potential therapeutics for related diseases. Herein, we report a series of new 3-thioureidopropanoic acid derivatives, which were designed to mimic the binding features of SIRT5 glutaryl-lysine substrates. Structure-activity relationship studies revealed several compounds with low micromolar inhibitory activities to SIRT5. Computational and biochemical studies indicated that these compounds exhibited competitive SIRT5 inhibition with respect to the glutaryl-lysine substrate rather than nicotinamide adenine dinucleotide cofactor. Moreover, they showed high selectivity for SIRT5 over SIRT1-3 and 6 and could stabilize SIRT5 proteins as revealed by thermal shift analyses. This work provides an effective substrate-mimicking strategy for future inhibitor design, and offers new inhibitors to investigate their therapeutic potentials in SIRT5-associated disease models.

Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses and is implicated in metabolism-related diseases. Small-molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein, we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, six compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of newly synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure-activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC50 value of 5.59 ± 0.75 μM. The biochemical studies revealed that 37 likely acts via competitive inhibition with the succinyl-lysine substrate, rather than the NAD+ cofactor, and it manifested substantial selectivity for SIRT5 over SIRT2 and SIRT6. This study will aid further efforts to develop new selective SIRT5 inhibitors as tools and therapeutics.

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases regulating metabolism and stress responses and are involved in human pathologies such as neurodegeneration. In this study, four fluorogenic small-molecule substrates, i.e., acetyl-(AcBKA), crotonyl-(CrBKA), succinyl-(SuBKA), and myristoyl-(MyBKA)-containing substrates, were synthesized and tested against three representative sirtuin isoforms (i.e., SIRT2, SIRT5, and SIRT6). Enzyme kinetic results indicate that the fluorogenic small-molecule substrates have similar sirtuin-isoform preference as compared to peptide substrates. ITC analyses reveal that AcBKA or MyBKA binding to SIRT2 is mainly driven by entropy, whereas SuBKA binding to SIRT5 is driven by enthalpy. The SIRT5:SuBKA complex crystal structure reveals a new substrate-binding mode that is different from peptide substrate binding modes, but involves Tyr102, Arg105, and other catalytically important residues on Loop S; this indicates that SuBKA is desuccinylated by SIRT5 probably through the catalytic mechanism proposed for peptide substrates. The biophysical and structural results presented herein will provide thermodynamic insights and key pharmacophore features for the development of selective sirtuin isoform-specific inhibitors.

Sirtuins (SIRTs) are NAD+-dependent lysine deacylases, regulating many important biological processes such as metabolism and stress responses. SIRT inhibitors may provide potential benefits against SIRT-driven human diseases. Development of efficient assay platforms based on fluorogenic substrates will facilitate the discovery of high-quality SIRT inhibitors. We here report 16 new fluorogenic peptide substrates (P1-P16) designed with structurally diverse tetrapeptides and acyl modifications. Tests of P1-P16 against SIRT isoforms identified several sensitive substrates for SIRT1, SIRT2, SIRT3 and SIRT5, which manifested lower KM values and higher catalytic efficiency, and particularly had less signal interference in inhibitor screening compared with our previously reported internally quenched fluorescent substrates. Co-crystallization of sensitive substrates P13 and P15 with SIRT5 revealed an unexpected binding mode, involving interactions with residues from active site bordering surfaces, different from that observed for other peptides derived from natural protein substrates. By using SIRT5 sensitive substrates, we found that TW-37, a Bcl-2 inhibitor, displayed low micromolar inhibition to SIRT5, which was further validated by isothermal titration calorimetry analyses, offering a new point to develop dual-action SIRT5/Bcl-2 inhibitors against cancers. This work provides assay platform and structural basis for developing new substrates and inhibitors targeting human SIRTs.

Background and aims 1~4% of acute hepatitis B (AHB) cases in adults progresses to acute liver failure (ALF).The predictors of ALF and prognosis for patients with ALF are not clear. This study investigated some of predictive and prognostic factors for AHB progression to ALF. Methods A retrospective analysis was used to assess the clinical and laboratory features of 293 patients diagnosed with AHB; the patients were divided into the following two groups: ALF (n = 13) and non-ALF (n = 280). Results In total,13 of the 293 (4.43%) patients developed ALF (10 recovered、3 died). The variables of age, anti-HBc IgM titers≥10 S/CO, HBeAg negativity, and total bilirubin (TB) at admission were significantly higher in ALF patients than in non-ALF patients. Compared to non-ALF patients, ALF patients had significantly lower values for prothrombin time activity (PTA), serum albumin, and HBV DNA. At discharge, ALF patients had lower TB normalization rates and much faster clearance of HBsAg, HBeAg and HBVDNA than non-ALF patients. In multivariate analysis, TB≥5×upper limit of normal (ULN) and HBeAg negative status were independent predictors for ALF development at admission, with 84.6% sensitivity, 85.7% specificity, a likelihood ratio of 5.91 and an area under the receiver operating characteristics curve (AUROC) of 0.850.Those who died had lower levels of peak PTA (

Human sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase, and is implicated in human diseases including cancer. Selective small-molecule inhibitors for SIRT2 are sought as chemical tools and potential therapeutics. Here we report the X-ray crystal structure guided structure-activity relationship studies of new N-(3-(phenoxymethyl)phenyl)acetamide derivatives with SIRT2, which led to the identification of potent, selective SIRT2 inhibitors. Crystallographic analyses reveal that the new inhibitors act via inducing the formation of an enlarged hydrophobic pocket and particularly mimicking the interactions made by myristoylated-lysine substrates. The most potent inhibitor 24a could dose-dependently elevate the acetylation level of α-tubulin in the non-small cell lung cancer H441 cells, which have a high expression level of SIRT2 as determinated by Western blotting analyses. Further cellular assays reveal that 24a restrains cell growth mainly through inhibiting cellular proliferation rather than inducing apoptosis. Moreover, 24a could suppress the migration and invasion of H441 cells. These results provide an excellent basis for further development of new potent, selective, and cell active SIRT2 inhibitors as chemical tools and potential therapeutics for SIRT2-driven non-small cell lung cancers.

The 5-fluorocytosine (5-FC) is a fluorinated cytosine analog that is used as an antifungal agent. In this work, we present the hydrogen-bonding base pairs involving 5-FC bound to the four bases in DNA: adenine (A), cytosine (C), guanine (G), and thymine (T). Full geometry optimizations have been performed for the studied complexes by MP2 method. The interaction energies were corrected for the basis set superposition error, using the full Boys–Bernardi counterpoise correction scheme. Hydrogen-bonding patterns of these base pairs were characterized using NBO analysis and AIM analysis. According to the calculated binding energies and structural parameters, the stability of the base pairs decreases in the following order: 5-FC:G > 5-FC:C > 5-FC:A > 5-FC:T.

The O 4-methylthymine (m4T) is a nucleobase lesion induced by the action of ionizing radiation on thymine residue in DNA. In this study, we present the hydrogen-bonding base pairs involving m4T bound to the four bases in DNA: adenine (A), cytosine (C), guanine (G), and thymine (T). Full geometry optimizations have been performed for the studied complexes by MP2 method. The interaction energies were corrected for the basis-set superposition error, using the full Boys–Bernardi counterpoise correction scheme. Hydrogen-bonding patterns of these base pairs were characterized using NBO analysis and AIM analysis. According to the calculated binding energies and structural parameters, the stability of the base pairs decrease in the following order: m4T:G > m4T:A > m4T:C > m4T:T.

Rosemary extract has a potent antioxidant activity and is widely used in the food industry. In this study, the lifespan prolonging and antioxidant activity of rosemary extract was evaluated by high-fat-induced oxidative damage in Drosophila melanogaster. The results revealed that the lifespan and climbing ability of fruit flies was enhanced significantly by feeding rosemary extract. Furthermore, feeding with rosemary extract significantly increased the enzyme activity of superoxide dismutase (SOD) and catalase (CAT), and significantly decreased the level of malonaldehyde. The gene expression of SOD, CAT, and nuclear factor erythroid-2 related factor 2 was enhanced and that for methuselah was significantly reduced. The comet assay showed that high-fat diet-induced DNA lesion was significantly reduced in larvae treated with the rosemary extract. Our results suggest that feeding with rosemary extract is effective to the extended lifespan in fruit flies by strengthening of the resistance to high-fat-induced oxidative stress and by stimulating, at least in part, the endogenous antioxidant response.

The aim of this study was to revise the provisions for aluminum-containing food additives in GB 2760-2011 (The National Food Safety Standard for Use of Food Additives), in order to reduce aluminum exposure among the Chinese population. According to the latest risk assessment results of JECFA and China on aluminum and the actual use of aluminum-containing food additives in certain products, the aluminum-containing food additive-related provisions in GB 2760-2011 were revised. Those revisions included narrowing down the applicable food categories and adjusting the maximum use level of aluminum potassium sulfate and aluminum ammonium sulfate, repealing nine aluminum-containing food additives in puffed food and repealing the use of sodium aluminum phosphate, sodium aluminosilicate and starch aluminum octenylsuccinate in all food. After revision of the use of aluminum food additive provisions, the weekly dietary intake of aluminum in the Chinese population can be reduced to a safe level.

Shear wall structures, frame-shear wall structures and frame-tube wall structures are usually used in tall buildings, especially in China seismic regions. How to simulate the mechanical behaviors of these walls is the key to elastic-plastic analysis for tall buildings. Based on two-spring model, a nonlinear model for spatial walls is proposed. In this model, the axial, shear and flexural elastic-plastic deformation of the walls can be considered, the deformation compatibility between the wall and beam elements is also considered. The model was used to analysis the elastic-plastic behavior of spatial walls. Calculation example for verifying the model indicates that the result obtained by this method has the characteristics of fewer degrees of freedom and high accuracy. Therefore the nonlinear model for spatial walls provides a practical and efficient analysis method for tall buildings with complex type.

Background: The reports of long-term imaging traces for sporadic Creutzfeldt–Jakob disease (sCJD) have been rare to date, although diffusion-weighted imaging (DWI) has high sensitivity and specificity in the diagnosis of sCJD in the early stage of disease. And sCJD-associated neuropathologic brainstem abnormalities on DWI are considered uncommon. Here, we provided a sequential neuroimaging of a late-onset sCJD with medulla oblongata motor nuclei lesion. Case presentation: We report the case of a 77-year-old woman who presented a typical late-onset sCJD clinical manifestation including rapidly progressive dementia, ataxia, and myoclonus, except vision loss. 14-3-3 protein of CSF was found to be positive, blood gene test detected that the polymorphism at codon 129 was M/M subtypes, genotyping the human prion protein gene (PRNP) did not reveal mutations related to hereditary CJD. The hyperintensity was found only in the bilateral cerebral cortices on initial DWI. One month later, increased basal ganglia signal in addition to cortical hyperintensity was found on the follow-up image, which was not consistent with the more frequently MRI profile of sCJD patients over 75 years old. PET/CT imaging detected extra regions with abnormalities as the left thalamus in addition to the hyperintense areas shown on DWI. MRS did not show abnormal metabolism in some areas of DWI abnormalities, but abnormal areas in MRS were accompanied by DWI abnormally high signal. In the late stage, disappearance of abnormal hyperintense lesions on DWI was observed. And very rare clinic characteristic is the subacute and focal involvement of right IX, X and XII nuclei, with abnormalities in the right of medulla oblongata on magnetic resonance imaging (MRI) and DWI from early to late stage, clinical manifestation showing weak pharyngeal reflex, tongue to left, and uvula to left at early stage, suggesting a medulla ischemic event. Sequential electroencephalography recordings showed no characteristic PSWCs in the whole course of the disease. Conclusion: The rapidly progressive clinical course with dementia, ataxia, and myoclonus plus corroborative neuroimaging and spinal fluid findings confirmed a clinicoradiographic diagnosis of Creutzfeldt-Jacob disease. This is an unusual report of an initial clinical presentation involvement of right IX, X and XII nuclei lesions of sCJD, expanding the known clinical spectrum of prion disease presentations.

Immunoassays greatly contribute to veterinary drug residue analysis. However, there are few reports on detecting neomycin residues by immunoassay. Here, a rapid and sensitive chemiluminescent enzyme immunoassay (CLIEA) was successfully developed for neomycin residue analysis. CLIEA demonstrated good cross-reactivity for neomycin, and the IC50 value was 2.4 ng/mL in buffer. The average recovery range was 88.5%-105.4% for spiked samples (10, 50, and 100 μg/kg), and the coefficient of variation was in the range of 7.5%-14.5%. The limit of detection of CLEIA was 9.4 μg/kg, and this method was compared with the liquid chromatography-tandem mass spectrometry method using naturally contaminated samples, producing a correlation coefficient of0.95. We demonstrate a reliable CLIEA for the rapid screening of neomycin in milk.

Rationale Endometrial stromal sarcoma (ESS) is rare, representing only approximately 0.2% of all uterine malignancies. Mixed type endometrial carcinomas (MT-ECs) are rare tumors with both type I and II features, and are difficult to diagnose. Cases of ESS and MT-ECs coexisting in the same patient are extremely rare. This study aimed to describe a case of ESS in combination with MT-ECs in a 47-year-old premenopausal woman. Patient concerns A woman presented to the hospital complaining of occasional abdominal pain and had high tumor markers: cancer antigen (CA) 19-9 (263.6 U/mL) and CA 125 (428.0 U/mL). Transvaginal ultrasound examination revealed a complex mass (12.3 × 9.1 × 6.3 cm) with solid and cystic components on the right rear wall of the uterus. Abdominopelvic computed tomography images showed a pelvic cystic-solid mixed mass. The patient underwent an exploratory midline laparotomy. The mass was hypothesized to be malignant on the uterine posterior wall. Tumor deposits were found on bilateral parametrium. On peritoneal implantation, multiple metastases were seen on the serosal surface of the bowel and greater omentum. A frozen section revealed a spindle cell sarcoma. Diagnoses Pathological reports following surgery revealed concurrent ESS and MT-ECs. Interventions The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, total omentectomy, and macroscopic clearance of the tumor. Adjuvant chemotherapy was given. Outcomes The patient was still alive when this report was written. Lessons Considering the rarity of ESS in combination with MT-ECs, this study presented an overview of the literature and discussed a number of histological and clinical issues. Nevertheless, etiology and pathogenesis of these tumors need further investigation.

This study was to analyze the risk of sulfites in food consumed by the Chinese people and assess the health protection capability of maximum-permitted level (MPL) of sulfites in GB 2760-2011. Sulfites as food additives are overused or abused in many food categories. When the MPL in GB 2760-2011 was used as sulfites content in food, the intake of sulfites in most surveyed populations was lower than the acceptable daily intake (ADI). Excess intake of sulfites was found in all the surveyed groups when a high percentile of sulfites in food was in taken. Moreover, children aged 1-6 years are at a high risk to intake excess sulfites. The primary cause for the excess intake of sulfites in Chinese people is the overuse and abuse of sulfites by the food industry. The current MPL of sulfites in GB 2760-2011 protects the health of most populations.

Although some evidence has been documented on EGFR/PI3K mediation of Akt activation in breast cancers, ILK and DNA-PK have not been investigated so far. The aim of this study was to analyze the expression of phosphorylated Akt (pAkt) in breast cancer, with respect to its upstream regulators. The immunostaining of pAkt (Ser473) in 70 invasive breast cancers revealed that status of CerbB2 could play a major role in Akt phosphorylation, while ILK was also involved in the stimulated level of pAkt. The results would provide an important clue for the activation of Akt and potential targeted therapy in breast cancer.

To examine the validity and reliability of the application of Chinese version of AD8 among patients with Alzheimer's disease (AD), and to explore the discriminative properties of AD8 including score boundaries, sensitivity and specificity in differentiating AD and normal controls.A total of 240 subjects were recruited, including 75 cognitively intact subjects as normal control and 165 patients with AD. Normal control and patients with AD were assessed with Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), and Clock Drawing Test (CDT). All informed normal controls and informants of patients with AD were asked about Chinese version of AD8, among which, 158 informants of patients with AD received AD8 examination again.(1) The Cronbach alpha for Chinese version of AD8 was 0.78. The intraclass correlation coefficient (ICC) of retest reliability was 0.96 (P0.01). (2) The correlation coefficients between each item of AD8 ranged from 0.36 to 0.69 (P0.01). Chinese version of AD8 total scores were strongly positively correlated with CDR global score (r = 0.82, P0.01), and CDR-SB(r = 0.80, P0.01), and negatively correlated with the total score of MMSE (r = -0.75, P0.01) and CDT (r = -0.53, P0.01). (3) For discrimination between normal controls and patients with AD, the AUC was 0.93. Using a cutoff of 2 or greater on Chinese version of AD8 to discriminate dementia, the sensitivity was 93.9%, and specificity was 76.0%.Chinese version of AD8 is a brief and sensitive screening measure with good validity and reliability.

To evaluate the immunotherapeutic potentials for human dendritic cells (DCs) loaded with different HPV16-associated antigens, including HPV16E7 (E) protein, HPV16E7 polypeptide (P), as well as CpG-oligodeoxynucleotide (ODN) 2006 as a promising immune adjuvant for vaccination against cervical carcinoma.DCs derived from human peripheral blood and cord blood were isolated and loaded with HPV-derived protein or peptides, in combination with CpG-ODN2006 as a potential adjuvant. The IL-12 level, the allogeneic T cell-stimulatory capacity and the cytotoxicity of cytotoxic T lymphocytes (CTLs) were evaluated in vitro. Furthermore, an immune reconstitution model of human cervical carcinoma in SCID mice was used to assess the anti-tumor effects in vivo. The tumor sizes, the expression of IgG and IFN-γ, and the presence of the human CD3(+), CD4(+) and CD8(+) T cells were measured in the mice inoculated with different DCs.The antigen-loaded DCs displayed obvious anti-tumor activities in vitro and in vivo, and showed no toxicity to normal cells. The level of IL-12, an important cytokine for immune response, was up-regulated in all mice inoculated with antigen-loaded DCs. Stimulation and activity of CTLs were increased after treatment with antigen-loaded DCs. Significantly, DCs loaded with HPV16E7 polypeptide (P) showed the most distinguished immunotherapeutic activities, and such effect was further enhanced when HPV16E7 polypeptide (P) was used in combination with CpG-ODN2006. Interestingly, the same results were obtained in vivo: the tumor size was decreased, and IgG and IFN-γ levels were increased after the SCID mice were inoculated with the loaded DCs.HPV16E7 polypeptide combined with the immune adjuvant CpG-ODN2006 could be a suitable HPV16-associated tumor antigen. The research provides a new strategy for generating DCs vaccines for immunotherapy of cervical cancer.

To evaluate the relationship between the aberrant expression of P16 and the clinic-pathological features in breast cancers.In our study, 72 cases of breast cancer were collected and the expressions of P16, HER-2 (human epidermal growth receptor-2), ER (estrogen receptor), PR (progesterone receptor), P53, Ki-67 were measured by immunohistochemistry. The correlations between the P16 and the clinic-pathological features (menstruation, tumor size, histological grade, lymph node metastasis were statistically analyzed.Aberrant expression of P16 was detected in 36.1%(26/72)of breast cancers. Not only was the staining of P16 increased,but also the subcellular localization was changed from nuclear to cytoplasm or whole cell staining. In general, the occasional cell staining (+) usually presented in nuclear, as expression increased, P16 showed mainly in cytoplasm or whole cells (+++) even diffusive staining in extracellular, and the moderate staining was multi-focal both in nuclear and cytoplasm. The expression of P16 was significantly increased in ER negative group compared with ER positive group (78.6% vs. 9.1%,P=0.000). Statistical analysis showed a significant correlation of high Ki-67 index with the group of P16 positive (Z =-0.263, P=0.003). In addition, significant difference was calculated between pre- and post-menopause (55.6% vs. 24.4%, P=0.008)and P16 expressions were also more credited to the poor-differentiated group in histological grading: 11.8% (2/17) for highly differentiated group, 27.6% (8/29) for moderately differentiated group and 61.5% (16/26) for poorly differentiated group, respectively (P=0.002).The aberrant expression of P16 in breast cancers correlated closely with loss of estrogen receptor, high proliferation index or high histological grade, predisposed to the patients of pre-menopause, implicating that the aberrant expression of P16 should be a predictor of poor response to endocrine therapy or more aggressive behavior.

The performance of phase-coded signals and a phase-coded signal generator based Direct Digital Synthesis(DDS) are presented in this paper. The binary phase coded waveforms are compared with polyphase coded waveforms. The comparison covers the ambiguity and autocorrection function and the simulation results are given. A realization structure of DDS is proposed. Various types of phase-coded waveforms can be easily designed using this structure by define an additional phase sequences. The realization method of other complex signals which are combined of phase-coded signal and step frequency or variable period signals are introduced.

To investigate the association of multi-modality neuroimaging features and cognitive function in mild cognitive impairment (MCI) and Alzheimer's disease (AD).Nine individuals with amnestic MCI (aMCI), fifteen patients with mild probable AD, and eleven age-controlled cognitively normal controls (NC) were recruited. All participants were administered with mini-mental status examination (MMSE) and Cognitive assessment screening instrument (CASI) to assess general cognitive function. Optimized voxel-based morphometry (VBM) was used for the analysis with 3-D high resolution anatomical images. Values of fractional anisotropy (FA) and mean apparent diffusivity coefficient (ADC) were measured from different brain regions on diffusion-tensor images (DTI). The relationship between structural atrophy and DTI-based measurements in the selected brain regions was examined.The scores of MMSE and CASI were correlated with the volumetric changes in such areas as temporal, frontal and parietal lobes, and cingulate gyrus and hippocampal gyrus (P0.001). The scores of MMSE and CASI were positively correlated with FA values, and negatively with ADC values in the white-matter-affected regions including temporal, frontal, parietal lobes, cingulate gyrus, and parahippocampal gyrus (P0.05).Cognitive decline was associated with atrophy and white matter microstructural alterations in temporal, frontal, parietal lobes, cingulate gyrus, and parahippocampal gyrus in MCI and AD. Multi-modality imaging technique may be important in elucidating the brain mechanism of cognitive impairment.

To explore the effects of the monomer and compound of the Chinese herbal drugs resveratrol, lycium barbarum polysaccharide (LBP) and icariin on 60Co-gamma-induced spermatogenic disturbance in mice based on the theory of modern Chinese medicine.A total of 105 male Kunming mice were randomly divided into seven groups, with 15 in each. Group A were normally raised and Groups B, C, D, E, F and G irradiated by 60Co-gamma 6 Gy followed by 60Co-gamma 4 Gy at the interval of 7 days. A week later, Groups C, D, E, F and G received intragastrically the suspension of resveratrol, resveratrol + LBP, resveratrol + icariin, resveratrol + LBP + icariin and resveratrol + LBP + icariin + L-carnitine, respectively, at the dose of 80 mg/(kg x d) for 60 days. The general condition, physical signs and body weight changes of the mice were recorded, and 24 hours after the intragastric medication, their testes were harvested to obtain the testicular weight and indexes, the levels of FSH, LH, T and E2 determined by ELISA, the T/E2 ratio calculated, and the histology of the testis tissues observed under the microscope.The testicular indexes of the mice were decreased by radiation-induced damage, but restored to some extent after intragastric medication, especially in Groups E, F and G. The levels of FSH, LH and T were obviously improved by LBP. The T level and testis weight were increased by Icariin. The level of T/E2 was elevated in Groups E, F and G. The best results were achieved in Group F, which exhibited almost complete recovery from reproductive endocrine disorder and spermatogenic damage.The Chinese medicinal monomer is effective for 60Co-gamma-induced spermatogenic disturbance in mice, and the compound suspension of resveratrol + LBP + icariin produces the best result.

Peroxynitrite (ONOO(-)) and hypochlorous acid (HOCl) are two highly reactive oxygen species generated in biological systems. The overproduction of peroxynitrite or hypochlorous acid is implicated in a broad array of human pathologies including vascular, immunological, and neurodegenerative diseases. However, unambiguous detection of these reactive oxygen species has been relatively difficult due to their short biological half-lives and multiple reaction pathways. Based on their specific chemical reactions, we have developed fluorescent probes HKGreen-1 and HKOCl-1 for highly sensitive detection of peroxynitrite and hypochlorous acid, respectively. Both probes have been demonstrated to be able to discriminate corresponding reactive species from other reactive oxygen and nitrogen species (ROS and RNS) in not only chemical systems but also biological systems. The endogenous production of peroxynitrite in neuronal cells under oxygen-glucose deprivation (OGD) conditions has been visualized for the first time by utilizing HKGreen-1 probe, whilst the endogenous production of hypochlorous acid in macrophage cells upon stimulation with LPS, IFN-gamma, and PMA has been imaged by utilizing HKOCl-1 probe.

Peroxynitrite (ONOO(-)) and hypochlorous acid (HOCl) are two highly reactive oxygen species generated in biological systems. The overproduction of peroxynitrite or hypochlorous acid is implicated in a broad array of human pathologies including vascular, immunological, and neurodegenerative diseases. However, unambiguous detection of these reactive oxygen species has been relatively difficult due to their short biological half-lives and multiple reaction pathways. Based on their specific chemical reactions, we have developed fluorescent probes HKGreen-1 and HKOCl-1 for highly sensitive detection of peroxynitrite and hypochlorous acid, respectively. Both probes have been demonstrated to be able to discriminate corresponding reactive species from other reactive oxygen and nitrogen species (ROS and RNS) in not only chemical systems but also biological systems. The endogenous production of peroxynitrite in neuronal cells under oxygen-glucose deprivation (OGD) conditions has been visualized for the first time by utilizing HKGreen-1 probe, whilst the endogenous production of hypochlorous acid in macrophage cells upon stimulation with LPS, IFN-gamma, and PMA has been imaged by utilizing HKOCl-1 probe.

The aim of the study is to investigate the prevalence of cognitive impairment 100 and frontotemporal dysfunction in Chinese patients with motor neuron disease (MND).patients diagnosed as MND underwent a series of survey including mini mental state examination (MMSE), neuropsychiatry inventory (NPI), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA).Demographics, site of onset, and disease severity-functional rating scale (FRS) were also investigated.The prevalence of mild cognitive impairment determined with MMSE score was 24.2%. Comparison between patients with normal and abnormal MMSE showed statistic differences in depression state and FRS score. Since patients with anxiety and depression would also have abnormal NPI, a follow up study after 3-month antidepressive therapy for the depression patients was made and 2 patients were found to have probably frontotemporal dysfunction lasting for more than 6 months.MND patients might have mild impairment of cognitive function and some of the patients were neuroethologically abnormal. 2 of the patients might have frontotemporal dysfunction.

A fluorescent probe, HKGreen-2, has been developed based on a specific reaction between ketone and peroxynitrite (ONOO(-)). This probe is highly sensitive and selective for the detection of peroxynitrite not only in abiotic but also in biological systems. With this probe, we successfully detected peroxynitrite generated in murine macrophage cells activated by phorbol 12-myristate 13-acetate (PMA), interferon-gamma (IFN-gamma), and lipopolysaccharide (LPS). This new probe will be a useful tool for studying the roles of peroxynitrite in biological processes.