1.The research progress of dynamic combinatorial chemistry.
Wei HE ; Pengwei SHE ; Zheng FANG ; Kai GUO
Acta Pharmaceutica Sinica 2013;48(6):814-23
As a novel branch of combinational chemistry, dynamic combinatorial chemistry (DCC) can be viewed as a technique which combines library synthesis and screening in one pot. By addition of molecular target, ligangds, which show binding affinity or strong interaction with the molecular target, can be amplified an young but rapidly growing branch of combinatorial chemistry, has been widely used in organic chemistry, biochemistry, material fields. Ligands in the library can be amplified, since synthesis of the library is screened by a molecular target. Therefore, these structures could be identified easily. Consequently DCC has been widely used in the lead discovery, material chemistry and other fields. On the basis of the principle and method of DCC, this review emphasizes the three factors of DCC, including molecular targets (bio-enzyme, lectin, nucleic acid, organic molecule, inorganic molecule); reaction (disulphide chemistry, ammoniation reduction reaction, hydrazone chemistry, etc.) and analytical method. Meanwhile, limitation, current situation and future development of DCC were also discussed in this paper.
2.Pulmonary vascular remodeling after left lung pneumonectomy in rats
Guo XU ; Xingji ZHAO ; Xiaoyong XIANG ; Jixiang WANG ; Kai SHE
Acta Laboratorium Animalis Scientia Sinica 2015;(4):415-419
Objective To investigate the existence of pulmonary vascular remodeling after left pneumonectomy in rats and the role of hypoxia inducible factor-lα( HIF-1α) and vascular endothelial growth factor ( VEGF) in pulmonary vascular remodeling.Methods Twenty-four healthy male Sprague-Dawley rats were randomly divided into experimental and control groups, 12 in each group.The rat models of pulmonary vascular remodeling were created by open-chest left pneumonectomy.After 12 weeks of feeding, the mean pulmonary artery pressure ( mPAP) and partial pressure of arterial oxygen ( PaO2 ) of each rat were measured.The ultrastructure of small arteries in the lung specimens were examined by e-lectron microscopy.Muscularized degree of three kinds of small pulmonary vessels ( muscularized artery MA, partially mus-cularized artery PMA, and non-muscularized artery NMA) were observed by light microscopy, and the percentage of each kind of pulmonary arteries ( MA%, PMA%, NMA%) were calculated.Arterial external diameter, media thickness of ves-sel ( MTV) , total vascular area, media area of vessel ( MAV) , MTV%and MAV%were calculated as indicators of pul-monary vascular remodeling.The expressions of HIF-1αand VEGF in artery were detected by immunohistochemistry.Re-sults The values of mPAP, MA%, PMA%, MTV, MAV, MTV% and MAV% in the experimental group were signifi-cantly higher than those in the control group (P<0.01), but the value of PaO2 and NMA%were significantly lower than those in the control group (P<0.01).The IOD value of HIF-1αand VEGF expressed in the pulmonary arterial wall of the experimental group were 26.47 ±4.16 and 42.04 ±3.79, respectively, significantly higher than those in the control group (6.12 ±2.14 and 11.53 ±2.29, P<0.01).Linear correlation analysis showed that the expression of HIF-1αand VEGF was positively correlated with MTV% and MAV%, negatively correlated with PaO2 , and the HIF-1αexpression was posi-tively correlated with VEGF expression.Conclusions A rat model of pulmonary vascular remodeling can be successfully established by left pneumonectomy.Hypoxia is a key factor in the development of pulmonary vascular remodeling, HIF-1αand VEGF may play an important role in its pathogenesis.
3.The research progress of dynamic combinatorial chemistry.
Wei HE ; Peng-Wei SHE ; Zheng FANG ; Kai GUO
Acta Pharmaceutica Sinica 2013;48(6):814-823
As a novel branch of combinational chemistry, dynamic combinatorial chemistry (DCC) can be viewed as a technique which combines library synthesis and screening in one pot. By addition of molecular target, ligangds, which show binding affinity or strong interaction with the molecular target, can be amplified an young but rapidly growing branch of combinatorial chemistry, has been widely used in organic chemistry, biochemistry, material fields. Ligands in the library can be amplified, since synthesis of the library is screened by a molecular target. Therefore, these structures could be identified easily. Consequently DCC has been widely used in the lead discovery, material chemistry and other fields. On the basis of the principle and method of DCC, this review emphasizes the three factors of DCC, including molecular targets (bio-enzyme, lectin, nucleic acid, organic molecule, inorganic molecule); reaction (disulphide chemistry, ammoniation reduction reaction, hydrazone chemistry, etc.) and analytical method. Meanwhile, limitation, current situation and future development of DCC were also discussed in this paper.
Combinatorial Chemistry Techniques
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methods
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Enzymes
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chemistry
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Lectins
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chemistry
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Nucleic Acids
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chemistry
4.Research progress in miRNAs mediated radiation-induced by stander effect
Yafei SHU ; Jing GU ; Min HOU ; Yali SHE ; Kai LIU ; Yifan DUAN
Chinese Journal of Radiological Medicine and Protection 2021;41(11):862-866
Radiation-induced bystander effect (RIBE) refers to that irradiated cells release signaling factors and induce responses in nonirradiated cells.In other words, it is the communication between irradiated and nonirradiated cells by intracellular signals. RIBE could influence the efficacy of tumor radiotherapy, but also has potential risk to the normal tissues outside of radiation field. Studies have found that ionizing radiation can induce the alteration of miRNA expression not only in the irradiated cells but also in adjacent nonirradiated tissues, and miRNAs may play an important role in the regulation of signaling pathways between irradiated and nonirradiated bystander cells. This article reviewed the roles of miRNAs in RIBE.
5.Treatment of ankylosis of the knee through a mini-incision assisted by arthroscope.
Jun-she CAO ; Kai HOU ; Wei YUE
China Journal of Orthopaedics and Traumatology 2011;24(9):747-749
OBJECTIVETo investigate therapeutic effects of mini-incision assisted by arthroscope for the treatment of ankylosis of knee.
METHODSFrom July 2007 to August 2009, 18 patients with ankylosis of knee were treated with mini-incision assisted by arthroscope. Among the patients, 15 patients were male and 3 patients were female, ranging in age from 27 to 56 years, with an average of 33.6 years. Before operation, 5 patients had comminuted fractures in the distal end of femur (including 1 patient with open fracture), 9 patients had comminuted fractures of tibial plateau, 2 patients had comminuted fractures of patella, 1 patient had comminuted fractures of patella combined with comminuted fracture of capitulum fibulae and injuries of complex structure at lateral knee, and 1 patient had floating knee. The duration between the primary operation and the arthrolysis ranged from 6 to 31 months (averaged, 10.6 months). The therapeutic effects were evaluated according to Judet criteria.
RESULTSAll the patients were followed up, and the duration ranged from 3 to 25 months (averaged, 11.4 months). All the patients had incision healing at the first stage without infection, wound dehiscence and liquifaction necrosis. The preoperative knee flexed motion ranged from 30 degrees to 80 degrees, with a mean of (44.72 +/- 11.60) degrees; and postoperative knee flexed range of motion improved to an average of (109.17 +/- 10.31) degrees (ranged, 95 degrees to 135 degrees). According to Judet evaluation, 16 patients got an excellent result, 2 good.
CONCLUSIONTreatment of ankylosis of the knee through a mini-incision assisted by arthroscope has advantages such as reducing the complications of incision on knee, little trauma and early recovery, which is a good operative mode to treat ankylosis of the knee after operation or trauma.
Adult ; Ankylosis ; surgery ; Arthroscopes ; Female ; Humans ; Knee Joint ; surgery ; Male ; Middle Aged
6.Effect of intranasal dexmedetomidine on agitation during emergence from general anesthesia with sevoflurane in pediatric patients: a meta-analysis
Yu ZHU ; Hong GAO ; Lei TIAN ; Kai LU ; Yuqi SHE ; Yi ZHONG
Chinese Journal of Anesthesiology 2018;38(9):1045-1048
Objective To systematically evaluate the effect of intranasal dexmedetomidine on agita-tion during emergence from general anesthesia with sevoflurane in pediatric patients. Methods Pubmed, Embase, The Cochrane Library, China National Knowledge Infrastructure, VIP, Wan-Fang databases were searched for randomized controlled trials involving the effect of intranasal dexmedetomidine on agitation during emergence from general anesthesia with sevoflurane in pediatric patients from the start of their data-base until June 2017, and the reference lists of all included studies were checked manually. Data were ex-tracted independently by two reviewers, and primary evaluation indexes included the incidence of emergence agitation and sedation score. Secondary evaluation indexes included emergence time, extubation time, du-ration of post-anesthesia care unit stay, postoperative consumption of analgesics, incidence of adverse reac-tions ( such as bradycardia, nausea and vomiting, pruritus, laryngeal spasm) during recovery from anes-thesia. The quality of methodology of included studies was assessed. Meta-analysis was conducted with Rev-Man 5. 3 software. Results Eight randomized controlled trials involving 520 pediatric patients were includ-ed in this meta-analysis. Compared with placebo group, the incidence of emergence agitation was signifi-cantly decreased, sedation score was increased, extubation time was prolonged ( P<0. 05) , no significant change was found in the duration of post-anesthesia care unit stay or incidence of postoperative nausea and vomiting in intranasal dexmedetomidine group ( P>0. 05) . The emergence time was prolonged in intranasal 0. 3-1. 0 μg∕kg dexmedetomidine group ( P<0. 05 ) , and no significant change was found in emergence time in intranasal dexmedetomidine 1. 0-2. 0μg∕kg group ( P>0. 05) . Conclusion Intranasal dexmedeto-midine can decrease the occurrence of agitation during emergence from general anesthesia with sevoflurane and raise the quality of emergence in pediatric patients.
7.Prevalence of depressive symptoms among adolescents
Li-Feng ZHENG ; Kai-Ren YANG ; Su-Xian TAN ; She-Hong YU ; Fang ZHENG
Journal of Preventive Medicine 2018;30(4):338-340,344
Objective To evaluate the prevalence of depressive symptoms and influencing factors among adolescents. Methods A total of 635 students aged 13 to 18 years were selected in March 2017 and were investigated with general information questionnaire, CES-D and CTQ-SF. Results 630 questionnaires are effective and the positive rate of depression was 29.84%(188/630) . The average score of CTQ was 32.15±2.98; 38.73% of the students were disregarded and only 2.22% of that were abused during their childhood. 40.00% of the students had no CTQ, 1 kinds of CTQ accounted for 31.43% , 2 kinds of CTQ accounted for 18.25%, and more than 3 CTQ accounted for 10.32%. Multivariate logistic regression analysis show that gender (OR=1.034, 95% CI: 1.012-1.056) , parents' marital status (OR=1.124, 95% CI: 1.087-1.162) , family atmosphere (OR=1.025, 95% CI: 1.024-1.158) , CTQ cumulative number (ORCTQ=1=1.528, 95% CI: 1.214-1.923; ORCTQ=2=3.067, 95% CI: 1.325-7.102; ORCTQ≥3=10.361, 95% CI: 3.059-35.093) were the risk factors for depression. Conclusion Gender, parents' marital status, family atmosphere and CTQ cumulative number were risk factors for depression in adolescents.
8.Characteristics and expression of Mip5, a novel gene associated with myocardial ischemia/reperfusion in rats.
Jian-She WANG ; Can YUAN ; Kang-Kai WANG ; Hua-Li ZHANG ; Shun-Mei E ; Mei-Dong LIU ; Ke LIU ; Guang-Wen CHEN ; Xian-Zhong XIAO
Journal of Central South University(Medical Sciences) 2005;30(5):515-520
OBJECTIVE:
To determine the characteristics of a novel gene Mip5 (GenBank accession number AY553870) and its expression under physiological and pathological conditions.
METHODS:
The characteristics of Mip5 were analyzed by bioinformatic programs including BLAST, spidey, psort, ClustalW and so on. RT-PCR was performed to detect Mip5 expression.
RESULTS
Bioinformatic analysis showed that Mip5 gene lied in the 13th chromosome and contained 8 exons and 7 introns, its open reading frame contained 909 bp and its protein production was 302 amino acid residues including 6 kelth domains. Under normal conditions, MIP5 expressed abundantly in the heart, brain and kidney, but its expression could not be detected in the liver and muscle. Expression of Mip5 gene was increased significantly after ischemia-reperfusion compared with the sham groups, and reached its peak at 3 h and recovered at 12 h after the reperfusion. Conclusion Mip5 gene is a novel gene containing a putative open reading frame of 302 amino acids residues and may play an important role in rat cardiomyocytes suffering ischemia processing.
Amino Acid Sequence
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Animals
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Base Sequence
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Chromosomes, Human, Pair 13
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genetics
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DNA, Complementary
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genetics
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Humans
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Male
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Molecular Sequence Data
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Myocardial Ischemia
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genetics
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Myocardial Reperfusion Injury
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genetics
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Open Reading Frames
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genetics
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Rats
9.Comparison of machine learning and Logistic regression model in predicting acute kidney injury after cardiac surgery: data analysis based on MIMIC-Ⅲ database
Wei XIONG ; Lifan ZHANG ; Kai SHE ; Guo XU ; Shanglin BAI ; Xuan LIU
Chinese Critical Care Medicine 2022;34(11):1188-1193
Objective:To establish an acute kidney injury (AKI) prediction model in patients after cardiac surgery by extreme gradient boosting (XGBoost) machine learning model, and to explore the risk and protective factors for AKI in patients after cardiac surgery.Methods:All patients who underwent cardiac surgery in Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ) database were enrolled, and they were divided into AKI group and non-AKI group according to whether AKI developed within 14 days after cardiac surgery. Their clinical characteristics were compared. Based on five-fold cross-validation, XGBoost and Logistic regression were used to establish the prediction model of AKI after cardiac surgery. And the area under the receiver operator characteristic curve (AUC) of the models was compared. The output model of XGBoost was interpreted by Shapley additive explanations (SHAP).Results:A total of 6 912 patients were included, of which 5 681 (82.2%) developed AKI within 14 days after the operation, and 1 231 (17.8%) did not. Compared with the non-AKI group, the main characteristics of AKI group included older age [years: 68.0 (59.0, 76.0) vs. 62.0 (52.0, 71.0)], higher incidence of emergency admission and complicated with obesity and diabetes (52.4% vs. 47.8%, 9.0% vs. 4.0%, 32.0% vs. 22.2%), lower respiratory rate [RR; bpm: times/min: 17.0 (14.0, 20.0) vs. 19.0 (15.0, 22.0)], lower heart rate [HR; bpm: 80.0 (67.0, 89.0) vs. 82.0 (71.5, 93.0)], higher blood pressure [mmHg (1 mmHg ≈ 0.133 kPa): 80.0 (70.7, 90.0) vs. 78.0 (70.0, 88.0)], higher hemoglobin (Hb), blood glucose, blood K + level and serum creatinine [SCr; Hb (g/L): 122.0 (109.0, 136.0) vs. 120.0 (106.0, 135.0), blood glucose (mmol/L): 7.3 (6.1, 8.9) vs. 6.8 (5.7, 8.5), blood K + level (mmol/L): 4.2 (3.9, 4.7) vs. 4.2 (3.8, 4.6), SCr (μmol/L): 88.4 (70.7, 106.1) vs. 79.6 (70.7, 97.2)], lower albumin (ALB) and triacylglycerol [TG; ALB (g/L): 38.0 (35.0, 41.0) vs. 39.0 (37.0, 42.0), TG (mmol/L): 1.4 (1.0, 2.0) vs. 1.5 (1.0, 2.2)] as well as higher incidence of multiple organ dysfunction syndrome (MODS) and sepsis (30.6% vs. 16.2%, 3.3% vs. 1.9%), with significant differences (all P < 0.05). In the output model of Logistic regression, important predictors were lactic acid [Lac; odds ratio ( OR) = 1.062, 95% confidence interval (95% CI) was 1.030-1.100, P = 0.005], obesity ( OR = 2.234, 95% CI was 1.900-2.640, P < 0.001), male ( OR = 0.858, 95% CI was 0.794-0.928, P = 0.049), diabetes ( OR = 1.820, 95% CI was 1.680-1.980, P < 0.001) and emergency admission ( OR = 1.278, 95% CI was 1.190-1.380, P < 0.001). Receiver operator characteristic curve (ROC curve) analysis showed that the AUC of the Logistic regression model for predicting AKI after cardiac surgery was 0.62 (95% CI was 0.61-0.67). After optimizing the XGBoost model parameters by grid search combined with five-fold cross-validation, the model was trained well with no overfitting or overfitting. ROC analysis showed that the AUC of XGBoost model for predicting AKI after cardiac surgery was 0.77 (95% CI was 0.75-0.80), which was significantly higher than that of Logistic regression model ( P < 0.01). After SHAP treatment, in the output model of XGBoost, age and ALB were the most important predictors of the final outcome, where age was the risk factor (average |SHAP value| was 0.434), and ALB was the protective factor (average |SHAP value| was 0.221). Conclusions:Age is an important risk factor for AKI after cardiac surgery, and ALB is a protective factor. The performance of machine learning in predicting cardiac and vascular surgery-associated AKI is better than the traditional Logistic regression. XGBoost can analyze the more complex relationship between variables and outcomes, and can predict the risk of postoperative AKI more accurately and individually.
10.Effect of salvianolic acid B on TNF-α induced cerebral microcirculatory changes in a micro-invasive mouse model.
Bo CHEN ; Kai SUN ; Yu-Ying LIU ; Xiang-Shun XU ; Chuan-She WANG ; Ke-Seng ZHAO ; Qiao-Bing HUANG ; Jing-Yan HAN
Chinese Journal of Traumatology 2016;19(2):85-93
PURPOSETo investigate the effects of salvianolic acid B (SAB) on tumor necrosis factor a (TNF-α) induced alterations of cerebral microcirculation with a bone-abrading model.
METHODSThe influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 μg/kg·bw TNF-α on cerebral venular leakage of fluorescein isothiocyanate (FITC)- albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G. The therapeutical effects of SAB on TNF-α induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg·h SAB starting at 20 min before or 20 min after TNF-α administration, respectively. The expressions of CD11b/CD18 and CD62L in leukocytes were measured with flow cytometry. Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells.
RESULTSCompared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-α intervention only caused responses of vascular hyperpermeability and leukocyte rolling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CD11b/CD18 and CD62L in leukocytes and E-selectin and ICAM-1 in endothelial cells induced by TNF-α.
CONCLUSIONSThe pre- and post-applications of SAB during TNF-α stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.
Animals ; Benzofurans ; pharmacology ; Blood Flow Velocity ; Cerebrovascular Circulation ; drug effects ; Craniotomy ; Disease Models, Animal ; E-Selectin ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Mice ; Mice, Inbred C57BL ; Microcirculation ; drug effects ; Random Allocation ; Reference Values ; Tumor Necrosis Factor-alpha ; administration & dosage