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 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.

Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(＜3％),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P＜0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P＜1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

Objective:To evaluate oncological and reproductive outcomes of women ≤40 years undergoing fertility-sparing surgery (FSS) for stage Ⅱ or Ⅲ borderline ovarian tumor (BOT).Methods:The patients with BOT and ≤40 years old with stage Ⅱ-Ⅲ BOT who underwent FSS enrolled from the First Affiliated Hospital of Zhengzhou University between January 2011 and March 2023 were analyzed retrospectively. The clinical data and follow-up results were obtained and analyzed. The univariate and multivariate Cox proportional hazard regression analysis were used to explore high-risk factors associated with prognosis. Additionally, pregnancy outcomes were also analyzed.Results:(1) A total of 79 patients with stage Ⅱ-Ⅲ BOT who have been treated with FSS were conducted, with an average age of (27.5±6.7) years old. The median tumor maximum diameter were 10.4 cm (range: 4.8-90.0 cm). The International Federation of Gynecology and Obstetrics (FIGO) stage was stage Ⅱ in 45 cases and stage Ⅲ in 34 cases. According to the pathological types, there were 48 cases of serous tumor, 21 cases of mucinous tumor, 1 case of endometrioid tumor, and 9 cases of mixed types. There were 41 cases of unilateral ovarian involvement, 38 cases of bilateral ovarian involvement. There were 5 cases of microinvasion, 17 cases of micropapillary subtype. Extra-ovarian invasive implants were found in 5 cases, and there were 31 cases of merged ascites. (2) Tumor outcomes: the median follow-up time from primary cytoreduction were 58 months (range: 8-146 months). At the end of the observation period, 24 cases (30%, 24/79) recurred, among them 5 cases had two recurrences and 2 cases had three recurrences. There were 2 cases (3%, 2/79) of death and 1 case (1%, 1/79) of survival with tumor. (3) Analysis of prognostic risk factors: the results of univariate analysis showed that mucinous tumor, tumor maximum diameter >13.15 cm, FIGO stage Ⅲ, merged ascites, micropapillary subtype, invasive implantation, and bilateral ovarian involvement were independent risk factors (all P<0.05) for disease-free survival (DFS). FIGO stage Ⅲ ( HR=4.555, 95% CI: 1.525-13.607; P=0.007) and micropapillary subtype ( HR=2.396, 95% CI: 1.003-5.725; P=0.049) were found to be related to DFS through the multivariable Cox proportional hazard regression analysis. (4) Pregnancy outcomes: among the patients with fertility intentions 36 cases (46%,36/79), 29 cases (81%, 29/36) had successful pregnancies, and 27 cases (75%, 27/36) had successful births. Conclusions:Patients with stage Ⅱ-Ⅲ BOT underwent FSS have favorable survival and pregnancy rates. Micropapillary subtypes and FIGO staging (stage Ⅲ) are the significant risk factors of DFS.

Among the supplementary applications for Chinese medicines， additional specifications of pills occupy a certain proportion. It is common situation that addition of water honey pills and water pills on the basis of honey pills. Due to the ingredients of Chinese medicine are complex， and honey may be related to the safety and effectiveness of the preparation as a special excipient. Therefore， the necessity of the change should be considered from multiple perspectives and aspects in combination with the characteristics of the pills， and the scientific and reasonable nature of the change should be proved through research. By thinking deeply of the review of the application for adding water honey pill and water pill specification supplement to honey pill， the author discusses the key contents that need to be paid attention to in pharmaceutical research of such changes， and puts forward the following suggestions：①The necessity of change should be considered in combination with clinical drug demand and benefit-risk ratio. ②Attach importance to the research on the change of process and excipient， and evaluate the impact of changes on drug safety and effectiveness. ③Strengthen quality and stability research， and select appropriate packaging materials to ensure stable and controllable sample quality after change. ④Reasonably expression of specifications and loading specifications.

Objective To understand the pathogenicity and multilocus sequence typing (MLST) characteristics of the pathogenic strain of Burkholderia pseudomallei (Bp) in Hainan,and provide a reference for studying the structural characteristics and phylogenetic characteristics of pathogenic Bp in Hainan.Methods The data of patients with melioidosis in Hainan,who were treated in Hainan General Hospital from 2011 to 2018,and Bp pathogenic strains isolated from patient infected specimens were collected.The Bp pathogenic strains were genotyped by MLST method,and the distribution characteristics of the sequence type (ST) were analyzed.The ST of all Bp pathogenic strains was analyzed by eBURST v3 software to establish the evolutionary relationship map.Results A total of 91 cases of melioidosis patients were studied,including 76 males and 15 females;the ages were mainly concentrated in 40-70 years old;clinical manifestations included sepsis,pulmonary infection and local abscess;and the most common diseases were diabetes.A total of 91 Bp pathogenic strains were observed,of which 85 Bp pathogenic strains were distributed in coastal areas of Hainan,accounting for 93.41％;identified by MLST method,39 ST were discovered,the most common were ST46 (13 strains),ST55 (12 strains),STS0 (8 strains) and ST58 (7 strains),accounting for 14.29％,13.19％,8.79％ and 7.69％,respectively;except ST46 was widely distributed in the coastal areas of Hainan,the ST55,ST50 and ST58 were concentrated in the southwest,northeast and southeast regions of Hainan.Compared with the MLST database,ST30 (3 strains) was currently found only in Hainan,ST562 (4 strains) had been reported in northern Australia,and the remaining ST models had been reported in southeast Asia.The eBURST v3 software divided the 39 ST into 3 subtypes and 18 individual types.Among them,the subtypes with ST300 as the original type had the most number of ST,including 17 ST,57 Bp pathogenic strains;compared with the MLST database,the ST300 was mainly distributed in southeast Asian regions such as Thailand.Conclusions The ST of Bp pathogenic strains in Hainan has high regional diversity and genetic diversity,and is closely related to Bp in southeast Asian regions such as Thailand.

Objective:To explore the changes of number of CD4+ CD25 + foxp3 + regulatory T cells (Treg)and natural killer cells (NK)in the peripheral immune organs and tumor tissue of the murine models of lung cancer,and to clarify their effects on the development of lung cancer.Methods:The C57BL/6 mice were divided into Lewis lung carcinoma cells (LLC)injection group and normal control group.The mice in LLC injection group were injected with LLC subcutaneously in the armpit to establish the tumor models,while the mice in normal control group were injected with the same amount of saline.The number of CD4+ CD25 + T cells,CD4+ CD25 + foxp3 + Tregs in the spleen,lymph nodes and lung cancer tissues,and the number of NK cells in the spleen tissue were labeled by cell surface or intracellular antibody staining,and detected by flow cytometry.Results:The ratios of CD4+ CD25 + T cells to CD4+ T cells,foxp3+ cells to CD4+ CD25 + T cells,and the number of CD4+ CD25 + foxp3 + Treg in the spleen and lymph nodes of the mice in LLC injection group were increased significantly compared with normal control group (P <0.05 or P <0.01).Moreover,the ratios of CD4+ CD25 + T cells to CD4+ T cells and foxp3 + cells to CD4+ CD25 + T cells in the tumor tissue were significantly higher than those in the spleen and lymph nodes of the mice in LLC injection group.However,the ratio of NK cells in the spleen tissue of the mice in lung cancer group was significantly decreased compared with normal control group (P <0.05).Conclusion:The increase of ratio and the number of Treg cells and the decrease of ratio of NK cells in the main immune organs of lung cancer mice may promote the development of tumor and inhibit the immune response to cancer cells in vivo .