1.Plasmid-mediated quinolone resistance in Escherichia coli strains isolated from food animals
Yunpeng WANG ; Shenghui CUI ; Jingyun LI ; Changqin HU ; Shaohong JIN ; Yue MA
Chinese Journal of Microbiology and Immunology 2010;30(5):477-482
Objective To study on plasmid-mediated quinolone-resistant in Escherichia coli strains isolated from fecal samples of chicken and swine from the nine farms around our country.Methods Antimi-crobial susceptibility testing was carried out by broth microdilution testing,gyrA,gyrB,parC,qnr and aac (6')- Ⅰ b-cr were examined by PCR,and the products were sequenced.Conjugation experiment was carried out to proved that the plasmid-mediated quinolone resistance was transferable.Results In the total 818 animal isolates,qnr and aac genes were detected in 38 (4.6%) and 75 (9.2%) strains.The qnrA,qnrB,and qnrS genes were detected in 1 (0.1%),9 (1.1%) and 28 (3.4%) of the isolates.All isolates were negative for qnrC,qnrD genes.Conclusion There is a close relationship between high level quinolone resistance and plasmid-mediated quinolone resistance.The results of the current study highlight food-producing animals as a potential reservoir of antimicrobial-resistant bacteria and clinically important resistance genes.More attention should be paid to the surveillance of such strains.
2.Contributions of different quinolone resistance mechanisms in Escherichia coli
Shenghui CUI ; Jingyun LI ; Yue MA ; Changqin HU ; Li ZHANG ; Shaohong JIN
Chinese Journal of Microbiology and Immunology 2008;28(4):338-342
Objective To characterize the roles of different quinolone resistance mechanisms in quinolone-resistant Escherichia coli isolates,including different topoisomerase point mutations,efflux pumps and outer membrane proteins.Methotis Through homologous gene recombination methods,different quinolone-resistant mechanisms of E. coli mutants were constructed and the susceptibility changes of these mutants to different antimicrobials were measured.Resuits Efflux pumps AcrAB and outer membrane protein TolC played different roles in different E. coli isolates.Compared with other mechanisms,the mutations in topoisomerases played a dominant role in quinolone resistance.Only the mutations jn parC had no effect on quinolone resistance,which further confirmed parC was the secondary target of quinolones in E.coli.Fluoroquinolone susceptible E.coli would automatically become highly resistant to quinolones after acquiring the point mutations in both gyrA(S83L,D87N)and parC(S80I,A108V),but not requiring the over-expres-sion of efflux.Conclusion The mutations in topoisomerases play a dominant role in E.coli quinolone resistance,and the mutations in both gyrA and parC are required.
3.Optimal computer aided measure for screw internal fixation in the cavitas glenoidalis through human coracoid process of scapula
Yimin CHEN ; Junyi HONG ; Dawei BI ; Haitao MA ; Shenghui LIAO ; Hui WANG ; Gang ZU
Acta Anatomica Sinica 2010;41(1):153-156
Objective To investigate a special optimization technique for computer aided measure, and provide anatomical basis for screw internal fixation in the cavitas glenoidalis through the coracoid process of scapula. Methods Thirty accurate scapula models were reconstructed from CT data sets. First, special optimization objective function was designed for single screw internal fixation configuration, and the optimal placement of screw was found automatically under constraints. Then, the placements of double screws internal fixation configuration were searched taking advantage of principal component analysis. Finally, statistical measure data were provided according to new anatomical reference landmarks for clinical use. Results For single screw internal fixation configuration, the distance from the optimal screw entry point P to the acromion process point X was (39.15±2.28) mm, to the coracoid process point Y was (28.66±2.68) mm, to the angulus superior point Z was (61.13±6.57) mm;The angle was (81.27±7.15)° between PX and PY, and (133.27±6.84)° between PX and PZ. The mean inclination of the lag screw was (104.08±4.41)° for the angle with line PX, (101.29±3.51)° with line PY, and (76.23±5.03)° with line PZ. For double screws configuration, the distance from the original single screw entry point P to the screw entry point E was (5.12±1.37)mm,to the screw entry point F was (3.88±0.94)mm. The angle between the long axis of coracoid process and line EF was (27.41±3.51)°. Conclusion The automatic optimization technique for computer aided measure is very efficient and has many advantages over the conventional manual dissection methods, and is convenient to design new anatomical reference landmark system for clinical use.
4.Antimicrobial resistant mechanisms analysis of outpatient Salmonella enterica serotype Typhimurium in Wuhan
Shenghui CUI ; Jingyun LI ; Yue MA ; Changqin HU ; Li ZHANG ; Shaohong JIN
Chinese Journal of Laboratory Medicine 2008;31(11):1253-1258
Objective To characterized the Salmonella enterica serotype typhimurium isolates recovered during 2002 to 2005 from outpatients in Tongji Hospital, Wuhan China. Methods The 36 isolates from Tongji Hospital were characterized by antimicrobial-susceptibility testing and screened for class Ⅰ integrons, beta-lactamase genes, qnr, aac(6')-Ib-cr and mutations in the quinolone resistance determining regions (QRDRs) by PCR and DNA sequence analysis. All isolates were also characterized by pulsed-fieldgel electrophoresis (PFGE) to determine the genetic relateness among these isolates. Results All isolates displayed multidrug resistance and most of them harbored class Ⅰ integrons. Ciprofloxacin-resistant isolates showed significant difference compared with ciprofloxacin-susceptible isolates after PFGE analysis. All 31 ciprofloxacin resistant isolates carried at least three mutations in the QRDR of GyrA and ParC. Three ciprofloxacin resistant isolates had accumulated additional mutation in ParE. Five isolates harboring the OXA-30. Enzyme showed intermediate resistant to eefepime. Conclusions Fluoroquinolone-resistant Salmonella typhimurium isolates were widely distributed among the outpatients in Wuhan and the resistant isolates accumulated multiple antimicrobial resistant mechanisms and showed unique genetic profiles. The state and local health authority must remain vigilant for the emergence of Salmonella typhimurium resistant to both third generation cephalosporins and fluoroquinolonos.
5.Chromosome-and plasmid-mediated fluoroquinolones-resistance in Escherichia coli strains isolated from food animals and healthy people around farm
Jingyun LI ; Shenghui CUI ; Yunpeng WANG ; Changqin HU ; Shaohong JIN ; Yue MA
Chinese Journal of Microbiology and Immunology 2008;28(8):739-743
Objective To study on chromosome-and plasmid-mediated fluoroquinolones-resistant in Escherichia coli isolated from fecal samples of chicken,swine and people around the farm.Methods Anti-microbial susceptibility testing was carried out by disk diffusion testing and bmth microdilution testing.gyrA,gyrB,parC,pareE,qnr and aac(6')-I b-cr were examined by PCR,and the products were sequenced.Ex-presion of aac(6')-I b-cr by conjunction was tested too.Results The resistance to antimicmbial agents was much higher in strains isolated from chicken than that from swine and human.Among the E coli strains examined by PCR,most resistant strains carried two mutations in gyrA and/or two mutations in parC.In ad-dition,some resistant strains had mutations in parE with MIC of ciprofloxacin>16μg/ml.No(resistance) mutation was found in gyrB.Seven strains(25.O%)and one strain(11.1%)had aac(6)-I b-cr,variant isolated from chicken and swine,respectively.The strains harboring cr variant enzyme reduced the suscepti-bility to ciprofloxacin and norfloxacin by N-acetylation of the drugs. Conclusion There is a close relation-ship between high level quinolone resistance and the numbers of amino acid exchange in DNA gyrase and to-poisomeraae IV,and aac(6)-I b-cr may play some role for fluoroquinolone resistance.
6.Clinical efficacy of Bobath therapy combined with traditional Chinese medicine fumigation and intradermal acupuncture on shoulder hand syndrome after stroke
Chunfeng SUN ; Zhonggen NI ; Shuxing LI ; Xiangdong MA ; Bin SHEN ; Shenghui JIN
Chinese Journal of Primary Medicine and Pharmacy 2020;27(13):1614-1618
Objective:To explore the clinical effect of Bobath manipulation combined with traditional Chinese medicine fumigation and intradermal acupuncture on shoulder hand syndrome(SHS) after stroke.Methods:From April 2017 to August 2019, 80 patients with SHS after stroke admitted to the People's Hospital of Deqing County were selected, and they were divided into control group and observation group according to the random digital table method, with 40 cases in each group.The control group was treated by Bobath therapy, and the observation group was treated by Bobath therapy combined with acupuncture(intradermal acupuncture) and traditional Chinese medicine fumigation.After 8 weeks of treatment, the ROM scale, FMA scale, BI scale and VAS scores were used to evaluate the improvement in the mobility of the shoulder and wrist joints, motor function of the upper limbs, quality of life and pain, and the clinical efficacy of the two groups was compared.Results:Compared with before treatment, the ROM scale score of all dimensions of shoulder and wrist mobility, FMA scale score and BI scale score of all patients after treatment increased significantly, and the VAS score decreased significantly, the differences were statistically significant(all P<0.05). Compared with the control group after treatment, the improvement of the indicators mentioned above of the observation group were better[shoulder joint flexion ROM score: (154.83±25.63)points vs.(133.82±22.03)points; shoulder joint abduction ROM score: (152.36±25.68)points vs.(133.35±19.96 )points; shoulder joint external rotation ROM score: (75.87±14.69)points vs.(60.82±16.57 )points; wrist joint palm flexion ROM score: (73.94±14.37)points vs.(57.37±9.47)points; wrist joint back extension ROM score: (60.83±7.61)points vs.(42.27±6.37 )points; FMA scale score: (45.74±6.82)points vs.(34.19±4.07)points; BI scale score: (70.36±12.09)points vs.(58.70±12.53)points; VAS score: (1.05±0.49)points vs.(3.37±1.14)points, t=3.703, 3.715, 3.257, 5.576, 7.964, 3.037, 8.746, 3.153, all P<0.05]. The total effective rate of the observation group was significantly higher than that of the control group[97.5%(39/40) vs.62.5%(25/40), χ 2=15.313, P<0.05)]. Conclusion:The combination of Bobath therapy with traditional Chinese medicine fumigation and intradermal acupuncture can improve the pain degree, joint mobility disorder, upper limb motor function and quality of life of SHS patients, the efficacy is better than single Bobath therapy.The clinical effect is accurate, and it is worthy of further promotion and application.
7.Fatal familial insomnia preliminarily diagnosed as frontotemporal dementia: a case report and literature review
Yajing SUN ; Mingrong XIA ; Hong YANG ; Weizhou ZANG ; Limin MA ; Shenghui WANG ; Hongju ZHANG ; Jiewen ZHANG
Chinese Journal of Neurology 2018;51(4):294-298
Objective To explore the clinical,imaging,genetic features in a case of fatal familial insomnia (FFI),and review related literatures.Methods A case of middle-aged woman diagnosed as frontotemporal dementia based on the preliminary manifestation of abnormal mental behavior was reported.The clinical features,imaging characteristics,electroencephalogram and polysomnogram of the patient were analyzed,and the blood samples from the patient and some of her familial members were collected for the sequencing of prion protein gene (PRNP).Results This patient was a middle-aged woman,whose clinical manifestations were abnormal mental behavior,rapid progressive dementia and intractable insomnia,abnormal night sleep behavior and laryngeal stridor.Brain MRI indicated frontotemporal lobe atrophy.Non-sleep disturbance was observed in polysomnography.The cerebrospinal fluid was negative for 14-3-3 protein.The results of PRNP sequencing revealed that the mutation of gene D178N/129M was detected.Conclusions Detection of PRNP plays an important role in the diagnosis of FFI.Patients suspected of FFI in clinic should be detected for genetic testing.Whether the frontotemporal lobe atrophy was caused by FFI or concurrent with FFI remains to be further verified.
9.lncRNA HCG18 regulates the proliferation and metastasis of non-small cell lung cancer cells through targeting miR-17-5p/HMGA2 axis
QU Baoliang ; MU Huaibo ; GOU Jianqiang ; YANG Yu ; MA Shenghui ; DU Chunyang
Chinese Journal of Cancer Biotherapy 2019;26(4):409-416
Objective: To investigate the mechanism of lncRNA HCG18/miR-17-5p/HMGA2 axis regulating the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells. Methods: Sixty-two pairs of NSCLC tissues and corresponding para-cancerous tissues collected at Central Hospital of Chengde City from June 2017 to June 2018 were used for this study; in addition, NSCLC cell lines (A549, NCI-H1299, H1650, NCI-H460) and human lung epithelial BEAS-B cells were also collected. mRNA expression levels of HCG18, miR-17-5p and high-mobility group AT-hook 2 (HMGA2) in NSCLC tissues and cell lines were measured by quantitative Real-time polymerase chain reaction (qPCR). Si-HCG18, miR-17-5p, miR-17-5p+HCG18 or pcDNA3.1-HMGA2 were transfected into A549 cells and NCI-H460 cells; CCK-8 assay was used to detect the proliferation of transfected cells, Transwell assay was used to detect the migration and invasion ability of cells, and Wb was used to analyze the expressions of HMGA2 and EMT associated proteins (E-cadherin, N-cadherin and vimentin). The target relationships between HCG18 and miR-17-5p, or between miR-17-5p and HMGA2 were confirmed by dual luciferase reporter gene assay. Mice A549 cell xenograft model with HCG18 knockdown was constructed, and the growth of transplanted tumor was observed. Results: lncRNA HCG18 was highly expressed in NSCLC tissues and cells (all P<0.01); HCG18 level was significantly increased in patients at late stage or with lymphnode metastasis; and high HCG18 level was correlated with poor prognosis and low survival rates of NSCLC patients (all P<0.01). Knockdown of HCG18 significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), up-regulated E-cadherin expression but suppressed N-cadherin and vimentin expression (all P<0.01), and the volume of xenograft was obviously decreased (P<0.05). Dual luciferase reporter gene assay confirmed the relationship between HCG18 and miR-17-5p as well as miR-17-5p and HMGA2. miR-17-5p transfection significantly inhibited NSCLC cell proliferation, migration and invasion (all P<0.01), and up-regulated E-cadherin expression, reversely suppressed N-cadherin and vimentin expression (all P<0.01); however, miR-17-5p + HCG18 transfection reversed the effect of miR-17-5p on NSCLCcells.Conclusion:HCG18promotes the proliferationandmigrationofNSCLCcellsthrough regulating miR-17-5p/HMGA2 axis.
10.Discovery of WS-157 as a highly potent, selective and orally active EGFR inhibitor.
Pengxing HE ; Shenghui NIU ; Shuai WANG ; Xiaojing SHI ; Siqi FENG ; Linna DU ; Xuyang ZHANG ; Zhilu MA ; Bin YU ; Hongmin LIU
Acta Pharmaceutica Sinica B 2019;9(6):1193-1203
EGFR tyrosine kinase inhibitor (EGFR-TKI) has been used successfully in clinic for the treatment of solid tumors. In the present study, we reported the discovery of from our in-house diverse compound library, which was validated to be a potent and selective EGFR-TKI. showed excellent inhibitory activities against EGFR (IC = 0.81 nmol/L), EGFR (IC = 1.2 nmol/L) and EGFR (IC = 1.1 nmol/L), but was less effective or even inactive against other nine kinases. also displayed excellent antiproliferative activities against a panel of human cancer cell lines, and exhibited the ability to reduce colony formation and wound healing the same as gefitinib. We found that upon oral administration showed better anti-tumor activity in A431 bearing xenograft mouse models compared to gefitinib. In addition, showed better intestinal absorption than gefitinib and had favorable pharmacokinetic properties and microsomal metabolic stability in different species. These studies indicate that has strong antitumor activity and , and could be used for the development of anti-lung cancer agent targeting EGFR.