Objective:To evaluate clinical efficacy of adjuvant radiotherapy (RT) for central neurocytoma (CN) after surgical resection.Methods:Clinical data of 136 CN patients admitted to Beijing Tiantan Hospital and Xuanwu Hospital from January 2001 to December 2020 were retrospectively analyzed. Preliminary interventions consisted of craniotomy (gross total resection, subtotal resection and partial resection, the latter two belonging to incomplete resection) and postoperative radiotherapy. Three-dimensional conformal or intensity-modulated radiotherapy was adopted, with a median radiotherapy dose of 54 Gy. Post-recurrence treatment included salvage surgery and radiotherapy. The overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Univariate analysis was performed by log-rank test to evaluate the effect of each prognostic factor on OS and PFS. The effects of multiple prognostic factors on PFS and OS were assessed by Cox regression model.Results:The median age was 28 years (range: 6-66 years). The median follow-up was 94.5 months (12-237 months). Among all patients, 79 cases underwent total resection, and 68 of them received adjuvant radiotherapy. Thirty-eight patients underwent subtotal resection, and 37 of them were treated with adjuvant radiotherapy. Sixteen patients received partial resection and adjuvant radiotherapy. Three cases received biopsy and postoperative radiotherapy. Among all patients, 3 cases died, including 2 from tumor recurrence and 1 from postoperative complication. Eight patients had recurrences during follow-up. Among them, 7 patients had recurrences at the primary site,1 had tumor dissemination to the spinal cord. The 5- and 10-year OS rates were 98.5% and 96.8%, and the 5- and 10-year PFS rates were 95.3% and 91.6% for the in the entire cohort. In the gross total resection without radiotherapy group, the 5- and 10-year PFS rates were 90.9% and 90.9%, and 96.6% and 96.6% in the gross total resection + radiotherapy group ( P=0.338). The 5- and 10-year OS rates were 100% and 100% in the gross total resection without radiotherapy group, and 98.5% and 98.5% in the gross total resection + radiotherapy group ( P=0.693). The 10-year PFS rates between the gross total resection±radiotherapy group and the incomplete resection+radiotherapy group was 95.8% vs. 90.3% ( P=0.368), and the 10-year OS rate was 98.6% vs. 94.7% ( P=0.436). Multivariate analysis showed that tumor site, degree of surgical resection, adjuvant radiotherapy and age exerted no significant effects on PFS and OS. A total of 81 patients had late neurotoxicities, including 69 cases at grade 1, 9 cases at grade 2, and 3 cases at grade 3. And 64.2% (52/81 cases) of patients suffered from short-term memory impairment. Conclusions:Gross total resection alone yields high efficacy for CN. Postoperative radiotherapy is not required. Incomplete resection combined with postoperative adjuvant radiotherapy can achieve equivalent clinical efficacy to gross total resection.

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.

ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach. MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team， an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases， including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， the Online Mendelian Inheritance in Man （OMIM）， and the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING）. Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges， the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets. ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium （DSS）-induced colitis in mice， which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 （IL-6） and interleukin-1β （IL-1β）（P<0.05）. Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis， 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores， prostaglandin-endoperoxide synthase 2（PTGS2） and mitogen-activated protein kinase 3（MAPK3） were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets. ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.

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.

Background::Biliary tract carcinoma (BTC) is relatively rare and comprises a spectrum of invasive tumors arising from the biliary tree. The prognosis is extremely poor. The incidence of BTC is relatively high in Asian countries, and a high number of cases are diagnosed annually in China owing to the large population. Therefore, it is necessary to clarify the epidemiology and high-risk factors for BTC in China. The signs associated with BTC are complex, often require collaborative treatment from surgeons, endoscopists, oncologists, and radiation therapists. Thus, it is necessary to develop a comprehensive Chinese guideline for BTC.Methods::This clinical practice guideline (CPG) was developed following the process recommended by the World Health Organization. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of evidence and make recommendations. The full CPG report was reviewed by external guideline methodologists and clinicians with no direct involvement in the development of this CPG. Two guideline reporting checklists have been adhered to: Appraisal of Guidelines for Research and Evaluation (AGREE) and Reporting Items for practice Guidelines in Healthcare (RIGHT).Results::The guideline development group, which comprised 85 multidisciplinary clinical experts across China. After a controversies conference, 17 clinical questions concerning the prevention, diagnosis, and treatment of BTC were proposed. Additionally, detailed descriptions of the surgical principles, perioperative management, chemotherapy, immunotherapy, targeted therapy, radiotherapy, and endoscopic management were proposed.Conclusions::The guideline development group created a comprehensive Chinese guideline for the diagnosis and treatment of BTC, covering various aspects of epidemiology, diagnosis, and treatment. The 17 clinical questions have important reference value for the management of BTC.