1.Application and mechanism of renal tubular perilipin 2 in predicting de-cline in renal function in diabetic kidney disease patients
Rui SHEN ; Xin YU ; Caifeng SHI ; Songyan QIN ; Yi FANG ; Aiqin HE ; Xiaomei WU ; Junwei YANG ; Yang ZHOU
Chinese Journal of Pathophysiology 2024;40(5):882-889
AIM:To investigate whether the expression of perilipin 2(PLIN2)in renal tubular cells could predict a decline in renal function in diabetic kidney disease(DKD)patients,and to explore the potential mechanisms in-volved in renal tubular cell injury induced by PLIN2 during the progression of DKD.METHODS:Control individuals(n=12)and DKD patients(n=51)were enrolled in this retrospective cohort study.Demographic and laboratory data were col-lected.A simplified linear mixed-effects model was applied to assess the estimated glomerular filtration rate(eGFR)slope.The relationship between PLIN2 and renal function decline in DKD patients was predicted by Spearman correlation analysis and a generalized linear model.BKS-db/db diabetic mice and streptozotocin-induced diabetic mice were used.Primary renal tubular cells were treated with glucose and transfected with small interfering RNA or plasmid.Western blot-ting and immunofluorescence staining were used to detect PLIN2 expression.Lipid droplets were stained with oil red O.The oxygen consumption rate(OCR)of mitochondria was measured using an extracellular flux analyser.RESULTS:The expression of PLIN2 was markedly higher in the tubules of DKD patients than in those of control subjects.After 24(12,39)months of follow-up,the eGFR slope of DKD patients was-7.42(-19.77,-2.09)mL/(min·1.73 m2·year).An in-crease in the baseline percentage of PLIN2-positive tubules was significantly associated with the eGFR slope during the fol-low-up period[hazard ratio(HR)=1.90,95%confidence interval(CI):1.00~3.58],indicating that tubular PLIN2 could predict a decrease in renal function in DKD patients.Both the accumulation of lipid droplets and the expression of PLIN2 were markedly greater in the tubules of diabetic mice than in those of control mice.Glucose treatment induced lipid droplet accumulation and PLIN2 expression in renal tubular cells.Knockdown of PLIN2 significantly alleviated glucose-in-duced lipid droplet accumulation,whereas PLIN2 overexpression aggravated glucose-induced lipid droplet accumulation.The decrease in mitochondrial OCR in renal tubular cells induced by glucose treatment was alleviated after PLIN2 knock-down.However,overexpression of PLIN2 directly decreased the mitochondrial OCR.CONCLUSION:The PLIN2 ex-pression in tubules predicts a decline in renal function in patients with DKD.The PLIN2 suppresses mitochondrial aerobic respiration and contributes to the accumulation of lipid droplets in renal tubular cells to promote the progression of DKD.
2.First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial
Xiaohua WU ; Jihong LIU ; Ruifang AN ; Rutie YIN ; Yu ZHANG ; Huaijun ZHOU ; Aiqin HE ; Li WANG ; Jieqing ZHANG ; Ziling LIU ; Wei DUAN ; Jianqing ZHU ; Ge LOU ; Guilin CHEN ; Ying CHENG ; Fengxia XUE ; Sonja NICK ; Haiyan WANG ; Donghang LI
Journal of Gynecologic Oncology 2024;35(5):e99-
Objective:
First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients.
Methods:
Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2).
Results:
Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP.
Conclusion
Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.
3.First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial
Xiaohua WU ; Jihong LIU ; Ruifang AN ; Rutie YIN ; Yu ZHANG ; Huaijun ZHOU ; Aiqin HE ; Li WANG ; Jieqing ZHANG ; Ziling LIU ; Wei DUAN ; Jianqing ZHU ; Ge LOU ; Guilin CHEN ; Ying CHENG ; Fengxia XUE ; Sonja NICK ; Haiyan WANG ; Donghang LI
Journal of Gynecologic Oncology 2024;35(5):e99-
Objective:
First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients.
Methods:
Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2).
Results:
Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP.
Conclusion
Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.
4.First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial
Xiaohua WU ; Jihong LIU ; Ruifang AN ; Rutie YIN ; Yu ZHANG ; Huaijun ZHOU ; Aiqin HE ; Li WANG ; Jieqing ZHANG ; Ziling LIU ; Wei DUAN ; Jianqing ZHU ; Ge LOU ; Guilin CHEN ; Ying CHENG ; Fengxia XUE ; Sonja NICK ; Haiyan WANG ; Donghang LI
Journal of Gynecologic Oncology 2024;35(5):e99-
Objective:
First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients.
Methods:
Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/ placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2).
Results:
Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP.
Conclusion
Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.
5.Directional screening and identification of potential cytotoxic components from Achnatherum inebrians by a combination of surface palsmon resonance and chromatography.
Wenbin ZHOU ; Man WANG ; Aiqin ZHANG ; Danrong HUANG ; Hua GUO ; Gangyi SHEN
Chinese Herbal Medicines 2023;15(2):329-336
OBJECTIVE:
To establish a method for directional screening of the cytotoxic components from the medicinal herb of Achnatherum inebrians by a combination of surface plasmon resonance (SPR) biosensor and chromatographic isolation technology.
METHODS:
Under the guidance of bioactive assessment based on binding abilities between objects and the α-Mannosidase (α-Man) target, the active components from different solvents extracts, different polar extraction parts and fractions were screened orderly and directionally using SPR. Components with a high binding ability to α-Man can be precisely oriented in a narrower fractions range and are easy to isolate. Three human cancer cells were used to evaluate the cytotoxic activity of component with the highest affinity to α-Man.
RESULTS:
Eight compounds were isolated and identificated from A. inebrians for the first time. Deoxyvasicinone possessed the highest affinity to α-Man among them. Moreover, deoxyvasicinone showed good effects on inhibited proliferation of human hepatoma cells HepG2 (IC50 = 5.7 μmol/L), human breast cancer cells MCF7 (IC50 = 7.21 μmol/L) and human lung cancer cells HCC827 (IC50 = 0.75 μmol/L), respectively. In particular, its inhibitory effect on HCC827 was stronger than the positive drug gefitinib (IC50 = 1.65 μmol/L).
CONCLUSION
A comprehensive strategy of directional screening potential cytotoxic components from herb based on biomolecular interaction and chromatography was established. Deoxyvasicinone as an effective anti-cancer component was initially isolated from A. inebrians. It is expected that this screening strategy could provide new perspectives for rapid screening and identification of active components from natural plants with the complex matrix.
6.Epidemic Characteristics of Dengue Fever in Pudong New Area of Shanghai in 2008- 2020
Huan WANG ; Aiqin ZHU ; Hongmei XU ; Weiping ZHU ; Yixin ZHOU
Journal of Public Health and Preventive Medicine 2022;33(3):68-71
Objective To analyze the epidemic characteristics of imported dengue fever in Pudong New Area of Shanghai from 2008 to 2020,and to explore its prevention and control strategy and measures. Methods The data of dengue fever cases in Pudong New Area from 2008 to 2020 were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiological method was used to analyze the epidemic characteristics. Results A total of 45 cases of dengue fever were reported in Pudong during 2008-2020, all the cases were mild, and no deaths were reported.The male-to-female ratio was 2.46:1. The group aged 20-49 years accounted for 86.67%.The most common occupation was commercial service personnel and cadres (25 cases, accounting for 55.56%). The peak of incidence was from July to October with a total of 35 cases (77.78%). All the cases were imported from abroad, mainly from Southeast Asia and South Asia (43 cases, 95.56%). 15 cases (33.33%) had been ill before entry. 22 cases (48.89%) were first treated in tertiary hospitals. The median time intervals from onset to first clinic visit, from first clinic visit to diagnosis, and from onset to diagnosis were 1.0 d, 5.0 d, and 7.0 d, respectively. Serotypes of dengue virus were mainly Type I, Type III and Type II, which were 9 cases, 7 cases, and 6 cases, respectively. Conclusion The epidemic situation of dengue fever in Pudong New Area from 2008 to 2020 is relatively stable, all imported from abroad. The focus of the prevention and control is to promote the health education for overseas travelers, strengthen the monitoring sensitivity at border ports, enhance the diagnostic level of medical institutions, and timely find and report cases.
7.Prevalence and associated factors of chronic renal insufficiency among the physical examination community population: a cross-sectional survey in Binhai county, Jiangsu province
Lingling XU ; Yang ZHOU ; Jin LIU ; Aiqin HE ; Dongling LI ; Hua YANG ; Junwei YANG
Chinese Journal of Nephrology 2022;38(6):520-527
Objectives:To investigate the epidemiological features and associated factors of chronic renal insufficiency (CRI) in Binhai county from Jiangsu province.Methods:This is a cross-sectional study including individuals aged≥18 years old and participating in health examinations of Binhai county from January to December 2018. Medical records were collected to analyze the epidemiology of CRI [estimated glomerular filtration rate <60 ml·min -1·(1.73 m 2) -1]. Multivariate logistic regression was used to analyze the associated influencing factors of CRI. Results:A total of 395 541 individuals residing in Binhai county were enrolled, with 190 258 males (48.1%) and age of (55.34±15.12) years old. The overall crude prevalence of CRI was 2.04% (8 065/395 541, 95% CI 2.00%-2.08%) in this adult population. Furthermore, the age- and gender-standardized overall prevalence of CRI was 1.22% (95% CI 1.18%-1.25%), with a rate of 1.47% (4 676/205 283, 95% CI 1.42%-1.52%) in women and a rate 0.95% (3 389/190 258, 95% CI 0.91%-1.00%) in men. There was a strong positive correlation between the risk of CRI and age (per 10-year increase, OR=2.449, 95% CI 2.402-2.497). Compared with individuals <30 years old, the OR of CRI in individuals aged 60-69, 70-79 and ≥80 years old were 3.827 (95% CI 3.010-4.864), 12.004 (95% CI 9.457-15.239) and 44.636 (95% CI 35.187-56.622) respectively. Females ( OR=1.142, 95% CI 1.083-1.203), increasing systolic blood pressure (per 10 mmHg increase, OR=1.062, 95% CI 1.048-1.076), increasing heart rate (per 10-beat/min increase, OR=1.071, 95% CI 1.044-1.098), elevating triglyceride (per 1.33 mmol/L increase, OR=1.140, 95% CI 1.119-1.162), elevating fasting blood glucose (5.6-6.9 mmol/L/<5.6 mmol/L, OR=1.158, 95% CI 1.086-1.233; ≥7 mmol/L/<5.6 mmol/L, OR=1.387, 95% CI 1.296-1.484) and central obesity ( OR=1.126, 95% CI 1.068-1.187) were independent risk factors for CRI. Conclusions:The age- and gender-adjusted prevalence of CRI in adults in Binhai county is 1.22%. Older age, females, central obesity, and high levels of triglyceride, systolic blood pressure, heart rate and fasting glucose are independent associated factors of CRI.
8.Correlation between socioeconomic status and diabetic kidney disease
Caifeng SHI ; Aiqin HE ; Xiaomei WU ; Jin LIU ; Yuting SHENG ; Xueting ZHU ; Junwei YANG ; Yang ZHOU
Clinical Medicine of China 2022;38(3):228-236
Objective:To explore the correlation between socioeconomic status (SES) and diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).Methods:A total of 276 T2D patients admitted to the Second Affiliated Hospital of Nanjing Medical University from January to June 2020 were enrolled in this cross-sectional study. The estimated glomerular filtration rate (eGFR) was calculated according to the urinary albumin/creatinine ratio (UACR) and the chronic kidney disease epidemiology collaboration equation(CKD-EPI formula) based on serum creatinine. The patients were divided into simple T2D group (184 cases) and DKD group (92 cases). Collect demographic and laboratory examination data, record education, income and occupation, and calculate standardized SES scores. According to SES scores, subjects were divided in three levels: SES≤9, SES≥10-≤12, and SES≥13. Student's t test was used for comparison of measurement data with normal distribution between two groups, and one-way ANOVA was used for comparison between multiple groups. Non-normal distribution was represented by M( Q1, Q3), and rank-sum test was used for comparison between groups. Counting data were expressed as frequency or percentage, and chi-square test was used for comparison between groups. Bofferoni test was further used for pairwise comparison of indicators with statistical significance among multiple groups. Spearman correlation analysis was used to analyze the correlation between variables. The risk factors were analyzed by binary Logistic regression. Results:The age of the subjects was (53.37±10.68) years, men accounted for 55.8% (154/276), the duration of diabetes was 60.00 (12.00, 134.00) months, and eGFR was (97.56±21.15) mL/(min·1.73 m 2). In simple T2D group and DKD group, prevalence of hypertension were 39.7% (73/184) and 57.6% (53/92), systolic blood pressure were (129.43±14.92) mmHg and (139.29±17.61) mmHg, diastolic blood pressure were (81.86±10.06) mmHg and (87.74±11.19) mmHg, serum albumin were (45.74±4.15) g/L and (43.99±5.05) g/L, triglycerides were (1.82±1.24) mmol/L and (2.64±2.92) mmol/L, high density lipoprotein cholesterol were (1.17±0.37) mmol/L and (1.07±0.26) mmol/L, serum uric acid were (298.44±90.73) μmol/L and (336.22±94.01) μmol/L, serum creatinine were (62.83±14.45) μmol/L and (87.75±57.37) μmol/L, eGFR were (102.6±14.28) mL/(min·1.73 m 2) and (87.47±28.04) mL/(min·1.73 m 2), UACR were (7.60 (4.63, 13.15)) mg/g and (93.95 (47.25, 310.25)) mg/g. Prevalence of hypertension, systolic blood pressure, diastolic blood pressure, triglycerides, serum uric acid, serum creatinine, UACR in DKD group were higher than those in simple T2D group. Serum albumin, high density lipoprotein cholesterol and eGFR in DKD group were lower than those in simple T2D group. There was significant difference between the two groups ( χ2=7.95, t values were 4.87, 4.40, 3.04, 3.26, 2.30, 3.22, 5.56, 5.95, Z=13.07, P values were 0.005, <0.001, <0.001, 0.003, 0.001, 0.022, 0.001, <0.001, <0.001, and <0.001, respectively). The number of males in the three groups with SES ≥13 group, SES≥10-≤12 group, SES ≤9 group were 61 (81.3%, 61/75), 55 (59.8%, 55/92), 38 (34.9%, 38/109), respectively. The number of cases with smoking history were 42 (56.0%, 42/75), 41 (44.6%, 41/92), 35 (32.1%, 35/109), respectively. The number of cases with drinking history were 38 (50.7%, 38/75), 32 (34.8%, 32/92), 26 (23.9%, 26/109), respectively. The ages were (47.77±10.76), (52.76±11.22), (57.74±7.96) years old, respectively. Body mass index (BMI) were (26.17±3.87), (24.96±3.93), (24.27±4.89) kg/m 2, respectively. High density lipoprotein cholesterol (HDL) were (1.03±1.03), (1.16±0.41), (1.21±0.32) mmol/L, respectively. Serum uric acid were (336.56±82.05), (293.78±94.78), (307.99±96.53) μmol/L, respectively. EGFR were (105.03±19.72), (99.77±19.44), (90.57±21.49) mL/(min·1.73 m 2),respectively.The difference between groups were statistically significant (χ 2=39.79, 10.55, 14.08, F=22.69, 4.03, 6.20, 4.53, 12.02, P values were <0.001, 0.005, 0.001, <0.001, 0.019, 0.002, 0.012, and <0.001, respectively). Pairwise comparison shows that male and eGFR in SES ≤9 group were lower than those in SES ≥13 group and SES≥10-≤12 group, age in SES ≤9 group was higher than that in SES ≥13 group and SES≥10-≤12 group. The difference was statistically significant (all P<0.05). Smoking history, alcohol history and BMI in SES ≤9 group were lower than those in SES ≥13 group, and the high density lipoprotein cholesterol in SES ≤9 were higher than that in SES ≥13 group. The difference was statistically significant (all P<0.05). Male, alcohol history and serum uric acid in SES≥10-≤12 group were lower than those in SES ≥13 group, and age and high density lipoprotein cholesterol in SES≥10-≤12 group were higher than those in SES ≥13 group. The difference was statistically significant (all P<0.05). Spearman correlation analysis showed that SES in T2D was positively correlated with male, smoking history, alcohol history, BMI, serum uric acid and eGFR ( r values were 0.38, 0.20, 0.24, 0.16, 0.13 and 0.31, P values were <0.001, 0.001, <0.001, 0.008, 0.028, and <0.001, respectively), and negatively correlated with age, high density lipoprotein cholesterol and UACR ( r values were -0.35, -0.24 and -0.14, P values were <0.001, <0.001, and 0.017, respectively). Logistic regression analysis showed that SES (OR=2.71,95% CI:1.10-6.68, P=0.031) was associated with T2DM combined with DKD. The risk of developing DKD increased when the SES was ≤9. Conclusion:The SES in patients with type 2 diabetes is closely related to DKD. Low SES may be a new risk factor for DKD in type 2 diabetic patients.
9.Effect of demographic sociological data on critical thinking of clinical research nurses
Fenghua YANG ; Ruirui HE ; Hongyan REN ; Aiqin ZHOU ; Fengxia CHEN ; Mengmeng LUO
Chinese Journal of Modern Nursing 2022;28(21):2907-2910
Objective:To explore the effect of demographic sociological data on the critical thinking of clinical research nurses, in order to provide reference for improving the level of clinical research.Methods:Using the convenient sampling method, a total of 110 clinical research nurses responsible for clinical research related work in three ClassⅢ Grade A hospitals in Zhengzhou City of Henan Province from January to June 2021 were selected as the research objects. Demographic Sociological Data Questionnaire and Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) were used to conduct surveys among nurses. Multiple linear regression was used to analyze the effect of demographic sociological data on critical thinking of clinical research nurses. A total of 110 questionnaires were distributed, and 106 valid questionnaires were recovered. The effective recovery rate of the questionnaires was 96.36% (106/110) .Results:The total score of CTDI-CV of 106 nurses was (296.25±24.12) . The results of multiple linear regression analysis showed that age, education, professional title and working years were the influencing factors of the level of critical thinking of clinical research nurses ( P<0.05) . Conclusions:The critical thinking ability of clinical research nurses is affected by age, professional title, educational background and working years. It is suggested to take effective measures to improve the critical thinking ability of nurses according to the actual situation, and then improve the clinical research level of nurses.
10.Exosomal miR-196a derived from liver cancer stem cell enhances liver cancer cells resistance to doxorubicin
Quan SONG ; Ningling DING ; Ying XU ; Kaiyue CAO ; Sufang ZHOU ; Aiqin ZHAO ; Yunzhi PAN ; Sai MA
Journal of International Oncology 2020;47(10):585-592
Objective:To screen the differentially expressed exosomal miRNAs derived from liver cancer stem cells (LCSCs) and its effect on the malignant biological characteristics of liver cancer cells.Methods:miRNA expression profile chip was used to analyze the differentially expressed exosomal miRNA derived from LCSCs. The effects of miRNA on malignant phenotypes of LCSCs were identified. The cells were further treated with doxorubicin at different concentrations (0, 150, 300 μmol/L), and the expression level of miR-196a was detected by quantitative real-time PCR (qRT-PCR). The apoptosis of liver cancer cells cultured by exosomes derived from LCSCs (Exo-NC group) and exosomes derived from miR-196a inhibited LCSCs (Exo-Inhibitor group) and the activity of caspase3/7 under the action of exosomes from LCSCs were detected. Nude mice were randomly divided into Do-PBS group, Do-Exo-Inhibitor group and Do-Exo-NC group using random number table method, with 5 mice in each group, and the effect of miR-196a on nude mice xenograft tumor model with liver cancer cells was analyzed.Results:In this study, exosomes were isolated and purified from CD133 + Huh7 stem cell culture supernatant. miR-7162-3p, miR-1910-5, miR-3613-3p, miR-196a and miR-155-5p were up-regulated, while miR-1246 and miR-3613-5p were down-regulated. miR-7162-3p, miR-196a and miR-155-5p in exosomes had important effects on the self-renewal ability of LCSCs. miR-1910-5p, miR-196a and miR-155-5p had important effects on the invasion ability of liver cancer stem cells, among which miR-196a had the most significant inhibitory effect. Treatment for 24 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin was 0.96±0.05, 1.23±0.05 and 2.33±0.03 respectively, with a statistically significant difference ( F=996.90, P<0.001). Treatment for 48 h, the miR-196a expression level of the 0, 150 and 300 μmol/L doxorubicin were 1.02±0.07, 2.35±0.05 and 2.89±0.55 respectively, with a statistically significant difference ( F=303.00, P<0.001). When the concentration of doxorubicin was 0 and 300 μmol/L, the apoptosis rates of the Exo-NC group were 9.37%±0.19% and 11.64%±0.27%, and those of the Exo-Inhibitor group were were 18.80%±1.91% and 22.79%±1.57%, with statistically significant differences ( t=4.41, P=0.048; t=4.96, P=0.038). When doxorubicin was not used, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.94±0.08 and 0.97±0.09, and those in the Exo-Inhibitor group were 1.56±0.01 and 1.58±0.01, with statistically significant differences ( t=11.41, P=0.008; t=6.07, P=0.026). Under 300 μmol/L doxorubicin, the ratios of caspase3/7 in the Exo-NC group at 24 h and 48 h were 0.95±0.07 and 1.36±0.08, and those in the Exo-Inhibitor group were 2.84±0.08 and 3.20±0.14, with statistically significant differences ( t=24.20, P=0.002; t=15.78, P=0.004). The results of xenograft tumor in nude mice showed that the tumor volumes of Do-PBS, Do-Exo-Inhibitor and Do-Exo-NC groups increased successively, which were (1 051.86±89.90) mm 3, (1 310.91±86.66) mm 3 and (2 185.14± 352.34) mm 3 respectively, with a statistically significant difference ( F=30.28, P<0.001). The weights of the transplanted tumors in the 3 groups increased successively, which were (0.36±0.10) g, (0.39±0.12) g and (0.76±0.16) g respectively, with a statistically significant difference ( F=11.81, P=0.002). The expression of miR-196a in tumors was significantly decreased after miR-196a inhibitor transfection. The expression levels of the 3 groups were 1.05±0.16, 0.38±0.08 and 2.17±0.26, with a statistically significant difference ( F=48.93, P<0.001). Conclusion:The exosomal secreted by LCSCs can enhance the resistance of liver cancer cells to doxorubicin by miR-196a.


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