Associations between isomers and alternatives of per- and polyfluoroalkyl substances and fasting blood glucose / 环境与职业医学

Background Previous research indicated that isomers and alternatives of per- and polyfluoroalkyl substances (PFAS) probably disturb glucose metabolism; however, current epidemiological evidence on the associations of PFAS with fasting blood glucose is inconsistent. Besides, studies on the joint association of multiple components of PFAS and fasting blood glucose as well as the key component are scarce. Objective To evaluate the associations of PFAS isomers and alternatives with fasting blood glucose and their joint effects, as well as identify the key component among population without glucose metabolism problems. Methods We selected 923 adults without glucose metabolism problems or missing data from the Isomers of C8 Health Project in China (2015—2016). Serum PFAS isomers and alternatives and fasting blood glucose were measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and automatic biochemical analyzer. We applied multiple linear regression to explore the associations of 16 pollutants which were detected among over 80% participants with fasting blood glucose. Meanwhile, we utilized qgcomp and Bayesian kernel machine regression (BKMR) models to explore the joint effects of PFAS isomers and alternatives mixture on target outcome indicators and identify the key component. Results The average age among the 923 participants in this study was (62.4±13.8) years old, including 472 men (51.1%) and 451 women (48.9%). Among selected PFAS isomers and alternatives, the highest serum concentration was ∑3+4+5m-PFOS (perfluoro-3/4/5-methylheptanesulfonate) with a median concentration of 10.20 ng·mL−1. The concentrations of linear perfluorooctane sulfonate (n-PFOS, 9.61 ng·mL−1), perfluorooctanoic acid (PFOA, 4.55 ng·mL−1), linear perfluorohexane sulfonic acid (n-PFHxS, 2.48 ng·mL−1), 6:2 chlorinated polyfluorinated ethersulfonic acid (6:2 Cl-PFESA, 1.90 ng·mL−1), perfluoro-6-methylheptanesulfonate (iso-PFOS, 1.85 ng·mL−1), perfluorobutanoic acid (PFBA, 1.81 ng·mL−1), perfluorinated n-nonanoic acid (PFNA, 1.39 ng·mL−1), and perfluoro-1-methylheptanesulfonate (1m-PFOS, 1.27 ng·mL−1) were higher than 1.00 ng·mL−1. After being adjusted for selected confounders, PFAS isomers and alternatives were positively associated with fasting blood glucose. With 1 ln unit concentration increment of 6:2 Cl-PFESA and PFNA, the estimated changes of fasting blood glucose were 0.18 (95%CI: 0.13, 0.23) mmol·L−1 and 0.24 (95%CI: 0.18, 0.30) mmol·L−1, respectively. The multi-pollutant models indicated a joint association of PFAS isomers and alternatives mixture with fasting blood glucose. The BKMR models reveals that as the quantiles of mixture elevated from the 50th to the 75th percentile, the values of fasting blood glucose increased 0.25 (95%CI: 0.21, 0.30) mmol·L−1, and the posterior inclusion probability of PFNA was 0.92, implying that PFNA was the key component. Conclusion PFAS isomers and alternatives are positively associated with fasting blood glucose. PFNA is the key component of the joint association.

Association of greenness surrounding schools and homes with adiposity levels in children and adolescents / 环境与职业医学

Background Evidence on the association between greenness and adiposity in children and adolescents is inconsistent and mostly from developed countries. Relatively limited evidence is from China. Objective To assess the association between greenness and adiposity in children and adolescents based on satellite remote sensing data. Methods From 2016 to 2018, a cross-sectional study was conducted among 52316 children and adolescents aged 5-18 years in three cities in the Pearl River Delta region of China. Basic sociological and demographic characteristics of the population and adiposity levels were collected through questionnaires. Land Remote-Sensing Satellite (Landsat) data and moderate-resolution imaging spectroradiometer (MODIS) products were used to quantify the greenness around the schools and homes, including normalized difference vegetation index (NDVI), vegetation continuous field (VCF), soil-adjusted vegetation index (SAVI), and enhanced vegetation index (EVI) calculated within 500 m and 1000 m buffers centered around the participants' homes or schools. A restricted cubic spline function was used to assess the exposure-response relationship. After categorizing greenness levels into quartiles with the first quartile as the reference, two-level generalized linear models were applied to assess the change in body mass index z-scores (zBMI) and the risk of overweight of children and adolescents in higher quartiles relative to the lowest quartile. In addition, counterfactual framework modelling was applied to assess the potential mediation effects of PM2.5 and NO2, and physical activity levels on the associations between greenness and adiposity levels. Results Of the 52316 children included, 8406 (16.1%) were overweight. A non-linear negative association of the level of greenness around the homes or schools and zBMI was found, with a significant lower zBMI in children and adolescents when a certain level of greenness was reached. After adjusting for confounders, the participants in the highest quartile had a significantly lower level of zBMI and a significantly lower risk of overweight compared with those in the lowest quartile of NDVI500 m and VCF500 m. The estimate change (\begin{document}$b$\end{document}) for zBMI was −0.07 (95%CI: −0.10-−0.04) and the odds ratio (OR) for overweight was 0.92 (95%CI: 0.85-0.99) for the students in the highest NDVI500 m quartile based on home address compared to those in the lowest quartile. Significant negative associations were also observed when 1000 m buffer, SAVI, and EVI were used. The mediation analysis showed that PM2.5 and NO2 partially mediated the negative association of NDVI500 m with zBMI , and the proportions of mediation were 50% (95%CI: 20%-80%) and 90% (95%CI: 50%-160%), respectively while no significant mediation effect was observed for physical activity level. Conclusion Higher levels of greenness surrounding homes or schools may be associated with a reduced risk of overweight and decreased zBMI in children and adolescents, and such associations may be partially mediated by reducing air pollutant concentrations.

Efficacy evaluation of apatinib in first-line and maintenance therapy of extensive small-cell lung cancer / 中国医师进修杂志

Objective:To observe the efficacy of apatinib combined with first-line chemotherapy and maintenance therapy of only apatinib in patients with extensive small-cell lung cancer.Methods:The clinical data of 56 newly diagnosed patients with extensive small-cell lung cancer in the Fifth People′s Hospital of Dalian City from January 2018 to June 2019 were retrospectively analyzed. Among them, 27 patients (experimental group) were treated with first-line chemotherapy combined with apatinib, and 29 patients (control group) were treated with first-line chemotherapy alone. In experimental group, the expression levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)-2 1 day before chemotherapy and 1 day after chemotherapy were detected by enzyme linked immunosorbent assay method. Response evaluation criteria in solid tumor (RECIST) was used to evaluate the efficacy. The occurrence of adverse reaction was recorded. The patients were followed up for 12 to 24 months, and progression-free survival and 1-year survival were recorded.Results:The objective response rate, median progression-free survival time and 1-year survival rate in experimental group were significantly higher than those in control group: 81.5% (22/27) vs. 55.2% (16/29), 10.5 months vs. 8.5 months and 81.5% (22/27) vs. 55.2% (16/29), and there were statistical differences ( P<0.05); there was no statistical difference in disease control rate between 2 groups ( P>0.05). In experimental group, the patients with complete response and partial response after chemotherapy were classified as effective subgroup (22 cases), and the patients with stationary disease and progressive disease were classified as ineffective subgroup (5 cases). There were no statistical difference in VEGF and VEGFR-2 before chemotherapy between 2 subgroups ( P>0.05). The VEGF and VEGFR-2 in effective subgroup were significantly lower than those in ineffective subgroup: (275.34 ± 16.15) ng/L vs. (330.24 ± 23.21) ng/L and (89.35 ± 4.34) ng/L vs. (112.34 ± 5.45) ng/L, and there were statistical differences ( P<0.01). There were no uncontrollable adverse reactions in 2 groups, and there was no statistical difference in the incidence of adverse reactions between 2 groups ( P>0.05). Conclusions:Application of apatinib in first-line therapy and maintenance therapy for patients with extensive small-cell lung cancer can improve clinical efficacy and survival benefit with controllable adverse reactions.

Clinical study of pidotimod in reducing pulmonary infection in patients with lung cancer undergoing chemotherapy / 中国医师进修杂志

Objective:To investigate the effect of pidotimod in reducing pulmonary infection in patients with lung cancer undergoing chemotherapy.Methods:One hundred and twenty patients with lung cancer in the Fifth People′s Hospital of Dalian City from July 2017 to July 2018 were selected. The patients were divided into control group and pidotimod group by random digits table method with 60 cases each. The patients were treated with standard two drugs chemotherapy containing platinum drug according to the pathological type, and the patients in pidotimod group were combined with pidotimod. The number of pulmonary infections during chemotherapy, number of completed scheduled chemotherapy and adverse reaction were observed. The correlation between pulmonary infection and pidotimod was analyzed by multivariate orderly Logistic regression.Results:The incidence of pulmonary infection in pidotimod group was significantly lower than that in control group: 18.33% (11/60) vs. 40.00% (24/60), and there was statistical difference ( χ2 = 6.845, P<0.01). The rate of completed scheduled chemotherapy in pidotimod group was significantly higher than that in control group: 55.00% (33/60) vs. 36.67% (22/60), and there was statistical difference ( χ2 = 4.062, P<0.05). Multivariate orderly Logistic regression analysis result showed that pidotimod could reduce the risk of pulmonary infection ( OR = 0.210, 95% CI 0.072 to 0.606, P = 0.004), and help to complete the scheduled chemotherapy ( OR = 2.323, 95% CI 1.080 to 5.003, P = 0.031). In pidotimod group, no obvious adverse reaction related to pidotimod application was detected, and chemotherapy was not affected. Conclusions:Application of pidotimod can reduce the chance of pulmonary infection in patients with lung cancer undergoing chemotherapy and help patients complete scheduled chemotherapy.

Characteristics of resting-state brain voxel-mirrored homotopic connectivity in patients with chronic schizophrenia / 中华行为医学与脑科学杂志

Objective:To investigate the brain characteristics of chronic schizophrenia by voxel-mirrored homotopic connectivity (VMHC).Methods:Forty seven patients with chronic schizophrenia from Tianjin Anding Hospital and 31 healthy controls from nearby communities were included in the study. The MRI data of the subjects were collected by Siemens Skyra 3.0 T MRI.Positive and negative symptoms scale (PANSS) was used to assess the illness severity of patients with chronic schizophrenia.SPM12 was used to process the collected MRI data. DPARSF was used to calculate the VMHC values of subjects in the two groups. The independent sample t test based on SPM12 was used to compare the VMHC values of the two groups. The significant brain regions in VMHC were regarded as regions of interest (ROI), and VBM8 was used to further analyze the gray matter volume of the ROI of the two groups. Results:Compared with healthy controls, the patients with chronic schizophrenia demonstrated decreased VMHC mainly located in lingual gyrus(voxel=208, T=4.98), occipital middle occipital gyrus(voxel=156, T=3.75) and postcentral gyrus(voxel=237, T=4.36) (FDR correction, q=0.05). Compared with healthy controls, the gray matter volumes in bilateral lingual gyrus(left(0.0034±0.0008), (0.0028±0.0013), t=-2.141, P=0.037; right(0.0025±0.0006), (0.0020±0.0011), t=2.268, P=0.028) and postcentral gyrus((0.0432±0.0051), (0.0372±0.0162), t=-2.070, P=0.045) increased, but non-significant change in postcentral gyrus of the patients with chronic schizophrenia. Conclusion:The abnormal VMHC mainly locate in lingual gyrus, middle occipital gyrus and postcentral gyrus in patients with chronic schizophrenia.

Investigation into the expression of c-MET in patients with lung adenocarcinomaand its prognostic correlation / 中国医师进修杂志

Objective@#To analyze the expression of c-MET and its prognostic correlation in patients with lung adenocarcinoma.@*Methods@#The clinical data and pathological specimen of patients with lung adenocarcinoma in Dalian 5th People′s Hospital from January 2006 to December 2011 were retrospectively analyzed. The expression difference of c-MET between lung adenocarcinoma tissue and normal adjacent tissues was compared. The correlation of c-MET with the pathology and clinical factors was also analyzed.@*Results@#A total of 82 patients were retrospective analyzed, including 82 pathological specimens of lung adenocarcinoma and 45 specimens of normal adjacent tissues. Among 53 patients with stage Ⅰ-Ⅱ lung adenocarcinoma, 31 cases had low expression of c-MET and 22 cases had high expression of c-MET. Among 29 patients with stage Ⅲ lung adenocarcinoma, 10 cases had low expression of c-MET and 19 cases had high expression of c-MET. There was a correlation between TNM stage and c-MET positive expression in lung adenocarcinoma (P=0.037). The positive expression rate of c-MET was not significantly correlated with age, sex and differentiation degree (P > 0.05). Among 82 cases of lung adenocarcinoma, 39 cases had low expression of c-MET and 43 cases had high expression of c-MET; 45 cases of para-carcinoma tissuehad low expression of c-MET. The positive expression rate of c-MET in lung adenocarcinoma tissues was significantly higher than that in para-carcinoma tissue (P < 0.01). Kaplan-Meier survival curve analysis showed that the median disease-free survival was 41.5 months in c-MET high-expression group and 55.3 months in low-expression group. The expression level of c-MET was closely related to disease-free survival in lung adenocarcinoma patients (P < 0.05).@*Conclusions@#The expression of c-MET is significantly increased in patients with lung adenocarcinoma. The expression level has relevance with TNM staging and prognosis.

Investigation into the expression of c- MET in patients with lung adenocarcinomaand its prognostic correlation / 中国医师进修杂志

Objective To analyze the expression of c-MET and its prognostic correlation in patients with lung adenocarcinoma.Methods The clinical data and pathological specimen of patients with lung adenocarcinoma in Dalian 5th People′s Hospital from January 2006 to December 2011 were retrospectively analyzed.The expression difference of c-MET between lung adenocarcinoma tissue and normal adjacent tissues was compared.The correlation of c-MET with the pathology and clinical factors was also analyzed. Results A total of 82 patients were retrospective analyzed, including 82 pathological specimens of lung adenocarcinoma and 45 specimens of normal adjacent tissues.Among 53 patients with stageⅠ-Ⅱlung adenocarcinoma, 31 cases had low expression of c-MET and 22 cases had high expression of c-MET. Among 29 patients with stage Ⅲ lung adenocarcinoma, 10 cases had low expression of c-MET and 19 cases had high expression of c-MET. There was a correlation between TNM stage and c-MET positive expression in lung adenocarcinoma (Pi0.037). The positive expression rate of c-MET was not significantly correlated with age, sex and differentiation degree (P > 0.05). Among 82 cases of lung adenocarcinoma, 39 cases had low expression of c-MET and 43 cases had high expression of c-MET; 45 cases of para-carcinoma tissuehad low expression of c-MET. The positive expression rate of c-MET in lung adenocarcinoma tissues was significantly higher than that in para-carcinoma tissue (P<0.01). Kaplan-Meier survival curve analysis showed that the median disease-free survival was 41.5 months in c-MET high-expression group and 55.3 months in low-expression group. The expression level of c-MET was closely related to disease-free survival in lung adenocarcinoma patients (P < 0.05). Conclusions The expression of c-MET is significantly increased in patients with lung adenocarcinoma. The expression level has relevance with TNM staging and prognosis.