2.Investigation of the molecular mechanism how genistein combined with 5-fluorouracil inhibits proliferation of human colon cancer cell line SW480
Hang LING ; Yuqing CHEN ; Meiqin GAO ; Wenmin ZHANG
Chinese Journal of Digestion 2015;(6):390-394
[Abstract ] Objective To investigate the molecular mechanism how genistein increased the sensitivity of colon cancer cell to 5-fluorouracil(FU)and promoted colon cancer cell apoptosis.Methods SW480 colon cancer cell line was chosen as experimental object.Genistein 80 μmol/L and 5-FU 30 μg/mL used separated or combined for 48 hours were set as drug experiment group.There were four experiment groups in this study:control group (without any drug),5-FU group,genistein group,5-FU and genistein combined group.The expression of survivin,Bcl-2,p21 ,caspase3 and caspase 9 in the tumor cells of each group at mRNA and protein level was deteced by real-time quantitative polymerase chain reaction (PCR) and Western blotting.The relative expression quantity of genes was determined by comparative threshold method (2 -ΔΔCT )andβ-actin was taken as an internal reference.Semi quantitative analysis was performed for protein relative expression quantity.The DNA combination activity of nuclear factor(NF)-κB of each group was measured by electrophoretic mobility shift assay (EMSA).Single factor analysis of variance was used for mean comparison among multiple groups and LSD test was for mean comparison between two groups.Results The expression of caspase3,caspase 9 and p21 of 5-FU and genistein combination group at mRNA (1 .903±0.122,2.726±0.050 and 2.541 ±0.393)and protein level (0.534±0.077,1 .161 ± 0.172 and 0.463±0.016)were all higher than those of control group (1 .001 ±0.052,1 .000±0.014 and 1 .001 ±0.037;0.080 ±0.043,0.248±0.059 and 0.139 ±0.021 ),genistein group (1 .559 ±0.038, 2.394±0.095 and 1 .686 ±0.061 ;0.335 ±0.052,0.478 ±0.059 and 0.304 ±0.018)and 5-FU group (1 .198±0.063,1 .051 ±0.043 and 1 .399±0.055 ;0.194±0.015 ,0.337 ±0.036 and 0.231 ±0.011 );the expression of survivin of 5-FU and genistein combined group at mRNA and protein level (0.165 ± 0.018 and 0.216±0.014)were all lower than those of control group,genistein group and 5-FU group (1 .001 ±0.033,0.775 ±0.044 and 0.395 ±0.030;0.594±0.079,0.375 ±0.014 and 0.295 ±0.014), and all the differences were statistically significant (gene,F = 802.865 ,52.760,39.992,187.288, 37.435 ;protein,F =10.466,44.483,19.490,200.011 ,45 .238;all P <0.01);the difference was also statistically significant in the expression of caspase3 and p21 of 5-FU group and genistein group compared with those of control group (LSD test,P <0.05 ).The results of EMSA assay showed that the DNA binding activity of NF-κB protein of genistein group (461.64 ±15.41 )and combined group (585.28 ±7.82) significantly decreased compared with that of control group (1 067.97 ±36.01)and 5-FU group (718.83± 23.18,LSD-test,P < 0.05).Conclusions Genistein combined with 5-FU seemed to have synergistic effects on apoptosis of colon cancer cell.The mechanism was that genistein inhibited the DNA binding activity of NF-κB mediated by genistein,further up-regulated caspase 3,caspase 9,p21 and down regulated survivin.Therefore,genistein may provide assistance in colon cancer chemotherapy.
3.Study on the phospholipid composition of human milk at different lactation stages
Runying GAO ; Ke WU ; Jie ZHU ; Meiqin CAI
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(8):1151-1155
Objective · To obtain the latest data on phospholipid composition of human milk in Shanghai and compare the differences in phospholipid composition at different lactation stages. Methods · Healthy postpartum women who delivered full-term infants in the Obstetrical Department of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between April and July, 2016 were enrolled. The colostrum, transitional milk, and mature milk were collected at Day 3, 10, and 45 after delivering babies, respectively. Human milk fat was extracted with Folch's method and phospholipids were separated with solid phase extraction (SPE). The phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin were quantitatively analyzed with HPLC/VWD. The differences in phospholipid composition at different lactation stages were compared with univariate analysis of variance and Games-Homell test. Results · One hundred women who provided at least one breast milk sample were enrolled. A total of 70 colostrum samples, 96 transitional milk samples, and 82 mature milk samples were collected. The total phospholipid content of mature milk [(281.93±118.54) μg/g] was significantly lower than that of colostrum [(381.99±205.90) μg/g]. At all lactation stages, the relative content of phosphatidylcholine was the highest (53.74%-59.36%), followed by sphingomyelin (28.12%-32.74%). The relative content of phosphatidylethanolamine was constant (P=0.617), the relative content of phosphatidylcholine gradually decreased (P=0.000), and that of sphingomyelin gradually increased (P=0.000) during the lactation. Conclusion · Sphingomyelin and phosphatidylcholine are major components of human milk phospholipids. The amount of phospholipids varies during the lactation. The total amount of phospholipids is lower in mature milk than in colostrum and transitional milk. The relative content of phosphatidylethanolamine is consistent at all lactation stages, the relative content of phosphatidylcholine gradually decreases, and that of sphingomyelin gradually increases.
4.Research in CaNa2EDTA in the treatment of chronic moderate lead poisoning in children
Xiaolan YING ; Zhenyan GAO ; Wenjuan MA ; Meiqin WU ; Jian XU ; Chonghuai YAN
Journal of Clinical Pediatrics 2017;35(9):673-677
Objectives To explore the efficacy of CaNa2EDTA in the treatment of chronic moderate lead poisoning, so as to optimize the chelation therapy for lead poisoning in children. Methods The clinical data of 14 patients with chronic moderate lead poisoning treated with CaNa2EDTA for 3 consecutive courses of lead removal during September 2014 to December 2016 were analyzed retrospectively. Twenty-four hour urinary lead levels during hospitalization were analyzed. The changes of blood lead levels before treatment, 3 days, and 5 days after treatment were also analyzed. Results In the 14 children (4 males and 10 females) average age was 2.35±1.47 years. After treatment with CaNa2EDTA for 3 consecutive courses, the blood lead levels were decreased significantly in all the patients, and the blood lead levels at 3 days after treatment were 0.76, 0.77, 0.72 times those at 5 days after treatment respectively. The decrease of blood lead levels per unit of drug in the first 3 days of treatment were significantly higher than those in 5 days of treatment (P<0.05). The decrease of blood lead levels at 3 days after treatment was 0.65, 0.71, 0.70 times , those in 5 days' treatment respectively. The decrease of urine lead levels per unit of drug in the first 3 days of treatment were significantly higher than those in 5 days of treatment (P<0.05). Conclusions CaNa2EDTA has an obvious effect on removal of lead.The efficiency of lead removal in 3 days of treatment was higher than in 5 days of treatment. Thus, a course of treatment for 3 days may be an altenative for a course of 5 days.
5.Clinical efficacy and optimal dose of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer
Shile GAO ; Donghui LU ; Meiqin LIU ; Xingjun XU ; Huan MA ; Yu ZHANG
Journal of International Oncology 2022;49(3):140-145
Objective:To explore the clinical efficacy of different doses of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and the adverse reactions.Methods:A total of 69 patients with NSCLC diagnosed in the No. 901 Hospital of the Chinese People′s Liberation Army Joint Logistics Support Force were selected from January 2018 to June 2020, and were divided into chemotherapy alone group (docetaxel+ cisplatin was used), apatinib group A [apatinib (0.25 g)+ docetaxel+ cisplatin was used] and apatinib group B [apatinib (0.50 g)+ docetaxel+ cisplatin was used] according to random number table method, with 23 cases in each group. The objective response rate (ORR), disease control rate (DCR), median overall survival (OS), median progression-free survival (PFS), and incidences of adverse reactions were compared between the three groups of patients.Results:One patients in the apatinib group B withdrew from the study due to acute myocardial infarction. After 4 cycless of treatment, the ORR of the patients in the chemotherapy alone group, apatinib group A and apatinib group B were 17.39% (4/23), 47.83% (11/23) and 54.55% (12/22) respectively, with a statistically significant difference ( χ2=7.41, P=0.024). The ORR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference ( χ2=6.77, P=0.009). There were no statistically significant differences in ORR between the apatinib group A and chemotherapy alone group, the apatinib group A and apatinib group B ( χ2=4.85, P=0.028; χ2=0.20, P=0.652). The DCR of the patients in the three groups were 47.83% (11/23), 78.26% (18/23) and 86.36% (19/22) respectively, with a statistically significant difference ( χ2=9.03, P=0.011). The DCR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference ( χ2=7.52, P=0.006). There were no statistically significant differences in DCR between the apatinib group A and the chemotherapy alone group, the apatinib group A and apatinib group B ( χ2=4.57, P=0.033; χ2=0.51, P=0.477). The median OS of the patients in the three groups were 6.8, 9.2 and 9.9 months respectively, with a statistically significant different ( χ2=8.91, P=0.022). Compared with the chemotherapy alone group, the median OS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences ( χ2=7.25, P=0.036; χ2=8.60, P=0.029). Compared with the apatinib group A, the median OS of the apatinib group B was prolonged, but there was no statistically significant different ( χ2=1.54, P=0.201). The median PFS of the patients in the three groups were 5.2, 7.7 and 8.2 months respectively, with a statistically significant different ( χ2=8.79, P=0.026). Compared with the chemotherapy alone group, the median PFS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences ( χ2=7.01, P=0.039; χ2=8.36, P=0.031). Compared with the apatinib A group, the median PFS of the apatinib group B was prolonged, but there was no statistically significant different ( χ2=1.68, P=0.186). There were statistically significant differences in the incidences of fatigue [34.78% (8/23) vs. 65.22% (15/23) vs. 72.73% (16/22), χ2=7.50, P=0.024], hypertension [4.35% (1/23) vs. 34.78% (8/23) vs. 68.18% (15/22), χ2=20.07, P<0.001], hand-foot syndrome [4.35% (1/23) vs. 43.48% (10/23) vs. 72.73% (16/22), χ2=22.28, P<0.001] and oral mucositis [8.70% (2/23) vs. 39.13% (9/23) vs. 72.73% (16/22), χ2=19.26, P<0.001] among the three groups. Compared with the chemotherapy alone group, the incidences of hypertension and hand-foot syndrome in the apatinib group A and the incidences of fatigue, hypertension, hand-foot syndrome and oral mucositis in the apatinib group B were increased, with statistically significant differences ( χ2=6.77, P=0.009; χ2=9.68, P=0.002; χ2=6.51, P=0.011; χ2=20.00, P<0.001; χ2=22.37, P<0.001; χ2=19.21, P<0.001). Conclusion:Apatinib (0.50 g) combined with chemotherapy has better short-term efficacy than chemotherapy alone in advanced NSCLC. Apatinib (0.25 g) and apatinib (0.50 g) can prolong the survival of patients, but increasing the treatment dose can not achieve longer survival benefit.
6. Related influencing factors of gynecological diseases in grassroot level female medical staffs
Canjian LU ; Lian GAO ; Wenlan YU ; Haihong LI ; Qingchun ZHOU ; Cuilan TENG ; Meiqin DENG ; Zhuoxin HUANG ; He ZHONG
China Occupational Medicine 2019;46(05):595-598
OBJECTIVE: To investigate the prevalence and relevant influencing factors of gynecological diseases of grassroot level female medical staffs. METHODS: A total of 2 308 female medical workers from county, town and village in hengxian County of Guangxi Zhuang Autonomous Region were selected as study subjects by cluster sampling method. The basic information, occupational history, reproductive health and fertility of these subjects were investigated by Reproducetive Health Survey Questionnaine of Female Workers. RESULTS: The total prevalence of gynecological diseases in female medical staffs was 21.6%. Among them, the prevalence of genital tract infections was 15.6%, and gynecological tumors was 6.0%. The top three gynecologic diseases were vaginitis(9.2%), uterine fibroids(4.3%) and cervicitis(3.5%). Multivariate logistic regression analysis results indicated that the younger the patients, the higher the risk of reproductive tract infectious diseases(P<0.01), and the lower the risk of gynecological tumors(P<0.01). The risk of reproductive tract infectious diseases and gynecological tumors in married patients was higher than that in unmarried staffs(P<0.05). The higher the number of abortions, the higher the risk of reproductive tract infectious diseases and gynecological tumors(P<0.01). The risk of reproductive tract infectious diseases was higher and the risk of gynecological tumors was lower in female shift workers than that of non-shift workers(P<0.05). CONCLUSION: Vaginitis, uterine fibroids and cervicitis are the main gynecological diseases in grassroot level female medical staffs. The incidence of gynecological diseases is related to age, history of marriage, childbirth and abortion, and work-shifts.
7.Evaluation of the short-term efficacy and safety of bevacizumab combined with doxorubicin liposomes in the treatment of patients with platinum-resistant recurrent epithelial ovarian cancer
LIU Meiqin ; LU Donghui ; GAO Shile ; XU Xingjun ; ZHANG Yu
Chinese Journal of Cancer Biotherapy 2021;28(8):818-823
[摘 要] 目的:探讨贝伐珠单抗联合多柔比星脂质体治疗铂类耐药复发性卵巢上皮性癌患者的近期疗效和不良反应,并随访生存情况。方法:选取中国人民解放军联勤保障部队第九〇一医院2018年1月至2019年12月收治的76例铂类耐药复发性卵巢上皮性癌患者,采用数字随机分组法分为对照组38例、观察组38例,对照组给予多柔比星脂质体单药化疗4个周期,观察组给予贝伐珠单抗联合多柔比星脂质体化疗4个周期,观察两组患者治疗后近期疗效和不良反应,以及血清肿瘤标志物人附睾蛋白4(human epididymis protein 4,HE4)、糖类抗原125(carbohydrate antigen 125,CA125)变化,并随访总生存期(OS)和无疾病进展生存期(PFS)。结果:对照组患者客观有效率(ORR)为40.54%、疾病控制率(DCR)为67.57%,观察组患者ORR为69.44%、DCR为88.89%,观察组ORR和DCR显著高于对照组(均P<0.05)。治疗后观察组患者血清HE4和CA125分别为(142.67±46.81)pmol/L、(31.79±11.65)U/L,显著低于对照组患者的(219.33±75.67)pmol/L、(57.05±17.85)U/L(均P<0.05)。两组患者的胃肠反应、骨髓抑制、肝肾功能损伤、心脏毒性、过敏反应、血栓栓塞和出血等不良反应相比较差异无统计学意义(均P>0.05);观察组患者高血压发生率显著高于对照组(P<0.05),但可控、可耐受。观察组患者中位OS 和中位PFS分别分别为17.2个月和10.9个月,显著长于对照组患者的14.1个月和7.8个月(均P<0.05)。结论:对于铂类耐药复发性卵巢上皮性癌患者,贝伐珠单抗联合多柔比星脂质体近期疗效可靠、安全性好、不良反应可耐受,值得临床推广。
9.Short term efficacy and toxicity of apatinib and docetaxel combined with cisplatin chemotherapy for advanced gastric cancer
GAO Shile ; LU Donghui ; LIU Meiqin ; WANG Chong ; WEI Lei ; XU Peng ; LIU Yan ; TANG Zhengzhong ; HU Zongtao
Chinese Journal of Cancer Biotherapy 2018;25(11):1131-1134
Objective: : To observe the short-term efficacy and toxicity of apatinib monotherapy as well as docetaxel plus cisplatin in advanced gastric cancer. Method: : According to inclusion and exclusion criteria, 108 patients with advanced gastric cancer in the 105th Hospital of PLA were selected. According to random table grouping method, there were 54 cases in group A and 54 cases in group B. Patients in group A received continuous oral administration of apatinib alone, while group B received docetaxel plus cisplatin chemotherapy, with 3 weeks as a cycle and 4 cycles for a course. The efficacy and side effects were evaluated 3 months later. Results: : In groupA, there were 4 cases of CR, 25 cases of PR, 18 cases of SD and 7 cases of PD; the ORR was 53.7% and DCR was 87%. In group B, there were 2 cases of CR, 19 cases of PR, 21 cases of SD and 12 cases of PD; the ORR was 38.9% and DCR was 77.8%. The ORR and DCR in group A were significantly better than those in group B (P<0.05). The main adverse reactions were gastrointestinal reaction, myelosuppression, hypertension and hand-foot syndrome, all of which were grade 1 to 2; The incidence of bone marrow suppression and gastrointestinal reaction in group A was lower than that in group B (P<0.05), while the incidence of hand-foot syndrome and hypertension in group B was lower than that in group A (P<0.01). Conclusion: :The short-term efficacy of targeted therapy of apatinib alone was better than that of docetaxel combined with cisplatin chemotherapy, and the toxicity and side effects of both regimens were controllable;Apatinib can be used as the primary regimen for the treatment of advanced gastric cancer.