1.Euonymus alatus delays progression of diabetic kidney disease in mice by regulating EGFR tyrosine kinase inhibitor resistance signaling pathway
Jinjin WANG ; Wenfei CUI ; Xuewei DOU ; Binglei YIN ; Yuqi NIU ; Ling NIU ; Guoli YAN
Journal of Southern Medical University 2024;44(7):1243-1255
Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.
2.Euonymus alatus delays progression of diabetic kidney disease in mice by regulating EGFR tyrosine kinase inhibitor resistance signaling pathway
Jinjin WANG ; Wenfei CUI ; Xuewei DOU ; Binglei YIN ; Yuqi NIU ; Ling NIU ; Guoli YAN
Journal of Southern Medical University 2024;44(7):1243-1255
Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.
3.Establishment and application of evaluation criteria for clinical rational drug use of atosiban based on AHP-TOPSIS method
Jinjin YIN ; Peili DU ; Xiangping TAN ; Zhengrong MEI ; Shengying SHI ; Shaozhi LIU
China Pharmacy 2023;34(1):86-90
OBJECTIVE To establish evaluation criteria for rational drug use of atosiban in clinic, and to provide reference for rational drug use of atosiban in clinic. METHODS Based on the drug instructions of atosiban acetate injection and related guidelines, the experts of the Evaluation Group of Rational Drug Use formulated the evaluation criteria of rational drug use, including 5 primary indexes and 8 secondary indexes. The weight coefficients of secondary indexes were calculated by analytic hierarchy process (AHP), and the use of atosiban acetate injection in 190 pregnant women from the Third Affiliated Hospital of Guangzhou Medical University (referred to as “our hospital”) was evaluated retrospectively by technique for order preference by similarity to an ideal solution (TOPSIS). The evaluation results were divided into three levels including reasonable, basic reasonable and unreasonable application based on the relative approach degree. RESULTS Among 190 pregnant women, 49 (25.8%) were treated with atosiban reasonably, 39 (20.5%) were treated with atosiban basic reasonably, and 102 (53.7%) were treated with atosiban unreasonably. The evaluation results obtained by AHP-TOPSIS method were consistent with the actual situation in clinic. The main problems of the unreasonably use were super indications, unreasonable usage and dosage, over the course of treatment and the lack of proper economic consideration. CONCLUSIONS The rationality evaluation criteria of atosiban’s clinical application are established by AHP-TOPSIS method; the evaluation results obtained by this method are quantifiable, scientific and reliable. The unreasonable use of atosiban is common in our hospital, and the management should be strengthened in clinical application.
4.Magnetic stimulation in the treatment of urinary retention after spinal cord injury
Jinjin JIANG ; Kaiyue YIN ; Na SONG ; Jiaojiao JIAO ; Wenqing HU
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(5):433-436
Objective:To observe any effect of magnetic stimulation of the primary motor cortex and sacral nerve roots on urinary retention after spinal cord injury.Methods:Forty patients experiencing urine retention after a spinal cord injury were randomly divided into an experimental group and a control group, each of 20. Both groups received conventional treatment and repeated magnetic stimulation of the roots of the sacral nerve. The experimental group also received repeated magnetic stimulation of the bilateral primary motor cortices (M1 region). Bladder capacity and pressure indices, residual urine volume and life quality were evaluated in both groups before and after 8 weeks of treatment.Results:After the treatment, the average maximum bladder pressure, first sensation capacity, residual urine volume and life quality score of both groups had improved significantly, but the improvements in average first sensation capacity, residual urine volume and life quality score of the experimental group were significantly greater than those of the control group. There was, however, no significant difference in the groups′ average maximum bladder pressure after the treatment.Conclusion:Magnetic stimulation of the primary motor cortex and sacral nerve roots can significantly improve the sensory function of the bladder, reduce residual urine volume and improve the life quality of persons experiencing urinary retention after a spinal cord injury.
5.A study on reliability and validity of Chinese version of the Denver Emergency Department Trauma Organ Failure Score
Min HAN ; Dan LYU ; Yin LI ; Jinjin ZHANG ; Li TIAN
Chinese Journal of Practical Nursing 2018;34(6):445-449
Objective To investigate Chinese version of the Denver Emergency Department Trauma Organ Failure Score and examine its reliability and validity. Methods The original Denver ED TOF Score was translated into Chinese and back translated and modified for cultural adaptation according to guidelines.A survey using Chinese version of the Denver ED TOF Score was conducted on 313 trauma patients in order to verify its reliability and validity. Results Factor analysis extracted three common factors, which explained 63.327% of variance of the total scale, and each item had high factor loading quantity(>0.4).The item-level content validity index of Chinese Denver ED TOF Score were 0.80 to 1.00. and the scale-level content validity index was 0.93.Its sensitivity was 84.0% and specificity was 81.6% when score of Chinese Denver ED TOF Score was two or more. The area under receiver operator characteristic curve for Chinese Denver ED TOF Score prediction of multiple organ failure was 0.878 (95% CI 0.812-0.944, P<0.01). The Chinese version of Denver ED TOF Score had higher internal consistency, with Cronbach Alpha coefficient 0.738 and intra- class correlation coefficients 0.994. Conclusions The Chinese version of Denver ED TOF Score has a high reliability and validity, which could be used as a tool for predicting and diagnosing development of MOF in adults following trauma.
6.Study on the correlation between frailty of elderly patients and short-term prognosis after abdominal surgery
Ting CAO ; Yue QUAN ; Jinjin ZHANG ; Dan LYU ; Yin LI ; Li TIAN
Chinese Journal of Practical Nursing 2018;34(36):2823-2827
Objective To study the correlation between preoperative frailty and short-term prognosis after abdominal surgery, and to explore its predictive value. Methods A total of 156 elderly patients undergoing abdominal surgery from July 2017 to December 2017 in Tianjin Third Center Hospital were prospectively observed and classified into non-frail group, pre-frail group and frail group according to the Fried's frailty phenotype before surgery. The postoperative hospital stay and incidence of adverse outcomes were compared among the three groups, and the effect of frailty on the risk prediction model of the American Society of Anesthesiology (ASA) was analyzed. Results The postoperative hospital stay and the incidence of adverse outcomes in the three groups were statistically significant (P<0.05). Negative binomial regression analysis found that preoperative frailty was associated with prolonged postoperative hospital stay (pre-frail incidence rate ratio was 1.428 (95% CI : 1.250-1.974);frail incidence rate ratio was 3.692 (95% CI : 1.282-4.230) .Logistic regression analysis found that preoperative frailty was associated with an increased risk of postoperative adverse outcomes (pre-frail: OR=2.303(95% CI : 1.810-4.127); frail: OR=3.512 (95% CI : 2.054-5.689)). Frailty increased the diagnostic value of the ASA risk prediction model (Z=3.718, P<0.01). Conclusions Frailty of elderly patients is an important predictor of short-term prognosis of abdominal surgery, and it increases the diagnostic value of ASA risk model. The preoperative frailty assessment of elderly patients undergoing abdominal surgery is helpful for preoperative clinical decision-making and prognosis evaluation.
7. Association between the time of sedentary behaviors and risk of type 2 diabetes
Yuanyuan SHI ; Yuqian LI ; Jinjin WANG ; Chongjian WANG ; Jingzhi ZHAO ; Lei YIN ; Jingjing FAN ; Wen ZHOU ; Linlin LI
Chinese Journal of Preventive Medicine 2017;51(8):734-739
Objective:
To explore the relationship between the time of sedentary behaviors and the risk of type 2 diabetes mellitus (T2DM) among rural adults in Henan Province.
Methods:
A total of 1 227 adults from Houzhai village in Zhengzhou City and Qiaomiao village in Jiaozuo City in Henan Province were randomly selected to participate in the survey; each of them finished a questionnaire and accepted physical examination and test of biochemical indicators. The participants were divided into case and control groups according to whether suffering from T2DM. A Pearson linear correlation and linear regression model analysis were used to investigate the relevance between the time of sedentary behaviors and fasting plasma glucose (FPG); meanwhile, a multi factor logistic regression model was used to analyze the relationship between the time of sedentary behaviors and T2DM.
Results:
The average FPG level among the participants was (5.4±2.5) mmol/L, and the average time of sedentary behaviors was (234.5±156.5) min per day. The prevalence rate of T2DM in subgroups whose time of sedentary behaviors were separately 0-<2.5, 2.5-<4.5, 4.5-<6.5 and ≥6.5 h/day were 15.8% (72/457), 19.3% (73/379), 16.7% (35/210) and 20.4% (37/181), respectively. There was a linear regression relationship between the time of sedentary behaviors(
8.Body mass index, waist circumference and waist-to-height ratio associated with the incidence of type ;2 diabetes mellitus:a cohort study
Xiangyu YANG ; Ming ZHANG ; Xinping LUO ; Jinjin WANG ; Lei YIN ; Chao PANG ; Guoan WANG ; Yanxia SHEN ; Dongting WU ; Lu ZHANG ; Yongcheng REN ; Bingyuan WANG ; Hongyan ZHANG ; Junmei ZHOU ; Chengyi HAN ; Yang ZHAO ; Tianping FENG ; Dongsheng HU ; Jingzhi ZHAO
Chinese Journal of Preventive Medicine 2016;50(4):328-333
Objective To investigate the association between body mass index (BMI), waist circumference (WC), waist?to?height ratio (WHtR), and the incidence risk of type 2 diabetes mellitus (T2DM). Methods In total, 20 194 participants≥18 years old were selected randomly by cluster sampling from two township (town) of the county in Henan province from July to August of 2007 and July to August of 2008 and the investigation included questionnaires, anthropometric measurements, fasting plasma glucose,and lipid profile examination were performed at baseline; 17 236 participants were enrolled in this cohort study. 14 720 (85.4%) were followed up from July to August 2013 and July to October 2014. Finally, 11 643 participants (4 301 males and 7 342 females) were included in this study. Incidence density and Cox proportional hazards regression models were used to evaluate the risk of T2DM associated with baseline BMI, WC, WHtR, and their dynamic changes. Results After average of 6.01 years following up for 11 643 participants, 613 developed T2DM and the incidence density was 0.89 per 100 person?years. After adjusted for baseline sex, age, smoking, drinking, family history of diabetes, as well as the difference of fasting plasma?glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL?C), systolic blood pressure (SBP), diastolic blood pressure (DBP) between baseline and follow?up, Cox Proportional?Hazards regression analysis indicated that T2DM risk of baseline BMI overweight group, BMI obesity group, abnormal WC group and abnormal WHtR group were significantly higher than that of the corresponding baseline normal groups , and the incidence risk of T2DM reached the highest for those whose baseline BMI, WC and WHtR were all abnormal, the corresponding HR (95%CI) were 2.05 (1.62-2.59), 3.01 (2.33-3.90), 2.34 (1.89-2.90), 2.88 (2.21-3.74), 3.32 (2.50-4.40), respectively. Whether baseline BMI/WC was normal or not, T2DM risk increased if baseline WHtR was abnormal, and the HR (95%CI) of baseline normal BMI/abnormal WHtR group, baseline abnormal BMI/abnormal WHtR group, baseline normal WC/abnormal WHtR group, baseline abnormal WC/abnormal WHtR group were 1.88 (1.29-2.74), 3.08 (2.34-4.05), 2.15 (1.53-3.00), 3.22 (2.45-4.23), respectively. The analysis for dynamic changes of BMI, WC, and WHtR indicated that in baseline normal WC or WHtR group, T2DM risk increased when baseline normal WC or WHtR developed abnormal at follow?up, and the corresponding HR (95%CI) were 1.79 (1.26-2.55), 2.12 (1.32-3.39), respectively. In baseline abnormal WC or WHtR group, T2DM risk decresed when baseline abnormal WC or WHtR reversed to normal at follow?up, and the corresponding HR (95%CI) were 2.16 (1.42-3.29), 2.62 (1.63-4.20), respectively. Conclusion BMI, WC, and WHtR were associated with increased T2DM risk. The more abnormal aggregation of BMI, WC, and WHtR presents, the higher T2DM risk was. T2DM risk could be decreased when abnormal WC or WHtR reversed to normal.
9.Body mass index, waist circumference and waist-to-height ratio associated with the incidence of type ;2 diabetes mellitus:a cohort study
Xiangyu YANG ; Ming ZHANG ; Xinping LUO ; Jinjin WANG ; Lei YIN ; Chao PANG ; Guoan WANG ; Yanxia SHEN ; Dongting WU ; Lu ZHANG ; Yongcheng REN ; Bingyuan WANG ; Hongyan ZHANG ; Junmei ZHOU ; Chengyi HAN ; Yang ZHAO ; Tianping FENG ; Dongsheng HU ; Jingzhi ZHAO
Chinese Journal of Preventive Medicine 2016;50(4):328-333
Objective To investigate the association between body mass index (BMI), waist circumference (WC), waist?to?height ratio (WHtR), and the incidence risk of type 2 diabetes mellitus (T2DM). Methods In total, 20 194 participants≥18 years old were selected randomly by cluster sampling from two township (town) of the county in Henan province from July to August of 2007 and July to August of 2008 and the investigation included questionnaires, anthropometric measurements, fasting plasma glucose,and lipid profile examination were performed at baseline; 17 236 participants were enrolled in this cohort study. 14 720 (85.4%) were followed up from July to August 2013 and July to October 2014. Finally, 11 643 participants (4 301 males and 7 342 females) were included in this study. Incidence density and Cox proportional hazards regression models were used to evaluate the risk of T2DM associated with baseline BMI, WC, WHtR, and their dynamic changes. Results After average of 6.01 years following up for 11 643 participants, 613 developed T2DM and the incidence density was 0.89 per 100 person?years. After adjusted for baseline sex, age, smoking, drinking, family history of diabetes, as well as the difference of fasting plasma?glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL?C), systolic blood pressure (SBP), diastolic blood pressure (DBP) between baseline and follow?up, Cox Proportional?Hazards regression analysis indicated that T2DM risk of baseline BMI overweight group, BMI obesity group, abnormal WC group and abnormal WHtR group were significantly higher than that of the corresponding baseline normal groups , and the incidence risk of T2DM reached the highest for those whose baseline BMI, WC and WHtR were all abnormal, the corresponding HR (95%CI) were 2.05 (1.62-2.59), 3.01 (2.33-3.90), 2.34 (1.89-2.90), 2.88 (2.21-3.74), 3.32 (2.50-4.40), respectively. Whether baseline BMI/WC was normal or not, T2DM risk increased if baseline WHtR was abnormal, and the HR (95%CI) of baseline normal BMI/abnormal WHtR group, baseline abnormal BMI/abnormal WHtR group, baseline normal WC/abnormal WHtR group, baseline abnormal WC/abnormal WHtR group were 1.88 (1.29-2.74), 3.08 (2.34-4.05), 2.15 (1.53-3.00), 3.22 (2.45-4.23), respectively. The analysis for dynamic changes of BMI, WC, and WHtR indicated that in baseline normal WC or WHtR group, T2DM risk increased when baseline normal WC or WHtR developed abnormal at follow?up, and the corresponding HR (95%CI) were 1.79 (1.26-2.55), 2.12 (1.32-3.39), respectively. In baseline abnormal WC or WHtR group, T2DM risk decresed when baseline abnormal WC or WHtR reversed to normal at follow?up, and the corresponding HR (95%CI) were 2.16 (1.42-3.29), 2.62 (1.63-4.20), respectively. Conclusion BMI, WC, and WHtR were associated with increased T2DM risk. The more abnormal aggregation of BMI, WC, and WHtR presents, the higher T2DM risk was. T2DM risk could be decreased when abnormal WC or WHtR reversed to normal.
10.Establishment of a L-02 cell model of hepatic steatosis.
Jinjin YIN ; Waijiao TANG ; Lu ZENG ; Benjie ZHOU
Journal of Southern Medical University 2014;34(6):837-842
OBJECTIVETo establish an in vitro cell model for investigating hepatic steatosis in non-alcoholic fatty liver disease.
METHODSL-02 cells cultured in 1640 containing 10% fetal bovine serum were divided into control group and model group. At 70%-80% confluency, L-02 cells in the model group were exposed to a long-chain mixture of free fatty acids (FFA, oleate and palmitate ) for 24 h, and cells in control group were treated with fresh medium. Lipid droplets in the cells were observed and total lipid content was determined with Oil Red O staining. The morphology of lipid droplets, trilyceride level, malonaldehyde content and cell apoptosis rate were evaluated to verify the cell model, and the effect of Huganqingzhi tablet on the lipid droplets was observed.
RESULTSA large number of lipid droplets were found in the cell model, which showed markedly increased level of triglyceride without significant changes of malonadehyde content or cell apoptosis rate. Intervention with two doses of Huganqingzhi tablet significantly decreased the number of lipid droplets and trilyceride content in the cell model.
CONCLUSIONhepatic steatosis L-02 cell model can be established by long-chain mixture of free fatty acids (oleate:spalmitate=2:1) for therapeutic drug studies.
Apoptosis ; Cell Line ; Drugs, Chinese Herbal ; pharmacology ; Fatty Acids, Nonesterified ; chemistry ; Fatty Liver ; Humans ; Malondialdehyde ; analysis ; Non-alcoholic Fatty Liver Disease ; Triglycerides ; analysis

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