3.The technologies of small molecule ligand-target protein interaction and high throughput ligand screening
Rui-fang DONG ; Yuan-zheng XIA ; Ling-yi KONG
Acta Pharmaceutica Sinica 2023;58(11):3242-3253
The interaction of drug and target protein is a critical part of new drug discovery. It is the premise for drugs to exert therapeutic effects by targeting specific binding sites of target proteins and thereby affecting its pharmacological activity. Currently, a variety of techniques are exploited to detect the interaction between drug ligands and target proteins. For example, cellular thermal shift assay (CETSA) and differential scanning fluorimetry (DSF) based on thermodynamics, mass spectrometry and nuclear magnetic resonance technology, etc. In addition, high-throughput ligand screening technology provides technical convenience for the search of specific ligand, and is a powerful tool to efficiently identify the interaction between drug ligand and target protein. Here, we summarize the detection techniques of interaction between small molecules and target proteins, and discuss the application of high-throughput ligand screening technology in drug research.
4.Label-free target identification for natural products based on proteomics
Rui-fang DONG ; Yuan-zheng XIA ; Ling-yi KONG
Acta Pharmaceutica Sinica 2023;58(8):2000-2015
Target identification and verification of natural products is an important and challenging work in the field of chemical biology. It is also an important job for researchers to apply chemical proteomics technology to biomedicine in order to identify target proteins of natural products. Target identification is critical to understanding its mechanisms and developing natural products as molecular probes and potential therapeutic drugs. Traditional approaches of small molecule target identification based on affinity have been shown to be successful, such as click-chemical probes, radioisotope labeling or photosensitized small-molecule probes. Nevertheless, these technologies require purified candidate target proteins, and modified small molecules with probes or linkers, such as adding agarose beads, biotin labels, fluorescent labeling or photo-affinity labeling. Many structure-activity relationship studies should be performed to ensure that the addition of small molecule labels undisturbed the original biological activity of the small molecules. Unfortunately, all these modifications are likely to alter their biological activity or binding specificity. To overcome the bottleneck of "target recognition", researchers have developed a series of new techniques for unmodified drug target identification. In this article, we reviewed the target identification techniques of natural product without structural modification in order to provide reference for the development of natural products.
5.Experience and thinking on establishing fine course of oral and maxillofacial surgery
lian, GUO ; zhi-yuan, ZHANG ; jia-wei, ZHENG ; xia, CAO ; yuan-jin, XU ; chi, YANG
Journal of Shanghai Jiaotong University(Medical Science) 2008;0(S1):-
Objective To explore the practical ways on establishing fine course of oral and maxillofacial surgery effectively. Methods Relying on the advantages of the discipline,great efforts had been made in step-by-step enhancement of the quality of teachers,teaching contents,teaching methods and administration. Results Through the establishing of fine course,we could improve the curriculum system,enhance the force of education team,and improve the quality of education. Conclusion Establishing fine course of oral and maxillofacial surgery depends on the environment of sharing educational resources,adjusting the curriculum system and establishing an excellent educational team.
6.Effect of methylprednisolone on reperfusion injury in severe uncontrolled hemorrhagic shock.
Fang XIA ; Jing-shan CAO ; Li-ying ZHAN ; Zhong-yuan XIA ; Zheng-yuan XIA ; Hai-bo HUANG
Chinese Journal of Traumatology 2003;6(6):359-362
OBJECTIVETo study the effect of methylprednisolone (MP) on reperfusion injury in severe uncontrolled hemorrhagic shock and explore the possible mechanism involved.
METHODSTwelve dogs were randomly divided into two groups, control group (Group I, n=6) and MP group (Group II, n=6). The animals were bled continuously from a femoral artery catheter to produce uncontrolled hemorrhagic shock models. Resuscitation with lactated Ringer's (LR) solution was initiated when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when resuscitation began. While in Group I, normal saline (NS) was injected instead. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before exsanguination (T(1)), when MAP decreased to 20 mm Hg (T(2)), 60 min (T(3)) and 120 min (T(4)) after resuscitation. Heart rate, MAP and cardiac output (CO) levels were recorded concomitantly.
RESULTSInfusion volume and hemorrhage volume shed from the superior mesenteric artery in Group I were higher than those in Group II (P<0.01 and P<0.05). After reperfusion, blood SOD levels decreased progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD levels at T(3) and T(4) decreased as compared with that at T(1) but a stepwise increase was present. At T(4), blood SOD level was significantly higher in Group II than in Group I (Plt;0.01). At T(3) and T(4), MDA levels were markedly lower in Group II than in Group I. During reperfusion, MAP was more steady in Group II than in Group I and survival rate after 120 min (at T(4)) was higher in Group II than in Group I (P<0.05).
CONCLUSIONSMP has a protective effect on severe uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism mainly involves the anti-lipid peroxidation activity of MP.
Analysis of Variance ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Lipid Peroxidation ; Male ; Methylprednisolone ; pharmacology ; Probability ; Random Allocation ; Reference Values ; Reperfusion Injury ; drug therapy ; physiopathology ; Sensitivity and Specificity ; Shock, Hemorrhagic ; drug therapy ; physiopathology ; Survival Rate
7.Construction and thinking of data element standard directory of traditional Chinese medicine clinical pharmacy information.
Xiao-Xia WANG ; Zhong-Zheng JIN ; Gui-Ming GUO ; Hua-Qiang ZHAI ; Shi-Yuan JIN
China Journal of Chinese Materia Medica 2014;39(9):1724-1727
The aim of this study was to develop the data element standard directory of traditional Chinese medicine (TCM) clinical pharmacy information, to provide application standards and models of TCM clinical pharmacy for the electronic medical record (EMR). The developed line of work is as follows: initially establish research through four forms: literature analysis, questionnaires, discussion groups, expert advice. The research range from the Chinese herbal medicine research, herbal origin, harvesting, processing, identification of traits, physical and chemical identification, modern research, character, taste, Indications, clinical application, processing, dispensing medicine, Chinese medicine specifications, usage, dosage, caution, efficacy indications to small packaging applications, drug research, management and other related issues, including traditional Chinese medicine theory, application and hospital management information; according to the general and part 16 content of the national "Health Information Data Element Standards", and the basic method of extracting data element to study and develop the data element of TCM clinical pharmacy information from the defining content. Correspondingly propose the ideas and methods of construction of the "Data Element Standard Directory of TCM Clinical Pharmacy Information", sort out medicine clinical information data element standard catalog, divided into basic categories, clinical application class, management class three parts, and set norms and standards of identifying data elements, definitions, allowable value of traditional Chinese medicine clinical information, and discuss the sources and standards of information collection, leaving the interface, standardized and scientific terminology, docking with the existing standards, maintenance and management program and oter issues.
China
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Data Mining
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methods
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statistics & numerical data
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Database Management Systems
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standards
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statistics & numerical data
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Electronic Health Records
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standards
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statistics & numerical data
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Evidence-Based Medicine
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methods
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statistics & numerical data
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Humans
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Information Dissemination
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methods
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Medicine, Chinese Traditional
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methods
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Phytotherapy
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methods
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statistics & numerical data
8.Sacrococcygeal gap injection for the treatment of failed back surgery syndrome.
Jin-Cai HOU ; Tian-Yuan ZHENG ; Dong-Yue LI ; Man-Xia ZHI
China Journal of Orthopaedics and Traumatology 2014;27(3):229-231
OBJECTIVETo explore the clinical effect of the sacrococcygeal space injection for the treatment of failed back surgery syndrome.
METHODSFrom July 1998 to October 2012,47 patients with failed back surgery syndrome were treated and included 39 males and 8 females with an average age of 61.5 years old ranging from 35 to 89 years old. Among them,41 patients experienced one time of operation, 6 patients with twice of operation. Forty-one patients underwent single,bilateral fenestration or central laminectomy decompression, discectomy. Six patients underwent total laminectomy discectomy and inter body fusion and pedicle screw fixation. All patients were examined by X-ray plain film, CT or MRI before treatment. The anticoagulation was discontinuation before treatment. The needle was put into the sacrococcygeal gap at prone position in the sense of frustration,suction without cerebrospinal fluid and blood,with injection of Mailuoning (Chinese characters: see text) 15 ml. The pain was assessed by VAS before and after treatment. The Oswestry low back pain disability index and survival quality interference degree were evaluated.
RESULTSAt 1 month after treatment,the pain VAS decreased from 59.24 +/- 17.35 before treatment to 19.19 +/- 11.19 after treatment (P < 0.05); The Oswestry low back pain disability index decreased from (41.35 +/- 9.87)% before treatment to (23.17 +/- 17.56)% after treatment (P < 0.05); The survival quality interference degree decreased from 6.5 +/- 2.2 before treatment to 2.6 +/- 1.4 after treatment (P < 0.05).
CONCLUSIONThe sacrococcygeal gap injection for treatment of failed back surgery syndrome has advantages of simple, safe, fewer complications, and low treatment cost.
Adult ; Aged ; Aged, 80 and over ; Drugs, Chinese Herbal ; administration & dosage ; Failed Back Surgery Syndrome ; diagnostic imaging ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Radiography ; Sacrococcygeal Region ; diagnostic imaging
9.Clinical features of mtDNA A3243G mutation in adult patients
Sheng YAO ; Ri-Liang ZHENG ; Hong-Yan BI ; Zhao-Xia WANG ; Yun YUAN ;
Chinese Journal of Neurology 2000;0(04):-
Objective To analysis the clinical manifestations of mtDNA A3243G mutation in adulthood.Methods The clinical features were investigated in 36 cases (28 patients from 5 families with the mutation and 8 sporadic cases),in whom mtDNA A3243G mutation was confirmed genetically in 23 cases (15 cases from 5 mutation families and 8 sporadic cases).Cranium radiology was performed in 14 cases.Muscal biopsies were performed in l0 cases.Results Among 28 cases in the 5 family,there were 9 cases (32.1%) with stroke like episodes,17 cases (60.7%) with diabetic mellitus and 16 cases (57.1%) with deafness.Such symptoms usually combined with each other and rarely existed alone. Cardiomyopathy and renal failure were uncommon.In the 23 cases with mtDNA A3243G mutation,14 cases (61.0%) had mitochondria] myopathy,encephalopathy,lactic acidosis,and stroke-like episodes (MELAS),mostly presenting cognitive abnormalities,dysarthria or aphasia and headache,3 cases (13.0%) were asymptomatic carriers,2 cases (8.7%) had autonomic dysfunction,2 cases (8.7%) had diabetic mellitus with or without nerve deafness,1 case (4.3%) had diabetic mellitus with infertilitas and cardiomyopathy,respectively.Cranial radiological images revealed the changes more commonly in the temporal and occipital lobes and less frequently in the frontal lobes.Ragged red fibers were confirmed in 9 of 10 cases with muscle biopsies.The proportion of mutant mtDNA A3243C was not significantly different between MEALS (28.75%?13.69%) and non-MELAS (25.08%?11.54%).Conclusions mtDNA A3243G mutation mainly results in the lesions in the central nerve system,pancreatic island and acoustic nerve in adulthood.Heart and kidney are less frequently involved.Cognitive abnormalities,aphasia and headache are the major symptoms of adult MELAS.Families have with more than 1 patient with diabetic mellitus and deafness,indicating that the mutation is other than MELAS mutation.We should pay more attention to the non-MELAS symptoms in the families with mtDNA A3243G mutation.
10.The students' satisfaction degree and cognitive attitude of the network construction of elaborate course of social medicine
Ping XIA ; Chuanjian LU ; Zhenmiao PANG ; Xingying XU ; Heng LONG ; Xiuqin YUAN ; Haiyan ZHENG ; Yanping QU
Chinese Journal of Medical Education Research 2014;(8):857-860,861
Objective This study aimed to survey students' satisfaction and cognitive attitude of elaborate course of social medicine to provide a basis for exploring appropriate teaching mode. Methods Purposive sampling was used with questionnaire to survey 646 students who had learned social medicine in 5 universities in Guangdong province. The survey included the social medicine curriculum, teaching situation, students' satisfaction and cognitive attitude of elaborate course of so-cial medicine. Descriptive statistical analysis was used to describe the demographic characteristics and curriculum. The t test and one-way ANOVA were used to compare the means of students' satisfaction and cognitive attitude of elaborate course in different universities, using the test level of 0.05. Results The lecture-based learning was the main teaching mode. 335(52.7%) students thought it necessary to learn social medicine, but only 27.2%of the students(173 students) were interested in social medicine and 65(10.2%) students could take the initiative to read about extracurricular books. Overall satisfac-tion with using network resources of elaborate course in two universities that had university-level elab-orate course of social medicine were (2.78 ± 0.55) and (3.01 ± 0.30) respectively and the difference was statistically significant(t=-3.97,P<0.01). The cognitive attitude of the students in 5 universities with using network resources of elaborate course was (3.09±0.66) and the difference was statistically significant(F=3.70,P<0.01). Conclusion Social medicine teaching has been paid attention to in 5 universities, but there were some common problems: ①putting emphasis on theory and ignoring prac-tice in teaching mode; ②putting emphasis on credit and ignoring effectiveness in learning; ③and putting emphasis on construction and ignoring using in network resources of elaborate course of social medicine.