1.Study on Compatibility and Efficacy of Blood-activating Herb Pairs Based on Graph Convolution Network
Jingai WANG ; Qikai NIU ; Wenjing ZONG ; Ziling ZENG ; Siwei TIAN ; Siqi ZHANG ; Yuwen ZHAO ; Huamin ZHANG ; Bingjie HUO ; Bing LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):228-234
ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks (GCN), named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data, including Qi, flavor, meridian tropism, and target genes. Integrating traditional characteristics of herb with modern bioinformatics, we developed an efficacy-oriented herb pair compatibility prediction model (HC-GCN) using graph convolutional networks (GCN). This model leverages machine learning to capture the complex relationships in herb pair compatibility, weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy (ACC), recall, precision, F1 score (F1), and area under the ROC curve (AUC). Its predictive effectiveness was then compared to five other machine learning models: eXtreme Gradient Boosting (XGBoost), logistic regression (LR), Naive Bayes, K-nearest neighbor (KNN), and support vector machine (SVM). ResultsUsing herb pairs with blood-activating effects as a demonstration, a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs, incorporating their Qi, flavor, meridian tropism, and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics, including ACC, recall, precision, F1 score, and AUC. Through the predictive analysis of the HC-GCN model, 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs, 44 include at least one herb with blood-activating effects. ConclusionIn this study, we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance, offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions, as well as their clinical applications.
2.Efficacy-driving Mechanism of Danhong Injection for Stable Angina Pectoris Based on Composition-activity Relationship of Target Modules
Siwei TIAN ; Wenjing ZONG ; Jun LIU ; Wei YANG ; Qikai NIU ; Siqi ZHANG ; Jing'ai WANG ; Huamin ZHANG ; Zhong WANG ; Bing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):121-128
ObjectiveTo explore the efficacy-driving mechanism of Danhong injection (DHI) in the treatment of stable angina pectoris (SAP) based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency (AF) in the Seattle Angina Questionnaire (SAQ) that was obtained in the previous clinical trial, the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source, and then weighted gene co-expression network analysis (WGCNA) was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition, the On-modules (Z value below 0) were identified by Zsummary. The topological indicators such as density, centrality, and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level, respectively. In addition, the driver genes were screened by the personalized network control (PNC) algorithm. Finally, rat H9C2 cells were used to establish the model of hypoxia/reoxygenation (H/R), which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP, and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally, the driver genes, Klotho and fibroblast growth factor 22 (FGF22), in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data, this study determined the composition-activity relationship of target modules of DHI for SAP, which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.
3.A comparative study of regulation of the homing ability of mesenchymal stem cells by hypoxia and hydrogen peroxide pretreatment
Yichen HUANG ; Mingxia JIANG ; Wenjing MA ; Qiaomi CHEN ; Rui BAI ; Bingshui XIU ; Mengwen SONG ; Jie NIU ; Zhiqiang LIU
Military Medical Sciences 2024;48(9):656-663
Objective To determine the optimal conditions for CXCR4 upregulation by comparing the expression levels of chemokine(C-X-C motif)receptor 4(CXCR4)in MSCs cultured with varying concentrations of oxygen and hydrogen peroxide(H2O2).Methods MSCs were cultured with 0.1%,1%,or 3%O2 and 50 μmol/L H2O2 for different lengths of time(3,6,12,and 24 h).The mRNA and protein expressions of CXCR4 in MSCs were measured by real-time quantitative PCR(qPCR),Western blotting,and immunofluorescence staining.The viability and chemotactic ability of MSCs were measured using CCK-8,wound-healing and Transwell migration assays.Results Both hypoxia and H2O2 treatment were found to upregulate MSC expressions of CXCR4 to some extent.The mRNA and protein levels of CXCR4 were higher after 6-12 h of culture of MSCs with 3%O2,and significantly higher when treated with H2O2 for 6 h.Cell viability was significantly increased after culture with 3%O2 compared with the control group and both 3%O2 and H2O2 pretreatment could enhance chemotactic migration in MSCs.Conclusion Culture with 3%O2 and H2O2 pretreatment can upregulate CXCR4 expressions in MSCs and enhance migration in cells,with superior effects observed with 3%O2.Therefore,treatment with 3%O2 represents the best choice for upregulating the chemotactic ability of MSCs.
4.Efficacy and safety of low-dose aspirin on preventing transplant renal artery stenosis: a prospective randomized controlled trial
Xiangyong TIAN ; Bingqing JI ; Xiaoge NIU ; Wenjing DUAN ; Xiaoqiang WU ; Guanghui CAO ; Chan ZHANG ; Jingge ZHAO ; Zhiwei WANG ; Yue GU ; Huixia CAO ; Tao QIN ; Fengmin SHAO ; Tianzhong YAN
Chinese Medical Journal 2023;136(5):541-549
Background::Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods::After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment ( n = 178), or a control group with only standard treatment ( n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS). Results::In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate ( P < 0.001), cholesterol ( P = 0.028), and low-density lipoprotein cholesterol ( P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference. Conclusion::Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration::Clinicaltrials.gov, NCT04260828.
5.Current status of perioperative nursing quality in 82 hospitals in Shanghai and its correlation with nursing human resource allocation
Rui LI ; Li WANG ; Wenjing XIA ; Shuzhen NIU ; Songqi WU ; Yan SHI
Chinese Journal of Modern Nursing 2023;29(36):4901-4907
Objective:To investigate the current situation of perioperative nursing quality and nursing human resource allocation in 82 hospitals in Shanghai and analyze the correlation between them.Methods:The convenient sampling method was used to select surgical wards in 82 secondary and tertiary hospitals in Shanghai that underwent nursing quality supervision in September 2022 as the research objects. Perioperative nursing quality data (patients' condition, perioperative nursing routine and operation process, etc.) and nursing human resource allocation data (bed-to-nurse ratio, nurse-to-patient ratio, etc.) of inpatients in 82 hospitals were collected from the platform of Shanghai Nursing Quality Control Center. Pearson correlation analysis was used to investigate the correlation between perioperative nursing quality and nursing human resource allocation in inpatients.Results:The standard-reaching rate of perioperative nursing quality in 82 hospitals in Shanghai is 56.1% (46/82). The overall standard-reaching rate of perioperative nursing quality in secondary hospitals is 30.4% (7/23), which was lower than 66.1% (39/59) of tertiary hospitals, and the difference was statistically significant ( P<0.05). The total score of perioperative nursing quality in 82 hospitals was (79.67±1.89), among which the item with the lowest score was "perioperative complication predictive nursing", followed by "perioperative nursing routine and operation process" and "patient safety risk assessment". The bed-to-nurse ratio of surgical wards in 82 hospitals was 1∶ (0.47±0.21) and the nurse-to-patient ratio was 1∶ (12.20±6.44). The proportion of nurses with bachelor degree or above was (68±11) %, the proportion of nurses with intermediate title or above was (38±7) %, and the proportion of nurses with 5 years of work experience or above was (52±8) %. The total level of perioperative nursing quality was negatively correlated with the nurse-patient ratio ( r=-0.367, P<0.01), and positively correlated with the bed-to-nurse ratio, the proportion of nurses with bachelor's degree or above, the proportion of nurses with intermediate professional title or above, and the proportion of nurses with 5 years of work experience or above ( r=0.506, 0.631, 0.552, 0.636; P<0.01) . Conclusions:The overall level of perioperative nursing quality in 82 hospitals in Shanghai is average, and it is positively correlated with bed-to-nurse ratio and negatively correlated with nurse-to-patient ratio. Hospital managers should improve the scientific and refined level of perioperative nursing management, improve the perioperative nursing risk control mechanism, refine the perioperative nursing operation process, construct the risk forecasting, early-warning and pre-control mode of surgical complications and optimize the nursing human resource structure, so as to promote the high-quality development of perioperative nursing.
6.Correlation between aluminum concentration and miR-134-3p expression in peripheral blood in occupational aluminum exposed workers
Jiarui HAO ; Wenjing LI ; Chunman YUAN ; Xiaoting LU ; Linping WANG ; Qiao NIU ; Jing SONG
Journal of Environmental and Occupational Medicine 2023;40(5):545-550
Background Previous studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet. Objective To evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers. Methods A total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q1-Q4) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models. Results The workers' medians (P25, P75) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q1 group, blood aluminum in the Q2, Q3, or Q4 group had an impact on related plasma miR-134-3p expression level and total MoCA score (P<0.05). With increasing blood aluminum concentration, the expression level of miR-134-3p in workers' plasma gradually increased, showing a positive correlation (b>0, Ptrend<0.001), while the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). As the expression level of miR-134-3p in plasma increased, the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). There was a linear relationship between peripheral blood aluminum concentration and plasma relative expression level of miR-134-3p of the workers in the middle school and below group and the high school group (Ptrend<0.05), b (95%CI)=1.796 (1.248, 2.344) and 1.192 (0.874, 1.510), and no correlation was found in the workers in the college and above group (Ptrend>0.05). Conclusion Occupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.
7.Association between residual cholesterol and the risk of subclinical renal damage
Xi ZHANG ; Zejiaxin NIU ; Guilin HU ; Mingfei DU ; Ting ZOU ; Xiaoyu ZHANG ; Lan WANG ; Chao CHU ; Yueyuan LIAO ; Qiong MA ; Dan WANG ; Keke WANG ; Hao JIA ; Chen CHEN ; Yu YAN ; Yue SUN ; Tongshuai GUO ; Jie ZHANG ; Weihua GAO ; Ziyue MAN ; Ke GAO ; Wenjing LUO ; Jianjun MU ; Yang WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(1):6-13
【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.
8.Association of genetic variants in NEDD4L with blood pressure responses to dietary salt and potassium intake
Zejiaxin NIU ; Mingfei DU ; Guilin HU ; Xi ZHANG ; Dan WANG ; Lan WANG ; Wenjing LUO ; Mingke CHANG ; Ting ZOU ; Xiaoyu ZHANG ; Yu YAN ; Chao CHU ; Yueyuan LIAO ; Qiong MA ; Keke WANG ; Hao JIA ; Chen CHEN ; Yue SUN ; Tongshuai GUO ; Jie ZHANG ; Weihua GAO ; Ziyue MAN ; Ke GAO ; Jianjun MU ; Yang WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(1):30-37
【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.
9.Association of genetic variants in uromodulin with blood pressure responses to dietary salt and potassium intake
Yan WU ; Mingfei DU ; Xi ZHANG ; Lan WANG ; Guilin HU ; Zejiaxin NIU ; Ting ZOU ; Xiaoyu ZHANG ; Chao CHU ; Yueyuan LIAO ; Qiong MA ; Dan WANG ; Keke WANG ; Hao JIA ; Chen CHEN ; Yu YAN ; Yue SUN ; Tongshuai GUO ; Jie ZHANG ; Weihua GAO ; Ziyue MAN ; Ke GAO ; Wenjing LUO ; Jianjun MU ; Yang WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(1):38-45
【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.
10.Associations of genetic variants in M3 receptor with blood pressure responses to salt and potassium intake
Xi ZHANG ; Guilin HU ; Zejiaxin NIU ; Mingfei DU ; Ting ZOU ; Xiaoyu ZHANG ; Lan WANG ; Chao CHU ; Yueyuan LIAO ; Qiong MA ; Dan WANG ; Keke WANG ; Hao JIA ; Chen CHEN ; Yu YAN ; Yue SUN ; Tongshuai GUO ; Jie ZHANG ; Weihua GAO ; Ruichen YAN ; Ke GAO ; Wenjing LUO ; Jianjun MU ; Yang WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(1):46-54
【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

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