1.SLCO1B1/ApoE gene polymorphisms associated with efficacy and safety of rosuvastatin
Zhongchao WANG ; Jun LI ; Longmei LIU ; Yingna HE
International Journal of Biomedical Engineering 2016;39(6):358-361
Objective To investigate the association between SLCO1B1/ApoE gene polymorphisms and lipid-lowering efficacy and safety of rosuvastatin.Methods DNA samples were extracted from blood using nano paramagnetic particle method.The SLCO1B1 521T>C and ApoE gene polymorphisms were screened by PCR-pyrophosphate sequencing method.Totally 152 patients received rosuvastatin orally at a dose of 10 mg/d.The lipidlowering efficacy was evaluated through detecting serum low-density lipoprotein cholesterol (LDL-C) level before and 8 weeks after the treatment.The incidence of myopathic adverse effect was assessed by follow-up of the occurrence of myalgia.Results The gene distribution of SLCO1B1 521T>C was 73.7%,23.7% and 2.6% respectively for TT,TC and CC in 152 patients,and the distribution of ApoE gene was 65.8%,13.2% and 21.0% respectively for ε3/ε3,ε3/ε2 and ε4/ε3.The genotype ε4/ε4,ε2/ε2 and ε4/ε2 were not detected.After orally receiving rosuvastatin 10 mg daily for 8 weeks,the decreased LDL-C levels showed significant differences (P<0.05) among ApoE genotype ε3/ε2,ε3/ε3 and ε4/ε3 groups,and the frequencies of myalgia showed significant differences in the three genotype groups of SLCO1B1 521T>C (P<0.05).Conclusion The gene polymorphism of SLCO1B1/ApoE was correlated with efficacy and safety of rosuvastatin.The combined detection of SLCO1B1/ApoE genes can be utilized to predict efficacy and risk,and then realize individualized medication.
2.Analysis of Early Monitoring for Heart Damage Caused by Anthracyclines Chemotherapy Drugs after Breast Cancer Surgery
Yuxin QI ; Jiao LIU ; Yingna HE ; Yanqing REN
China Pharmacy 2017;28(17):2356-2359
OBJECTIVE:To investigate the early changes of ECG,cTnⅠ,LDH,α-HBDH and CKMB in patients with anthra-cyclines chemotherapy-induced heart damage after breast cancer surgery,and to explore their significances in the diagnosis of early heart damage. METHODS:Medical information of 152 cases of anthracyclines chemotherapy after breast cancer surgery in our hos-pital during Jan. 2015-Jun. 2016 were analyzed retrospectively. According to diagnosis criteria of drug-induced cardiotoxicity,the occurrence of heart damage was evaluated during hospitalization and 1-year follow-up. According to evaluation results,those pa-tients were divided into heart damage group(50 cases)and control group(102 cases). The early changes of ECG,cTnⅠ,LDH, CKMB and α-HBDH were analyzed before chemotherapy(T0),24 h after first chemotherapy(T1),24 h after second chemothera-py(T2),24 h after forth chemotherapy. RESULTS:At T1,T2,T3,the proprotion of ECG abnormalities in heart damage group was significantly higher than control group;the serum levels of cTnⅠ,LDH,CKMB andα-HBDH in heart damage group were signifi-cantly higher than control group, with statistical significance (P<0.01). CONCLUSIONS:For anthracyclines chemotherapy drugs-induced heart damage after breast cancer surgery,early regular monitoring of ECG,cTnⅠ,LDH,CKMB and α-HBDH can improve the efficiency of early diagnosis of heart damage,and improve prognosis.
3.Cytotoxic effect of geniposide and its metabolite genipin on HepG2 cells and mechanism
Yanqing REN ; Yurou TIAN ; Chen LI ; Yingna HE ; Jingmei MA ; Liying NIU ; Xinguo WANG
Chinese Pharmacological Bulletin 2016;32(12):1755-1760,1761
Aim To compare the cytotoxicity of geni-poside (GS)and its metabolite genipin (GP)on hu-man hepatocelluar HepG2 cells and explore the sub-stance and mechanism of hepatotoxicity induced by Fructus Gardeniae.Methods The cytotoxic effect of GS and GP was analyzed by MTT method;the antioxi-dant enzyme activities of manganese superoxide dis-mutase (Mn-SOD),catalase (CAT)and levels of glu-tathione (GSH)were detected by respective kits;the change of intracellular reactive oxygen species (ROS ) was measured by 2′,7′-dichlorofluorescin diacetate (DCFH-DA)staining method;multiparameter cytotox-icity analysis (cell loss,nuclear size and morphologi-cal changes,DNA content,cell membrane permeabili-ty,mitochondrial membrane potential changes,cyto-chrome C release ) were measured simultaneously by high content screening (HCS)assays.Results No cytotoxicity was found in GS (20~1 000 μmol·L-1 ) groups (P>0.05 ),but GP was found to exert obvi-ous cytotoxic effect,and 50μmol·L-1 GP could obvi-ously inhibit HepG2 cell proliferation (P<0.05 ),and the IC50 value was (450.00 ±26.15)μmol·L-1;GS showed no obvious effects on Mn-SOD, CAT, GSH ,ROS (P >0. 0 5 ),GP could significantly decrease the activity of Mn-SOD,CAT and the level of GSH,and obviously increase the content of ROS (P<0.05 or P <0.01 );treatment with 50,500,1 000μmol·L-1 GP resulted in loss of mitochondrial mem-brane potential,cytochrome C release and increased cell permeability (P<0.05 or P<0.01),500,1 000μmol· L-1 GP could also show abvious nuclear con-densation,increased total nuclear intensity and cell loss (P<0.0 1 ).Opposed with GP,GS had no signif-icant effect on the cytotoxic parameters (P>0.05 ). Conclusion GP is the direct substance of hepatotox-icity induced by Fructus Gardeniae,and the mecha-nism might be associated with oxidative stress,mito-chondria injury and apoptosis.
4.Validation Study on Efficacy Difference of Green Forsythiae Fructus and Ripe Forsythiae Fructus in the Classic Formula
Yingna SUN ; Yonghua YUE ; Cong LIU ; Pan HE ; Guanya BAI ; Yan NI
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(5):39-43
Objective To compare the efficacy difference of Green Forsythiae Fructus and Ripe Forsythiae Fructusby using Lianqiao powder and Yinqiao powder in the classic formula; To provide experimental evidence for the guidance of one for dual-use of the Forsythiae Fructus. Methods The guinea pig sore model was made with Staphylococcus aureus. 40 guinea pigs were randomly divided into blank group, model group, Lianqiao powder Green Forsythiae Fructus group and Lianqiao powder Ripe Forsythiae Fructus group. The blank group and the model group were fed with normal saline, while Lianqiao powder Green Forsythiae Fructus group and Lianqiao powder Ripe Forsythiae Fructus group were treated with 1.2 g raw medicine/kg liquid Lianqiao powder Green Forsythiae Fructus and Lianqiao powder Ripe Forsythiae Fructus for 7 d. The symptom score, blood and pathological changes of guinea pig soreness were observed. The model of acute lung injury was induced by 10% LPS aerosol inhalation. 40 rats were randomly divided into blank group, model group, Yinqiao powder Green Forsythiae Fructus group and Yinqiao powder Ripe Forsythiae Fructus group. The blank group and the model group were fed with normal saline, while Yinqiao powder Green Forsythiae Fructus group and Yinqiao powder Ripe Forsythiae Fructus group were treated with 4 g raw medicine/kg liquid Yinqiao powder Green Forsythiae Fructus and Yinqiao powder Ripe Forsythiae Fructus for 10 d. The levels of IL-6, TNF-α and IL-1β in the lung lavage fluid were detected. Results The effect of Lianqiao powder Green Forsythiae Fructus on the wound healing of guinea pig sore wound was faster than that of Lianqiao powder Ripe Forsythiae Fructus, but there was no significant difference between Lianqiao powder Green Forsythiae Fructus group and Lianqiao powder Ripe Forsythiae Fructus group in inhibiting the secretion and pathological changes of guinea pig sore wound. The levels of IL-6, TNF-α and IL-1β in Yinqiao powder Green Forsythiae Fructus group was lower than that in Yinqiao powder Green Forsythiae Fructus group, without statistical significance. Conclusion It is verified that there is efficacy differences between Green Forsythiae Fructus and Ripe Forsythiae Fructus in the different Chinese herbal compound.
5.Xinfukang drug-containing serum on bone marrow stem cell transcription and secretion of SDF-1α
Bohong KAN ; Yijing WANG ; Xiantong HU ; Qing GAO ; Yingchang FAN ; Yingna HE ; Kongyin ZHAO
International Journal of Biomedical Engineering 2014;37(5):275-278
Objective To clarify the effects of Xinfukang containing-serum on stromal cell-derived factor-1α (SDF-1α) translation and protein secretion of bone marrow stem cells (BMSCs).Methods BMSCs were isolated and amplified using bone marrow culture method,and were identified by flow cytometry.mRNA and protein secretion of SDF-1α were detected by quantitative PCR (q-PCR) and enzyme linked immunosorbent assay (ELISA),respectively.Results The expression of SDF-1α mRNA were significantly increased after 72 h in drug-containing serum,and SDF-1α mRNA in the experimental group was approximately 200 times as that in the control group (P<0.05).Secretion of SDF-1 α in the experimental group (277.561 1 ± 15.651 8) pg/ml was nearly doubled compared with that in the control group (153.107 1±14.765 1) pg/ml (P<0.05).Conclusions BMSCs from whole bone marrow adherent culture have high purity,and drug-containing serum can promote BMSCs to express SDF-1 α mRNA and secretion of SDF-1 α.
6.Predictive Value of NLR,PLR and sPESI Score for 30-day Mortality in Patients with Acute Pulmonary Embolism
Yingna HAN ; Jing WANG ; Jingyu HE
Journal of Medical Research 2024;53(1):161-164,169
Objective To investigate the predictive value of neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),and the simplified pulmonary embolism index(sPESI)score for 30-day death in patients with acute pulmonary embolism(APE).Methods The clinical data of 291 APE patients admitted to Xuanwu Hospital of Capital Medical University from January 2017 to December 2021 were retrospectively analyzed.White blood cell count(WBC),NLR,PLR,sPESI score,and other indicators were calculated at admission.The patients were followed up within 30 days and were divided into the death group and the survival group accord-ing to the prognosis.The differences in the above indexes between the two groups were compared.Multivariate Logistic regression was used to analyze the independent risk factors for 30-day mortality in APE patients.The area under the receiver operating characteristic(ROC)curve of NLR,PLR,and combined sPESI scores in predicting mortality was compared.Results Among the APE patients,11 cases(3.78%)died and 280 cases(96.22%)survived within 30 days.The WBC,NLR,PLR,and sPESI score in the death group were sig-nificantly higher than those in the survival group(P<0.05).Multivariate Logistic regression analysis showed that PLR,NLR,and sPESI score were independent risk factors for 30-day mortality in APE patients(P<0.05).The area under ROC curve(AUC)of PLR in pre-dicting the 30-day death of APE patients was 0.799(P=0.001).The AUC of NLR was 0.827(P=0.001).The AUC of sPESI score was 0.874(P=0.001).There was no significant difference in the AUC of PLR,NLR,and sPESI score in predicting death(P=0.181,0.340);the AUC of NLR combined with sPESI score was 0.925(P=0.001),which was greater than that of NLR(P=0.004).The AUC of PLR combined with sPESI score was 0.901(P=0.001),which was greater than that of PLR(P=0.002).Conclusion NLR,PLR,and sPESI score are independent risk factors for 30-day mortality in APE patients,and all of them have certain prognostic values.The prognostic value of PLR and NLR combined with sPESI score was higher than that of PLR and NLR alone.
7.Construction and in vitro evaluation of DC-targeted aptamer-modified Pseudomonas aeruginosa DNA vaccine delivery system
Shiqin HUANG ; Min SHI ; Yingna HE ; Hanxun YUE ; Xian YU
Journal of China Pharmaceutical University 2019;50(6):743-752
This study aimed to construct a DC-targeted aptamer-modified Pseudomonas aeruginosa(PA)DNA vaccine delivery system. The cationic liposome was prepared by ethanol injection method. The cationic liposome loading pVAX1-OprF-VP22(Lip-pOprF-VP22)was prepared by electrostatic adsorption method. The encapsulation efficiency of Lip-pOprF-VP22 with different mass ratios of DOTAP/pDNA on pVAX1-OprF-VP22, cytotoxicity and transfection rate to DC2. 4 in vitro were discussed. The particle size and zeta potential of Lip-pOprF-VP22 with best mass ratio were tested. Aptamer-modified cationic liposome loading pVAX1-OprF-VP22(Apt-Lip-pOprF-VP22)was prepared by post-insertion method. The expression of OprF protein after transfection of DC2. 4 and its effect on the maturation of bone marrow-derived dendritic cells(BMDCs)were detected. Data showed that as the mass ratio of DOTAP/pDNA increased, the encapsulation efficiency of Lip-pOprF-VP22 on pVAX1-OprF-VP22 was gradually increased. When the mass ratio was 5 ∶1, pVAX1-OprF-VP22 was encapsulated well. When Lip-pOprF-VP22 with different mass ratios was applied to DC2. 4 for 24 h or 48 h, the survival rates of DC2. 4 were all above 80%. When the mass ratio of DOTAP/pDNA increased from 2 ∶1 to 10 ∶1, the transfection rate increased first and then decreased. When the mass ratios of DOTAP/pDNA were 4 ∶1 and 5 ∶1, the transfection rates were relatively high. When the mass ratio of DOTAP/pDNA was 5 ∶1, the particle size of Lip-pOprF-VP22 was(171. 67±1. 27)nm, and the Zeta potential was(11. 30±0. 57)mV. Furthermore, Apt-Lip-pOprF-VP22 can express more OprF protein and significantly promote the maturation of BMDCs. In conclusion, Apt-Lip-pOprF-VP22 can target to DC and promote the maturation of DC.
8.Construction and in vivo evaluation of a thermosensitive hydrogel system loading with Pseudomonas aeruginosa DNA vaccine
SHI Min ; YONG Qin ; HE Yingna ; HUANG Shiqin ; ZHAO Xuan ; YU Xian
Journal of China Pharmaceutical University 2021;52(2):186-194
A thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine was constructed and the immune efficacy of the system was evaluated. The PLGA-PEG-PLGA thermosensitive hydrogel containing Pseudomonas aeruginosa DNA vaccine was prepared by a simple physical mixing method. The gelation temperature, cytotoxicity, and release curve in vitro were tested.The degradability of hydrogel in vivo was evaluated. The mice were divided into control group (PBS), hydrogel group (Hydrogel), in vivo-jetPEI/plasmid DNA group (in vivo-jetPEI/pDNA), and hydrogel + in vivo-jetPEI/plasmid group (Gel+in vivo-jetPEI/pDNA). Mice were immunized three times with a ten-day interval. Two weeks after the last immunization, the mice were sacrificed. The proliferation of splenic lymphocytes, serum specific IgG antibodies and IFN-γ in supernatant of splenic lymphocytes were detected. The gelation temperature of PLGA-PEG-PLGA hydrogel was (32 ± 0.5) ℃. There was no obvious toxicity to cells in vitro, and about 80% of plasmid DNA was released after 7 days in vitro. PLGA-PEG-PLGA hydrogel was biodegradable, and degraded almost completely after 15 days in vivo. The spleen lymphocytes proliferated; the levels of specific IgG antibodies and IFN-γ of in vivo-jetPEI/pDNA and Gel+in vivo-jetPEI/pDNA groups increased. The hydrogel could enhance the immune response induced by DNA vaccine.Results suggest that the thermosensitive hydrogel system consisting of PLGA-PEG-PLGA hydrogel and Pseudomonas aeruginosa DNA vaccine is a promising new strategy for the development of PA vaccine.