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Early secreted antigenic target of 6 kDa protein (ESAT-6) is the major virulence factor of Mycobacterium tuberculosis (MTB), which can resist the clearance of MTB in bodies by inhibiting macrophage phagocytosis and autophagy reaction, thus impeding the immune defense function of the body against MTB infection. In addition, ESAT-6-induced apoptosis of macrophage and massive necrosis of innate immune cells can foster MTB proliferation and colonization, leading to systemic MTB infection. Moreover, ESAT-6 hampers the protective immune response of Th1 cells, reducing the secretion of pro-inflammatory cytokines and contributing to immune dysfunction, thus accelerating the course of MTB infection. During the process, the high immunogenicity of ESAT-6 can be leveraged as a dominant antigen in the development of new TB vaccines, making it a promising candidate with broad prospects for further development.
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Humains , Mycobacterium tuberculosis , Vaccins , Cytokines , Apoptose , Autophagie , SepsieRésumé
OBJECTIVES@#Clinical research plays a vital role in disease research and population health. The public is the main source of clinical research volunteers. Understanding the public's cognition of clinical research plays a decisive role in the development of clinical research. This study aims to understand the Chinese public's cognition for clinical research and the influencing factors.@*METHODS@#The questionnaire based on Chinese-translated Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment (PARTAKE) was used to investigate the public's cognition for clinical research.@*RESULTS@#Of the 2 513 valid respondents, 91.84% had heard of "clinical research", 91.76% of the respondents believed that clinical research was beneficial to society, 65.90% were willing to participate in clinical research, 87.50% believed that confidentiality was a very important thing, 73.70% believed that their personal information had been protected when participating in clinical research, and, 46.40% did not know whether volunteers participating in clinical research could receive adequate compensation. Educational levels, employment status, and annual income impacted in public perceptions of willingness to participate in clinical research, especially in privacy protection, informed consent, whether clinical research is intended for society, compensation for clinical research, and safety of clinical research (all P<0.01).@*CONCLUSIONS@#The Chinese public's cognition level for clinical research is acceptable, but there is still a lot of room for improvement in privacy protection, informed consent, and compensation. By designing a reasonable knowledge training program for clinical research and using the multimedia, improving access to the relevant knowledge, more public will know about clinical research recruitment information, which is of great significance for the development of clinical research in China.
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Humains , Chine , Peuples d'Asie de l'Est , Niveau d'instruction , Enquêtes et questionnaires , Opinion publique , Savoir , Recherche biomédicaleRésumé
AIM: In order to bridge the gap between pharmacogenomic research and its clinical application, we propose the concept of genetic electronic identity, named "GeneFace", and developed an electronic information system which integrated "drug-gene" interactions and recommendations for personalized medicine. METHODS: Based on the self-developed Precision Medicine knowledgebase, which concludes drug directions, guidelines or important literatures with high level of evidence, we developed GeneFace with Java-based open-resource application framework Spring Boot, further developed a mobile App with cross-platform framework Uni-APP. RESULTS: The App includes six modules: genetic testing appointment, genetic knowledge introduction, individualized medication advice, medication records, Geneface interpretation, and Precision Medicine knowledgebase. By detecting the genotype of more than 300 gene loci upon first use, users import the results to form a personal "drug-gene identity card". Then scan or enter the drug name in "GeneFace", the App would automatically give corresponding medication recommendations, including: risks for possible adverse drug reactions, risks for reducing the efficacy or even ineffectiveness, and possibility for dose adjustment, etc., which increase the safety of clinical drug use. People can obtain pharmacogenomics knowledge and basic drug information in the "GeneFace" app. CONCLUSION: Development as a digital therapeutic product, the expanded application of GeneFace can rapidly promote clinical applications of basic pharmacogenomics research and significantly improve drug use safety, which creating a new model for accelerating the clinical application of personalized medicine.
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AIM: Describe the general situation of the First-In-Human trials of the drugs, and summarize the design and results of the First-In-Human trials. METHODS: We searched the literature of the First-In-Human trials in 2009-2020 on PubMed and screened out the literature that met the research purpose. The basic information of the literature was collected. Data analysis was conducted to summarize relevant outcomes. RESULTS: A total of 559 First-In-Human trials were included in this study. The types of drugs included small molecule drugs (52.42%, 293/559), macromolecule drugs (45.62%, 255/559), and a small amount of cells and viruses (1.97%, 11/559) and so on. Regarding the determination of the starting dose, whether it was in macromolecules (23.86%, 21/88) or small molecules (30.15%, 41/136), No Observed Adverse Effect Level (27.68%, 62/224) was mainly used as the main reference basis, followed by preclinical research (21.88%, 49/224) and Minimal Anticipated Biological Effect Level (8.48%, 19/224), etc. In the dose escalation test, 50.19%(135/269) of the studies used the traditional standard 3+3 dose escalation method, followed by the accelerated titration method (7.06%, 19/269), and the improved 3+3 method (6.69%, 18/269), etc. CONCLUSION: The design of First-In-Human clinical trials has certain regularity in the content and results of the research design. In the subsequent trials, it is important to scientifically design the First-In-Human trials, and promote the safe and effective development of the First-In-Human trials of the drugs.
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AIM: To study the pharmacokinetic characteristics of single-dose oral moxifloxacin hydrochloride tablets under fasting and fed conditions, and use moxifloxacin hydrochloride tablets produced by Bayer Pharma AG as a reference to compare the pharmacokinetic parameters of the two preparations, and evaluate the human bioequivalence of the two preparations. METHODS: A single-center, randomized, open, two-period, and self-crossover design was adopted to conduct a fasting and fed bioequivalence study of 23 healthy subjects each. The 0.4 g dose preparations were taken orally per cycle on fasting or fed administration. The plasma concentrations of moxifloxacin at different times after administration were determined by HPLC-MS/MS. The main pharmacokinetic parameters were calculated, and the bioavailability of the test preparation relative to the reference preparation was evaluated. RESULTS: After subjects in the fasting group took the test preparation T and the reference preparation R, the main pharmacokinetic parameters of moxifloxacin hydrochloride were: C
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AIM: To evaluate the bioequivalence of the test and reference preparations of solifenacin succinate tablets administered once orally under fasting and fed conditions in Chinese healthy volunteers. METHODS: The study was designed as single-center, randomized, open, self-crossover and twenty four healthy volunteers were recruited respectively in fasting and fed conditions. Subjects were assigned to receive a single oral of the test or reference formulation per period at a dose of 10 mg. The plasma concentration of solifenacin was analyzed by LC-MS/MS. The major pharmacokinetic parameters were calculated by WinNonlin 7.0, then the bioequivalence was evaluated.RESULTS: The main pharmacokinetic parameters of a single oral solifenacin succinate under fasting condition for test and reference preparation were as follows: C
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Objective This paper selects indicators,such as SCI journal publication fee,impact factors,annual Web of Science Documents,volume of publications in China,articles cited and so on,to conduct the feasibility analysis of using publication fee /impact factor (BI) as evaluation index of SCI journals.Methods Information from Web of Science,InCites,Journal Citation Reports database and the real-time data of 2013-2017 years SCI publication fees in Central South University,the third Xiangya Hospital were collected,SPSS and EXCEL was used to conduct Correlation and Basic analysis.Results In 2013-2017,a total number of 31 kinds of SCI journals were included in sample size,the SCI journal impact factor was positively correlated with the publication fee.BI was negative correlated with IF,The publication fee was not related to annual Web of Science Documents,volume of publications in Mainland China and Cites/Paper.Conclusions The SCI journal publication fee/impact factor (BI) can be used as a macro evaluation index for SCI journals.The BI values also can provide reference and reference of decision support and journal selection for scientific research personnel and scientific research administrators.
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Objective To assess the reliability and validity of the Chinese version on Alcohol Use Disorders Identification Test (AUDIT) among medical students in China and to provide correct way of application on the recommended scales.Methods An E-questionnaire was developed and sent to medical students in five different colleges.Students were all active volunteers to accept the testings.Cronbach's α and split-half reliability were calculated to evaluate the reliability of AUDIT while content,contract,discriminant and convergent validity were performed to measure the validity of the scales.Results The overall Cronbach's α of AUDIT was 0.782 and the split-half reliability was 0.711.Data showed that the domain Cronbach's α and split-half reliability were 0.796 and 0.794 for hazardous alcohol use,0.561 and 0.623 for dependence symptoms,and 0.647 and 0.640 for harmful alcohol use.Results also showed that the content validity index on the levels of items I-CVI)were from 0.83 to 1.00,the content validity index of scale level (S-CVI/UA) was 0.90,content validity index of average scale level (S-CVI/Ave) was 0.99 and the content validity ratios (CVR) were from 0.80 to 1.00.The simplified version of AUDIT supported a presupposed three-factor structure which could explain 61.175% of the total variance revealed through exploratory factor analysis.AUDIT semed to have good convergent and discriminant validity,with the success rate of calibration experiment as 100%.Conclusion AUDIT showed good reliability and validity among medical students in China thus worth for promotion on its use.
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Objective To assess the reliability and validity of the Chinese version on Alcohol Use Disorders Identification Test (AUDIT) among medical students in China and to provide correct way of application on the recommended scales.Methods An E-questionnaire was developed and sent to medical students in five different colleges.Students were all active volunteers to accept the testings.Cronbach's α and split-half reliability were calculated to evaluate the reliability of AUDIT while content,contract,discriminant and convergent validity were performed to measure the validity of the scales.Results The overall Cronbach's α of AUDIT was 0.782 and the split-half reliability was 0.711.Data showed that the domain Cronbach's α and split-half reliability were 0.796 and 0.794 for hazardous alcohol use,0.561 and 0.623 for dependence symptoms,and 0.647 and 0.640 for harmful alcohol use.Results also showed that the content validity index on the levels of items I-CVI)were from 0.83 to 1.00,the content validity index of scale level (S-CVI/UA) was 0.90,content validity index of average scale level (S-CVI/Ave) was 0.99 and the content validity ratios (CVR) were from 0.80 to 1.00.The simplified version of AUDIT supported a presupposed three-factor structure which could explain 61.175% of the total variance revealed through exploratory factor analysis.AUDIT semed to have good convergent and discriminant validity,with the success rate of calibration experiment as 100%.Conclusion AUDIT showed good reliability and validity among medical students in China thus worth for promotion on its use.
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Objective To investigate the clinical significance of γ-interferon release test (IGRA) in the diagnosis of entry-exit people with tuberculosis.Methods A total of 64 patients with tuberculosis and 46 healthy people were detected by IGRA,tuberculin skin test (TST),LAM,38× 103 and 16 × 103.The results of different methods were compared and analyzed.Results The sensitivity of IGRA detection method (88.9 %) and specificity (95.8 %) were both higher,while the sensitivity (92.7 %) of the TST method was higher and the specificity (76.7 %) was lower.Conclusion The sensitivity and specificity of IGRA in the detection of tuberculosis are higher,and it has important clinical application value.
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Objective:To explore and discuss the differences of pregnancy contents and inform formats in in-formed consent form ( ICF) for the drug clinical trial between China and foreign countries. Methods:We collected Chinese and foreign ICFs for drug clinical trial that had been audited by the Ethics Committee of the third Xiangya Hospital for the past five years. Based on the relevant domestic and foreign law, we concluded the element stand-ards and inform formats about pregnancy inform. By analyzing the integrity of the whole elements, the inform rate of every element and the using rate of every inform format, we compared the differences of pregnancy contents and in-form formats between Chinese ICFs and foreign ICFs. Results:The total number of ICFs was 177 in this study, in-cluding 107 Chinese ICFs and 70 foreign ICFs. The integrity rate of pregnancy in Chinese ICFs was statistically lower than them in foreign ICFs (19% vs. 56%, P=0. 000). Compared with foreign ICFs, the low informed ele-ments were the study of the pregnancy risk (32% vs. 73%, P=0. 000), the pregnancy test during the following-up period (33% vs. 56%, P=0. 002) and the measurements for contraception (22% vs. 53%, P=0. 000). Conclusion:The integrity level of pregnancy content in Chinese ICFs was lower than that of the foreign ICFs. And the three elements including pregnancy risk study, pregnancy test during the following-up period and measure-ments for contraception was obviously defected. Pregnancy informing forms of informed consent in China was inferi-or to abroad.
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The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C max of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C max of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of C max, AUC0-t and AUC0-∞ of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations.
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Purpose To summarize the imaging features of inflammatory bowel diseases (IBD) with double-filling method using multi-slice CT enterography (MSCTE), and to evaluate the clinical significance of MSCTE in diagnosis of IBD. Materials and Methods MSCTE data with double-filling method of 52 patients with IBD were retrospectively analyzed. 52 IBD patients included 42 cases of Crohn's disease (CD) and 10 cases of ulcerative colitis (UC). Bowel dilatation and lesions display were evaluated. Results Among 52 patients, ileum dilated optimal in 10 cases (19.23%) and good in 42 cases (80.77%); jejunum dilated good in 21 cases (40.38%) and poor in 31cases (59.62%). Exhaustive evaluation for large bowel diseases were good in 50 cases (96.15%). The ileocecal junction displayed well in 52 cases (100.00%). Among the 42 cases of CD, 20 cases (47.62%) had lesions limited in the small intestine, 22 cases (52.38%) had lesions involved both small intestine and colon. Among 10 cases of UC, 9 cases had lesions limited in the colon, and 1 case with the terminal ileum and the colon involved simultaneously. The MSCTE findings of 52 patients included bowel wall thickening and abnormal enhancement in 52 cases, stenosis in 28 cases, increased mesenteric vascularity in 46 cases, enlarged mesenteric lymph nodes in 27 cases, phlegmon in 10 cases, incomplete intestinal obstruction in 4 cases, abscess or inflammatory masses in 7 cases, fistulas in 3 cases, perianal lesion in 12 cases, serous cavity effusion in 15 cases, sacroiliitis in 13 cases, the urinary and biliary stones in 18 cases, and hepatosplenomegaly in 9 cases. Conclusion MSCTE with double-filling method can delineate the wall lesions of small bowels and colons very well, and can also display extraintestinal lesions and complications. It obviously improves the accuracy of localization and qualitative diagnosis on IBD.
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Objective:To unify the content determination method for chlorphenamine maleate tablets and injections. Methods:An Inertsil C8(150 mm × 4. 6 mm,5 μm)column was used,the mobile phase was phosphate buffer( ammonium phosphate monobasic 11. 5g was dissolved in water,1 ml phosphoric acid was added and diluted to 1 000 ml by water)-acetonitrile(70:30),the flow rate was 1. 0 ml·min-1 ,the column temperature was room temperature,the sample volume was 10 μl and the detection wavelength was 262 nm. Results:The linear range of chlorpheniramine was 0. 017 8-0. 445 0 mg·ml-1(r=0. 999 9);the average recovery of the tablets and injections was 100. 2%(RSD=0. 4%,n=9)and 100. 3%(RSD=0. 9%,n=9),respectively. Conclusion:The method is simple,reproducible and accurate,and can provide reliable basis for the standards of chlorpheniramine maleate tablets,injections and dropping pills.
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Objective To observe the clinical effect of budesonide combined with ambroxol hydrochloride on the treatment of infant bronchopneumonia through oxygen atomizing inhalation .Methods One hundred and twenty -two cases of infant patients suf-fered with bronchopneumonia were randomly divided into two groups , control group (60 cases), the patients accept conventional treat-ment such as antibiotics, oxygen inhalation and anti-cough;treatment group (62 cases), patients were given budesonide combined with ambroxol hydrochloride through oxygen atomizing inhalation , beside conventional treatment .Main clinical signs and pulmonary symp-toms disappear time and treatment efficacy in two groups were observed and analyzed .Results The total effectiveness was obviously higher in treatment group(91.9%) than that of control group(81.7%) ( P <0.01).Wheezing disappearance time, wheezing sounds disappear time , crackles disappear time and cough disappear time in treatment group were significantly shorter than that in the control group ( P <0.01 ) .There were no adverse reactions on infant patients in both groups .Conclusions The effect of budesonide com-bined with ambroxol hydrochloride on the treatment of infant bronchopneumonia through oxygen atomizing inhalation was significant , and it is worthy of promotion in the clinic .
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Objective:To improve the determination method for penicillin V potassium tablets. Methods:An Inertis ODS-SP C18 column (150 mm × 4. 6 mm, 5 μm) was used. The mobile phase consisted of A and B(60∶40) [ A: pH 3. 5 phosphate buffer(0. 5 mol·L-1 potassium dihydrogen phosphate solution, adjusting pH to 3. 5 with phosphoric acid)-acetonitrile-water (10∶30∶60);B:pH 3. 5 phosphate buffer-acetonitrile-water (10∶55∶35)]. The flow rate was 1. 0 ml·min-1, the detection wavelength was 268nm, the column temperature was room temperature and the injection volume was 10 μl. Results:The linear range of penicillin V potassium was 0. 032 9-0. 821 6 mg·ml-1(r=0. 999 9, and the average recovery was 99. 9%( RSD=0. 6%, n=9). Conclusion:The method is reproducible and accurate, and can be used in the content determination of penicillin V potassium tablets and capsules.
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OBJECTIVE@#To investigate the variation of senescent endothelial function by regulating the sphingosine-1-phosphate receptor type 2 (S1P2) expression in cultured human umbilical vein endothelial cells (HUVECs).@*METHODS@#The S1P2 receptor expression was regulated by transfecting the cDNA or shRNA of S1P2 in cultured HUVECs. The expression levels of S1P2 receptor in HUVECs were detected by RT-PCR and Western blot. EC chemotaxis was measured by the transwell migration assay. The wound healing assay was performed by a scratch wound model on EC monolayer. Matrigel morphogenesis assay was employed to assess the in vitro angiogenic responses.@*RESULTS@#After up-regulating the S1P2 expression in young ECs, the S1P-stimulated formation of a tubular-like network in Matrigel was dramatically diminished in transfected ECs (P<0.05). Quantification of the wound healing assay showed that transfected ECs grew much slower than young ECs (P<0.05). The chemotactic capability was significantly decreased in transfected ECs (P<0.05). Furthermore, the senescent-associated impairments were revoked by the downregulation of S1P2 receptor in senescent HUVECs.@*CONCLUSION@#The impaired functions (chemotactic, wound-healing and morphogenetic responses) in senescent HUVECs in vitro are mediated by S1P2 receptor.
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Humains , Cellules cultivées , Vieillissement de la cellule , Génétique , Cellules endothéliales de la veine ombilicale humaine , Biologie cellulaire , Physiologie , Interférence par ARN , Petit ARN interférent , Génétique , Récepteurs aux lysosphingolipides , Génétique , Métabolisme , Récepteurs de la sphingosine-1-phosphate , Transfection , Régulation positiveRésumé
Objective To explore the expression and significance of matrix metalloproteinase-2 (MMP-2) and basic fibroblast growth factor (bFGF) in human glioma.Methods The expression levels of bFGF and MMP-2 in 56 cases of human glioma and 9 cases of normal brain tissue specimen were detected by immunohistochemistry technique.Furthermore,the correlation between the expression of the bFGF and MMP-2 was compared.Results In normal brain tissue,grade Ⅰ,Ⅱ and grade Ⅲ,Ⅳ,the positive expression of bFGF were (9.51 + 2.69)%,(24.78 ±- 7.57 )%,(41.23 ± 12.35 )%,respectively,and MMP-2were (7.18 ± 2.12)%,(21.56 ± 3.85 )%,(54.32 + 7.32)%,respectively.The differences were significant among them (P <0.05).bFGF and MMP-2 were positive correlated (r =0.71,P <0.01).Conclusions There is an intrinsic correlation between the expression of the bFGF and MMP-2 and histological grade of human gliomas.These findings suggest that the synergistic interaction of bFGF and MMP-2 play an important role during the tumor invasion.
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Objective To evaluate the clinical efficacy and safety of antofloxacin hydrochloride tablet for the treatment of acute bacterial infections. Methods A multi-center randomized control, double blind and double dummy clinical trial was conducted; levofloxacin tablet was chosed as controlled drug. The duration of treatment was 7-14 days in both groups. Results A total of 719 patients were enrolled in the study, in which 359 patients treated with antofloxacin and 360 patients treated with levofloxacin were included. Three hundred and thirty and 337 patients completed the study and met with all the criteria for perprotocol analysis, respectively. By the end of chemotherapy, the cured rates in per protocol set (PPS)population were 79.7% and 77.4%, the effective rates were 95.2% and 96. 7%, and the bacterial clearance were 96. 7% and 97. 5% for the treating and control group, respectively. The clinical and bacterial efficacy of antofloxacin and levofloxacin was comparable by the analysis of infectious sites. Three hundred and fifty-seven and 356 patients in antofloxacin and levofloxacin groups were evaluated the safety.The drug adverse events occurred both in 10. 1%, and drug adverse reactions accurred in 7. 8% and 7.9%patients in the two groups. The most common drug adverse reactions were mild gastroenteric symptoms. No QTc prologation was detected in all the patients. One patient in each group had mild blood glucose increase at the end of therapy, but the glucose returned to normal level without any intervention. No statistic significant difference between the two groups in clinical efficacy and safety was detected (P>0.05).Conclusions Antofloxacin hydrochloride tablet was effective and safe for the treatment of acute bacterial infections.
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OBJECTIVE To investigate the uses of antibacterials,the characteristics of bacterial distribution and the drug resistance and provide a foundation for reasonable application of antibacterials.METHODS Germs isolation and cultivation were carried out according to National Clinical Testing Operation Procedures(2nd edition).Germs definition and resistance test were carried out by using VITEK 2 Compact microbiological assay system.Statistical analysis was processed by using WHONET 5.4.RESULTS Totally 7815 strains of bacteria were isolated from clinical samples,most of which were Gram-negatives(G-)(58.0%,56.3% and 59.5%,respectively in the 3 years).The tendency of Gram-positives(G+) didnot charee obviously(about 20%).Theresistance were increasing.The resistance rate of Staphylococcus aureus was more than 70.0 % to the most antibacterials.Up to now,there was no vancomycin-resistant isolate.CONCLUSIONS We should use antibacterials reasonably and efficiently to delay and control drug resistance,according to the susceptibility test.