1.Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases
Xuheng SUN ; Yijun WANG ; Wei ZHANG ; Yajun GENG ; Yongsheng LI ; Tai REN ; Maolan LI ; Xu'an WANG ; Xiangsong WU ; Wenguang WU ; Wei CHEN ; Tao CHEN ; Min HE ; Hui WANG ; Linhua YANG ; Lu ZOU ; Peng PU ; Mingjie YANG ; Zhaonan LIU ; Wenqi TAO ; Jiayi FENG ; Ziheng JIA ; Zhiyuan ZHENG ; Lijing ZHONG ; Yuanying QIAN ; Ping DONG ; Xuefeng WANG ; Jun GU ; Lianxin LIU ; Yeben QIAN ; Jianfeng GU ; Yong LIU ; Yunfu CUI ; Bei SUN ; Bing LI ; Chenghao SHAO ; Xiaoqing JIANG ; Qiang MA ; Jinfang ZHENG ; Changjun LIU ; Hong CAO ; Xiaoliang CHEN ; Qiyun LI ; Lin WANG ; Kunhua WANG ; Lei ZHANG ; Linhui ZHENG ; Chunfu ZHU ; Hongyu CAI ; Jingyu CAO ; Haihong ZHU ; Jun LIU ; Xueyi DANG ; Jiansheng LIU ; Xueli ZHANG ; Junming XU ; Zhewei FEI ; Xiaoping YANG ; Jiahua YANG ; Zaiyang ZHANG ; Xulin WANG ; Yi WANG ; Jihui HAO ; Qiyu ZHANG ; Huihan JIN ; Chang LIU ; Wei HAN ; Jun YAN ; Buqiang WU ; Chaoliu DAI ; Wencai LYU ; Zhiwei QUAN ; Shuyou PENG ; Wei GONG ; Yingbin LIU
Chinese Journal of Digestive Surgery 2022;21(1):114-128
Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.
2.Regulation of miRNA-618 on the proliferation and apoptosis of acute monocyte leukemia THP-1 cells
Feng LI ; Gang WANG ; Peng BU ; Linhua YANG
Journal of Leukemia & Lymphoma 2021;30(3):156-160
Objective:To investigate the effect of miRNA-618 (miR-618) on the cell proliferation and apoptosis of acute monocyte leukemia THP-1 cells.Methods:Real-time polymerase chain reaction (PCR) was used to detect the relative expression level of miR-618 in THP-1 cells and monocytes isolated from peripheral blood of the healthy people. Overexpression of miR-618 plasimid vector was constructed and empty vector was treated as the negative control; and then the two vectors were transfected with THP-1 cells; finally, miR-618 overexpression group and negative control group were set. THP-1 cell proliferation and apoptosis of both groups were detected by using CCK-8 method and flow cytometry, respectively. TargetScan was used to predict the target gene of miR-618 and it was verified by using luciferase reporter assay.Western blot was used to detect the protein levels of THP-1 cells in miR-618 overexpression group and negative control group, and predicted miR-618 target gene in peripheral blood monocytes of the healthy people.Results:PCR showed that the expression level of miR-618 was lower in THP-1 cells compared with that in monocytes isolated from peripheral blood of the healthy people ( P < 0.05). CCK-8 assay showed that compared with the negative control group, the proliferation ability of THP-1 cells in miR-618 overexpression group was decreased (the absorbance values at 0, 24, 48 and 72 h after transfection: 0.20±0.03 vs. 0.20±0.03, 0.28±0.02 vs. 0.35±0.03, 0.34±0.03 vs. 0.43±0.04, 0.39±0.02 vs. 0.53±0.05, all P < 0.05), and the late apoptosis rate was increased [(27.1±0.1)% vs. (14.9±0.1)%, t=2.13, P=0.03]. The target gene of miR-618 was ARPP19 predicted by using TargetScan software. Luciferase reporter assay showed that the relative luciferase activity of THP-1 cells in group transfected with wild-type ARPP19 gene plasmid+miR-618 gene plasmid was higher than that in the blank control group and group transfected with wild-type ARPP19 gene plasmid+miR-618 empty vector (0.170±0.003 vs. 0.100±0.004, 0.100±0.001, all P < 0.05). Western blot indicated the expression level of ARPP19 protein in THP-1 cells of miR-618 overexpression group was lower than that of the negative control group, while the expression levels of ARPP19 protein of peripheral blood monocytes of the healthy people in both groups were similar. Conclusion:miR-618 can inhibit the cell proliferation and promote apoptosis of THP-1 cells by inhibiting the expression of of THP-1 cells ARPP19 in acute monocyte leukemia.
3.Application of Chitosan and its Derivatives in Drug Carriers
Hairong WANG ; Hongyu JI ; Jiayu FENG ; Chengcheng ZHANG ; Linhua WU
China Pharmacist 2018;21(2):324-327
Chitosan and its derivatives with good characteristics such as non-toxicity,good biocompatibility and degradability,mu-cosal adhesion and permeability promotion etc,have been widely researched and applied in the field of drug carriers. Based on the re-cently published papers at home and abroad,the application and action mechanism of chitosan and its derivatives as drug carriers were analyzed and discussed,and the application and research progress of chitosan and its derivatives as anti-tumor drug targeting carriers, sustained-release and controlled-release drug carriers,ophthalmic drug carriers,gene carriers and gel bases were reviewed.
4.The efficacy and safety of linagliptin in elderly patients with type 2 diabetes: a pooled analysis of eight placebo-controlled clinical trials
Xiaohui GUO ; Zhikai FENG ; Linhua XU
Chinese Journal of Internal Medicine 2017;56(8):588-594
Objective To evaluate the efficacy and safety of dipeptidyl peptidase-4 inhibitor,linagliptin,in subjects aged 60 years or older with type 2 diabetes mellitus (T2DM).Methods Data from eight 24-week,multinational,multicenter,randomized,double-blind,placebo-controlled,parallel-group studies were analyzed.Patients aged 60 years or older with T2DM were received oral linagliptin (5 mg/d) or placebo in combination with mefformin,or metformin plus sulfonylurea.Efficacy was assessed by the changes in glycosylated hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) from baseline to 24 weeks of treatment.Safety endpoint included the frequency and intensity of adverse events.Results A total of 1 421 patients (placebo 429,linagliptin 992) were included in the full analysis set (FAS).Mean ages of the subjects were (67.4 ± 5.6) years in the linagliptin group and (66.7-± 5.6) years in the placebo group.Baseline HbA1c was (8.0 ±0.8) % in the linagliptin group and (8.1 ±0.9) % in the placebo group.At the end of 24-week,placebo-adjusted reduction in HbAlc in subjects with linagliptin was (0.7 ±0.1)% (95% CI 0.6-0.8,P <0.000 1),and placebo-adjusted reduction in FPG in subjects with linagliptin was (0.88 ±0.12) mmol/L(95% CI 0.65-1.11,P <0.000 1).Overall safety and tolerability in the two groups were similar.Adverse events occurred in 57.1% of patients in the placebo group and 61.1% of patients in the linagliptin group,and the incidence of adverse events leading to discontinuation was 3.2% in the placebo group and 3.8% in the linagliptin group.Serious adverse events occurred in 1.6% of patients in the placebo group and 2.8% of patients in the linagliptin group.Investigator-defined hypoglycaemia occurred in 7.3% of patients in the placebo group and 11.9% of patients in the linagliptin group.Among them,most were mild or moderate hypoglycaemia,and severe hypoglycaemia only occurred in 0.2% of patients in the placebo and 0.5% in the linagliptin groups.Overall incidence of hypoglycaemia in linagliptin group was slightly higher than that in placebo group,which might be due to the fact that more patients were taking sulfonylureas in linagliptin group than in placebo group (26.8% linagliptin;18.4% placebo).No difference could be viewed in hypoglycaemia between the two groups in patients without sulfonylureas (1.2% linagliptin,1.1% placebo)Moreover,no severe hypoglycaemia was reported in subjects without sulfonylureas.The incidences of other adverse events were similar in both groups.Conclusion Linagliptin was efficacious in lowering glucose with a safety profile similar to placebo in type 2 diabetic patients aged 60 years or older.
5.Association between sleep and leukocyte telomere length in middle-aged and older adults
Huifen LIU ; Feng LI ; Yehong WANG ; Jianghui CHEN ; Dongxu PENG ; Jing CHEN ; Linhua TAN ; Xue MI ; Benhua ZHAO
Chinese Journal of Epidemiology 2017;38(7):889-892
Objective To understand the association between peripheral leukocytes telomere length (TL) and sleep in middle-aged and old adults.Methods A total of 176 middle-aged and old adults were investigated by using the Pittsburgh Sleep Quality Index and questionnaire.TL was measured by fluorescence quantitative PCR.The correlation and regression analysis between sleep and telomere length was performed.Results TL had a mean T/S ratio of 0.995 ± 0.23.There was a negative correlation between TL and age (r=-0.241,P=0.003).With increasing age,sleep quality became worse (r=-0.230,P<0.01),the time to fall asleep became longer (r=0.227,P<0.01),sleep duration was shorter (r=-0.486,P<0.01),sleep efficiency became worse (r=-0.226,P<0.01).After controlling for the effects of gender,age,marital status,income level,residence,smoking,drinking,physical exercise and disease status,multiple linear regression analysis indicated that sleep quality (β3=0.057,P<0.01),time to fall asleep (β =-0.046,P<0.01),sleep duration (β3=0.086,P<0.01) were independent influencing factors of telomere length,suggesting that the people who had better sleep quality,the shorter time to fall asleep,the longer sleep time would have longer telomere length.Conclusions Sleep is a relevant factor affecting TL in middle-aged and elderly population.Good sleep may delay aging by slowing TL.We encourage to conduct health education about the importance of sleep quality in community.
6.Infection in patients with acute leukemia during initial induction chemotherapy and its relation to therapeutic efficacy
Nannan ZHANG ; Ruijuan ZHANG ; Linhua YANG ; Yang CHEN ; Jing XU ; Feng XUE ; Bin YIN ; Feng GAO
Chinese Journal of General Practitioners 2017;16(12):937-940
Objective To analyze the infection features,risk factors,and the relationship with the efficacy in patients with acute leukemia during initial induction chemotherapy.Methods The clinical data of 200 patients with newly diagnosed acute leukemia from January 2015 to February 2016 in the Second Hospital of Shanxi Medical University were retrospectively analyzed.Results The infection rate of patients with acute leukemia under induction chemotherapy was 84.0% (168/200).Among 168 patients with infection,159 cases (94.6%) had known infection sites,the top three infection sites were the lungs,gastrointestinal tract and the oral cavity.Total 213 strains of pathogens were identified,Gram-negative bacilli accounted for 39.0% (n =83),Gram-positive cocci for 34.3% (n =73),fungi for 23.5% (n =50) and the virus for 3.3% (n =7).Multivariate regression analysis showed that agranulocytosis was the independent risk factor for acute leukemia patients during induction chemotherapy (OR =14.370,95% CI:2.576-116.518,P < 0.01).The rate of complete remission (CR) and CR with incomplete hematologic recovery (CRi) in infection group was 74.4% (125/168),and the rate of CR + CRi in non-infected group was 87.5% (28/32),and there was no significant difference between the two groups.(χ2 =2.564,P =0.109).Conclusion During the induction therapy for acute leukemia patients,the rate of infection and the rate of fungal infection are high;lung is the most common site,Gram-negative bacteria is more common;agranulocytosis increases the chance of infection;and the infection may not affect the disease remission rate.
7.Expression relevance of GATA-1 and GATA-2 in bone marrow CD71 +cells of high-altitude polycythemia rat model
Fang LIU ; Wei WEI ; Linhua JI ; Tingting FENG ; Shulin WANG ; Jiyu SHI
Chinese Journal of Pathophysiology 2016;32(10):1863-1869
[ ABSTRACT] AIM:To investigate the expression relevance of transcription factors GATA-1 and GATA-2 in the bone marrow CD71 +cells of a high-altitude polycythemia (HAPC) rat model.METHODS:Male SD rats (n=48) were randomly divided into normal control group and HAPC model group .HAPC model was established at an altitude of 4 300 m in the natural environment and verified by the morphology and quantity of the bone marrow cells and hematologic parameters detection .A relative change in the trend of bone marrow CD 71 +cell numbers was detected by flow cytometry analysis .The expression of GATA-1 and GATA-2 at mRNA and protein levels in the CD 71 +cells was examined by RT-qPCR and West-ern blot .CD71 +cells were cultured under hypoxic condition and transfected with the optimal interference sequence of GA -TA-1shRNA1 for 96 h.The expression of GATA-1 and GATA-2 at mRNA and protein levels was detected by RT-qPCR and Western blot .RESULTS:The establishment of the animal model with HAPC was successful as the bone marrow smears and the hematologic parameters showed compared with the control .The quantity of the bone marrow CD 71 +cells of HAPC rats were significantly increased and the expression of GATA-1 at mRNA and protein levels in the CD 71 +cells were higher than those of the control .The expression of GATA-2 at mRNA and protein levels was similar to that of the control .The correla-tion analysis showed that the expression of GATA-1 was negatively correlated with that of GATA-2 in the control, while no obvious correlation between them was observed in the HAPC rats .The expression of GATA-1 at mRNA and protein levels in HAPC group was lower than that in control group after interfered by GATA-1 shRNA1 for 96 h, but no obvious diversity of GATA-2 expression between the 2 groups was observed .CONCLUSION:GATA-1 and GATA-2 are abnormally expressed and their negative correlation is destroyed in HAPC , which may be one of the pathogenesis of HAPC .
8.Influence of HIF-2α on the expression of GATA-1 in bone marrow CD71 + cell of high altitude polycythemia rat model
Fang LIU ; Wei WEI ; Jin DING ; Ying CHEN ; Tingting FENG ; Linhua JI ; Jiyu SHI
Chinese Journal of Hematology 2016;37(8):696-701
Objective To explore the influence ofhypoxia-inducible factor-2 αlpha (HIF-2α) on the expression of erythroid-specific transcription factor GATA-1 in bone marrow CD71+ cells of rat model with high altitude polycythemia (HAPC).Methods A total of 48 male SD rats were selected and randomly divided into normal control group and HAPC group.HAPC model was established at an altitude of 4 300 meters in the natural environment and verified by bone marrow cell classification and counting,hematologic parameters and serum EPO detection.Bone marrow CD71 + cells were separated by a combination of methods with density gradient centrifugation and magnetic activated cell sorting.The changes of expression level of HIF-2α,GATA-1 mRNA and proteins were detected by Q-PCR and Western blot.CD71 + cells were cultured under hypoxia condition and transfected with selected optimal HIF-2α shRNAi3 for 96 h.And the expression level of HIF-2α and GATA-1 mRNA and proteins were detected by Q-PCR and Western blot.Results The results of bone marrow cell counts,the hematologic parameters and the serum EPO content showed that the HAPC rat model was successfully established.The expression of HIF-2α and GATA-1 mRNA and protein in bone marrow CD71 + cells of HAPC group was higher than that in control group (P<0.05).And HIF-2α and GATA-1 of HAPC group were positively correlated at the expression levels of mRNA and protein,respectively (r=0.923,P<0.01;r=0.838,P<0.01).However,the expression of HIF-2α and GATA-1 mRNA and protein in HAPC group was significantly lower than that in control groups after interfered by HIF-2α shRNAi3 for 96 h (P<0.05).Conclusion The effect of HIF-2α on GATA-1 expression may be correlated with the pathogenesis of HAPC.
9.Preliminary study on the thioredoxin reductase in K562 cells and anti-leukemia effect of BBSKE in vitro
Jiangfang FENG ; Lianrong XU ; Jingjing WANG ; Yunfei BIAN ; Li ZHANG ; Linhua YANG
Journal of Leukemia & Lymphoma 2011;20(5):266-268,274
Objective To explore the activity of thioredoxin reductase (TrxR) in chronic myeloid leukemia cell line K562 and the anti-leukemia effect of BBSKE (a novel inhibitor of TrxR) in vitro. Methods The activity of TrxR on K562 cell lineage and fresh bone marrow cell from healthy adult was analyzed by insulin reduction assay. The inhibition of proliferation was measured by CCK-8 assay. The anti-leukemia effect of BBSKE was detected by laser scanning confocal microscope,agarose gel electrophoresis and flow cytometry with Annexin V -FITC/PI staining. Results TrxR activity of K562 cell lineage was significantly higher than that of normal bone marrow mononuclear cells. The apoptosis of K562 cells could be induced at concentrations of 10 μmol/L BBSKE after treated for 24 hours. The typical DNA ladder bans were observed by agarose gel electrophoresis. The apoptotic rates of K562 cells were (10.28±2.74) %. Application of 10 μmol/L BBSKE for 48 hours could also induce apoptosis of fresh bone marrow cell from chronic myeloid leukemia patients, and the apoptotic rates were (5.70±0.48) %. Conclusion TrxR activity in chronic myeloid leukemia cells was significantly higher than that of normal cells. BBSKE inhibits the TrxR activity and the proliferation of K562 by inducing apoptosis.It might be a potential medication for chronic myeloid leukemia.
10.The clinical significance of immune-related marker detection in idiopathic thrombocytopenic purpura
Jianfang CHEN ; Linhua YANG ; Jianjun FENG ; Lixian CHANG ; Xiue LIU ; Yujin LU
Chinese Journal of Internal Medicine 2010;49(9):765-768
Objective To assess the clinical significance of detecting the immune markers in idiopathic thrombocytopenic purpura (ITP). Methods The frequencies of circulating B cells secreting platelet-specific antibody, platelet-specific antibody, the percentage of T lymphocyte subsets, the percentage of reticulated platelet and the level of thrombopoietin in 64 ITP patients and 31 healthy controls were measured with enzyme-linked immunospot assay (ELISPOT),modified monoclonal antibody immunobilization of platelet antigens assay (MAIPA), flow cytometry and sandwich enzyme-linked innnunosorbent assay respectively. Results Compared with the controls[1.3 ± 0. 5/105 peripheral blood mononuclear cell (PBMC), (0.33±0.06,0.41±0.03), (22.08±4.54)% and (8.19±2.46)%], the frequencies of circulating B cells secreting platelet-specific antibody (7.6±4.6/105 PBMC in acute ITP group, 5.3±3.0/105 PBMC in chronic ITP group), platelet-specific antibody (including the anti-GP Ⅱ b/Ⅲa antibody, anti-GP Ⅰ b/X antibody) (0.51 ±0.11, 0.48±0.06 in acute ITP group; 0.49±0.10,0.46±0.09 in chronic ITP group), the percentage of CD8+ T Lymphocyte (27.09±9.86 ) %, the percentage of reticulated platelet in ITP patients[the megakaryocyte cytosis group (24. 85 ± 19. 18)%, the normal megakaryocyte group (23.89±18.90)%]were significantly increased ( all P<0.05).The frequencies of circulating B cells secreting platelet-specific antibody in acute ITP patients were notably increased (P<0.05) compared to the chronic ITP patients. In T lymphocyte subsets, the percentage of CD3+T lymphocyte and CD4+ T lymphocyte and the ratio of CD4+/CD8+ in the patients with ITP[(60.88±14.59)%, (28.41±10.55)%, 1.18±0.59]were notably decreased than those in the healthy controls [(69.89±6.43)%, (35.38±5.05) %, 1.64±0.29, P<0.05]. There was no apparent difference of the level of thrombopoietin between ITP patients with megakaryocyte cytosis (72. 09 ± 41.64 ) and health controls (75.37± 26. 32, P > 0. 05 ), however, the level of thrombopoietin of ITP patients with normal megakaryocyte apparently increased (118.60±70.72, P<0.05). Conclusion Detecting the frequencies of circulating B cells secreting platelet-specific antibody, platelet-specific antibody, the percentage of T lymphocyte subsets, the percentage of reticulated platelet and the level of thrombepoietin in the patients with ITP may improve the diagnosis and guide clinical therapy.

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