1. Clinical value of genetic polymorphism analysis of hypertension drugs for individualized treatment of hypertension patients in the southern Anhui region
Shujun WAN ; Mengying ZHANG ; Min ZHONG ; Xiaolong ZHU ; Yingying ZHANG ; Kun LV ; Shujun WAN ; Mengying ZHANG ; Min ZHONG ; Xiaolong ZHU ; Yingying ZHANG ; Kun LV ; Qilei CHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(1):68-75
AIM: To analyze the distribution frequency of gene polymorphisms of β receptor blockers, angiotensin receptor antagonists, angiotensin converting enzyme inhibitors, calcium antagonists, and diuretics in hypertensive patients from southern Anhui province, and provide a theoretical basis for gene detection of hypertension drugs and personalized medication. METHODS: Drug gene testing information from 839 hospitalized patients with hypertension at Yijishan Hospital of Wannan Medical College from July 2021 to April 2023 were collected, and the distribution frequency of each gene locus were analyzed. RESULTS: The genotype frequencies of ACE (I/D) I/I, I/D, and D/D were 42.1%, 46.0%, and 11.9%, respectively. the genotype frequencies of ADRB1 (1165G>C) G/G, G/C, and C/C were 8.3%, 40.0%, and 51.6%, respectively. The genotype frequencies of AGTR1 (1166A>C) A/A, A/C, and C/C were 90.2%, 9.8%, and 0.0%. The genotype frequencies of CYP2C9*3 (1075A>C) *1/*1, *1/*3, and *3/*3 were 91.3%, 8.7%, and 0.0%, respectively; the genotype frequencies of CYP2D6* 10 (100C > T) *1/*1, *1/*10, and *10/*10 were 25.0%, 36.6%, and 38.4%, respectively. The genotype frequencies of CYP3A5*3 (6986A>G) *1/*1, *1/*3, and *3/*3 were 7.0%, 39.0%, and 54.0%, respectively. The frequencies of NPPA (2238T>C) T/T, T / C, and C / C genotypes were 97.9%, 2.1%, and 0.0%, respectively. In addition, there was a significant difference in the genotype distribution frequency of multiple drug related gene loci in southern Anhui compared to other regions in China (P< 0.05). CONCLUSION: The genotype distribution frequency of hypertensive drug related gene loci had certain bias in southern Anhui, and were significant different from other regions in China, indicating that conducting genetic polymorphism testing of hypertensive drugs had certain guiding significance for the individualized application of hypertensive drugs in southern Anhui.
2.Protection and Mechanism of Daucosterol Against Oxidative Stress Induced by Hydrogen Peroxide in Human Renal Tubular Epithelial Cells
Yingying JIANG ; Liangen LIN ; Wang LV
Journal of Medical Research 2024;53(10):144-148
Objective To investigate the protective effect and mechanism of Daucosterol on H2O2-induced oxidative stress in hu-man renal duct epithelial cells(HK-2 cells).Methods HK-2 cells were cultured in vitro,and treated with different concentrations of H2O2(1 μmol/L,5μmol/L,10μmol/L,50μmol/L and 100pmol/L)for 24h in H2O2 treatment group;In Daucosterol intervention group,HK-2 cells were pretreated with 50μmol/L Daucosterol for 2h and then treated with different concentrations of H2O2.CCK-8 assay was used to detect cell viability in each group.Hochest33342/PI fluorescence staining and caspase-3 immunofluorescence assay were used to analyze cell apoptosis.The levels of reactive oxygen species(ROS)were analyzed using DCFH-DA fluorescent probe stai-ning.Western blot assay was used to analyze the expression levels of Bax,Bcl-2 and NOX4.Results The inhibition rates in 50μmol/L and 100μmol/L H2O2 treatment groups were 20.74%±3.32%and 53.90%±2.37%;the inhibition rates in Daucosterol intervention group were 10.29%±1.69%(t=4.859,P=0.008)and 37.38%±3.95%(t=6.212,P=0.003),respectively,and the differ-ences were statistically significant.The results of Hochest33342/PI fluorescence staining showed significantly more Hochest33342 fluores-cence signal aggregation and PI fluorescence positive cells in H2O2 treatment group than in Daucosterol intervention group.Immunofluores-cence assay showed that the expression level of caspase-3 in H2O2 treatment group was significantly higher than that in Daucosterol inter-vention group.ROS level in Daucosterol intervention group was significantly attenuated compared with H2O2 treatment group.The results of Western blot showed that the expression level of NOX4 protein in H2O2 treatment group was higher than that in the control group,but significantly decreased in Daucosterol intervention group;The expression level of Bax protein also decreased in Daucosterol intervention group,compared with H2O2 treatment group.Conclusion Daucosterol intervention can alleviate H2O2-induced oxidative stress in HK-2 cells and reduce apoptosis to exert a protective effect.
3.Predicting Pathological Complete Response in Breast Cancer After Two Cycles of Neoadjuvant Chemotherapy by Tumor Reduction Rate: A Retrospective Case-Control Study
Litong YAO ; Xiaoyan LIU ; Mozhi WANG ; Keda YU ; Shouping XU ; Pengfei QIU ; Zhidong LV ; Xinwen ZHANG ; Yingying XU
Journal of Breast Cancer 2023;26(2):136-151
Purpose:
We aimed to identify effectiveness-associated indicators and evaluate the optimal tumor reduction rate (TRR) after two cycles of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer.
Methods:
This retrospective case-control study included patients who underwent at least four cycles of NAC at the Department of Breast Surgery between February 2013 and February 2020. A regression nomogram model for predicting pathological responses was constructed based on potential indicators.
Results:
A total of 784 patients were included, of whom 170 (21.68%) reported pathological complete response (pCR) after NAC and 614 (78.32%) had residual invasive tumors. The clinical T stage, clinical N stage, molecular subtype, and TRR were identified as independent predictors of pCR. Patients with a TRR > 35% were more likely to achieve pCR (odds ratio, 5.396; 95% confidence interval [CI], 3.299–8.825). The receiver operating characteristic (ROC) curve was plotted using the probability value, and the area under the ROC curve was 0.892 (95% CI, 0.863–0.922).
Conclusion
TRR > 35% is predictive of pCR after two cycles of NAC, and an early evaluation model using a nomogram based on five indicators, age, clinical T stage, clinical N stage, molecular subtype, and TRR, is applicable in patients with invasive breast cancer.
4.Neotuberostemonine and tuberostemonine ameliorate pulmonary fibrosis through suppressing TGF-β and SDF-1 secreted by macrophages and fibroblasts via the PI3K-dependent AKT and ERK pathways.
San FU ; Xianrui SONG ; Yingying HU ; Qingwei ZHU ; Xinmiao LV ; Xiaoyan TANG ; Mian ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2023;21(7):527-539
Activated fibroblasts and M2-polarized macrophages may contribute to the progression of pulmonary fibrosis by forming a positive feedback loop. This study was aimed to investigate whether fibroblasts and macrophages form this loop by secreting SDF-1 and TGF-β and the impacts of neotuberostemonine (NTS) and tuberostemonine (TS). Mice were intratracheally injected with 3 U·kg-1 bleomycin and orally administered with 30 mg·kg-1 NTS or TS. Primary pulmonary fibroblasts (PFBs) and MH-S cells (alveolar macrophages) were used in vitro. The animal experiments showed that NTS and TS improved fibrosis related indicators, inhibited fibroblast activation and macrophage M2 polarization, and reduced the levels of TGF-β and SDF-1 in alveolar lavage fluid. Cell experiments showed that TGF-β1 may activated fibroblasts into myofibroblasts secreting SDF-1 by activating the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways. It was also found for the first time that SDF-1 was able to directly polarize macrophages into M2 phenotype secreting TGF-β through the same pathways as mentioned above. Moreover, the results of the cell coculture confirmed that fibroblasts and macrophages actually developed a feedback loop to promote fibrosis, and the secretion of TGF-β and SDF-1 was crucial for maintaining this loop. NTS and TS may disturb this loop through inhibiting both the PI3K/AKT/HIF-1α and PI3K/PAK/RAF/ERK/HIF-1α pathways to improve pulmonary fibrosis. NTS and TS are stereoisomeric alkaloids with pyrrole[1,2-a]azapine skeleton, and their effect on improving pulmonary fibrosis may be largely attributed to their parent nucleus. Moreover, this study found that inhibition of both the AKT and ERK pathways is essential for maximizing the improvement of pulmonary fibrosis.
Animals
;
Mice
;
Pulmonary Fibrosis/metabolism*
;
Transforming Growth Factor beta/pharmacology*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
MAP Kinase Signaling System
;
Alkaloids/pharmacology*
;
Fibroblasts
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Macrophages/metabolism*
5.Expression of MiR-455-5p in epithelial ovarian cancer and its target gene function
Bowen LV ; Jun QIAN ; Jie WANG ; Jingrong QIAN ; Yingying LU ; Liju SU ; Tongshu YANG ; Wenhui LI
Practical Oncology Journal 2019;33(2):115-121
Objective The aim of this study was to investigate the expression of miR-455-5p in epithelial ovarian cancer and its effect on the development of epithelial ovarian cancer. Methods The miRNA expression data of normal ovarian epithelial tis-sues and epithelial ovarian cancer tissues GSE83693 were downloaded from the GEO database. Differential expression analysis was used to obtain differential expression data of miRNAs in epithelial ovarian cancer. The expression of miR-455 -5p was analyzed whether there is difference expression between normal ovarian epithelium and epithelial ovary cancer tissues; qRT-PCR was used to verify the differential expression prediction results; bio-informatics software was used to analyze the KEGG pathway enrichment and GO gene function annotation of miR-455-5p target genes,and to explore the disorders of dyregulated miR-455-5p in the devel-opment of epithelial ovarian cancer. Results A total of 101 cases of differentially expressed miRNAs were screened,34 cases were up-regulated and 67 cases were down-regulated. Among them,miR-455-5p was down-regulated significantly(P<0. 01),and the different fulds were -2. 9019. The results of qRT-PCR showed that the expression of miR-455-5p in epithelial ovarian cancer cells(SKOV-3,OVCAR-3 and A2780)was significantly lower than that in normal ovarian epithelial cells(IOSE-80),and the dif-ferential expression was statistically significant(P<0. 05). The results of KEGG pathway enrichment analysis showed that miR-455-5p regulated target genes mainly involved in five pathways,including TGF-β signaling pathway,Hippo signaling pathway,ECM-receptor interaction,transcriptional dysregulation pathway in cancer,and chronic granule cellular leukemia,which were associated with tumors. GO functional annotation analysis showed that the target genes regulated by miR-455-5p in the above pathway was mainly involved in protein phosphorylation,promoted cell proliferation and migration,inhibited apoptosis,promoted epithelial-mesenchymal transition,regulated transcription and regulated cell cycle,etc. ,which associated with tumorigenesis. Conclusion The expression of miR-455-5p is down-regulated in epithelial ovarian cancer. The miR-455-5p target genes are involved in the pathogenesis and function of epithelial ovarian cancer,and are associated with the development of epithelial ovarian cancer.
6.DPP-4 inhibitor Sig Leo Dean on the newly diagnosed type 2 diabetes mellitus and its effect on blood pressure and body weigh
Yiqi CAI ; Quan LV ; Yingying WANG ; Xicheng RUAN ; Xibo JIN
Chongqing Medicine 2017;46(11):1476-1477,1481
Objective To investigate the clinical efficacy of DPP-4 inhibitors in the treatment of newly diagnosed type 2 diabetes mellitus and its effect on blood pressure and body weight.Methods A total of 100 newly diagnosed elderly patients with type 2 diabetes mellitus were enrolled in this study from July 2013 to June 2015 in this hospital.They were divided into observation group and control group(n=50).The control group was treated with placebo on the basis of diet control and exercise.The observation group was treated with sitagliptin on the basis of diet control and exercise.Fasting plasma glucose(FPG),2 h postprandial blood glucose(2 h PG) and glycated albumin (GA) were measured before and after treatment,and the incidence rate of hypoglycemia,blood pressure,body weight and other adverse reactions were monitored.Results After treatment,two groups of patients,condition were significantly improved,FPG,2 h PG,GA changes in observation group were significantly better than that of control group,the difference were statistically significant(P<0.05).There was no significant difference in blood pressure,body weight and body mass index before and after treatment,and also between the two groups(P>0.05).The incidence of adverse reactions in the observation group and the control group were 10.0% and 8.0%,The incidence of adverse reactions in the two groups was not statistically significant(P>0.05).Conclusion The clinical efficacy of DPP-4 inhibitor siglitazide in the treatment of newly diagnosed elderly patients with type 2 diabetes mellitus is good,and it is very useful in the treatment of these patients.
7.Pathogenesis of influenza A (H5N1) virus-induced viral pneumonia in the rhesus macaque
Dongming LI ; Tianwen LAI ; Shaochang DENG ; Dong WU ; Yu ZHANG ; Min CHEN ; Yingying LV ; Bin WU
Chinese Journal of Zoonoses 2014;(8):806-811
At present ,the mechanism of highly pathogenic avian influenza H5N1 virus causing human infection or death is still not fully clear .In order to better understand the pathogenesis of the disease ,the rhesus macaques were infected with H5N1 virus (AF148678/ACGoose/Guangdong/11961H5N1) .We analyzed the clinical symptoms ,characteristics of the virus invades body ,pathological changes ,and immune response to discuss the pathogenesis of viral pneumonia induced by H 5N1 virus infection from the early time to the recovery time .The rhesus macaques were infected with H5N1 virus through nasal .Clinical signs were assessed daily ,and major organs and blood were collected for detection of blood routine analysis ,viruses were isola-ted and titrated from organs ,and pathologic and immunohistochemical were also conducted .As a result ,the rhesus macaques in-fected with H5N1 virus experienced fever ,dyspnea ,and anorexia .The respiratory tract was the major target of the virus and the virus could not replicate in organs outside the respiratory tract .Positive staining cells by immunohistochemistry were bronchial epithelial cells and alveolar macrophages .Rhesus macaques experienced temporary severe pneumonia after 1-3 days ,mainly be-cause of neutrophils infiltration ;gradual recovery 6 days later ,mainly with macrophage infiltration ;lung tissue presented recov-ery state after 14 days ,mainly with T lymphocytes infiltration .Finally ,we concluded that the predilection of the H 5N1 virus to infect the lower airway suggests that it may be a limiting factor in human-to-human transmissibility of the H5N1 virus .The pathogenesis may include virus invasion ,replication and immune injury .
8.Feasibility and safety of three periprocedure anticoagulation therapy in patients over 75 years ;undergoing radiofrequency ablation for atrial ifbrillation
Jiabin TONG ; Haifeng SHI ; Tong ZOU ; Hao CHEN ; Junpeng LIU ; Hua WANG ; Yingying LI ; You LV ; Jia CHONG ; Min DONG ; Jiefu YANG
Chinese Journal of Interventional Cardiology 2014;(4):220-224
Objective To observe the safety and efficacy of different periprocedural anticoagulation strategies in patients undergoing catheter ablation of atrial ifbrillation. Methods Eighty-five patients aged over 75 undergoing catheter ablation of atrial fibrillation from Jul 2011 to Nov 2013 were enrolled. They all took warfarin and transesophageal echocardiograms were performed to rule out left atrium appendage thrombus before ablation. They were divided into 3 groups. In Group 1 (30 cases), warfarin was stopped and bridged with low molecular weight heparin (LMWH) 3 days before procedure and LMWH bridging followed by warfarin alone after procedure. In Group 2 (32 cases), warfarin was continued during periprocedural period. In Group 3 (23 cases), Dabigatran or Rivaroxaban alone was used 4 hours after procedure respectively. Unfractionated heparin was used during procedure in all three groups. These three anticoagulation strategies were compared in bleeding, embolism events and other complications during 3-month follow-up. Results In Group 1, there were 1 new-onset ischemic stroke during hospitalization, 7 lower extremity hematomas, 1 subdural hemorrhage during 3-month follow-up and 6 minor bleeding events. In Group 2, there were 4 lower extremity hematomas and 4 minor bleeding events during 3-month follow-up. As for Group 3, only 2 lower extremity hematomas during hospitalization was observed in each without any minor bleeding events during follow-up. Conclusions Catheter ablation in elderly atrial ifbrillation patients was safe and effective in general. Compared with traditional anticoagulation strategy, continuing warfarin or novel oral anticoagulants could reduce bleeding complications without increasing thromboembolism risk.
9.Analysis of clinical etiology in 270 children patients with severe pneumonia complicated with congenital heart disease
Yingying LI ; Xiaoyun WU ; Shan LIU ; Tiewei LV ; Jie TIAN
International Journal of Laboratory Medicine 2014;(15):2026-2028,2030
Objective To analyze the clinical features of severe pneumonia complicated with congenital heart disease (CHD) . Methods The clinical data of 270 children patients with severe pneumonia complicated with CHD (CHD group) were collected to analyze the relative medical history ,etiology ,bacterial drug resistance and clinical outcomes .Moreover ,636 age-matched children pa-tients with pure severe pneumonia were selected as the control group .Results In the CHD group ,250 cases were infants and 35 ca-ses suffered from repeated pneumonia .Compared with the control group ,the CHD group was earlier in onset and more prone to re-peated pneumonia .Among 270 cases ,totally 220 cases were checked out the pathogens ,but no statistically significant difference in the detection rates of pathogens between the CHD group and the control group was found (P>0 .05);179 cases were infected by bacteria ,in which 126 cases were Gram-negative bacteria ,the positive rate of bacterial infection and the detection rate of Gram-nega-tive bacterial were relatively higher than those in the control group ,the difference was statistically significant (P<0 .05);95 cases were infected by virus ,with respiratory syncytial virus being the most common pathogen ,30 cases were infected by fungi ,with Can-dida albicans being predominant ,the infection rates of virus and fungus had no statistical difference between two groups (P>0 .05);in the drug sensitive test ,the detection rate of extended spectrum beta lactamase (ESBLs)-producing positive bacteria in the CHD group was higher than that in the control group ,the difference was statistically significant (P<0 .05) .Main Gram-negative bacteria Pneumonia klebsiella pneumonia subspecies ,Escherichia coli and haemophilus inf luenzae were highly sensitive to imipenem ,mero-penem ,levofloxacin and ciprofloxacin ;main Gram-positive bacteria Staphylococcus aureus and streptococcus pneumoniae were highly sensitive to vancomycin and gentamicin .Especially ,pneumonia klebsiella pneumonia subspecies ,Escherichia coli and haemophilus influenzaewere100% resistanttopenicillin.TheaveragelengthofhospitalstayintheCHDgroupwas (20.9±12.5)d,207cases developed the respiratory failure ,88 cases appeared the heart failure and 205 cases were effective in treatment ;compared with the control group ,the CHD group had a longer length of hospital stay ,higher occurrence rate of heart and respiratory failure and lower treatment effective rate (P<0 .05) .Conclusion Because of the earlier onset ,more prone to repeated pneumonia ,more sensitive to bacterial infection ,esp .Gram-negative bacteria ,more ESBLs production ,longer hospital stay and more prone to complications ,com-pared with the control group ,children with severe pneumonia complicated with CHD require active treatment .
10.Application of Quality Control Circle in Health Education in Stroke Rehabilitation Nursing
Hong FENG ; Jiaxing XIE ; Shuhui LI ; Wenjuan FU ; Na LIU ; Yingying JIA ; Meiyan LV ; Limin ZHAO ; Ningning YANG
Chinese Journal of Rehabilitation Theory and Practice 2014;(8):794-797
Objective To explore the effect of quality control circle (QCC) on health education in stroke rehabilitation nursing. Methods Such activities were conducted in the VIP ward of neurological rehabilitation in our hospital as: theme selecting, activity planning, status mastering, cause analyzing, countermeasures formulating and implementing, etc., in accordance with QCC theory from January to April, 2014. Results The satisfaction of stroke patients to health education rose from 80.1% to 91.1% (P<0.001), and the dissatisfaction to guidance of activities of daily living and prevention of complications decreased significantly (P<0.05) after the implementation of QCC program. All the circle members benefited from the improvement of QCC technique, team work, professional knowledge, communication and coordination, activity confidence, duty and honor. Conclusion Carrying out the QCC activities can play a positive role on health education in stroke rehabilitation nursing.


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