Objective To explore the role and mechanism of glycogen synthase kinase 3β(GSK3 β)/fission protein 1(Fis1)signa-ling pathway in the apoptosis of osteoblast induced by methylglyoxal.Methods LiCl was used as GSK3β inhibitor,and the cells were randomly divided into 4groups:control group,MG group,LiCl group,LiCl+MG group.The cell proliferation activity was detected by MTT assays.The cell apoptosis was analyzed by Tunel assays.The protein expression levels of GSK3β and Fis1 were detected by Western blot.Mitochondrial morphology was analyzed by MitoTracker Deep Red.Results MTT assay showed that MG inhibited the proliferation activity of osteoblast.Tunel staining showed that MG induced osteoblast apoptosis.Western blot assay showed that the phosphorylation lev-el of GSK3β decreased and the expression level of Fis1 protein increased after MG treatment.MitoTracker Deep Red staining showed that mitochondrion were fragmented after MG treatment.After the addition of GSK3β inhibitor LiCl,compared with the MG group,the MG-inhibited cell proliferation activity and apoptosis were significantly restored.Meanwhile,the phosphorylation level of GSK3β protein was increased,the expression level of Fis1 protein was decreased,and the mitochondrial morphology was restored.Conclusion MG may pro-mote the increase of mitochondrial division and induce osteoblast apoptosis by regulating GSK3 β/Fis1 signaling pathway.

Objective To investigate the clinical application of 3D printed bolus with specific density in breast cancer radiotherapy,and to evaluate its effects on dose distribution and positioning.Methods Forty post-mastectomy patients undergoing intensity-modulated radiotherapy were randomly enrolled for 3D printed bolus(n=20)and conventional bolus(n=20),and all patients were fixed in the supine position using styrofoam.Conventional positioning was performed based on in-room lasers and body markers,with daily Catalyst HD optical surface monitoring combined with weekly CBCT verification.The absolute dose,patients'skin surface dose,surgical incision,planned field,target area doses(VCTV50Gy,VPTV50Gy)and organs-at-risk doses in patients with different boluses were recorded,and the conformity index and homogeneity index were calculated,and the setup errors using CBCT and Catalyst HD were also analyzed.Results The difference in absolute dose between different boluses was trivial,but the skin surface dose with 3D printed bolus was significantly higher than with conventional bolus[(54.83±0.44)Gyvs(54.43±0.51)Gy,P<0.05].Patients with 3D printed boluses had a higher conformity index than with conventional boluses(0.69±0.04 vs 0.65±0.02).For different boluses,there was no significant difference in VCTV50 Gy,while the VPTV50 Gy and organs-at-risk doses were lower in those with 3D printed bolus than conventional boluses(P<0.05),with heart Vmean of 9.68%±3.24%vs11.43%±3.60%.In patients with 3D printed boluses,both planned field arrangement and surgical incision affected the target doses,and the doses of the target area without an internal breast wrap was greater than those with internal breast wrap(P<0.05).When the field was not wrapped around the internal breast,the surgical incisions only affected VPTV50 Gy,and the VPTV50 Gy was greater with the transverse fusiform incision than with the oblique vertical incision(P<0.05),which were 95.58%±0.51%vs95.44%±0.71%.The optical monitoring accuracies with different boluses differed only in the left-right direction(P<0.05),with(0.08±0.57)cm and(-0.15±0.46)cm for 3D printed and conventional boluses.Conclusion Compared with conventional bolus,3D printed bolus can improve dose distribution and optical monitoring accuracy.The surgical incision and planned field arrangement under 3D-printed bolus would exert effects on target doses.

Objective:To explore the influence of the contours of different parts of the human body on the setup errors of Catalyst HD optical surface imaging (OSI) system-guided radiotherapy.Methods:Using the 3D printing technology, arc- and oval arc-shaped phantoms with base angles of 5°-45° (step length: 5°) were designed to simulate the contours of different body parts of patients. A Catalyst HD system was employed for monitoring, during which the gains and integration time of the system were adjusted. The treatment couches were manually moved (range: -5 mm to 5 mm, with a step length of 2 mm). The ratios of transverse to longitudinal dimensions of all phantoms were recorded. The recorded items also included couch value errors in the anterior-posterior (AP), inferior-superior (SI), and left-right (LR) directions for transversely and longitudinally placed phantoms, as well as the setup errors monitored using the Catalyst HD system. Then, this study presented an analysis of the correlation between phantoms for different body contours and the gains and integration time of the Catalyst HD system. The purpose was to compare the setup errors under the two different placement conditions of phantoms and to analyze the correlation between the monitored values of the Catalyst HD system and couch values.Results:There was a significant linear negative correlation between the gain and the logarithm of integration time required for monitoring using the Catalyst HD system, with a slope of -0.001. There was a certain functional relationship between the intercept and the ratio of the transverse to longitudinal dimensions of the phantoms. Under the same gain, the integration time decreased with an increase in the base angles of phantoms. The Catalyst HD system showed different monitoring accuracy under different placement conditions of the phantoms ( Z = -8.59 to -0.02, P < 0.05), with the monitoring accuracy in the LR and AP directions higher in the transverse position. The correlation between the monitored values of the Catalyst HD system and the actual couch values increased in the LR and SI directions with an increase in the base angle of the phantoms, showing a strong correlation in the case of base angles of ≥ 25°. Furthermore, the correlation was always significant in the AP direction ( R > 0.9). Conclusions:When the best surface images are obtained using the Catalyst HD system, the gains and integration time of the system are correlated with body surface contours. The Catalyst HD system shows high monitoring accuracy in the AP direction. This system shows high accuracy in all directions when the ratios of transverse to longitudinal dimensions are ≤ 2 or the base angles ≥ 25°.

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

Objective:To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI.Methods:In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 β, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 β, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time.Results:The median age ( P5- P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service ( P5- P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group ( P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion:The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

Objective To investigate the capability of empathy for pain in migraineurs without aura.Methods Thirty migraineurs without aura and thirty matched healthy controls were recruited.Picturecued Empathy for pain paradigm was used to compare the capability of empathy in the migraine group with that in the control group.Results Compared with the control group,the migraine group had diminished ability to discriminate painful from nonpainful pictures,and the discrimination accuracy was significantly reduced ((2.55±0.61) vs (2.88±0.38);t=-2.505,P=0.01).In the task laterality,there was no difference in discrimination accuracy between two groups(P＞0.05).The rating scores of patients were evidently smaller than those of control group ((3.01±0.52) vs (3.37±0.47);t=-2.827,P=0.006).Pearson correlation analysis showed that the age of migraineurs was negatively correlated with the discrimination accuracy(r=-0.393,P =0.031),and there was no correlation between migraineurs' educational years,disease course,severity,Mini-mental State Examination,Hamilton Anxiety Scale,Hamilton Depression Scale,Verbal Fluency Test,Stroop Test and the idex of empathy for pain (all P＞0.05).Conclusion Migraineurs without aura have deficiency in the capability of empathy for pain.

OBJECTIVETo investigate the effect of occupational exposure to toluene diisocyanate (TDI) on the workers' health.

METHODSA total of 76 workers exposed to TDI (exposure group) and 64 management staff members (control group) were selected from a factory as the study subjects. Area sampling was performed for the place with exposure to TDI according to the method in GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace, and gas chromatography was applied to measure the concentration of TDI in workplace air. The workers' personal information was collected with questionnaire, pulmonary ventilation function was determined with a portable spirometer, hematological parameters were analyzed by automatic blood analyzer and blood chemistry analyzer, and the indicators of oxidative damage and energy metabolism were measured by the reagent kit provided by Nanjing Jiancheng Bioengineering Institute. SPSS 17 software was applied for statistical analysis.

RESULTSThe exposure group had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second(FEV1.0), and FEV1.0/FVC ratio than the control group (P <0.05). Compared with the control group, the exposure group had significantly higher red blood cell count, platelet distribution width, mean platelet volume, lymphocyte count, and neutrophil count(P<0.01), and significantly lower activities of lactate dehydrogenase(LDH), superoxide dismutase, and succinodehydrogenase (SDH)(P <0.01). In the exposure group, the length of exposure was negatively correlated with the activities of SDH and LDH in the serum (r=-0.319, P <0.05; r=-0.239, P <0.05), and the length of exposure was not found to be correlated with the activity of SOD and pulmonary function indices.

CONCLUSIONTDI can induce inflammatory response and lung ventilation function impairment in workers exposed to TDI, as well as oxidative stress and imbalance of energy metabolism. Therefore, it can cause damage to workers' health, and protective measures should be enhanced.

Case-Control Studies ; Erythrocyte Count ; Forced Expiratory Volume ; Humans ; Inflammation ; physiopathology ; L-Lactate Dehydrogenase ; blood ; metabolism ; Leukocyte Count ; Lung ; physiopathology ; Occupational Exposure ; adverse effects ; Pulmonary Ventilation ; Succinate Dehydrogenase ; blood ; metabolism ; Superoxide Dismutase ; metabolism ; Toluene 2,4-Diisocyanate ; adverse effects ; Vital Capacity

OBJECTIVE To establish an in vitro test method and to evaluate the genotoxicity of chemicals using primary cultured mouse hepatocytes and the changes in phosphorylated histone H2AX(γH2AX)expression levels to provide a more reliable marker of the identification of genotoxicity. METHODS Hepatocytes were isolated from BALB/c mice by an improved two-step collagenase diges?tion method and then cultured in sandwich configuration. The primary cultured hepatocytes were treat?ed with various concentrations of four known genotoxic agents bleomycin(BLM),benzo(a)pyrene〔B (a)p〕,styrene and styrene-7,8-oxide(SO)within the range of 40 μmol · L-1 and two non-genotoxic agents azathioprine(Aza)and ciclosporin A(CsA)at different time points within 24 h. The cytotoxicity induced by these toxicants was assessed by CCK-8 assay. Then,the changes in γH2AX expression levels in treated cells were determined by flow cytometry. RESULTS The four genotoxic agents could be detected and two non-genotoxic agents could not be detected by this method. The γH2AX expression level was the highest when hepatocytes were exposed to BLM and SO for 3 h,or B(a)p and styrene for 6 h(P<0.01). The production of γH2AX was 25.67,18.36,12.43 and 14.25 for the four types of genotoxic agents,respectively,and was approximately 19,13,9 and 11 times that of the vehicle control group(P<0.01)at the optimum time point and concentration. There was a significant positive corre?lation between the indicated concentrations of genotoxic chemicals and γH2AX expression levels(P<0.01). In addition,the production ofγH2AX indicated no marked increase in two non-genotoxic agents such as Aza and CsA in comparison with the control group. CONCLUSION This test method can effec?tively distinguish genotoxic agents from non-genotoxic agents,and direct genotoxic agents from indirect genotoxic agents in the absence of S9. γH2AX might be a reliable marker for the identification of the potential genotoxicity of chemicals.

Objective To investigate the effects of chronic exposure to monochloroacetic acid on the lung function and whole blood counts in occupational exposed workers,and provide new markers for occupational health surveillance.Methods We conducted a cross-sectional molecular epidemiology study of 121 workers who were occupationally exposed to monochloroacetic acid and 69 unexposed workers frequencymatched by age and smoking status from the same geographic region.The lung function was measured by portable lung function instrument,and the lymphocyte subsets were measured by flow eytometry.Linear regression was used to test for differences in the levels of each marker between exposed and control workers.Results FEV1.0/FVC was significantly decreased in both male and female workers exposed to monochloroacetic acid compared to unexposed workers (P＜0.01) after adjusting for potential confounders,which were highly consisteut when stratified by smoking status.Among male workers,monochloroacetic acid exposure was associated with significant decrease in the levels of CD8+ T cells (P＜0.05) and monocytes (P＜0.05),and these statistically significant differences were observed between exposure and control workers only among smokers,not among non-smokers.However,there were no significant differences in the levels of whule blood cells and lymphocyte subsets between two groups anong female workers.Conclusion The chronic monochloroacetic acid exposure was associated with pulmonary dysfunction and immunosuppression,which mainly occurred among nale workers and smokers.

Objective To investigate the effects of chronic exposure to monochloroacetic acid on the lung function and whole blood counts in occupational exposed workers,and provide new markers for occupational health surveillance.Methods We conducted a cross-sectional molecular epidemiology study of 121 workers who were occupationally exposed to monochloroacetic acid and 69 unexposed workers frequencymatched by age and smoking status from the same geographic region.The lung function was measured by portable lung function instrument,and the lymphocyte subsets were measured by flow eytometry.Linear regression was used to test for differences in the levels of each marker between exposed and control workers.Results FEV1.0/FVC was significantly decreased in both male and female workers exposed to monochloroacetic acid compared to unexposed workers (P＜0.01) after adjusting for potential confounders,which were highly consisteut when stratified by smoking status.Among male workers,monochloroacetic acid exposure was associated with significant decrease in the levels of CD8+ T cells (P＜0.05) and monocytes (P＜0.05),and these statistically significant differences were observed between exposure and control workers only among smokers,not among non-smokers.However,there were no significant differences in the levels of whule blood cells and lymphocyte subsets between two groups anong female workers.Conclusion The chronic monochloroacetic acid exposure was associated with pulmonary dysfunction and immunosuppression,which mainly occurred among nale workers and smokers.