Comparison of Quality Change During Processing Process of Achyranthis Bidentatae Radix from Different Origins Based on Color-component Correlation Analysis / 中国实验方剂学杂志

ObjectiveTaking Achyranthis Bidentatae Radix（ABR） from different origins as samples， to quantitatively analyze the chemical composition and chromaticity of ABR with different processing degrees， and clarify the correlation and change law between color and composition in the processing process of ABR， so as to provide reference for the quality evaluation of processed products of ABR. MethodThe colorimeter is used to measure the chromaticity values of three kinds of processing degrees of ABR in different origins to show the color value change trend during the processing process， and the color parameters of wine-processed and salt-processed products of ABR with different processing degrees were analyzed by principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA） and other analysis methods. The contents of eight representative components of ABR were measured by high performance liquid chromatography（HPLC）， the correlation between chromaticity and each representative component was analyzed by Pearson correlation analysis， and the applicability of the selected eight representative components was further verified by Fisher linear discriminant analysis， and the wine-processed and salt-processed products of ABR with different processing degrees were grouped according to the degree of processing， and 48 samples of wine-processed and salt-processed products with different processing degrees were used as training samples. Taking the contents of 5-hydroxymethylfurfural， polypodine B， β-ecdysterone， 25R-inokosterone， 25S-inokosterone， ginsenoside Ro， chikusetsusaponin Ⅳa and polysaccharides as variables， the discriminant function was established respectively， and 12 samples of wine-processed and salt-processed products of ABR with different processing degrees were back-tested to verify the discriminant function and test the reliability of the function. ResultPCA and OPLS-DA results showed that ABR samples with different processing degrees were classified into clusters， and the results could significantly distinguish different processed products. During the process of wine and salt processing， the contents of 5-hydroxymethylfurfural， ginsenoside Ro， and chikusetsusaponin Ⅳa gradually increased with the deepening of the processing degree， while the contents of polypodine B， β-ecdysterone， 25R-inokosterone， 25S-inokosterone and polysaccharides showed a gradual decreasing trend， indicating these 8 components increased and decreased to different degrees in the process of wine and salt processing. The results of Pearson correlation analysis showed that the 5-hydroxymethylfurfural content of the samples with different processing degrees of wine-processed and salt-processed products were negatively correlated with the brightness value（L*） and the total color difference value（E*ab）（P<0.01）， and positively correlated with the red-green value（a*） and the yellow-blue value（b*）（P<0.01）， and that the content of polypodine B and polysaccharides were positively correlated with L* and E*ab（P<0.01）. The discriminant functions of wine-processed and salt-processed products of ABR were established by Fisher linear discriminant analysis， and their accuracy rates in the training samples were 93.75% and 95.83%， respectively. Twelve test samples of wine-processed and salt-processed products with different processing degree were back substitution， and the correct rate was 100%. ConclusionThe trend of composition and color changes of ABR with different processing degrees in different production areas is relatively consistent， and the color value can better distinguish ABR with different processing degrees， and the color of ABR is related to some representative components in the processing process， indicating that the color can provide reference for the identification of the processing degree of ABR and the prediction of component content.

Associations of genetic variants in M3 receptor with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【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.

Association of genetic variants in uromodulin with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【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.

Association of genetic variants in NEDD4L with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【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.

Associations of genetic polymorphisms in Corin with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

Association between residual cholesterol and the risk of subclinical renal damage / 西安交通大学学报(医学版)

【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.

Rapamycin-induced β-Globin Family Locus Remodeling Regulates the Gene Switching Expression / 中国生物化学与分子生物学报

β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.

Establishment of infrared fingerprints and multivariate statistical analysis of Achyranthes bidentata / 中国药房

OBJECTIVE To establish the infrared fingerprints of Achyranthes bidentata from different producing areas ，and to conduct multivariate statistical analysis. METHODS The infrared fingerprints of 61 batches of A. bidentata samples were established by Spectrum for Window 3.02 and OMNIC 9.2 software. Taking the relative peak height of common peaks of infrared fingerprint as the variable ，the normal distribution analysis was carried out by Excel 2016 software；SPSS 22.0 software was used for cluster analysis and principal component analysis ，and the comprehensive score was calculated ；the orthogonal partial least squares-discriminant analysis was carried out by SIMCA 14.1 software，and the marker wave numbers affecting the quality of A. bidentata were screened by taking the variable importance in projection （VIP）＞1 as the standard. RESULTS The correlation coefficients of infrared spectra of 61 batches of A. bidentata samples were 0.967 2-0.997 7；there were 13 common peaks. The results of normal distribution analysis showed that the normal distribution curve of relative peak height of common peaks for A. bidentata from Henan and Hebei did not cross ，and the normal distribution curve of A. bidentata from Henan and Inner Mongolia crossed. The results of cluster analysis showed that when the distance between groups was 15，61 batches of A. bidentata samples could be clustered into 3 categories，including N 1-N12 were clustered into one category ，N13-N45 were clustered into one category，and N 46-N61 were clustered into one category. The results of principal component analysis showed that the cumulative variance contribution rate of the first three principal components was 91.121％；comprehensive score of qq.com A. bidentata （number N 40） in Jiabu village ，Jiaozuo City ， Henan Province was the highest （2.39）， and that of A.bidentata（number N 4）in Xin ’an village ，Anguo City ，Hebei Province was the lowest （－2.89）. The results of orthogonal 163.com partial least squares-discriminant analysis showed that 61 batches of A. bidentata samples were divided into three categories ，including N 1-N12 were clustered into one category ，N13-N28 were clustered into one category and N 29-N61 were clustered into one category. Seven marker wave numbers affecting the quality were selected. The corresponding wave numbers of VIP from large to small were 1 059，927，2 933，813，1 732，1 128 and 3 367 cm－1，1 732 cm－1 was the characteristic obsorption peak of saponins ，1 059，1 128，927 cm－1 were the characteristic obsorption peaks of glycosides. CONCLUSIONS Infrared fingerprint combined with normal distribution analysis ，cluster analysis ，principal component analysis and orthogonal partial least squares-discriminant analysis can be used to identify A. bidentata from different producing areas.

Effects of different habitat processing methods on the quality of Cyperus rotundus / 中国药房

OBJECTIVE To investigate the eff ects of different habitat processing methods on the quality of Cyperus rotundus ， such as sun-drying after steaming ，sun-drying after boiling and direct sun-drying ，and to investigate the optimal habitat processing method of C. rotundus from the perspective of chemical component. METHODS The fingerprint of C. rotundus was established by high performance liquid chromatography （HPLC）combined with the Similarity Evaluation System for Chromatographic Fingerprint of TCM （2012 edition）. The similarity evaluation was conducted to determine the common peak. Cluster analysis （CA）combined with principal component analysis （PCA）and partial least squares-discriminant analysis （PLS-DA）was used to differentiate and compare C. rotundus treated by different habitat processing methods. And the contents of cyperrenone ，α-cyperone，luteolin and ferulic acid in C. rotundus were determined by HPLC. RESULTS There were 22 common peaks in the HPLC fingerprints of C. rotundus reated by different habitat processing methods ；their similarities were higher than 0.9；common peak 16 and common peak 20 were cyperrenone and α-cyperone. CA results showed that C. rotundus boiled for 4，8 and 12 min were clustered into one category，the rest of the samples clustered into one category. PCA results showed that comprehensive score of C. rotundus steamed for 10 and 15 min and boiled for 2 min were the highest. The steaming treatment had small effect on comprehensive score of samples，while the boiling treatment had a great effect on the quality of the samples ；the overall score of samples decreased sharply after boiling for 2 min. Results of PLS-DA showed that variable importance projection （VIP）of peak 20（α-cyperone），peak 16 （cyperrenone），peak 22，peak 17 and peak 22 in HPLC fingerprints were all higher than 1. The results of content determination showed that there was significant difference in the contents of α-cyperone，cyperrenone and luteolin in samples treated by different habitat processing methods.With the increase of steaming and boiling time ，the contents of α-cyperone，cyperrenone and luteolin showed a significant downward trend ，and boiling had a great impact on them. CONCLUSIONS Too long boiling treatment greatly；2019 destroys the chemical composition of C. rotundus ， andsteaming for 10，15 min or boiling for 2 min is the optimal processing method.

Association between body mass index trajectories in children and adolescents of Hanzhong city of Shanxi province and subclinical renal damage in adulthood: a 30-year longitudinal follow-up study / 中华肾脏病杂志

Objective:To investigate the association between body mass index (BMI) trajectories in children and adolescents and subclinical renal damage (SRD) in adulthood.Methods:4 623 participants aged 6-18 years old were recruited from the ongoing cohort of Hanzhong adolescent hypertension study in 1987, and the subjects were followed up in 1989, 1992, 1995, 2005, 2013 and 2017, respectively. Group-based trajectory modeling was used to identify distinct BMI trajectories in longitudinal analysis. Generalized linear model was applied to examine the association between different BMI trajectories and SRD incidence in adulthood.Results:A total of 2 678 subjects from childhood to adulthood were enrolled in this study. All subjects were divided into three groups according to three distinct BMI trajectories: low-increasing BMI group ( n=1 017), moderate-increasing BMI group ( n=1 353), and high-increasing BMI group ( n=308). Over follow up for 30 years, a total of 248 participants (9.3%) developed SRD. Urinary albumin-to-creatinine ratio (uACR) in low to high-increasing BMI group was 0.9(0.6, 1.4), 1.0(0.7, 1.7), 1.6(0.8, 3.2), respectively ( P trend<0.001), and estimated glomerular filtration rate was 98.5(87.6, 111.6) , 96.2(86.4, 109.7), 95.3 (87.5, 125.0) ml·min -1·(1.73 m 2) -1, respectively ( P trend=0.025). The generalized linear model analysis showed that uACR was increased linearly from low to high-increasing BMI group [ β=3.16(95% CI 1.02-5.31), Ptrend=0.004]. There was no correlation or linear trend between BMI trajectory and estimated glomerular filtration rate [ β=-2.30(95% CI-5.18-0.57), Ptrend=0.117]. Compared with the low-increasing BMI group, the high-increasing BMI group had greater odds of experiencing SRD in adulthood after adjusting for multiple confounders such as age, gender, medical history and lifestyle ( OR=2.83, 95% CI 1.84-4.36, Ptrend<0.001). Conclusions:Higher BMI trajectorie is correlated with higher level of uACR and risk of SRD in middle age. Identifying long-term BMI trajectorie from early age may assist in predicting individuals′ renal function in later life.

Experience in diagnosis and treatment of pulmonary changes after radical surgery for thyroid cancer / 中华内分泌外科杂志

Objective:To investigate the causes, diagnosis and treatment of postoperative pulmonary changes in patients with thyroid cancer.Methods:Data of 378 patients with thyroid cancer surgery admitted from Oct. 1, 2019 to Jan. 31, 2020 were retrospectively analyzed. SPSS 23.0 statistical software was adopted to analyze the effect of gender, age, smoking history, BMI, operation way and the surgical approach on postoperative changes in the lungs. The two groups of counting data were compared using χ2 method. Results:Age, gender, smoking history and surgical approach had no significant influence on postoperative pulmonary change ( P>0.05) . Lung changes in patients receiving thyroid cancer plus lateral neck dissection were greater than those receiving radical thyroid cancer alone ( P=0.001) , and lung changes in patients receiving bilateral neck dissection were greater than those receiving unilateral neck dissection ( P=0.027) . The pulmonary changes in patients with underweight and obesity were greater than those in patients with normal weight and hyperreorganization ( P=0.019) . Conclusions:Lateral neck dissection and patients’ body mass index are important factors affecting the postoperative lung changes in thyroid cancer patients. Thyroid cancer patients undergoing lateral neck dissection should actively check their lung changes through chest radiographs after surgery, especially for lean and obese patients, and patients undergoing bilateral neck dissection.

Association of genetic variants in renalase with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we conducted chronic salt loading and potassium supplementation interventions, aiming to examine the association between genetic variants in renalase and blood pressure (BP) responses to dietary interventions of salt and potassium intake. 【Methods】 In 2004, 514 subjects from 126 families were recruited in Shaanxi Province to establish the salt-sensitive hypertension study cohort. Among them, 334 non-parent subjects were selected and sequentially maintained on a 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. Ten single nucleotide polymorphisms (SNPs) in the renalase gene were genotyped on the MassARRAY platform. 【Results】 SNP rs2576178 of the renalasegene was significantly associated with systolic BP (SBP) and mean arterial pressure (MAP) responses to low-salt intervention (SBP: β=-2.730, P<0.05; MAP: β=-1.718, P<0.05). In addition, SNP rs12356177 was significantly associated with diastolic BP response to low-salt diet (β=-1.608, P<0.05). However, we did not find any association for the renalase SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. 【Conclusion】 Genetic variants in renalase gene are significantly associated with BP response to low-salt diet, suggesting that renalase may be mechanistically involved in BP salt-sensitivity.

KLF7 Affects Development of Broiler Adipose Tissue by Inhibiting Hypoxia￣Inducible Factor 1 Alpha Transcription / 中国生物化学与分子生物学报

Krüppel-like factor 7 (KLF7) is a negative regulator of adipogenesis, whereas hypoxia-inducible factor 1 (HIF1) promotes anoxic-induced adipose tissue development in mammals. Our previous ChIP-seq analysis showed that one of the KLF7 binding peaks was present upstream of hypoxia-inducible factor 1 alpha (HIF1α), indicating that KLF7 may regulate HIF1α transcription. For this purpose, ChIP-PCR was used to verify ChIP-seq results, which showed that KLF7 directly bound to the HIF1α upstream region. Dual luciferase reporter and qRT-PCR results showed that KLF7 overexpression significantly decreased the luciferase reporter activity of HIF1α (- 4 432/- 4 182) (P < 0. 01) and inhibited HIF1α expression. After the deletion of KLF7 binding motif “TGCGCAGCAA” (- 4 300/-4 290) predicted by bioinformatics, the luciferase reporter activity of HIF1α (-4 432/-4 182) was significantly enhanced compared with wild-type plasmid (P<0. 01). Furthermore, Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) at the age of 1-7 weeks from the 19

Pharmacological Analysis of Xuanfei Huazhuo Prescription in Treatment of Coronavirus Disease-2019 / 中国实验方剂学杂志

Objective:The targets and signaling pathways of Xuanfei Huazhuo prescription (XFHZP) for the treatment of coronavirus disease-2019 (COVID-19) were explored, and its possible action mechanisms were described through network pharmacology and basic analysis of modern pharmacology. Method:The compounds and targets in XFHZP were collected through TCMSP and BATMAN-TCM databases. The targets of COVID-19 were studied by GeneCards, NCBI and CTD databases. The PPI network was constructed through STRING database. The networks of "herb-meridian" and "traditional Chinese medicines-compounds-targets-disease" were generated by Cytoscape 3.7.0. Then, Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis and Gene Ontology（GO） analysis were made for shared targets through the Omicshare platform. In addition, the disease targets of multiple organ injury, immune injury and severe acute respiratory syndrome (SARS) were retrieved and then mapped with XFHZP. The ratio of intersection targets to XFHZP's targets was calculated. Result:XFHZP has 10 traditional Chinese medicines in total, including 6 medicines with the meridian tropism to lung, 5 medicines with the meridian tropism to the spleen and 5 medicines with the meridian tropism to the stomach. There were 409 compounds and 2 271 targets. There were 8 same inflammatory factors in targets between XFHZP and COVID-19, and each inflammatory factor corresponded to multiple compounds. XFHZP and COVID-19 had 135 intersection targets, and 36 key targets were screened out. A total of 172 signaling pathways were screened out through KEGG signal pathway enrichment (P<0.05). There were 4 000 biological processes, 254 cell components, and 408 molecular functions (P<0.05) according to GO analysis. XFHZP had many common targets with various organ damage targets and immune damage targets, with the ratio of about 7.6%-97.8%. XFHZP had 173 intersection targets with SARS. Conclusion:XFHZP may treat COVID-19 through anti-inflammatory, organ protecting and immune effects. It will provide a certain theoretical basis for the development of drugs for COVID-19.

Network pharmacology study on anti-stroke of Xiaoshuan Tongluo formula based on systematic compound-target interaction prediction models / 药学学报

Xiaoshuan Tongluo formula is effective in treating mental retardation and speech astringency caused by cerebral thrombosis, but its mechanism remains unclear. In this investigation, by collecting the chemical constituents from Xiaoshuan Tongluo formula and the targets related to stroke, we obtained 1 251 constituents from the formula and 10 drug targets related with stroke. We established 18 prediction models of compound-target interaction for 10 stroke-related targets, using molecular docking method and machine learning methods includes Naive Bayesian and recursive partitioning based on the input of molecular fingerprints and molecular descriptors. Using these models, we predicted the active chemical constituents from Xiaoshuan Tongluo formula and their drug targets, 153 potential active constituents were discovered, 22 among them could interact with at least two drug targets related with stroke. On this basis, the chemical constituent-target network was constructed using network construction software, and then the important metabolic pathways of the targets were identified by using Gene-Ontology (GO) enrichment analysis, such as blood coagulation, positive regulation of angiogenesis, positive regulation of ion transport and so on. On this basis, a target-pathway network was constructed. In conclusion, using machine learning, molecular docking, virtual screening, data mining and network construction, this study explored and partially revealed the active chemical constituents and chemical constituent-target-pathway network action mechanism of Xiaoshuan Tongluo formula against stroke, which will provide important information for its further study.

Effects of Ivermectin on Migration and Invasion of Human Gastric Cancer Cells BGC- 823 and MGC- 803 and Its Mechanism / 中国药房

OBJECTIVE： To study the effects of ivermectin on the migration and invasion of human gastric cancer cell lines BGC-823 and MGC-803 and its mechanism. METHODS： After treated with 0， 2.5， 5， 10， 20， 40 μmol/L ivermectin for 24 h， inhibitory rate of human gastric cancer cell lines BGC-823 and MGC-803 were detected by MTT assay. Effects of 5 μmol/L ivermectin and phosphate buffercontaining 0.67‰ dimethyl sulfoxide （control group） for 24 h on the migration and invasion of` gastric cancer cells BGC-823 and MGC-803 were observed by Transwell chamber invasion assay.Western blot assay was used to detect the protein expression of TGF-β1， TGF-βR， Smad2 and Smad3 in epithelial-mesenchymal transition （EMT） markers E-cadherin， N-cadherin， Vimentin， Snail and EMT transduction pathway TGF-β/smad of BGC-823 and MGC-803 cells after treated with 5， 10 μmol/L ivermectin and phosphate buffercontaining 0.67‰ dimethyl sulfoxide （control group） for 24 h. RESULTS： Ivermectin could inhibit the growth of BGC-823 and MGC-803， inhibitory rate of it was positively correlated with its concentration. Compared with control group， the number of migration and invasion BGC-823 and MGC-803 cells were decreased significantly after treated with 5 μmol/L ivermectin （P＜0.01 or P＜0.001）； the expression of E-cadherin protein was enhanced significantly in BGC-823 and MGC-803 cells after treated with 5 and 10 μmol/L ivermectin （P＜0.05 or P＜0.01 or P＜0.001）； the protein expression of N-cadherin， Vimentin， Snail， TGF-βR， Smad2 and Smad3 were decreased significantly （P＜0.05， P＜0.01 or P＜0.001）； protein expression of TGF-β1 was decreased significantly after treated with 10 μmol/L ivermectin （P＜0.05）. CONCLUSIONS： Ivermectin can significantly inhibit the migration and invasion of gastric cancer cells BGC-823 and MGC-803， and inhibiting the biological activity of EMT by reducing the expression of TGF-β/smad pathway is one of the mechanisms that inhibit the migration and invasion of gastric cancer cells.

Repositioning drug discovery for Alzheimer's disease based on global marketed drug data / 药学学报

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the life of the elderly and there is no effective therapy to treat or delay the onset of this disease. Due to the multifactorial etiology of this disease, the multi-target-directed ligand (MTDL) approach is an innovative and promising method in search for new drugs against AD. In order to find potential multi-target anti-AD drugs through reposition of current drugs, the database of global drugs on market were mined by an anti-AD multi-target prediction platform established in our laboratory. As a result, inositol nicotinate, cyproheptadine, curcumin, rosiglitazone, demecarium, oxybenzone, agomelatine, codeine, imipramine, dyclonine, melatonin, perospirone, and bufexamac were predicted to act on at least one anti-AD drug target yet act against AD through various mechanisms. The compound-target network was built using the Cytoscape. The prediction was validated by molecular docking between agomelatine and its multiple targets, including ADORA2A, ACHE, BACE1, PTGS2, MAOB, SIGMAR1 and ESR1. Agomelatine was shown to be able to act on all the targets above. In conclusion, the potential drugs for anti-AD therapy in the database for global drugs on market was partially uncovered using machine learning, network pharmacology, and molecular docking methods. This study provides important information for drug reposition in anti-AD therapy.

Influencing factors for venous patency rate in patients with deep venous thrombosis of lower limbs treated with inferior vena cava filter combined with catheter-directed thrombolysis / 新乡医学院学报

Objective To investigate the influencing factors for venous patency rate in patients with deep venous thrombosis(DVT) of lower limbs treated with inferior vena cava filter(IVCF) combined with catheter-directed thrombolysis.Methods A total of 120 patients with DVT of lower limbs who underwent IVCF combined with catheter-directed thrombolysis were selected from March 2014 to March 2017 in Zhumadian Central Hospital.The patients were divided into poor effect group (patency rate ＜ 50％) and good effect group (patency rate ≥ 50％) according to venous patency rate after treatment.The clinical data were compared between the two groups.The influencing factors for venous patency rate in patients with DVT of lower limbs after IVCF placement and catheter-directed thrombolysis were analyzed by logistic regression.Results Among the 120 pauems with DVT of lower limbs,the venous patency rate was less than 50％ in 62 cases (poor effect group),and the venous patency rate was equal to or greater than 50％ in 58 cases (good effect group).The proportion of patients with high blood pressure,diabetes mellitus and malignant tumor in good effect group was significantly lower than that in poor effect group (P ＜0.05);there was a significant difference in DVT staging and location between the two groups (P ＜ 0.05);the levels of platelet count,white blood cell count and plasma fibrinogen in good effect group were significantly lower than those in poor effect group (P ＜ 0.05).There was no significant difference in sex,age,operation history,trauma history and D-dimer level between the two groups (P ＞ 0.05).Multivariate logistic regression analysis showed that white blood cell count,plasma fibrinogen,DVT staging and location were the influencing factors for venous patency rate after IVCF placement and catheter-directed thrombolysis in patients with DVT of lower limbs (P ＜ 0.05);but hypertension,diabetes mellitus,malignant tumor and platelet count were not related to the venous patency rate (P ＞ 0.05).Conclusion White blood cell count,plasma fibrinogen,DVT staging and location are the influencing factors for venous patency rate after IVCF placement and catheter-directed thrombolysis in patients with DVT of lower limbs.Relevant measures should be formulated in order to improve the treatment effectiveness.

Network mechanism of effective constituents from the compound Yizhihao against influenza / 中国药理学与毒理学杂志

Influenza caused by influenza virus,seriously threaten human life and health.Drug treatment is one of the effective measurement. However, there are only two classes of drugs, one class is M2 blockers and another is neuraminidase (NA)inhibitors. The recent antiviral surveillance studies reported a global significant increase in M2 blocker resistance among influenza viruses, and the resistant virus strains against NA inhibitor are also reported in clinical treatment.Therefore thediscovery of new medicines with low resistance has become very urgent.As all known,traditional medicines with multi-target features and network mechanism often possess low resistance. Compound Yizhihao, which consists of radix isatidis,folium isatidis,Artemisia rupestris,is one of the famous traditional medicine for influenza treatment in China, however its mechanism of action against influenza is unclear. In this study, the multiple targets related with influenza disease and the known chemical constituents from Compound Yizhihao were collected, and multi-target QSAR (mt-QSAR) classification models were developed by Na?ve Bayesian algorithm and verified by various datasets. Then the classification models were applied to predict the effective constituents and their drug targets.Finally,the constituent-target-pathway network was constructed,which revealed the effective constituents and their network mechanism in Compound Yizhihao. This study will lay important basis for the clinical uses for influenza treatment and for the further research and development of the effective constituents.

Network mechanism on effective constituents from Polygala Tenuifolia for anti-Alzheimer Disease / 中国药理学与毒理学杂志

OBJECTIVE To clarify out the network pharmacology mechanism of Polygala tenuifolia against Alzheimer disease(AD).METHODS Firstly,we collected the chemical constituents from Polyg-ala tenuifolia and key targets toward AD.Machine learning algorithms were applied to construct classifi-ers for predicting the effective constituents. Secondly, docking models were utilized for further evalua-tion.Finally,we built constituent-target,target-target network and target-biology pathway network.RE-SULTS 104 chemical constituents Polygala tenuifolia from were collected.Through prediction of blood-brain penetration and validation,36 chemical constituents were selected among 100 chemical constitu-ents,their action targets mainly focused on AChE,COX-2,TNF-α,insulin-degrading enzyme and APP. Their main structure types include Polygala saponins, Polygala glycosides, Polygala shrubby ketones, polygala xanthones and sterols,which acted on AchE,APP,M-TAU,GSK3β and 5HT1A with high fre-quency.Gene-Ontology and KEGG enrichment analysis showed that the main pathways of these con-stituents involve in neurotransmitter release,synaptic conduction and synaptic plasticity,apoptosis reg-ulation,phosphorylation pathway,Ca2+signaling pathway,and so on.CONCLUSION This study uncov-ered a network mechanism of Polygala tenuifolia against Alzheimer disease,which may provide impor-tant information for the further study and new drug development.