Thermal ionization mass spectrometry (TIMS) offers the excellent precision and accuracy of the Sr and Nd isotopic ratio analysis for geological samples, but this method is labour intensive, expensive and time-consuming. In this study, a new analytical protocol by TIMS is presented that aims at improving analytical efficiency and cutting down experimental cost. Using the single-step cation exchange resin technique, mixed Sr and rare earth elements (REEs) fractions were separated from matrix and evaporated to dryness. Afterwards, mixed Sr+REEs fractions were dissolved and loaded onto the same Re filament using 1μL of 2M HCl. Then, Sr and Nd were sequentially measured without venting using TIMS. In contrast to conventional TIMS methods, the merits of this analytical protocol are its cost- and time-saving adaptations. The applicability of our method is evaluated by replicated measurements of (87)Sr/(86)Sr and (143)Nd/(144)Nd for nine international silicate rock reference materials, spanning a wide range of bulk compositions. The typical internal precision in this study is ca. 0.001%(RSE) for (87)Sr/(86)Sr and (143)Nd/(144)Nd; the analytical results obtained for these standard rocks show a good agreement with reported values, indicating the effectiveness of the proposed method.

AIM To develop a prognostic approach for gastrointestinal stromal tumors (GISTs) using a cluster of indicators and follow-up information. METHODS One hundred and four GISTs that had not been subjected to targeted therapies were collected and classified by NIH risk assessment and anatomic location. By immunohistochemistry, the expressions of PTEN, Ki-67, CD44s matrix metalloproteinase (MMP)-9 and TIMP-1 were detected on tissue microarray. Univariate and multimarker survival analyses were performed and then a COX hazard proportion model was constructed to evaluate a cluster of predictors of GIST. RESULTS Our data showed small intestinal GIST are more aggressive than gastric GIST. The NIH risk assessment correlated with disease-free survival for either gastric GIST or small intestinal GIST. Immunohistochemical analysis revealed that Ki-67 labeling indexes (LIs)< 5% predicted higher disease-specific survival (DSS) in gastric and small intestinal GIST. CD44s positivity and PTEN LIs ≥ 50% correlated with higher DSS in gastric GIST. MMP-9 and TIMP-1 had no correlation with survival. Multimarker analysis revealed that the expression pattern of PTEN LIs ≥ 50% combined with Ki-67 LIs < 5% and CD44s positivity reliably predicted favorable outcomes for gastric GIST (P = 0.009), as did the combination of PTEN LIs ≥ 50% and Ki-67 LIs < 5% for small intestinal GIST (P = 0.011). Authors also found that high NIH risk grade was correlated with DSS in patients with gastric GIST and disease-free survival in patients with small intestinal GIST. CONCLUSION PTEN LIs ≥ 50%, Ki-67 LIs < 5% and CD44s positivity provides an accurate, favorable prognosis for gastric GIST. PTEN LIs ≥ 50% and Ki-67 LIs < 5% does the same for small intestinal GIST. Ki-67 LIs enhances the NIH assessment.

Effects of active modified atmosphere packaging (initial O(2)/CO(2): 5/5; 30/5; and 80/0) and passive packaging [initial O(2)/CO(2): 20.8/0 (air)] on the antioxidant capacity and sensory quality of fresh-cut 'Yaoshan' pear stored at 4 °C for 12 days were investigated. Samples stored in high O(2)(30% and 80%) packages had higher phenolics and anthocyanin contents compared with those in passive and low O(2) packages. After 12 days of storage, phenolics and anthocyanin contents of 80% O(2) samples were 2.5 and 12 times, respectively, higher than those in the passive package and 3 and 2 times higher than those in low O(2) package. High O(2) modified atmosphere packaging was effective in keeping free radical scavenging capacity as measured by the DPPH assay. The sensory evaluation indicated that surface color of cut fruits were stable for at least 12 days in the high O(2) modified atmosphere packaging. The results suggested that high O(2) modified atmosphere packaging could be used to inhibit browning and prolong the shelf life of fresh-cut 'Yaoshan' pears in spite of more than 50% loss in vitamin C content.

Numerous studies have demonstrated that learning and memory abilities in the course of normal aging cognitive abilities tend to decline and Nrf2 expression appears to decline with aging. So, Nrf2 pathway has been identified as a promising therapeutic target for neurodegenerative diseases. The organosulfur compounds, allicin can activate Nrf2, because it has an electrophilic center, which can serve as an attack site for nucleophiles, such as specific protein sulfhydryl groups present on Keap1. However, the influence of allicin on aging-induced cognitive deficits has not been examined. In this study, we assess the effects of allicin on endogenous antioxidant defenses in hippocampus of cognitively impaired aged mouse. Our results indicate that treatment of allicin significantly ameliorated ageing-induced cognitive dysfunction through enhancing of Nrf2 antioxidant signaling pathways. Therefore, allicin could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in aging and Alzheimer's disease.

A single-step separation scheme is presented for Sm-Nd radiogenic isotope system on very small samples (1-3 mg) of silicate rock. This method is based on Eichrom(®) LN Spec chromatographic material and affords a straightforward separation of Sm-Nd from complex matrix with good purity and satisfactory blank levels, suitable for thermal ionization mass spectrometry (TIMS). This technique, characterized by high efficiency (single-step Sm-Nd separation) and high sensitivity (TIMS on NdO(+) ion beam), is able to process rapidly (3-4 h), with low procedure blanks (<10 pg) and very small sample (1-3 mg). Replicate measurements by TIMS on (143)Nd/(144)Nd ratios and Sm-Nd concentrations are presented for eleven international silicate rock reference materials, spanning a wide range of Sm-Nd contents and bulk compositions. The analytical results show a good agreement with recommended values within ±0.004% for the (143)Nd/(144)Nd isotopic ratio and ±2% for Sm-Nd quantification at the 95% confidence level. It is noted that the uncertainty of this method is about 3 times larger than typical precision achievable with two-stage full separation followed by state-of-the-art conventional TIMS using Nd(+) ion beams which require much larger amounts of Nd. Hence, our single-step separation followed by NdO(+) ion beam technique is preferred to the analysis for microsamples.

OBJECTIVE: To describe the clinical features of infection, and the antibiotic susceptibility of epidemic strains, and investigate plasmid maps and integrons of the isolates from an outbreak of Shigella sonnei infection at an elementary school in southwest China. STUDY DESIGN: Cross-sectional study. SETTING: An elementary school and five hospitals in Chengdu in southwest China. RESULTS: There were 1,134 students in the school. 937 (82.6%) students had signs and symptoms. Of the 568 (60.6%, 568/937) hospitalized students, 93.3% 86.8%, 72.4%, and 28.9% of the hospitalized patients had diarrhea, fever, abdominal pain, and vomiting, respectively. S. sonnei strains were isolated from the stool samples of 36.0%(337/937) students. All of the outbreak isolates had the same high-level antimicrobial resistance and plasmid profiles, which were different from that of sporadic strains. All the outbreak S. sonnei isolates were positive for the integrin gene and contained class 2 integron; however, two outbreak isolates contained class 1 and class 2 integrons. CONCLUSIONS: Diarrhea, fever, and abdominal pain were the three most common clinical manifestations observed in patients infected with S. sonnei. High-level antibiotic resistance was observed among Shigella species.

Objectives:  This study aims to determine the role of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine associated with cell proliferation and tumour growth in vivo. Materials and methods:  Our team used RNA interference technology to knock down MIF expression in human HeLa cervical cancer cells and to establish a stable cell line lacking MIF function. Results:  Our results showed that long-term loss of MIF had little effect on cell morphology, but significantly inhibited their population growth and proliferation. The HeLa MIF-knockdown cells retained normal apoptotic signalling pathways in response to TNF-alpha treatment; however, they exhibited unique DNA profiles following doxorubicin treatment, suggesting that MIF may regulate a cell cycle checkpoint upon DNA damage. Our data also showed that knockdown of MIF expression in HeLa cells led to increased cell adhesion and therefore impaired their migratory capacity. More importantly, cells lacking MIF failed to either proliferate in soft agar or form tumours in vivo, when administered to nude mice. Conclusion:  MIF plays a pivotal role in proliferation and tumourigenesis of human HeLa cervical carcinoma cells, and may represent a promising therapeutic target for cancer intervention.

BACKGROUND Glyoxalase I (GLO1), which is the major enzyme that catalyzes the metabolism of methylglyoxal (MG), may play an important role in the pathogenesis of diabetic microvascular complications. AIM To investigate whether the C-7T and A419C polymorphisms of the GLO1 gene are associated with nephropathy and retinopathy in Chinese Type 2 diabetic patients. SUBJECTS AND METHODS A total of 364 Type 2 diabetic patients and 301 healthy controls were enroled in the study. Diabetic microvascular complications were determined by urinary albumin excretion measurements and ophthalmological examinations. Genetic analyses were performed using either Taqman PCR or direct sequencing. The effect of C-7T polymorphism on promoter activity was measured by reporter gene assays. RESULTS The albumin/ creatinine ratio (ACR) and prevalence of nephropathy and retinopathy were significantly higher in diabetic patients with GLO1 -7CC genotype than in patients with -7CT and -7TT genotypes (p=0.02, p=0.02, and p=0.04, respectively). The - 7CC genotype is independently associated with ACR (β=0.13, p=0.01) and the risk for retinopathy [odds ratio (OR): 2.30, 95% confidence interval (CI): 1.25-4.24, p<0.01]. The luciferase activity of the -7T promoter was higher than that of the -7C promoter (13.2±0.2 vs 11.7±0.8, p=0.04). No differences were found between ACR and the prevalence of nephropathy and retinopathy for A419C polymorphism in Type 2 diabetic patients. CONCLUSIONS GLO1 C-7T polymorphism alters promoter activity and confers susceptibility to nephropathy and retinopathy to Type 2 diabetic patients.

BACKGROUND Previous studies suggested that a finite course of peginterferon alfa-2a may offer an alternative rescue therapy for patients with lamivudine resistance. However, because of the limitation of study design and small sample size, it is difficult to make definitive conclusion. AIM To explore the role of peginterferon alfa-2a, in the rescue treatment of HBeAg-positive chronic hepatitis B patients with lamivudine resistance. METHODS In this randomised study, chronic hepatitis B patients with lamivudine resistance were treated with peginterferon alfa-2a for 48 weeks (n=155) or adefovir for 72 weeks (n=80). All enrolled patients were treated with lamivudine for the first 12weeks. RESULTS At 6 months posttreatment, 14.6%(18/123) of peginterferon alfa-2a-treated patients achieved HBeAg seroconversion, in contrast to 3.8%(3/80) of adefovir-treated patients after 72 weeks continuous therapy (P=0.01). For peginterferon alfa-2a-treated patients, the rate of HBeAg seroconversion at week 72 was significantly higher in patients who had HBsAg decline >0.5 Log(10) IU/mL from baseline at week 24, compared with patients with HBsAg decline ≤0.5 Log(10) IU/mL from baseline at week 24 (25.5% vs. 7.7%, P=0.01). After 72 weeks continuous adefovir treatment, 22.5% of patients achieved HBV DNA <80 IU/mL, compared with 10.6% in peginterferon alfa-2a-treated patients at 6months off-treatment (P=0.02). CONCLUSIONS Overall, the response to peginterferon alfa-2a among patients with lamivudine resistance was suboptimal. HBeAg seroconversion rate at week 72 by 48 weeks peginterferon alfa-2a treatment was higher than continuous adefovir therapy. Monitoring HBsAg levels can help to predict response to peginterferon alfa-2a.

BACKGROUND   Sensory sensitization is one of the main pathophysiological hypotheses in functional gastrointestinal disorders (FGIDs). As sensitization may affect various sensory modalities, we aimed to develop a reproducible gastric pain model utilizing polymodal pathways for use in functional and other pain disorders. METHODS In this double-blind, cross-over study 42 healthy subjects swallowed one capsule containing either capsaicin 0.5mg or nocebo every 15min until moderate pain (intensity >30 on 100mm visual analogue scale) was attained for at least 5min. Pain was rated every minute. Capsaicin titration was repeated thrice for reliability calculation. KEY RESULTS Moderate pain in the upper abdomen was successfully achieved in 38 of 42 subjects (90%) with capsaicin titration and in one of 42 (2%) with nocebo. The median dosage required to induce moderate pain for at least 5min was two capsules (interquartile range 1-3) and the median gastric pain intensity was 47 (41-53). The median duration of moderate pain was 8min (5-12). Moderate pain was successfully reproduced with capsaicin in all subjects on study days 2 and 3, with an excellent Cronbach reliability coefficient of >0.8. CONCLUSIONS & INFERENCES Standardized gastric pain can be conveniently achieved in a majority of healthy subjects using a simple oral capsaicin titration, with minimal adverse events. The between-test reproducibility is high and nocebo responses are negligible. This technique stimulating a multimodal physiological pathway will be useful in the investigation of sensory changes in FGIDs, including functional dyspepsia.