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.

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.

Objective To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.Methods C57Thy1-YFP/GAD67-GFP mice were randomized into control group(with no treatment)and chronic unpredictable mild stress(CUMS)group(n=15)subjected to CUMS for 8 weeks.Depression-like behaviors of the mice were assessed using sucrose preference test,open field test,and forced swimming test,and their spatial learning and memory abilities were evaluated using Morris water maze test.The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala(CeA)and the prelimbic cortex(PrL)using whole-cell patch-clamp technique.Results Compared with the control mice,CUMS mice showed significantly decreased sucrose preference,total distance moved,number of grid-crossings,entries into the central area,and time spent in the central area in the open field test(P<0.01).In the forced swimming test,CUMS mice exhibited obviously shortened time of struggling,swimming,and climbing with increased immobility time.In Morris water maze test,CUMS mice showed significantly increased escape latency and path length,decreased percentage of distance and swimming time within the target quadrant,and increased first entry latency into the target zone and swimming time within the opposite quadrant.Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL,while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.Conclusion CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

Objective To explore the relationship between alterations of neural network plasticity and spatial learning and memory functions in mouse models with depression-like behaviors.Methods C57Thy1-YFP/GAD67-GFP mice were randomized into control group(with no treatment)and chronic unpredictable mild stress(CUMS)group(n=15)subjected to CUMS for 8 weeks.Depression-like behaviors of the mice were assessed using sucrose preference test,open field test,and forced swimming test,and their spatial learning and memory abilities were evaluated using Morris water maze test.The changes in the firing patterns of different neuronal subtypes were detected in the central nucleus of the amygdala(CeA)and the prelimbic cortex(PrL)using whole-cell patch-clamp technique.Results Compared with the control mice,CUMS mice showed significantly decreased sucrose preference,total distance moved,number of grid-crossings,entries into the central area,and time spent in the central area in the open field test(P<0.01).In the forced swimming test,CUMS mice exhibited obviously shortened time of struggling,swimming,and climbing with increased immobility time.In Morris water maze test,CUMS mice showed significantly increased escape latency and path length,decreased percentage of distance and swimming time within the target quadrant,and increased first entry latency into the target zone and swimming time within the opposite quadrant.Exposure to CUMS resulted in significantly enhanced energy barrier and increased absolute refractory period and inter-spike interval of glutamatergic neurons in the CeA and GABAergic neurons in the PrL,while the opposite changes were observed in GABAergic neurons in the CeA and glutamatergic neurons in the PrL.Conclusion CUMS-induced depression may lead to plastic changes in the excitatory and inhibitory neuronal networks within the CeA and PrL to cause impairment of spatial learning and memory abilities in mice.

Objective:To investigate the clinical effect of posterior fossa decompression combined with dural reconstruction in the treatment of Chiari malformation-Ⅰ(CM-Ⅰ) complicated with syringomyelia (SM).Methods:The clinical data of 50 patients with CM-Ⅰ complicated with SM who were treated in Yan′an University Xianyang Hospital from June 2019 to January 2021 were analyzed. They were divided into the study group (27 cases) and the control group (23 cases) according to the surgical methods. The former received posterior fossa decompression combined with dural reconstruction, while the latter received posterior fossa decompression alone. The clinical symptom improvement, neurological function, cerebrospinal fluid dynamics and syringomyelia changes were compared between the two groups before and after the surgery, and postoperative complications were compared.Results:The overall clinical symptom improvement rate between the two groups had no significant difference ( P> 0.05). After the surgery, the scores of pain, sensory disturbance, dyskinesia and ataxia in the study group were higher than those in the control group: (4.56 ± 0.35) points vs. (4.28 ± 0.43) points, (3.61 ± 0.82) points vs. (3.15 ± 0.73) points, (3.81 ± 0.44) points vs. (3.59 ± 0.50) points, (4.43 ± 0.41) points vs. (4.09 ± 0.53) points, there were statistical significant ( P<0.05). After the surgery, the cerebrospinal fluid stroke volume (SV) and mean flow (MF) in the study group were higher than those in the control group: (0.05 ± 0.02) ml vs. (0.04 ± 0.01) ml, (0.05 ± 0.01) ml/s vs. (0.04 ± 0.01) ml/s; the maximum peak flow velocity (V max) of the head and tail in the study group were lower than those in the control group: (3.14 ± 1.05) mm/s vs. (3.87 ± 1.13) mm/s, (5.56 ± 1.38) mm/s vs. (6.43 ± 1.22) mm/s, there were statistical significant ( P<0.05). There were no significant differences in the rate of reduction or disappearance of syringomyelia, the rate of no change and the rate of increase of syringomyelia after the surgery between the two groups ( P>0.05). There was no significant difference in the incidence of postoperative complications between the two groups ( P>0.05). Conclusions:Posterior fossa decompression combined with dural reconstruction in CM-Ⅰ complicated with SM can better improve cerebrospinal fluid dynamics, and promote the reduction of syringomyelia without increasing postoperative complications.

Objective To analyze the similarities and differences between four-point hand-knee position and hand-foot kneeling positions in trunk muscle activation and co-contraction, explore the possibility of hand-foot kneeling position as core stabilization exercises, so as to provide suggestions for actual training.Methods Nineteen healthy volunteers randomly performed exercises of four-point hand-knee position (4 motions) and hand-foot kneeling position (3 motions), while surface electromyography (sEMG) signals were collected from bilateral rectus abdominis, external oblique, erector spine, and multifidus muscles. The average sEMG and muscle co-contraction index (CCI) based on the sEMG signals were analyzed and compared.Results Significant differences were found in the sEMG and CCI within and between the two positions. Under four-point hand-knee position with the right hand and left leg lifting, the activation of all muscles was higher than that in the starting position. In four-point hand-knee position with the left leg lifting, the activation of ipsilateral multifidus muscle was significantly higher than that in hand-foot kneeling position. The activation degree of external oblique muscle and rectus abdominis was higher in hand-foot kneeling position with right hand lifting. A total of 28 muscle matching methods were obtained by pair-to-pair matching of 8 muscles. The starting posture in four-point hand-knee position fluctuated the least, indicating that the spine was the most stable, while the index of other exercises fluctuated in a larger range.Conclusions The possibility of hand-foot kneeling position as core stabilization exercises was proved from two aspects, namely, muscle activation and CCI. The hand-foot kneeling position and four-point hand-knee position can be used for strengthening abdominal muscles and back muscles, respectively. The four-point hand-knee position with contralateral upper and lower limbs lift is a more advanced exercise for trunk muscles, but sports injuries should be avoided.

Objective:To evaluate the efficacy of robot-assisted partial nephrectomy (RAPN)and laparoscopic partial nephrectomy(LPN)in the treatment of giant (>7cm) renal angiomyolipoma (RAML).Methods:The clinical data of 43 patients with giant RAML(>7cm) who underwent surgery in Zhejiang People's Hospital from October 2014 to May 2020 was retrospectively analysed, including 23 routine RAPN and 20 routine LPN. The median age of patients in the RAPN group was 45(17-65) years old, with 4 males and 19 females.The median body mass index(BMI) was 20.3(18.0-25.7) kg/m 2. Tumors located on the left side in 11 cases and on the right side in 12 cases. Tumors located on upper pole in 9 cases, middle pole in 5 cases , lower pole in 5 cases. The median R. E.N.A.L. score was 8(4-12) points and the largest tumor diameter was 7.5(7.1-17.0) cm. The median age of patients in the LPN group was 53(27-78) years old, with 1 males and 19 females. The median BMI was 21.4(19.0-25.5) kg/m 2. Tumors located on the left side in 9 cases and right side in 11 cases. Tumors located on the upper pole in 7 cases, middle pole in 4 cases and lower pole in 5 cases. 4 cases were multiple tumors, 2 cases were bilateral, and 2 cases were unilateral. The median R. E.N.A.L. score was 8(4-12) points and the median maximum diameter of tumor was 7.3(7.0-20.0) cm. There was no statistically significant difference in general information between the two groups ( P>0.05). The operation time, warm ischemia time, intraoperative blood loss, postoperative complications, postoperative recovery, renal function and other indicators of the two groups were compared, as well as the follow-up results. Results:The operations in both groups were successfully completed, and none of them were transferred to open surgery. Patients in the RAPN group had markedly lower median operation time [115(90-220) vs.145(120-240) min], and reduced median time of warm ischemia [15(10-25) vs. 23(20-28) min] than those in the LPN group, the difference between the two groups was statistically significant ( P<0.05). There were no significant differences in the median time of eating [1(1-2) vs. 1(1-3)d], time of extubation [4(3-16) vs. 5(3-14)d], postoperative absolute time in bed [4(3-7) vs. 4(2-12)d], hospitalization time [7(5-16) vs. 8(4-14)d], creatinine change[11.3(1.6-44.8) vs. 18.2(1.0-54.8)μmol/L], eGFR change [21.5(1.8-43.5) vs. 22.1(5.6-51.3) ml/(min·1.73m 2)], and hemoglobin change[22.5(11-43) vs. 23.0 (9-62) g/L] between the two groups( P>0.05). The incidence of postoperative complications in the RAPN group and the LPN group were 0 and 15%(3/20), respectively, and the difference was statistically significant ( P<0.05). 3 patients had blood transfusion during the operation, because 2 patients had renal wound hemorrhage. During the operation, ultrasonic scalpel electrocoagulation to halt bleeding and hemostatic cotton padding were performed, which improved after suture. One case had active hemorrhage from the renal wound arteries after surgery, which improved after blood transfusion and embolization. Another 2 patients had postoperative fever, improved after anti-infection and antipyretic treatment. There was no leakage of urine after operation in RAPN group and LPN group. The RAPN group was followed up for 6 months to 45 months with a median time of 12 months, and the LPN group was 8 months to 50 months with a median time of 15 months. No tumor recurrence or delayed renal stump bleeding was identified. Conclusions:Compared with LPN, RAPN therapy of giant RAML can shorten the operation time and warm ischemia time, and decrease postoperative complications, the two have similar short-term follow-up results in terms of tumor control and renal function protection.