Objective To explore the situation of impaired cardiac microcirculatory perfusion,left ventricular remodeling and myocardial fibrosis in patients with essential hypertension(abbreviated as hypertension)and their clinical significance.Methods Eighty patients with hypertension were selected as hypertension group,and another 80 healthy individuals who underwent physical examina-tions during the same period were selected as control group.Based on the severity of hypertension,patients in the hypertension group were divided into low-risk group and moderate-to-high-risk group.The indicators of impaired cardiac microcirculatory perfusion[left ventricular myocardial blood flow(MBF),right ventricular MBF,coronary flowreserve(CFR)],left ventricular remodeling[left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV)]and myocardial fibrosis[left ventricular isovolumic relaxation time(IVRT),the ratio of the peak velocity of E wave to A wave in the diastolic blood flow spectrum of the mitral valve orifice(E/A),type Ⅰ procollagen carboxy-terminal peptide(P Ⅰ CP),type Ⅲprocollagen amino-terminal peptide(PC Ⅲ)]were compared between the control group and the hy-pertension group.Pearson's correlation coefficient method was used for correlation analysis.The differences in the above-mentioned indicators among different risk groups were compared.Receiver operating characteristic(ROC)curves were drawn to evaluate the diagnostic efficacy of impaired cardiac microcirculatory perfusion,left ventricular remodeling and myocardial fibrosis for the severity of hypertension.Results In the hypertension group,left ventricular MBF,right ventricular MBF and CFR were all lower than those in the control group,LVEDV and LVESV were larger than those in the control group,LVEF was lower than that in the control group,IVRT was longer than that in the control group,the levels of P Ⅰ CP and PC Ⅲ were higher than those in the control group,and E/A was lower than that in the control group(P＜0.05).The results of Pearson's correlation coef-ficient analysis showed that LVEF was positively correlated with CFR and E/A,and negatively cor-related with IVRT and PC Ⅲ;LVEDV was positively correlated with CFR,IVRT,P Ⅰ CP and PCⅢ;LVESV was positively correlated with IVRT,P Ⅰ CP and PC Ⅲ,and negatively correlated with E/A;left ventricular MBF was positively correlated with CFR and E/A,and negatively correlated with IVRT,P Ⅰ CP and PC Ⅲ;right ventricular MBF was positively correlated with CFR and E/A,and negatively correlated with IVRT,P Ⅰ CP and PC Ⅲ.In the moderate-to-high-risk group,IVRT was longer than that in the low-risk group,LVEDV was larger than that in the low-risk group,P ⅠCP,PC Ⅲ,E/A,LVEF,left ventricular MBF,right ventricular MBF and CFR were all lower than those in the low-risk group,and LVESV was smaller than that in the low-risk group,with statistical-ly significant differences(P＜0.05).The results of ROC curve analysis showed that the areas under the curves for diagnosing the severity of hypertension by impaired cardiac microcirculatory perfusion,left ventricular remodeling and myocardial fibrosis were 0.962,0.969 and 0.945 respectively,the sensitivities were 91.4％,97.1％and 88.6％respectively,and the specificities were 95.6％,88.9％and 93.3％respectively.Conclusion Hypertension can cause impaired cardiac microcirculatory perfusion and promote the processes of left ventricular remodeling and myocardial fibrosis.Impaired cardiac microcirculatory perfusion,left ventricular remodeling and myocardial fibrosis have good di-agnostic efficacy for the severity of hypertension.

Hypervirulent Klebsiella pneumoniae (hvKP) is a highly virulent variant of Klebsiella pneumoniae and can cause systemic invasive infection. The worldwide prevalence of hvKP infection continues to increase. Diabetic patients, especially those with poor glucose control, are at a higher risk for hvKP infection. The infection of hvKP in diabetic patients is characterized by high incidence, rapid progression and high fatality rate. The mechanisms underlying the susceptibility to hvKP in patients with diabetes include hyperglycemia-induced bacterial translocation, endothelial-epithelial barrier damage, immune evasion, high-load bacteremia, microthrombosis and hvKP carbon/iron metabolism-based regulation of virulence. A thorough understanding of the mechanisms underlying the susceptibility to hvKP in diabetic patients will be great significant to further improve clinical understanding and attention, and provide early prevention and effective diagnosis and treatment. This article summarizes the progress in the mechanisms of susceptibility to hvKP in diabetic patients in recent years.

Objective To explore the clinical value of noninvasive left ventricular pressure-strain loop(LV-PSL)technique in evaluating myocardial work and left ventricular remodeling before and after percutaneous coronary intervention(PCI)in patients with acute myocardial infarction(AMI).Methods Seventy patients with AMI admitted to our hospital(coronary heart disease group)and 50 healthy adults(control group)who underwent physical examination during the same period were selected,The conventional echocardiographic indexes,left ven-tricular global longitudinal strain(GLS)and left ventricular myocardial work indexes,[global work index(GWI),global work efficiency(GWE),global constructive work(GCW),global wasted work(GWW)]were examined before and 7 days after operation in control group and coronary heart disease group.The differences of the above indexes between the coronary heart disease group and control groups were compared.According to the results of coronary angiography,AMI patients were further divided into a coronary heart disease single-branch group(34 cases)and a coronary heart disease multi-branch group(36 cases),and the differences of the above indexes between the two groups were compared.Analyze the correlation between left ventricular myocardial work indexes and GLS,conventional echocardiographic indexes.Result Left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume(LVEDV)and GWW were higher incoronary heart disease group than in control group before and 7 days after surgery,while left ventricular ejection fraction(LVEF),GWI,GWE,GCW and GLS were lower than control group,with statistical significance(all P<0.05).At 7 days after surgery,LVESV,LVEDV and GWW in the coronary heart disease group were lower than those before surgery,while LVEF,GWI,GWE,GCW and GLS were higher than those before surgery,with statistical significance(all P<0.05).LVESV,LVEDV and GWW at 7 days before and after surgery in the coronary heart disease multi-branch group were higher than those in the coronary heart disease single-branch group,while LVEF,GWI,GWE,GCW and GLS were lower than those in the coronary heart disease single-branch group,with statistical significance(all P<0.05).Correlation analysis showed that GWW was negatively correlated with GLS and LVEF,while GWE,GCW and GWI were positively correlated with GLS and LVEF(all P<0.001).Conclusion LV-PSL technique has good application value in evaluating left ventricular function and left ventricular remodeling in AMI patients before and after PCI,and provides a new non-invasive method for clinical practice.

Qizhi Weitong granules composed of Bupleuri Radix， Paeoniae Radix Alba， Aurantii Fructus， Cyperi Rhizoma （processed）， Corydalis Rhizoma （processed）， and Glycyrrhizae Radix et Rhizoma have the effects of soothing the liver， regulating Qi movement， and harmonizing the stomach to relieve pain. This preparation is thus used for the treatment of liver depression， Qi stagnation， chest distension， and epigastric pain. It has become a first-line medication for the treatment of epigastric pain after years of clinical practice. At present， researchers have carried out extensive studies on Qizhi Weitong granules， including the optimization of the extraction and purification process， identification of chemical components， characterization of absorbed components， establishment of quality control methods， validation of pharmacological effect on digestive system diseases， exploration of the mechanism， and observation of clinical efficacy. The studies have achieved fruitful results. This article summarizes the research achievements related to Qizhi Weitong granules in recent years from pharmacological substances， quality control， pharmacological effect， mechanism of action， and clinical efficacy， aiming to provide ideas for in-depth research and modern development of Qizhi Weitong granules.

ObjectiveTo elucidate the pharmacodynamic substances responsible for the anti-inflammatory and analgesic effects of Cyperi Rhizoma by structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， this study explored the in vivo efficacy of the flavonoids in Cyperi Rhizoma. The flavonoids in Cyperi Rhizoma and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， and available articles. The targets of the anti-inflammatory and analgesic effects were collected from DisGeNET and Online Mendelian Inheritance in Man （OMIM）. The common targets shared by flavonoids and the effects were selected as the direct targets of flavonoids endowing Cyperi Rhizoma with anti-inflammatory and analgesic effects， and protein-protein interaction （PPI） network of the core targets was constructed. The method of structure-activity omics was employed to correlate the structure and efficacy of one or more classes of chemical components in Cyperi Rhizoma with the targets as a bridge. The components were classified according to structure. Molecular docking of components to core targets was carried out via SYBYL-X 2.1.1， PyMol， and Discovery Studio 4.5 visualizer. Two targets with the highest binding affinity were selected to explore the relationship between compound structures and targets. ResultThe flavonoids in Cyperi Rhizoma exerted anti-inflammatory and analgesic effects on the mouse model of pain induced by formaldehyde. Eighteen components and 115 direct targets were screened out， and the core targets with high activities were protein kinase B1 （Akt1）， interleukin-1β （IL-1β）， cellular tumor antigen p53 （TP53）， prostaglandin-endoperoxide synthase 2 （PTGS2）， and matrix metalloproteinase-9 （MMP-9）. According to the structures， the flavonoids in Cyperi Rhizoma were classified into bioflavonoids， flavonols， flavones， and flavanes. The molecular docking results showed that flavonoids of Cyperi Rhizoma had the highest binding affinity to TP53 and PTGS2. The results of structure-activity omics showed that bioflavonoids represented the best binding structure to the targets， while their polyhydroxyl etherification resulted in a significant decrease in the binding affinity to PTGS2. Glycosides had higher binding affinity to PTGS2. The introduction of the long-chain hydrocarbon group to the A ring of flavonols facilitated the binding to TP53， while the change of B ring substituents was not the main factor affecting the binding affinity. The 3，4-dihydroxyl flavane outperformed 3-hydroxyl flavane in the binding to TP53， while the two compounds showed similar binding affinity to PTGS2. ConclusionThe method of structure-activity omics was used to analyze the material basis for the anti-inflammatory and analgesic effects of flavonoids in Cyperi Rhizoma. Structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo reveal the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma by structure-activity omics. MethodOn the basis of the previous study about the screening of active components in vitro， this study explored the effects of flavonoids in Glycyrrhizae Radix et Rhizoma in vivo. The flavonoids in Glycyrrhizae Radix et Rhizoma and their direct targets for the anti-inflammatory and analgesic effects were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， PharmMapper， Swiss TargetPrediction， DisGeNET， and Online Mendelian Inheritance in Man （OMIM）. STRING and Cytoscape 3.7.2 were employed to establish the protein-protein interaction （PPI） network of key targets. Molecular docking was performed to simulate the binding of five targets with high degrees to flavonoids in Glycyrrhizae Radix et Rhizoma， on the basis of which the key core targets were selected. The targets were used as a bridge to correlate the structures and effects of one or more classes of chemical components in Glycyrrhizae Radix et Rhizoma. According to the binding affinity between flavonoids with different structures in Glycyrrhizae Radix et Rhizoma and targets， the relationships between compound structures and core targets were discussed. ResultThe flavonoids in Glycyrrhizae Radix et Rhizoma reduced the content of prostaglandin E₂ （PGE₂） in the rat model of pain induced by formalin， demonstrating definite anti-inflammatory and analgesic effects. Sixty active compounds （flavonoids） with anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma were obtained. With the total score as the standard， prostaglandin-endoperoxide synthase 2 （PTGS2） and mitogen-activated protein kinase 3 （MAPK3） were selected as the key core targets of Glycyrrhizae Radix et Rhizoma for the anti-inflammatory and analgesic effects. Except that flavones showed selectivity of binding to MAPK3， the other flavonoids of Glycyrrhizae Radix et Rhizoma showed strong binding to PTGS2 and MAPK3， and the structures containing glycoside fragments showed stronger binding affinity to the targets. The introduction of chain olefins in the ring of chalcones facilitated the binding to the targets. The isopentenyl fragment in flavonols may cause the difference in binding affinity. The parallel combination of a ring into pyran ring in flavanes was not conducive to the binding to the target. The electric charge， liposolubility， and steric hindrance of the substituent group on the B ring of isoflavones directly affected the binding affinity. ConclusionThis study adopts structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Glycyrrhizae Radix et Rhizoma. Structure-activity omics provides new ideas and methods for predicting the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo elucidate the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba from structure-activity omics. MethodOn the basis of the previous in vitro efficacy study by our research group， a mouse model of foot swelling was induced by methyl aldehyde and used to study the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba in vivo. The core targets of the active compounds for the anti-inflammatory and analgesic effects of Paeoniae Radix Alba were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. Molecular docking was conducted for the total glucosides of Paeoniae Radix Alba with the core targets， and the key core targets with high binding affinity were screened out according to the comprehensive score of each target and active structure. The structure-activity relationship was analyzed with targets as a bridge through the combination of compound structures and pharmacological effects. ResultThe total glucosides of Paeoniae Radix Alba had good anti-inflammatory and analgesic effects in vivo. The core targets of 23 active components of Paeoniae Radix Alba were epidermal growth factor receptor （EGFR）， signal transducer and activator of transcription 3 （STAT3）， vascular endothelial growth factor A （VEGFA）， cellular tumor antigen p53 （TP53）， and proto-oncogene transcription factor （JUN）. According to the structure of the parent nucleus， there were 16 pinane monoterpene glycosides， 4 pinene monoterpene glycosides， 2 monoterpene lactone glycosides， and 1 monoterpene ketone. The key core targets screened out by molecular docking were EGFR and STAT3. The structure-activity analysis of the active compound structures and the key core targets showed that the introduction of ketone group and benzene ring group on the parent nucleus affected the binding activity. ConclusionThis study analyzed the material basis for the anti-inflammatory and analgesic effects of total glycosides of Paeoniae Radix Alba from structure-activity omics， providing new ideas and methods for revealing the pharmacodynamic substances in traditional Chinese medicine.

The complex chemical composition and limited research ideas of traditional Chinese medicine （TCM） have led to the unclear material basis and mechanism of the medicinal effects， which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study， we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore， a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM， thus promoting the modern research and the innovative development of TCM.

ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics. MethodOn the basis of the previous in vitro screening study， we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge， the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids， a study of structure-activity omics was carried out to summarize the rules of their connection. ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo， involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain， and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction （PPI） and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine， and the core targets were prostaglandin endoperoxide synthase 2 （PTGS2）， glutamate receptor metabotropic 5 （GRM5）， estrogen receptor 1 （ESR1）， solute carrier family 6 member 4 （SLC6A4）， and fusion oncoproteins （FOS）. According to the differences of mother nucleus， the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories， including protoberberine， berberine， and aporphine， which had high binding affinities with PTGS2， GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine， appropriate substituents with hydroxyl， alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine， the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues， which greatly improves the binding affinity. ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma， and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E₂ （PGE₂） in the mouse model， showcasing a significant inhibitory effect on the inflammatory pain caused by PGE₂. Nine components and 39 targets of saikosaponins， as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out， and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction （PPI） analysis showed that the main active components of Bupleurum Radix were saikosaponins a， b₁， b₂， b₃， c， d， e， f， and v， and the key targets were fms-related receptor tyrosine kinase 1 （FLT1）， kinase insert domain receptor （KDR）， fibroblast growth factor 2 （FGF2）， vascular endothelial growth factor A （VEGFA）， and signal transducer and activator of transcription 3 （STAT3）. Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks， including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo， providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.