Objective:To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS.Methods:In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI -) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results:The linear ranges of TCC and TCS were 0.5-100.0 μg/L and 1.0-100.0 μg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 μg/L, and 0.5 and 1.0 μg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 μg/L.Conclusion:QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.

Objective:To establish a method for the determination of two perfluorinated compounds in urine by liquid chromatography-tandem mass spectrometry.Methods:In November 2022, urine samples were extracted by acidic methanol, purified by WAX solid phase extraction column, and eluted with methanol water, then Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) was used with 1.0 mmol/L ammonium acetate solution and methanol as mobile phase. The gradient elution was carried out, the detection was carried out by electrospray negative ion multiple response monitoring (MRM) mode, and the quantitative method was internal standard method.Results:Perfluorooctanoic acid and perfluorooctane sulfonic acid had a good linear relationship in the concentration range of 0.5-50.0 μg/L, and the correlation coefficient was >0.999. The limit of detection was 0.017 μg/L, and the limit of quantitation was 0.005 μg/L. The average recoveries were 96.3% and 101.8%, respectively. Days of precision were 3.5%-6.2% and 3.1%-7.4%, respectively, daytime precision were 4.3%-6.8% and 4.7%-8.1%, respectively.Conclusion:The established method of liquid chromatography-tandem mass spectrometry is high sensitivity and accuracy, and is suitable for the determination of perfluorooctanoic acid and perfluorooctane sulfonic acid in human urine.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To establish a method for the determination of triclocarban (TCC) and triclosan (TCS) in urine by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after purification by QuEChERS.Methods:In May 2022, urine samples were extracted by acetonitrile, purified by QuEChERS, separated by Waters Acquity UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm), and eluated with water-acetonitrile as mobile phase gradient at a flow rate of 0.3 ml/min. The detection was conducted in negative ion mode (ESI -) and multiple reaction monitoring (MRM) scanning, it was quantified with a internal standard method, and the methodology was verified. Results:The linear ranges of TCC and TCS were 0.5-100.0 μg/L and 1.0-100.0 μg/L, and the correlation coefficients were 0.9997 and 0.9991, respectively. The limits of detection and quantitation of TCC and TCS were 0.17 and 0.33 μg/L, and 0.5 and 1.0 μg/L, respectively. The recoveries of TCC and TCS were 100.1%-102.8% and 96.7%-108.6%, and the relative standard deviations were 4.9%-6.7% and 4.1%-8.3%, respectively, at 2.0, 10.0 and 80.0 μg/L.Conclusion:QuEChERS-UPLC-MS/MS method is simple, rapid, sensitive and reproducible, and can be used for rapid and accurate simultaneous detection of TCC and TCS exposure levels in occupational population.

Objective:To establish a method for the determination of two perfluorinated compounds in urine by liquid chromatography-tandem mass spectrometry.Methods:In November 2022, urine samples were extracted by acidic methanol, purified by WAX solid phase extraction column, and eluted with methanol water, then Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) was used with 1.0 mmol/L ammonium acetate solution and methanol as mobile phase. The gradient elution was carried out, the detection was carried out by electrospray negative ion multiple response monitoring (MRM) mode, and the quantitative method was internal standard method.Results:Perfluorooctanoic acid and perfluorooctane sulfonic acid had a good linear relationship in the concentration range of 0.5-50.0 μg/L, and the correlation coefficient was >0.999. The limit of detection was 0.017 μg/L, and the limit of quantitation was 0.005 μg/L. The average recoveries were 96.3% and 101.8%, respectively. Days of precision were 3.5%-6.2% and 3.1%-7.4%, respectively, daytime precision were 4.3%-6.8% and 4.7%-8.1%, respectively.Conclusion:The established method of liquid chromatography-tandem mass spectrometry is high sensitivity and accuracy, and is suitable for the determination of perfluorooctanoic acid and perfluorooctane sulfonic acid in human urine.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To establish a method for the rapid determination of the three metabolites of xylene, 2-methylmarmaluronic acid, 3-methylmarmaluronic acid and 4-methylmarmaluronic acid, in urine of occupationally exposed workers by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) .Methods:In July 2022, urine samples were diluted and extracted with pH=6.86 phosphate cache solution, cleaned up by a MAX solid-phase extraction (SPE) column and separated by an Accucore Ph/Hexyl column (100 mm×2.1 mm, 2.6 μm) with a gradient of 5 mmol/L ammonium formate-0.1% formic acid aqueous solution and methanol as mobile phases. The analysis was carried out in electrospray ionization mode and full mass-data dependent secondary mass spectrometry mode, and quantified by external standard method. The characteristics of each index of this method were analyzed.Results:A good linearity was obtained in the concentration range of 1.0-200.0 μg/L for 2-methylmuramic acid, 3-methylmuramic acid and 4-methylmuramic acid with the correlation coefficients of 0.9979-0.9993. The limits of detection of the method were 0.18-0.24 μg/L. While the spiked recoveries at the three concentrations (1.0 μg/L, 100.0 μg/L, and 180.0 μg/L) were in the range of 83.0%-93.7%, with the relative standard deviations of 2.2%-7.9%.Conclusion:The UPLC-HRMS method is simple, rapid, sensitive and accurate, and is suitable for the simultaneous determination of the three metabolites of xylene in the urine of occupationally exposed workers.

Objective:To establish a method for the rapid determination of the three metabolites of xylene, 2-methylmarmaluronic acid, 3-methylmarmaluronic acid and 4-methylmarmaluronic acid, in urine of occupationally exposed workers by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) .Methods:In July 2022, urine samples were diluted and extracted with pH=6.86 phosphate cache solution, cleaned up by a MAX solid-phase extraction (SPE) column and separated by an Accucore Ph/Hexyl column (100 mm×2.1 mm, 2.6 μm) with a gradient of 5 mmol/L ammonium formate-0.1% formic acid aqueous solution and methanol as mobile phases. The analysis was carried out in electrospray ionization mode and full mass-data dependent secondary mass spectrometry mode, and quantified by external standard method. The characteristics of each index of this method were analyzed.Results:A good linearity was obtained in the concentration range of 1.0-200.0 μg/L for 2-methylmuramic acid, 3-methylmuramic acid and 4-methylmuramic acid with the correlation coefficients of 0.9979-0.9993. The limits of detection of the method were 0.18-0.24 μg/L. While the spiked recoveries at the three concentrations (1.0 μg/L, 100.0 μg/L, and 180.0 μg/L) were in the range of 83.0%-93.7%, with the relative standard deviations of 2.2%-7.9%.Conclusion:The UPLC-HRMS method is simple, rapid, sensitive and accurate, and is suitable for the simultaneous determination of the three metabolites of xylene in the urine of occupationally exposed workers.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Objective:To investigate the expression of Pyruvate dehydrogenase kinase 1(PDK1), phosphorylated Pyruvate dehydrogenase (p-PDH) and Pyruvate kinase isozyme type M2 (PKM2) based on Warburg effect pathway in cervical cancer tissues, and explore the roles of these molecules on prognosis and recurrence after postoperative radiation.Methods:The expressions of PDK1, p-PDH and PKM2 in primary tissues of 102 patients with cervical cancer were detected by immunohistochemistry, including 63 patients receiving postoperative radiation. The expression of the three molecules on prognosis and the efficacy of postoperative radiation on cervical cancer were analyzed separately and corporately.The level of mRNA were verified by using the 300 patients from GEO database. Kaplan-Meier method and COX proportional hazards regression model were used for univariate and multivariate analysis.Results:High expression of PDK1 and all the three indicators (PDK1 high/p-PDH high/PKM2 high) were positively correlated with pelvic lymphnode metastasis ( χ2=10.890, 7.407, P<0.05). PDK1 high/p-PDH high/PKM2 high, Federation International of Gynecology and Obstetrics (FIGO) staging, pelvic lymph node metastasis and postoperative radiation could affect the overall survival (OS) and disease-free survival (DFS) ( P<0.05). Multivariate analysis showed that PDK1 high /PDH high/PKM2 high, FIGO staging and postoperative radiation were the independent prognosis factors for OS and DFS( P<0.05). The verification result of the GEO dataset showed that PDK1 high/PDH high/PKM2 high was the risk factor for DFS( P<0.05). Pathological type, pelvic lymph node metastasis and PDK1 high/p-PDH high/PKM2 high could affect the DFS of those patients with postoperative radiation ( P<0.05). In addition, the multivariate analysis showed that pathological type and PDK1 high /p-PDH high/PKM2 high were the independent prognosis factors for DFS( P<0.05). Conclusions:The patients of PDK1 high /p-PDH high/PKM2 high phenotype have poor prognosis and DFS with postoperative radiation, which may be a high-risk group with poor prognosis and high recurrence rate after postoperative radiotherapy of stageⅠ-Ⅱ B cervical cancer.This study provides a novel strategy for stratified treatment of cervical cancer.