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@#Objective - - （BCL2L2）- （ ） To investigate the differential expression of the fusion gene BCL 2 like protein 2 poly A （PABPN1） （ ） binding protein nuclear 1 induced by sodium arsenite SA and its methylated metabolites in 16HBE cells and the Methods ） ， related mechanism. i The 16HBE cells exposed to SA at concentrations of 1.5 3.0 and 4.5 µmol/L were set as -， - - low medium and high dose arsenic exposure groups. The 16HBE cells exposed to 4.5 µmol/L monomethylarsonic acid （ ）， （ ） ， MMA dimethylarsonic acid DMA and SA were set as MMA group DMA group and SA group. The 16HBE cells without ， BCL2L2-PABPN1 toxic stimulation were set as control group. After the cells were cultured for 48 hours the expression of was - （ - ） ） （ ） detected by quantitative real time polymerase chain reaction qRT PCR . ii Two small interfering RNA siRNA silencing 基金项目：国家自然科学基金（ ）； 年云南省科技厅昆明医科大学应用基础研究联合专项面上项目 82160607 2021 （ ） 202101AY070001-054 作者简介：施雅（ —），女，在读大学本科生，主要从事劳动卫生与环境卫生学研究；尹锦瑶（ —），女，在读劳动卫生与环境卫 2001 1995 生学硕士研究生，主要从事劳动卫生与环境卫生学研究；施雅和尹锦瑶为共同第一作者 通讯作者：何越峰教授，博士研究生导师，- ： E mail heyuefeng@kmmu.edu.cn中国职业医学 年 月第 卷第 期 ， ， ， · · 2022 10 49 5 Chin Occup Med October 2022 Vol.49 No.5 523 BCL2L2-PABPN1， - fragments were designed and transfected into 16HBE cells to knockdown which were set as siRNA 1 group - - BCL2L2-PABPN1 and siRNA 2 group. Non transfected control group without knockdown of transfection was set up. After ， BCL2L2-PABPN1 - culturing for 48 hours the expression level of in the three groups of cells was detected by qRT PCR. The cell - survival rate and early apoptosis rate were detected by MTS method and JC 1 mitochondrial membrane potential detection ， （ ） ， method respectively. The apoptosis was detected by Hoechest33342/propidium iodide PI double staining and the expression - Results ） level of P53 signaling pathway related proteins was detected by Western blotting. i The relative expression of BCL2L2-PABPN1 （P ） BCL2L2- in 16HBE cells increased with the increasing SA doses <0.01 . The relative expression of PABPN1 - ， - - in high dose arsenic exposure was higher than that in control group low dose and medium dose arsenic exposure （ P ） BCL2L2-PABPN1 ， groups all <0.05 . The relative expression of in SA group was higher than those in control group MMA （ P ） BCL2L2-PABPN1 group and DMA group all <0.05 . The relative expression of showed no significant difference between ， （ P ） ） BCL2L2-PABPN1 control group MMA group and DMA group all >0.05 . ii The relative expression levels of and cell - - - （ P ） survival rate in siRNA 1 group and siRNA 2 group were lower than those in non transfected control group all <0.05 . ， （P ） However there was no significant difference in the early apoptosis rate among the three groups >0.05 . The results of - Hoechest33342/PI double staining showed that the number of nuclear shrinkage and early apoptotic cells in siRNA 1 group and - - ， - siRNA 2 group was higher than that in non transfected control group. The relative protein expression levels of P53 phospho ， - - ， - - （ P ） p53 BCL 2 associated death promoter P21 and cytochrome C in siRNA 1 group and siRNA 2 group were higher all <0.05 , - - P and the relative protein expression levels of P53 up regulated modulator of apoptosis were lower (all <0.05), when compared - Conclusion with the non transfected control group. SA may block the apoptosis of 16HBE cells by inducing the expression of BCL2L2-PABPN1 fusion gene . The mechanism may be related to the activation of P53 signaling pathway. The SA methylated BCL2L2-PABPN1 BCL2L2-PABPN1 - metabolites MMD and DMA had no effect on the expression of . may affect anti apoptosis BCL2L2 PABPN1 through affecting the synergistic effect of and genes.
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Objective@#To explore the value of dual-energy CT-based volumetric iodine-uptake (VIU) in the evaluation of chemotherapy efficacy in advanced gastric cancer.@*Methods@#Inclusion criteria of subjects: (1) without previous systematic therapy; (2) with complete clinical information before and after chemotherapy; (3) without contraindications of chemotherapy. Exclusion criteria of subjects: (1) unfinished duration and times of chemotherapy; (2) unmeasurable primary lesions; (3) poor imaging quality or poor gastric filling. Clinical and image data of 52 patients with advanced gastric cancer who were diagnosed by pathology from gastroscopic biopsy, and needed chemotherapy evaluated by imaging and clinical information in the First Affiliated Hospital of Wenzhou Medical University from February 2017 to February 2018 were collected and analyzed. Of 52 patients, 38 were male and 14 were female with the median age of 65 (31-88) years old. All the patients underwent a dual-energy, dual phase-enhanced CT scanning before chemotherapy and after the third chemotherapy session. The parameters of the lesions measured before and after chemotherapy in portal vein phase were as follows: the maximum diameter (the largest diameter among those measured in the cross-sectional, coronal, and sagittal planes), average CT value (the regions of interest were manually pinpointed under cross-sectional planes with largest diameter of the tumor, which did not include regions less than 2 mm to the edge of the tumor) and VIU (lesion volume × iodine concentration). The change rates of maximum lesion diameter, average CT value and VIU before and after chemotherapy were calculated [(post-chemotherapy parameters-pre-chemotherapy parameters)/ pre-chemotherapy parameters]. The efficacy of chemotherapy was evaluated by RECIST 1.1 (the change of maximum tumor diameter after chemotherapy), Choi (the change of average CT value after chemotherapy) and VIU (the change of VIU after chemotherapy), respectively, which was categorized by complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients with CR, PR, and SD were assigned to the effective group, while those with PD were classified as the ineffective group. Paired t - test or Wilcoxon signed ranks test was used to compare the changes of parameters before and after chemotherapy, whereas Spearman correlation analysis and Kappa test were used for the correlation analysis and the consistency test between the three evaluation criteria (Kappa≥0.75 indicated good consistency).@*Results@#After chemotherapy, the average CT value [(74.01±16.75) HU vs. (81.06±15.87) HU, t=2.202, P=0.030] and median VIU (668.53×102 μg vs. 272.52×102 μg, Z=4.761, P<0.001) decreased significantly, while the difference of the maximum diameter was not statistically significant [(66.71±34.49) mm vs. (78.45±35.62) mm, t=1.708, P=0.091]. The median change rate of VIU (–53.33%) was greater than that of CT values (–5.75%) with significant difference (Z=-5.408, P<0.001). According to the RECIST 1.1 criteria, 47 patients (90.4%, including 19 with PR and 28 with SD) were effective and 5 patients (9.6%) were ineffective. According to the Choi criteria, 45 patients (86.5%, including 37 with PR and 8 with SD) were effective and 7 patients (13.5%) were ineffective. According to the VIU criteria, 46 patients (88.5%, including 41 with PR and 5 with SD) were effective and 6 patients (11.5%) were ineffective. Efficacy comparison among these three criteria showed no significant difference (χ2=0.377, P=0.828). As compared to RECIST 1.1 evaluation, the proportion of PR evaluated by Choi and VIU was significantly higher (χ2=16.861, P<0.001), whereas the proportion of SD was significantly lower (χ2=24.089, P<0.001). There was no significant difference in the proportions of PR and SD between VIU and Choi criteria (χ2=0.887, P=0.346). Consistency and correlation analysis showed that the VIU and Choi evaluation criteria presented the highest consistency and correlation (Kappa=0.912, P<0.001; r=0.916, P<0.001).@*Conclusion@#VIU is a feasible parameter for the evaluation of chemotherapy efficacy in advanced gastric cancer, and may be more sensitive than the evaluation criteria based on maximum diameter or change of CT value in the tumor.
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Purpose To investigate the mutation rate of EGFR,KRAS,ALK and ROS1 in non-small cell lung cancer (NSCLC) and its association with clinical or pathological characteristics.Methods 86 NSCLC tissues were included.Fluorescence PCR was used to detect the EGFR,KRAS mutation and ALK,ROS1 fusion gene.The association between EGFR,KRAS,ALK and ROS1 gene and age,gender,smoking history,histological type,lymph node metastasis and other clinical pathological features were analyzed.Results The total mutation rate of the driver gene in NSCLC patients was 62.8％ (54/86).EGFR mutation rate was 76％ (41/54).KRAS mutation rate was 9.3％ (5/54).ALK gene fusion mutation rate was 13.0％ (7/54),and in one of the patients,EGFR 19 deletion mutation and ALK fusion co-exist.ROS1 gene fusion mutation was 3.8％ (2/54).EGFR gene mutation rate was higher in adenocarcinoma and female (P ＜ 0.05),but no significant association was found in age,smoking history and lymph node metastasis (P ＞0.05).KRAS,ALK,ROS1 genes had no obvious correlation with clinical pathological features (P ＞ 0.05).Conclusion The EGFR mutation and ALK fusion was rather high in patients with NSCLC.More attention should be paid to them.Though KRAS,ROS1 mutations and double mutations were low in NSCLC patients,they should not be ignored.
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Objective:To forecast the reduce of medical direct expenses of China from 2016 to 2020,under the circumstances that some outpatients and inpatients of tertiary hospitals and secondary hospitals could be distributed to primary medical institutions.Methods:According to the number of outpatients,number of inpatients,medical expenses of outpatients per visit,and medical expenses of inpatients per visit in the first grade,second grade and third grade public hospitals from 2006 to 2015,the corresponding visit numbers and costs from 2016 to 2020 were forecasted based on liner regression model.The percentages of transferable patients out of all patients in different levels of institutions could be equal to 10％,20％ and 30％.The direct medical expense could be saved after the distribution were calculated.Results:If the trend of health service utilization from 2016 to 2020 were equal to the sample,the third grade hospitals would keep the fast increasing of outpatient expenses and patients.8％,16％ and 24％ of the total expenses would be saved if 10％,20％ and 30％ patients in third and second were led to the second and first grade medical institutions.Conclusion:It needed to slowdown the increasing trend of medical expenses,lead patients visit hospitals reasonably,strengthen the construction capacity of second grade medical and health institutions,meanwhile,the medical and health service system construction should adjust the distribution ratio.
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Objective:To forecast the reduce of medical direct expenses of China from 2016 to 2020,under the circumstances that some outpatients and inpatients of tertiary hospitals and secondary hospitals could be distributed to primary medical institutions.Methods:According to the number of outpatients,number of inpatients,medical expenses of outpatients per visit,and medical expenses of inpatients per visit in the first grade,second grade and third grade public hospitals from 2006 to 2015,the corresponding visit numbers and costs from 2016 to 2020 were forecasted based on liner regression model.The percentages of transferable patients out of all patients in different levels of institutions could be equal to 10％,20％ and 30％.The direct medical expense could be saved after the distribution were calculated.Results:If the trend of health service utilization from 2016 to 2020 were equal to the sample,the third grade hospitals would keep the fast increasing of outpatient expenses and patients.8％,16％ and 24％ of the total expenses would be saved if 10％,20％ and 30％ patients in third and second were led to the second and first grade medical institutions.Conclusion:It needed to slowdown the increasing trend of medical expenses,lead patients visit hospitals reasonably,strengthen the construction capacity of second grade medical and health institutions,meanwhile,the medical and health service system construction should adjust the distribution ratio.
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Objective To investigate the expression of melatonin MT1 receptor in rats with acute necrotizing pancreatitis (ANP) and the protective effects of melatonin (MT) pre-intervention for the pancreas. Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into three groups:sham-operation group, ANP group and MT-pretreated group. The models of ANP were induced by retrograde injection sodium taurocholate into the bili-pancreatic duct. MT group undergoing intraperitoneal injection 50 mg/kg 30 minutes before the establishment of ANP models. Four, 8 and 12 hours after the onset of operation, the levels of serum amylase and pathological changes of the pancreas were observed. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNFα) in the pancreas were measured. The expression of MT1 protein and MT1 mRNA in pancreas were separately analyzed by immunohistochemistry and real-time PCR. Results (1) Pancreatic pathological damage in ANP groups was progressive exacerbated. It was obviously ameliorated in MT group as compared with ANP group ( P ＜ 0.05 ); (2) Compared with SO group, the levels of serum amylase, MDA and TNFα in the pancreas were significantly increased in ANP group (P ＜0.05 or P ＜0.01 ). They were markedly decreased in MT group as compared with ANP group [ 12 h, (2348.00 ±278.90)U/L vs (3194. 83 ±538.10)U/L,(2.255 ± 0.472 ) μmol/L vs ( 2.960 ± 0.722 ) μ mol/L, ( 102.929 ± 29.399 ) ng/L vs ( 378. 544 ±183.454)ng/L, P ＜ 0.05 ]. The level of SOD was decreased in ANP group compared with SO group (P ＜0.05) and increased in MT group[ 12h, (11.448 ± 1.594)U/L vs (8.427 ± 1.950)U/L, P＜0.05] ;(3)Compared with SO group, the expression of MT1 protein and MT1 mRNA in ANP group were down-regulated as the severity of the disease increased ( P ＜ 0.05 ). They were significantly higher in MT group than ANP group. Conclusions Melatonin pre-intervention is able to increase SOD level and decrease MDA, TNFα levels, thereby reducing pancreatic injury. The MT1 might play an important role in the pathogenesis of ANP. MT might exert protective effects for the pancreas in ANP rats through increase the expression of MT1.
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Objective To examine the effect and mechanism of sodium ferulate inhibiting P38 MAPK in macrophage on neurotoxicity which was mediated by fribrilar-amyloid-induced.Methods The isolated peritoneal macropohages were cultured.P38 MAPK protein in nuclear extracts was analyzed by Western blot and production of tumor necrosis factor-?(TNF-?) was detected by ELISA.For neuron-macrophage co-cultures,Microtubute-associated protein-2(MAP-2) expression was detected by immunocytochemical technique.The level of LDH in the medium was measured.Results The production of TNF-? and P38 MAPK protein in nuclear extracts increased significantly by incubation with A?25-35.LDH efflux in neuron-macrophage co-culture medium increased and MAP-2 expression decreased significantly(P
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<p><b>BACKGROUND AND AIM</b>The Krüppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity (LOH). However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas (HCCs). We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines.</p><p><b>METHODS</b>We analyzed the exon-2 of KLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting.</p><p><b>RESULTS</b>KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression of KLF6 mRNA or protein was down-regulated in 8 (34.7%) or 9 (39.1%) of 23 HCC tissues. Wild-type KLF6 (wtKLF6) inhibited cellular proliferation and prolonged G1-S transition by inducing the expression of p21WAF1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant (mKLF6) had no effects.</p><p><b>CONCLUSION</b>Our findings suggest that KLF6 may be involved in pathogenesis of HCC.</p>