Integration of solid-phase microextraction and surface-enhanced Raman spectroscopy for in-vivo screening of polybrominated diphenyl ether.

The monitoring of polybrominated diphenyl ethers (PBDEs) is of great significance owing to their high persistence, bioaccumulation, and toxicity to humans and animals. In this study, a sensitive and reproducible probe that integrates solid-phase microextraction and surface-enhanced Raman spectroscopy (SPME-SERS) was developed for screening PBDEs in multiphase specimens, including live fish, water, and electrical products. A roughed Cu fiber with an Ag layer was fabricated with dual functions. BDE-15 was readily extracted and detected on the SPME-SERS probe consisting of propanethiol-modified Ag nanoplates on a Cu wire. A clear linear relationship (R2 = 0.988) was established between the SERS intensity at 782 cm-1 and the logarithmic concentrations (from 100 ppb to 100 ppm), with a detection limit of 15 ppb. This proposed method enables continuous in vivo monitoring in fish without complicated pretreatments. The results obtained by this SPME-SERS approach were validated by high-performance liquid chromatography and showed good agreement. This "extracting and detecting" SPME-SERS method provides a potential tool to monitor the occurrence, formation, and migration of PBDEs.

Rapid and robust analysis of aristolochic acid I in Chinese medicinal herbal preparations by surface-enhanced Raman spectroscopy.

The use of Chinese herbs containing aristolochic acid can induce the exchange of adenine and thymine in gene mutations and even cause liver cancer. To eliminate the harm of aristolochic acids (AAs) to humans, a rapid and robust method of AAs screening is a prerequisite. In this work, a facile and robust Surface-enhanced Raman spectroscopy (SERS) method was used for the qualitative and quantitative detection of AAs in Chinese medicinal herbal preparations based on the mandelic acid modified Ag nanoparticles SERS substrate. Qualitative and quantitative SERS detection of Aristolochic acid I (AAI) was achieved with a good linear relationship ranging from 0.2 - 120.0 µM and a limit of detection (LOD) of 0.06 µM. The proposed method demonstrates a refined strategy for sensitivity analysis of AAs with the advantages of easy operation, time-saving, high sensitivity, and molecular specificity, making it a preferred platform for the screening of AAI in regular inspections of herbal products and regulatory supervision of the supply chain.

YTHDF1 promotes intrahepatic cholangiocarcinoma progression via regulating EGFR mRNA translation.

BACKGROUND AND AIM: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive disease with the underlying mechanisms poorly understood. YTHDF1, an N6 -methyladenosine (m6 A) reader protein, has important physiological functions in regulation of tumor development. However, the effect of YTHDF1 on ICC progression remains unknown yet. METHODS: The expression level of YTHDF1 in human ICC tissue was examined in The Cancer Genome Atlas database and our cohort. The role of YTHDF1 was detected using two human ICC cell lines in vitro. An ICC tumorigenesis mouse model was established via hydrodynamic transfection of AKT/YAP plasmids. m6 A sequencing, RNA immunoprecipitation sequencing, and RNA sequencing were carried out to explore the mechanism of YTHDF1 modulating ICC progression. RESULTS: Here, we find that YTHDF1 is upregulated in ICC and associated with shorter survival of ICC patients. Depletion of YTHDF1 inhibits cell proliferation, migration, and invasion, while overexpression of wild-type YTHDF1, but not m6 A reader domain mutant YTHDF1, significantly enhances tumor cell growth and aggressive abilities in vitro. Moreover, overexpression of YTHDF1 promotes the AKT/YAP transfection-induced orthotopic ICC tumorigenesis and progression in vivo. Mechanistically, we identify that YTHDF1 regulates the translation of epidermal growth factor receptor (EGFR) mRNA via binding m6 A sites in the 3'-UTR of EGFR transcript, thus leading to aberrant activities of downstream signal pathways that impact tumor progression. CONCLUSIONS: Our data uncover the oncogenic function and m6 A reader-dependent mechanism of YTHDF1 in regulation of ICC progression. Restricting abnormal oncogenic mRNA translation by targeting YTHDF1 may be a novel and promising strategy for ICC treatment.

Ethyl carbamate in Chinese liquor (Baijiu): presence, analysis, formation, and control.

Ethyl carbamate (EC) is a genotoxic and carcinogenic compound that is also a by-product of fermented foods (bread, sour milk, soy cheese, etc.) and alcoholic beverages (wine, sake, distilled liquor, etc.). Studies have showed that ethyl carbamate is ingested by humans primarily through the consumption of alcoholic beverages. Many countries have thus established EC limits for alcoholic beverages. Chinese liquor (Baijiu) is a traditional and unique distilled liquor, which has a huge consumption in China due to its excellent color, flavor, and taste. Therefore, the control of EC in Chinese liquor is of great significance. This review summarized for the first time the progress in presence level, analysis method, formation mechanism, and elimination strategy of EC of Chinese liquor in recent decades. KEY POINTS: • GC-MS and HPLC are the main methods to quantify EC in Chinese liquor. • EC is formed in the fermentation, distillation, and storage stage. • EC content can be reduced from raw material, microorganism, and production process.

Long-Term Survival of Patients With Chemotherapy-Naïve Metastatic Nasopharyngeal Carcinoma Receiving Cetuximab Plus Docetaxel and Cisplatin Regimen.

Purpose: Metastatic nasopharyngeal carcinoma (mNPC) remains incurable. This prospective study aimed to investigate whether adding cetuximab to cisplatin-based induction therapy could improve efficacy and survival for chemotherapy-naïve mNPC patients. Patients and Methods: Eligible chemotherapy-naïve mNPC patients were enrolled, including those initially diagnosed with mNPC (IM) and those with first-relapse metastases after radiotherapy (RM). Patients all received induction chemotherapy (IC) including docetaxel and cisplatin plus cetuximab. Those who obtained objective remission after IC would continue to receive radiotherapy concurrent with cetuximab and cisplatin, and further capecitabine as maintenance. Contemporaneous patients who received conventional therapy served as controls. Results: Forty-three patients were enrolled, including 17 IM and 26 RM patients. Thirty-nine (90.7%) patients had WHO III subtype. The overall response and complete response (CR) rates were, respectively, 79.1 and 34.9% after induction therapy and 76.7 and 46.5% after chemoradiotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) rates reached 34.9 and 30%, respectively. Subgroup analysis showed that compared with RM patients, IM patients had a higher 5-year OS (58.8 vs. 19.2%) and PFS (52.9 vs. 19.2%). The IM group had a higher CR rate of induction treatment than the RM group (52.9 vs. 23.1%). No treatment-related death was observed. Twelve patients (27.9%) remained alive with disease-free survival times from 60+ to 135+ months. Control patients showed a substantially lower survival rate (5-year OS, 10.9%) and few long-term survivors. Conclusions: This regimen resulted in significantly improved efficacy and survival, which indicates a potentially curative role for chemotherapy-naïve mNPC, especially in newly diagnosed patients. A phase III clinical trial (NCT02633176) is ongoing for confirmation.

Development and Validation of a Risk Score for Prediction of Venous Thromboembolism in Patients With Lung Cancer.

This study aimed to develop and validate a risk score for early prediction of venous thromboembolism (VTE) in patients with lung cancer. A total of 827 patients with lung cancer from February 2013 to February 2018 in our hospital were retrospectively analyzed. Demographic and clinicopathological variables independently correlated to VTE were applied to develop the risk score in the development group while examined in the validation group. The regression coefficients of multivariable logistic regression test were applied to assign a risk score system. The incidence of VTE was 12.3%, 12.7%, and 11.8% in all patients, in the development and validation groups, respectively. The 496 patients in the development group were classified into 3 groups: low risk (scores ≤3), moderate risk (scores 4-5), and high risk (scores ≥6). The risk of VTE was significantly and positively related to the risk scores in both development and validation groups. The risk score system aided proper stratification of patients with either high or low risk of VTE in the development and validation groups (c statistic = 0.819 and 0.827, respectively). This risk score system based on the factors with most significant correlation showed good predictive ability and is potentially useful for predicting VTE in patients with lung cancer. However, it was developed and validated by a retrospective analysis and has significant limitations, and a prospective validation with all the classic variables assessing the thrombotic risk is needed for a solid conclusion.

TBH score: a new model to predict and prevent severe liver damage after chemotherapy for cancer patients.

PURPOSE: To explore a quantitative predictive model for the risk of chemotherapy-induced severe liver damage (CISLD). MATERIALS AND METHODS: In total, 3870 consecutive cancer patients initially treated with chemotherapy were retrospectively collected and randomly assigned to a training (n=2580) or internal validation (n=1290) set in a 2:1 ratio to construct and validate the model. Additional external validation was performed using another data set (n=413). A total of 486 patients were prospectively enrolled to assess the clinical significance of the model. CISLD was defined as grade ≥3 hepatotoxicity. RESULTS: CISLD was found in 255 (9.9%), 128 (9.9%) and 36 (8.7%) patients in the training, internal and external validation sets, respectively. Serum triglyceride, body mass index and history of hypertension formed the basis of the score model. Patients could be stratified into low, intermediate and high-risk groups with <10%, 10-30% and >30% CISLD occurrence, respectively. This model displayed a concordance index (C-index) of 0.834 and was validated in both the internal (C-index, 0.830) and external (C-index, 0.817) sets. The incidence of CISLD was significantly reduced in those who received preventive hepatoprotective drugs compared to those who did not among patients assessed as the intermediate risk group (8.9% vs 17.5%, p=0.042) and the high risk group (15.6% vs 55.8%, p=0.043). CONCLUSIONS: The new score model can be used to accurately predict the risk of CISLD in cancer patients undergoing chemotherapy. Clinically, this can be translated into a reference tool for oncologists in the clinical decision-making process before chemotherapy to provide appropriate prevention and interventions for patients with a high risk of CISLD.

Allyl methyl trisulfide protected against acetaminophen (paracetamol)-induced hepatotoxicity by suppressing CYP2E1 and activating Nrf2 in mouse liver.

In order to investigate the protective effects of allyl methyl trisulfide (AMTS) on acetaminophen (APAP)-induced hepatotoxicity, 75 KM mice were randomized into 5 groups, i.e. a control group, an APAP group, and three AMTS/APAP groups. The mice in the AMTS/APAP groups and APAP group were gavaged with 25-100 mg kg-1 AMTS or corn oil for 7 d followed by intraperitoneal injection of 300 mg kg-1 APAP, while mice in the control group were treated with a vehicle. We found that AMTS significantly attenuated APAP-induced hepatotoxicity shown by reduced mortality, decreased serum aminotransferase activities, and improved liver histological morphology. APAP overdose resulted in a significant increase of hepatic malondialdehyde (MDA) level and a decrease of the protein levels of NQO-1, γ-GCS, HO-1, and SOD, which was suppressed by AMTS pretreatment. Furthermore, AMTS inhibited the APAP-induced elevation of hepatic p62 and LC3II protein levels. Interestingly, AMTS attenuated the APAP-induced decline of hepatic CYP2E1 protein levels, but AMTS alone led to the decrease of CYP2E1 protein expression in mouse liver. Collectively, these data suggest that AMTS could attenuate APAP-induced hepatotoxicity by suppressing CYP2E1 and activating Nrf2.

Curcumin exerts cytotoxicity dependent on reactive oxygen species accumulation in non-small-cell lung cancer cells.

AIM: Curcumin induces cytotoxic cell death in several human cancer cells. Here, we have investigated the effects of curcumin on non-small-cell lung cancer (NSCLC) with an aim to identify underlying mechanisms of its cytotoxic effect. MATERIALS & METHODS: The effects of various concentrations of curcumin on the NSCLC cell lines A549 and SPC-A1 were evaluated by MTT assay, colony-forming assay and flow cytometry. Additionally, protein expression associated with different signaling pathways was assessed using western blotting. RESULTS: Curcumin exhibited cytotoxicity against NSCLC, evident from the inhibition of cell proliferation, G2/M arrest, DNA damage, endoplasmic reticulum stress and mitochondrial apoptosis. The anticancer effect was related to reactive oxygen species (ROS) accumulation and could be reversed by ROS scavengers, catalase and N-acetyl-l-cysteine. Curcumin decreased mitochondrial transmembrane potential and induced ROS production, thereby activating the DNA damage/repair pathway and mitochondrial apoptosis. CONCLUSION: These results indicate that curcumin could be an effective therapeutic candidate for NSCLC.

Recombinant human thrombopoietin (rh-TPO) for the prevention of severe thrombocytopenia induced by high-dose cytarabine: a prospective, randomized, self-controlled study.

The aim of this randomized phase II study was to investigate the optimal timing of the administration of thrombopoietin to prevent cytarabine-induced thrombocytopenia. Fifty-two patients who were scheduled for high-dose cytarabine treatment were randomly assigned to receive either the standard prophylactic mode (starting thrombopoietin, 15,000 units/day on days 2-11) or the pre-chemo mode (starting thrombopoietin, 15,000 units/day on days -4, -2, and 2-9) during the first cycle of chemotherapy with a switch to the other mode in the second cycle. The thrombocytopenia rate in the standard mode and the pre-chemo mode were PLT < 50 × 109/L, 67.3% versus 46.2% (p = .001); and PLT < 25 × 109/L, 48.1% versus 26.9% (p = .001). The platelet transfusion rate was reduced in pre-chemo mode, with 7 patients requiring 10 units of platelets, whereas 13 patients required 24 units in standard mode (p = .038). Grade III/IV thrombopoietin-related toxicity was not observed. The prophylactic use of thrombopoietin was effective and safe. Trial registration: ChiCTR-OPB-15007591.

Low NR3C2 levels correlate with aggressive features and poor prognosis in non-distant metastatic clear-cell renal cell carcinoma.

NR3C2 has previously been described as a tumor suppressor gene in several cancers; however the prognostic significance and biological function of NR3C2 in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) remain largely unclear. The prognostic value of NR3C2 expression was evaluated using data from The Cancer Genome Atlas (TCGA) and 181 patients with non-metastatic ccRCC undergoing nephrectomy in our center. Predictive nomograms were generated and identified independent prognosticators to assess ccRCC patient overall survival (OS) and progression free survival (PFS) at 1, 5, and 8 years. The functional involvement of NR3C2 in RCC was examined in both in vitro and in vivo models upon overexpression of NR3C2. NR3C2 was found to be downregulated in tumor tissues and was correlated with several clinicopathological parameters, including the T status (p <0.001) and histological Fuhrman grade (p = 0.002). Both Cox regression analysis and Kaplan-Meier survival curves showed that low NR3C2 expression correlated with poor OS (HR = 2.21, p = 0.014) and PFS (HR = 1.71, p = 0.051). The incorporation of NR3C2 status into the T stage, UISS, or SSIGN scores helps to refine individual risk stratification. The newly built nomograms involving NR3C2 expression could better predict OS and PFS. Overexpression of NR3C2 inhibited RCC cell proliferation, colony formation, invasion, migration, and vasculogenic mimicry in vitro and reduced the growth of RCC xenografts in vivo. Together, these results suggest that NR3C2 may serve as a potential prognostic factor in non-metastatic ccRCC patients after nephrectomy and is involved in RCC oncogenesis.

ß-arrestin1-medieated inhibition of FOXO3a contributes to prostate cancer cell growth in vitro and in vivo.

Recently, ß-arrestin1 has been indicated as a prostate cancer promoter through promoting cell proliferation and epithelial to mesenchymal transition, but its underlying mechanism remains unclear. Here, our data revealed that ß-arrestin1 could promote cell growth through inhibiting the transcriptional activity and expression of FOXO3a in prostate cancer cells in vitro and in vivo. We found that ß-arrestin1 could promote the cell and tumor growth of prostate cancer, and ß-arrestin1 expression represented a negative correlation with FOXO3a expression but not FOXO1 expression in prostate cancer cell lines and tissues. In addition, forced expression of ß-arrestin1 induced a significant decrease of FOXO3a expression but had no clear effect on FOXO1 expression. Mechanistically, ß-arrestin1 could interact with FOXO3a and MDM2, respectively, and promote the interaction between FOXO3a and MDM2, whereas it had no obvious interaction with FOXO1. Furthermore, ß-arrestin1 could inhibit the transcriptional activity of FOXO3a via Akt and ERK1/2 pathways. Together, our results revealed a novel mechanism for ß-arrestin1 in the regulation of the prostate cancer procession through inhibiting FOXO3a.

TRPM7 Regulates AKT/FOXO1-Dependent Tumor Growth and Is an Independent Prognostic Indicator in Renal Cell Carcinoma.

Transient receptor potential melastatin 7 (TRPM7) is important for the tumorigenesis and progression of several cancers. However, little is known about TRPM7 expression and its clinical significance in clear cell renal cell carcinoma (ccRCC). The expression dynamics of TRPM7 was examined in a clinical cohort of RCC specimens by qPCR, immunoblotting, and IHC staining. A series of in vitro and in vivo assays were performed to elucidate the function of TRPM7 in RCC and the underlying mechanisms. For the first time, results demonstrate that TRPM7 expression is markedly higher in RCC cell lines and clinical samples and had a positive correlation with T status, tumor size, and poor patients' overall survival and progression-free survival. Preclinical studies using multiple RCC cells and a mouse model indicate that TRPM7 promotes cell proliferation and colony formation in vitro and tumor growth in vivo Mechanistically, TRPM7 promotes AKT phosphorylation, leading to repression of the FOXO1 expression and transcriptional activity. Moreover, luciferase reporter assays demonstrate that miR-129-3p directly targets the 3'-UTR of TRPM7 and acts as a negative regulator of TRPM7. These findings reveal an important role for TRPM7 in the regulation of RCC growth and represent a novel prognostic biomarker for this disease.Implications: TRPM7 is an independent prognostic indicator in RCC, and targeting the TRPM7 signaling pathway may be a novel therapeutic approach for the treatment of RCC. Mol Cancer Res; 16(6); 1013-23. ©2018 AACR.

Partial versus radical nephrectomy for T1b-2N0M0 renal tumors: A propensity score matching study based on the SEER database.

PURPOSE: Controversy continues on the tailored therapy for patients with larger renal cell carcinoma (RCC). We investigated whether partial nephrectomy (PN) can improve patient prognosis compared to radical nephrectomy (RN) and the indications for each approach in patients with T1b-2N0M0 RCC. MATERIALS AND METHODS: A total of 9907 patients were identified from the Surveillance, Epidemiology, and End Results database from 2004 to 2012. Propensity scores were used to balance the selection bias of undergoing PN. Overall (OS) and cancer-specific survival (CSS) of patients undergoing PN and RN were compared. Cases were subdivided to investigate the advantages of each procedure. RESULTS: Overall, 1418 (14.3%) patients underwent PN. Before matching, PN led to better OS and CSS than RN in both Kaplan-Meier analysis and Cox regression (each p<0.01). For 1412 matched cohorts, PN was no longer associated with significantly better OS (HR: 1.19, 95% CI: 0.98-1.44), but still with a better CSS (HR: 1.66, 95% CI: 1.18-2.27) compared with RN. Further subgroup analysis indicated that patients, who were male, single living, old than 65 years, with T1b stage or clear-cell histologic type, may obtained more oncologic benefit from PN compared to RN. CONCLUSIONS: When tumor localization and technical feasibility have been taken into account, similar long-term survival was achieved in overall among two nephrectomy modalities, but patients, who were male, old than 65 years, with T1b stage or clear-cell histologic type, got a better survival after receiving PN compared to RN.

Association of Sustained Response Duration With Survival After Conventional Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma.

Importance: Defining early reliable surrogate end points for survival in patients with hepatocellular carcinoma (HCC) after conventional transarterial chemoembolization (cTACE) is of great value. Objective: To evaluate the association between sustained response duration (SRD) and overall survival (OS) after cTACE for intermediate HCC. Design, Setting, and Participants: This multicenter cohort study enrolled 2403 consecutive patients in China with naive intermediate HCC between June 1, 2000, and December 31, 2008, as the primary cohort, and 331 consecutive patients with intermediate naive HCC between January 1, 2011, to June 30, 2012, as the validation cohort. All patients received cTACE as an initial treatment. Initial response and best response were defined as the radiological response after first cTACE or best radiological response after 2 or more sessions of cTACE, respectively. Responders were those who experienced complete response or partial response. Sustained response duration was defined as the time between the date when complete response, partial response, or stable disease was achieved and the date progressive disease occurred after cTACE. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors. Information about patients in the study was collected from January 1, 2018, to March 31, 2018, and analysis of these data was performed in April 2018. Main Outcomes and Measures: Overall survival. Results: A total of 2734 total patients (2499 of 2734 [91.4%] male; median [range] age, 56.5 [18-75] years) were included in the analysis. In the primary cohort, SRD of 6 months or more was found to have the strongest association with 5-year OS after cTACE among different durations of sustained response. Patients with SRD of 6 months or more (387 of 430 male; median [range] age, 57 [18-75] years) had the longest median (range) OS (67.7 [64.8-72.1] months), followed by initial responders (760 of 874 male; median [range] age, 56 [18-75] years; median [range] OS, 55.8 [55.0-57.7] months) and best responders (939 of 1032 male; median [range] age, 57 [18-75] years; median [range] OS, 53.2 [52.2-54.6] months). Response duration of 6 months or more was found to be an independent prognostic factor for OS (hazard ratio, 0.145; 95% CI, 0.124-0.170; P < .001). The significance of SRD as a factor associated with OS was confirmed in the validation cohort. Conclusions and Relevance: Sustained response duration of 6 months or more was associated with OS and may serve as an early surrogate end point after cTACE for intermediate HCC.

FSCN1 predicts survival and is regulated by a PI3K-dependent mechanism in renal cell carcinoma.

While overexpression of FSCN1 is reported in several cancers, the prognostic significance of FSCN1 in renal cell carcinoma (RCC) and the molecular mechanisms involved remain largely unclear. We retrospectively enrolled 194 patients with non-metastatic clear-cell RCC undergoing nephrectomy in our center between 2008 and 2011. FSCN1 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and survival were evaluated. Functional effects of a modulated FSCN1 expression were analyzed with regard to invasion in RCC cell lines and metastasis in vivo. Here, we reported that FSCN1 was up-regulated in RCC tissues compared to non-tumor tissues, and associated with poor overall survival and recurrence-free survival. Its expression was not associated with age, tumor size, and clinical TNM stage. The incorporation of FSCN1 into the T stage and histologic grade would help to refine individual risk stratification. Preclinical studies using multiple RCC cells and orthotopic xenografts mice model indicated that FSCN1 could promote RCC cell invasion in vitro, and metastasis in vivo. Mechanistically, overexpression of FSCN1 led to an up-regulation of MMP9 and N-Cadherin. Notably, treating RCC cells with PI3 K/AKT inhibitors or knockdown GSK-3ß decreased the expression of FSCN1, and then attenuated RCC invasion. Together, our results demonstrate that FSCN as an oncogene is a potential novel prognostic biomarker for RCC patients after nephrectomy, and can promote RCC metastasis.

Over-expression of protein tyrosine phosphatase 4A2 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma.

Protein tyrosine phosphatase 4A2 (PTP4A2) has been implicated as an oncogenic protein in several human cancers. However, the level of PTP4A2 expression and its prognostic significance in nasopharyngeal carcinoma (NPC) remains unknown. In this study, Western blotting (WB), quantitative real-time PCR (qT-PCR) and immunohischemistry (IHC) was applied to evaluated the expression levels of PTP4A2 in NPC cell lines and tumor tissues combining two independent cohorts. Receiver-operator curve (ROC) analysis was used to assessed the optimal cut-off score in training cohort (266 cases). This cut-off score was subjected to determine the association of PTP4A2 expression with patients' clinical characteristics and survival outcome in the validation cohort (201 cases) and the overall population (467 cases). We found that PTP4A2 were significantly overexpressed in NPC cell lines compared with normal nasopharyngeal epithelial cell. Moreover, overexpression of PTP4A2 was positively correlated with advanced T classification (P<0.001) and TNM stages (P<0.001). And higher PTP4A2 expression was an independent prognostic factor for adverse overall survival (P<0.05) and poor disease-free survival (P<0.05). Our results demonstrated that the overexpression of PTP4A2 was closely associated with poor survival outcome in patients with NPC and may represent a novel prognostic biomarker and therapeutic target for this disease.

[Readspace solid-phase microextraction-gas chromatography for determination of 2,5-hexanedione in urine].

OBJECTIVE: To establish a method for determination of 2,5-hexanedione in urine by headspace solid-phase microextraction-gas chromatography. METHODS: After extraction by solid-phase microextraction head, 2,5-hexanedione in urine was determined by gas chromatography and was quantified by external standard method. RESULTS: The concentration of 2,5-hexanedione in urine showed a linear relationship within the range of 0.1-20.0 µg/ml. The regression equation was y=261.36x-1.903 3, r=0.999 2. The minimum detectable concentration was 0.01 µg/ml. The recovery rate was 92.6%-97.1%, with a relative standard deviation (RSD) of 3.3%-5.8%. The intra-day and inter-day RSDs were 3.8%-6.2% and 4.7%-6.3% respectively. CONCLUSION: This determination method has no requirement for organic solvents, features simple and rapid operation, possesses higher detection sensitivity, and applies well to the determination of 2,5-hexanedione in urine.

[A study on biomarkers of styrene].

OBJECTIVE: To study the biomarkers of styrene and to provide theoretical basis for bio-monitoring of styrene. METHODS: Urinary mandalic acid (MA), phenylglyoxalic acid (PGA) and mercapturic acid (MUA) of styrene were examined by high performance liquid chromatography (HPLC). RESULTS: The correlation regression equations between exposure dose and MA, PGA and MUA level in morning urinary samples were: y = 2.58x + 70.82; y = 1.66x + 37.42; y = 0.05x + 0.55 respectively. The correlation regression equations between exposure dose and MA, PGA and MUA level in post-shift urinary samples were: y = 1.85x + 89.02; y = 1.33x + 4.32; y = 0.04x + 0.68 respectively. All showed close dose-response relationship. CONCLUSIONS: The level of MA, PGA and MUA in morning or post-shift urinary samples may be used as bio-monitoring indexes of styrene.