1.Induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 through regulating the Fas/FasL sig-naling pathway and the inhibitory effect on the growth of transplanted tumor in nude mice
Minna YAO ; Wei ZHANG ; Kai GAO ; Ruili LI ; Ying YIN ; Chao GUO ; Yunyang LU ; Haifeng TANG ; Jingwen WANG
China Pharmacy 2025;36(18):2238-2243
OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 (PP9) through the regulation of the Fas/Fas ligand (FasL) signaling pathway, and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions, HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity, apoptosis rate, as well as the protein expressions of Fas, FasL, cleaved caspase-8 and cleaved caspase-3. Additionally, Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object, and 5-fluorouracil (20 mg/kg) as the positive control, the effects of 10 mg/kg PP9 on tumor volume, tumor mass, and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group, 2, 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells, but significantly increased the apoptosis rate, the protein expressions of Fas, FasL, cleaved caspase-8 and cleaved caspase-3 (P<0.05 or P<0.01). However, the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway (P<0.01). Compared with the control group, the tumor volume (on day 27), mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased, while the protein expression of cleaved caspase-3 was significantly increased (P<0.01). CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile, PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.
2.Lenvatinib modulates tumor immune microenvironment to synergistical-ly enhance immune checkpoint inhibitor treatment of hepatocellular car-cinoma
Jiamin LI ; Ruimeng YANG ; Ruili WEI ; Wang YAO ; Wanli ZHANG ; Xinqing JIANG
Chinese Journal of Pathophysiology 2024;40(5):786-795
AIM:To explore the efficacy of lenvatinib(Len)in enhancing the therapeutic effects of immune checkpoint inhibitor for hepatocellular carcinoma(HCC)and to delve into its immunomodulatory mechanisms within the tumor microenvironment.METHODS:The effects of various concentrations of Len on the migration of human umbilical vein endothelial cells(HUVECs)and the secretion of CXC chemokine ligand 10(CXCL10)were investigated,and the mechanism by which Len modulates CXCL10 secretion was validated.An orthotopic HCC model was established,and the mice bearing tumors were randomly allocated into 4 groups:PBS group,BMS-202(PD-1/PD-L1 inhibitor)group,Len group,and Len/BMS-202 group.The progression of the orthotopic liver tumors was monitored with small animal in vivo im-aging techniques.On the 13th day after the treatment,mice were sacrificed and tumor tissues were harvested for analysis.Immunofluorescence was employed to identify apoptosis,vascular architecture,and hypoxic status within the tumor tis-sue.The expression levels of proliferation marker Ki67,transforming growth factor-β(TGF-β),and the infiltration de-grees of CD4+T cells and CD8+T cells in the tumor tissue were monitored with immunohistochemistry.The secretion of im-mune factors interferon-γ(IFN-γ),CXCL10 and TGF-α in the mouse serum was quantified with ELISA.Above all data were followed by statistical analysis.RESULTS:(1)Len could facilitate endothelial cell migration within a specific range and potentiated the response of tumor cells to IFN-γ by blocking fibroblast growth factor receptor(FGFR),thereby increasing the secretion of CXCL10 from the tumor cells.(2)Compared with PBS group,tumor growth was slower in all treatment groups,with Len/BMS-202 group showing the most significant inhibition of tumor growth in tumor-bearing mice(P<0.05).(3)Compared with PBS group and monotherapy groups,Len/BMS-202 significantly promoted tumor tissue apoptosis and inhibited tumor cell proliferation(P<0.05).(4)Compared with PBS group and BMS-202 group,both Len group and Len/BMS-202 group manifested a substantial enhancement in pericytes coverage rate(P<0.01),concomitantly showing a marked improvement in hypoxic conditions(P<0.01).(5)Compared with PBS group and monotherapy groups,Len/BMS-202 group showed a significant increase in the infiltration of CD4+T cells and CD8+T cells within the tumor(P<0.01),along with a marked decrease in the expression of TGF-β(P<0.01).(6)Compared with PBS group,all treatment groups collectively induced varying degrees of secretion of IFN-γ,CXCL10 and TGF-α in mouse serum(P<0.05),with Len/BMS-202 group demonstrating the most pronounced effects(P<0.01).CONCLUSION:Lenvatinib may augment the therapeutic efficacy of BMS-202 in HCC by facilitating tumor vascular normalization,alleviating hypoxic conditions,and enhancing the secretion of CXCL10,thereby synergistically activating the tumor immune microenvironment.
3.Application of cup-stacking task based on the dyadic coping model in patients with ischemic stroke
Ruili MA ; Ruinan YAO ; Xiaojin ZHU ; Wenjia SUN ; Yating ZHOU
Chinese Journal of Practical Nursing 2024;40(30):2336-2342
Objective:To evaluate the effects of cup-stacking task based on the dyadic coping model in patients with ischemic stroke, in order to provide reference for clinical nurses to effectively rehabilitate these patients and improve their disease coping ability.Methods:This was a quasi-experimental study, a total of 90 patients with upper extremity motor function disorder after ischemic stroke admitted to the Neurology of the First Affiliated Hospital of Zhengzhou University were selected as participants from October 2022 to March 2023. Among them, 45 patients admitted from October 2022 to December 2022 were selected as the control group, 45 patients admitted from January 2023 to March 2023 were selected as the experimental group. Patients in the control group received routine care and patients in the experimental group received cup-stacking task based on the dyadic coping intervention model. The dyadic coping between the two groups and their spouses were compared before intervention and after intervention(3 months after discharge), the upper extremity motor function, activities of daily living, anxiety, rehabilitation self-efficacy between the two groups were compared before the intervention and after intervention.Results:A total of 5 patients were dropped and 43 patients of the control group and 42 patients of the experimental group completed the study at last. In the control group, there were 28 males, 17 females, aged (61.84 ± 7.13) years old; while their spouses were 17 males, 26 females, aged (61.02 ± 6.79) years. In the experimental group, there were 28 males, 14 females, aged (62.36 ± 7.03) years old; while their spouses were 14 males, 28 females, aged (60.95 ± 6.81) years. After the intervention, the scores of the dyadic coping between the experimental group patients and their spouses were (135.05 ± 8.52), (139.24 ± 9.67) points, which were higher than (119.26 ± 12.23), (120.02 ± 12.34) points of the control group, the differences were statistically significant ( t=6.92, 8.00, both P<0.05); the scores of the upper extremity motor function, activities of daily living, rehabilitation self-efficacy of the experimental group patients were (55.48 ± 4.78), (79.55 ± 6.83), (83.64 ± 10.30) points, which were higher than (51.44 ± 6.20), (72.74 ± 8.93), (70.28 ± 13.13) points of the control group, the differences were statistically significant ( t=3.36, 3.94, 5.21, all P<0.05); the score of anxiety was (13.26 ± 2.96) points, which was lower than (18.53 ± 3.35) in the control group, and the difference was statistically significant ( t=-7.69, P<0.05). Conclusions:The cup-stacking task based on the dyadic coping model can effectively improve the dyadic coping level of patients after ischemic stroke and their spouses, improve the patients′ upper extremity motor function and rehabilitation self-efficacy, so as to facilitate disease recovery and improve the quality of life, which is worthy of clinical promotion.
4. Prevalence and related factors on diabetes among HIV/AIDS receiving antiretroviral therapy in Dehong Dai and Jingpo Autonomous Prefecture
Runhua YE ; Jing LI ; Shitang YAO ; Jibao WANG ; Dongdong CAO ; Yindi ZHANG ; Yun SHI ; Pinyin LI ; Yuanwu XU ; Hua WEI ; Guifang XIAO ; Jinting SUN ; Xing DUAN ; Yikui WANG ; Jin YANG ; Na HE ; Yingying DING ; Song DUAN
Chinese Journal of Epidemiology 2019;40(6):654-659
Objective:
To study the prevalence and correlates of diabetes among HIV/AIDS who were on antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefectures (Dehong), Yunnan province.
Methods:
The database of HIV/AIDS receiving ART in Dehong was downloaded by using the basic information system of AIDS prevention and control in China. In this cross-sectional study, HIV/AIDS patients who were currently on ART and aged 18 years or above, were consecutively recruited, between July 2017 and June 2018, in Dehong. All the subjects underwent hemoglobin A1c (HbA1c) testing. Patient with diabetes was defined as meeting any of these indicators (HbA1c ≥6.5%, baseline FPG ≥7.0 mmol/L, FPG ≥7.0 mmol/L in the most recent visit). Both univariate and multivariate logistic regression analysis were carried on to evaluate the correlates of diabetes among the HIV/AIDS patients.
Results:
In total of 4 376 HIV/AIDS patients were included for analysis, with the average age as (43.7±10.1) years, proportion of males as 53.8% (2 356/4 376) and the HCV positive rate as 24.1% (1 055/4 376). The mean years was (8.9±3.8) years after the HIV diagnosis was made, and the mean duration on treatment was (6.8±2.9) years. The prevalence of diabetes was 11.4% (500/4 376). Through multivariate logistic regression analysis, data showed that the risk factors of diabetes of HIV/AIDS on ART were: aged 40 years or above, being male, HCV positive, baseline body mass index ≥24.0 kg/m2, elevated TG ≥1.70 mmol/L in the most recent visit and baseline antiretroviral regimens under Efavirenz (EFV).
Conclusions
Prevalence rate of diabetes appeared higher in HIV/AIDS patients who were on ART in Dehong. Prevention and control measures should be targeted on HIV/AIDS patients who were with risk factors of diabetes as being elderly, male, HCV positive, overweight and higher TG. Further esearch is needed to evaluate the association between the use of EFV and diabetes.
5.Improvement of the Quality Standard for Fuzheng Capsules
Minna YAO ; Deqiang LIU ; Ning MA ; Wei ZHANG ; Ruili LI ; Zhifu YANG ; Aidong WEN
China Pharmacist 2018;21(6):1086-1089
Objective: To establish the quality standard for Fuzheng capsules. Methods: TLC was adopted to identify Astragali Radix and Glycyrrhiza uralensis. The method validation for Fuzheng capsules was conducted by microbial limit test as described in the appendixes of Chinese Pharmacopeia (2015 edition). The content of epimedii in Epimedium brevicornu was determined by HPLC. The chromatographic separation was carried out on an Agilent TC-C18(2) (250 mm×4. 6 mm, 5 μm) column. The mobile phase consis-ted of acetonitrile-water( 30: 70) with gradient elution at a flow rate of 1. 0 ml·min-1,and the injection volume was 5 μl. The detec-tion wavelength was 270 nm. Results: The spots in TLC were clear without any interference. The methods of plating and direct inocu-lation could be used for the microbial limit test. The linear range was 0.101-1.008 μg (r =0.999 7). The average recovery was 99. 36% with the RSD of 0. 81% (n=6). Conclusion: The method is simple with high specificity and good repeatability, which can be used as the quality control method for Fuzheng capsules.
6.Quality Standard Improvement for Shenzhi Xiaoping Capsules
Wei ZHANG ; Ruili LI ; Jinyi CAO ; Qun DU ; Yan ZHANG ; Zhifu YANG ; Aidong WEN ; Minna YAO
China Pharmacist 2018;21(10):1888-1891
Objective: To establish the quality standard for Shenzhi Xiaoping capsules. Methods: The characteristics of Astragali Radix were identified by microscopy. TLC was adopted to identify Astragali Radix, Fructus Aurantii and Glycyrrhiza uralensis. The con-tent of ginsenoside Rb1in Panax ginseng was determined by HPLC. Results: The microscopic characteristics were obvious. The TLC spots were clear with highly specific identification and good separation. The linear range of ginsenoside Rb1was 47. 06-376. 5 μg· ml-1(r=0. 999 9), and the average recovery was 102. 7% with the RSD of 1. 1% (n=6). Conclusion: The method is simple and specific, which can be used for the quality control of Shenzhi Xiaoping capsules.
7.Study on drop-out from antiretroviral therapy among adult HIV-infected individuals in Dehong prefecture, Yunnan province.
Shitang YAO ; Yun SHI ; Pinyin LI ; Yuanwu XU ; Wenqin YANG ; Yindi ZHANG ; Chunying YIN ; Liuqing CUN ; Zhijian ZHAI ; Na HE ; Email: NHE@SHMU.EDU.CN. ; Song DUAN ; Email: DHDUANSONG@SINA.COM.CN.
Chinese Journal of Epidemiology 2015;36(7):667-671
OBJECTIVETo examine the proportion and reasons of drop-out from antiretroviral therapy (ART) among 8 367 adult HIV-infected individuals in Dehong prefecture, Yunnan province.
METHODSAll adult HIV-infected patients receiving ART before September 30 of 2014 were examined for the situation of drop-out from ART.
RESULTSThe proportion of drop-out from ART among adult HIV-infected patients in Dehong prefecture was 14.4% (1 202/8 367). Results from the univariate logistic regression analyses indicated that drop-out from ART was significantly correlated with factors as: living area, gender, age, marital status, HIV transmission route, baseline CD4⁺ T cell counts and initial treatment regimen of the patients. After adjusted for potential confounding variables by multiple logistic regression model, drop-out from ART was significantly correlated with residential area, marital status, HIV transmission route, baseline CD4⁺ T cell count and initial treatment regimen of the patients. HIV-infected patients who were living in Mangshi city, Lianghe county or Yingjiang County, being married or living with partner, HIV infection through sexual contact, with baseline CD4⁺ T cell counts ≤ 200 cells/mm³, and ART included in the initial treatment regimen etc., were less likely to drop out from ART. The proportion of drop out from ART was significantly decreasing along with the increasing time of ART. Data from specific investigation revealed that among the 1 202 patients who dropped out from ART, 704 (58.6%) were lost to follow-up, 303 (25.2%) did not adhere to treatment, 74 (6.2%) moved out the region, 64 (5.3%) were Burmese that had returned to Burma, 29 (2.4%) stopped the treatment according to doctors' advice, 18 (1.5%) were incarcerated and 10 (0.8%) were under other reasons. Reasons for the drop-out varied, according to the situation of patients.
CONCLUSIONThe proportion of drop-out from ART varied significantly according to the characteristics of HIV-infected patients in Dehong prefecture that underscoring the needs for tailored responses to reduce drop-out of ART. Focus should be targeted on reducing the loss to follow-up and improving the treatment adherence.
Adult ; Anti-Retroviral Agents ; therapeutic use ; China ; HIV Infections ; drug therapy ; Humans ; Patient Dropouts ; statistics & numerical data
8.Ultrasound assayed detrusor thickness may predict the bladder outlet obstruction in old men
Ruili ZHANG ; Jianguo WEN ; Jinhua HU ; Qingwei WANG ; Shenzheng WANG ; Anfeng LOU ; Guoxian ZHANG ; Yaxiong YAO
Chinese Journal of Geriatrics 2010;29(9):745-747
Objective To evaluate the relationship between ultrasound-assayed detrusor thickness and bladder outlet obstruction (BOO) in old men with benign prostatic hyperplasia (BPH).Methods The 106 BPH patients underwent the urodynamic examination on which the diagnosis of BOO was dependent. The obstruction was defined as the Abrams-Griffiths nomogram (A-G index)≥40 and the grade of linear passive urethral resistance relation (LinPURR)≥Ⅱ . When bladder capacity reached 150 ml, the detrusor thickness was measured by abdominal ultrasound. Results Compared with unobstructed group, the maximum flow rate and average flow rate were both lower in obstructed group [(10.1±3.0) ml/s vs. (17.4±3.1) ml/s, (5.5±2.2) ml/s vs. (11.2±2.2) ml/s, t= 10.26and 11.03, both P<0.01]. And the residual urine volume and maximum detrusor pressure were significantly higher in obstructed group than in unobstructed group [(47.6 ± 24.3) ml vs. (17.0 ±5.6) ml, (39.3±14.4) cm H2Ovs. (26.8±8.0) cm H2O, t=6.32 and 4.07, P<0.01 or 0.05].Detrusor thickness was positively correlated with maximum detrusor pressure (r= 0.419, P<0.01),but negatively correlated with maximum flow rate (r =- 0.749, P< 0.01 ), mean flow rate (r=-0.853, P<0.01) and voided volume (r=-0.556, P<0.01). There was significant difference in detrusor thickness between obstructed group and unobstructed group [(3.0± 0.2) mm vs. (2.5 ±0.2) mm, t= 11.2,P<0.05]. According to the diagnostic standard of detrusor thickness≥3.0 mm,it had a sensitivity of 90% and a specificity of 84.6%, a positive predictive value of 93.1% and a negative predictive value of 78.6%. Conclusions Detrusor thickness of 3.0 mm or greater has a certain predictive value for BOO in old men.
9.Establishment of two-dimensional gelelectrophoresis technique for rabbit serum proteomics
Ruili YAO ; Mingshun ZHANG ; Hongjie LI ; Shuyun DONG ; Shixin WANG ; Guiling FENG
Chinese Journal of Tissue Engineering Research 2009;13(28):5440-5443
BACKGROUND: Rabbit serum samples are widely used in basic researches, and two-dimensional gelelectrophoresis (2-DE) is the most classic technique for protein separation. Therefore, it is of great significance to establish a stable technique system of 2-DE for rabbit serum.OBJECTIVE: To establish a 2-DE technique system for rabbit serum protein separation. DESIGN, TIME AND SETTING: A single sample observational experiment was performed at Tianjin Key Laboratory of Biomarkers for Occupational and Environmental Hazard of Chinese People's Armed Police Forces Medical College from June to July in 2008. MATERIALS: Six healthy rabbits were provided by the Animal Experimental Center of Tangshan Vocational Technical College METHODS: Health rabbit serum was dissolved in rehydration sample loading buffer before and after eliminating high abundance proteins to make proteins in it schizolysis adequately. After reductive alkylation, the samples were loaded into the rehydration tray to undergo passive rehydration for 14 hours. Isoelectric focusing (IEF) electrophoresis was followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). After sliver staining, the gel was analyzed by PDQuest7.4. MAIN OUTCOME MEASURES: ①Efficiency of eliminating high abundance proteins. ②Two-dimensional eleotrophoregrams (2-D electrophoregrams)RESULTS: Distinct 2-D eleotrophoregrems were obtained with high resolution and good reproducibility. The removal of high abundance proteins in serum failed to result in better 2-D electrophoregrams.CONCLUSION: We have successfully established a 2-DE technique for rabbit serum proteome, which can lay the foundation for the further study of serum proteomics of diseases.
10.Effects of Hydroxyethyl starch on hemodynamics and coagulation during cardiopulmonary bypass
Jianmin QIAO ; Ruili YAO ; Libing GAO ; Weisan WANG
Clinical Medicine of China 2008;24(5):425-427
Objective To observe the effects of 6%hydroxyethyl starch(Volven 130/0.4)infusion on hemodynamics and coagulation.Methods 60 cases of open heart surgical children under cardiopulmonary bypass were randomly divided into two groups(30 cases for each):The control group(group C)were infused with 400 ml plasma and volven group(group V)were infused with 400 ml Volven before cardiopulmonary bypass.Then mean aterial pressrue(MAP),heart rate(HR),and central venous pressure(CVP)were measured.The venous blood samples were collected before and after infusion for the measurements of the following parameters:haematocrit(HCT),blood sedimentation(BSR),platelet count(PLC),prothrombin time(PT),and activated whole blood clot time(ACT).Those indexes before operation,15 min after bypass,after returning to ICU,and 24 hours after operation were observed.Results HCT and PLC after infusion were significantly lower than that before infusion.BSR after infusion was significantly faster than that before infusion.There were no significant changes in MAP,HR,CVP,PLC,ACT and PT.Conclusion 6%Hydroxyethyl starch infusion is safe and beneficial during cardiopulmonary bypass.

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