Objective:To explore the safety and feasibility of the simultaneous combined operation in children with congenital heart disease complicated with non-cardiac malformation.Methods:A total of 72 children undergoing combined surgery or simple heart surgery in the Department of Cardiac Surgery, Children′s Hospital, Capital Institute of Pediatrics from January 2017 to January 2019 were enrolled.According to the severity of the disease, patients in the combined operation group (group A) and the simple heart surgery group (group B) were separately subdivided into the low risk group (group L) and the high risk group (group H). There were 36 children in group A, with the age ranging from 1.5 to 168.0 months old (median: 18.0 months). There were 36 cases in group B, with the age ranging from 1.0 to 170.0 months old (median: 19.0 months). Patients in groups A and B were sent to the cardiac intensive care unit(ICU) after operation.The cardiopulmonary bypass (CPB) time, aortic clamping (ACC) time, tracheal intubation time, intensive care unit (ICU) retention time, brain natriuretic peptide (BNP), alanine aminotransferase (ALT) and creatinine (Cr) were recorded.Besides, the cardiac output index (CI), cardiac circulation efficiency (CCE), maximum pressure gradient (dp/dt), lactic acid (Lac), blood glucose (Glu), inotropic score (IS) were also recorded at the time of returning to ICU (T0), 4 hours after operation (T1), 8 hours after operation (T2), 12 hours after operation (T3), 24 hours after operation (T4) and 48 hours after operation (T5), respectively.Results:(1) Intra-group comparison in group A: the age [(39.9±37.0) months], height [(94.1±20.1) cm] and weight [(14.4±6.7) kg] of children at low risk (group L-A) were significantly higher than those at high risk (group H-A) [(7.5±3.7) months, (68.1±6.4) cm, (7.8±2.2) kg] (all P<0.01). The CPB time [(37.0±23.6) min], ACC time [(19.1±13.4) min], endotracheal intubation time [(7.1±4.7) h], ICU retention time [(1.1±0.3) d] and BNP 24 hours after operation [(2 257.3±952.0) ng/L] in group L-A were significantly lower than those in group H-A [(84.7±28.4) min, (41.9±30.7) min, (71.0±67.6) h, (8.7±5.7) d and (5 327.2±992.9) ng/L] (all P<0.01). Glu, IS, CI, CCE were significantly different between patients at low risk and patients at high risk ( P<0.05). At the time of T0-T5, the Glu( F=4.43, P<0.05) and IS ( F=26.99, P<0.01)of group L-A were lower than those of group H-A, and the CI ( F=18.39, P<0.01)and CCE ( F=5.28, P<0.05) of group L-A were higher than those of group H-A.(2) Comparison between groups A and B: there was no significant difference in age, height, weight, CPB time, ACC time, hemodynamic parameters, arterial blood gas parameters and postoperative clinical indexes between patients at high risk or patients at low risk in group A and group B (all P>0.05). Conclusions:(1) For the patients at low risk, hemodynamics remains stable after the combined operation.The combined operation does not increase the endotracheal intubation time and ICU retention time, so it is safe and feasible.(2) For the patients at high risk, hemodynamics is also stable after the combined operation.However, their IS is higher than that of patients at low risk at any time point, and the incidence of postoperative adverse events is higher than that of patients at low risk.It is necessary to evaluate the condition and operation plan of the children before operation.

Objective:To explore the tricuspid annular plane systolic excusion(TAPSE) in children with left-to-right shunt after congenital heart disease surgery and to understand the early systolic function of right heart in thesepatient.Methods:From June 2018 to December 2018, a prospective study was conducted in 20 infants after repair of left-to-right shunt congenital heart disease, including 10 males(50%) and 10 females(50%) , aged from 1 to 12 months, with a median of 4.5(2.0, 6.8) months, a body mass of 3.0-9.0 kg with median of 6.0(3.7, 7.7) kg.On the first postoperative day, blood was taken from central venous for N-terminal pro-B-type natriuretic peptide(NT pro-BNP) test, TAPSE and left ventricular ejective fraction(LVEF) was measured by echocardiography.The effects of aortic occlusion time, cardiopulmonary bypass time, preoperative pneumonia and preoperative heart failure on TAPSE were compared. The relationship between TAPSE and heart rate, systolic pressure, central venous pressure, vasoactive drug score, endotracheal intubation time, detention time in intensive care unit, NT pro-BNP and LVEF after operation was analysed.Results:The aortic cross-clamping time was 15-87 minutes, with median 31(28, 50) minutes. The cardiopulmonary bypass time was 35-117 minutes, with an average of(68±22)minutes. The time of tracheal intubation was 4-117 hours, with an average of(50±35) hours. The stay time in CICU was 1-14 days, with a median of 5(2, 7) days.The LVEF was 0.18-0.66, with median 0.53(0.42, 0.57). The TAPSE was 2.0-10.0 mm, with an average of(5.2±2.0) mm. On the first day after operation, NT pro-BNP was 1 548-35 000 pg/ml, with an average of(9 446±8 130) pg/ml.TAPSE was negatively correlated with postoperative intubation time( r=-0.576, P= 0.007) and detention time in ICU( r=-0.765, P=0.000), and positively correlated with postoperative LVEF( r=0.461, P=0.041)( P<0.05). TAPSE was negatively correlated with heart rate( r=-0.303, P=0.193), central venous pressure( r=-0.425, P=0.062), vasoactive drug score( r=-0.418, P=0.067) and NT Pro BNP( r=-0.348, P=0.132), and positively correlated with systolic pressure( r=0.146, P=0.54), but there was no statistical significance in each item.Compared with patients with TAPSE≥5mm, the detention time and tracheal intubation time were longer than those TAPSE<5 mm, the central venous pressure and NT-pro BNP was higher than those TAPSE<5 mm( P<0.05), the difference was statistically significant, other indicators had no significant difference. Conclusion:It is simple and feasible to measure TAPSE by echocardiography in children after operation with left-to-right shunt congenital heart disease.TAPSE decreased postoperatively suggested that the function of right ventricle decreased at the early stage after surgery, and with left ventricle systolic function decreased, which eventually led to the increase of NT pro-BNP, the need for higher doses of vasoactive drug support, longer tracheal intubation time and the stay time in CICU.Attention should be paid to the right heart function of children after congenital heart surgery.

OBJECTIVES: Intracerebral hemorrhage (ICH) has the highest mortality and disability rates among various subtypes of stroke. Previous studies have shown that the gut microbiome (GM) is closely related to the risk factors and pathological basis of ICH. This study aims to explore the causal effect of GM on ICH and the potential mechanisms. METHODS: Genome wide association study (GWAS) data on GM and ICH were obtained from Microbiome Genome and International Stroke Genetics Consortium. Based on the GWAS data, we first performed Mendelian randomization (MR) analysis to evaluate the causal association between GM and ICH. Then, a conditional false discovery rate (cFDR) method was conducted to identify the pleiotropic variants. RESULTS: MR analysis showed that Pasteurellales, Pasteurellaceae, and Haemophilus were negatively correlated with the risk of ICH, whileVerrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae, Akkermansia, Holdemanella, and LachnospiraceaeUCG010 were positively correlated with ICH. By applying the cFDR method, 3 pleiotropic loci (rs331083, rs4315115, and rs12553325) were found to be associated with both GM and ICH. CONCLUSIONS There is a causal association and pleiotropic variants between GM and ICH.
Humans ; Genome-Wide Association Study ; Gastrointestinal Microbiome/genetics* ; Genetic Predisposition to Disease ; Cerebral Hemorrhage/genetics* ; Stroke

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 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 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.