Objective To investigate the effect of resistance nodulation division (RND) efflux pumps on reduced susceptibility to tigecycline in carbapenem-resistant Acinetobacter baumanii.Methods Totally 631 isolates of Acinetobacter baumanii were collected from 16 hospitals in 7 provinces in 2010.Genes oxa-51 and oxa-23 were detected by PCR method,and the ST profiles were determined by multilocus sequence typing (MLST).The disk susceptibility assay was used to determine the inhibition zone diameters of β-lactams,aminoglycosides,macrolides,tetracyclines,carbapenems,tigecycline and polymyxin.The minimum inhibitory concentration (MIC) of tigecycline was determined by E-test in strains with inhibition zone diameters ≤ 12 mm on tigecycline.The expression of operon genes adeB,adeG and adeJ was determined with efflux pump inhibitor NMP (N-methyl-2-pyrrolidone) for detection of efflux pump inhibitor phenotype.The isolates of Acinetobacter baumanii which were resistant both to tigecycline and carbapenems and with the inhibited phenotype of efflux pump inhibitor were collected as the experiment group,the isolates which were susceptible to tigecycline but resistant to carbapenems were collected as the control group,and ATCC 19606 was used as the reference strain.The expressions of adeABC,adeFGH and adeIJK were quantified by q-PCR at the transcriptional level.Genes adeR,adeS and adeL were amplified and sequenced using PCR method to find polymorphic locus and insertion sequences.Results There were 32 isolates of Acinetobacter baumanii with reduced susceptibility to tigecycline and carbapenem-resistant.Eight isolates were with the inhibited phenotype by efflux pump inhibitor.And 4 strains which were susceptible to tigecycline but resistant to carbapenems were selected as the control.The expressions of adeABC in A518,Z1219 and A527 of experiment group were 13-fold,5-fold and 7-fold higher than reference strain ATCC19606,respectively.The expressions of adeFGH and adeIJK were up-regulated slightly in some isolates.Transcript of adeABC was not found in control group strains A207 and A1731,and the expressions of adeABC,adeFGH and adeIJK were not up-regulated in other isolates.The single nucleotide polymorphism (SNP) was detected in adeR (E220K) and adeS (A130D),respectively.ISAab1 insertion sequence was identified in adeS of adeABC-over expressed isolates.No mutation was found in adeL.Conclusion High expression of adeABC pump may play an important role in tigecycline resistance in carbapenem-resistant Acinetobacter baumannii,mainly due to the insertion of ISAba1 sequence in its regulator gene adeS,but other mechanism of tigecycline resistance may not be excluded.

To develop an ophthalmic preparation of Shedan, an in situ forming gel was prepared with the formulation containing 18% of poloxamer 407 and 5% of poloxamer 188 by response surface designs plus central composite designs. The rheology results showed that LVE range gamma should limited within 0.5%, Shedan high-frequency region, and the thixotropy recovery time is less than 5 seconds. The phase transition temperature was 33.25 °C according to curve of storage modulus and loss modulus determined by temperature scanning. Surface tension and osmometer of it determined by surface tension meter and dew point osmometer were 36.43 mN · m(-1), and 320.6 mOsm · kg(-1), respectively. Fluorescein sodium was selected as the marker to monitor the corneal residence time, and the results showed that Shedan gel could prolong drug residence for 180 min. In line with zero-order kinetics, releases of muscone and salvianolic acid B in vitro depends on gels erosion. The results of rabbit ocular irritation experiments suggested that Shedan in situ forming gel was biocompatible and nonirritant. In conclusion, a novel Shedan in situ forming gel was developed and characterized for potential drug treatment of retinal vein occlusion.
Animals ; Benzofurans ; chemistry ; Cycloparaffins ; chemistry ; Female ; Gels ; chemistry ; Male ; Ophthalmic Solutions ; Poloxamer ; chemistry ; Rabbits ; Retinal Vein Occlusion ; drug therapy ; Viscosity

Objective To investigate the relationship between severe toxicity during high-dose methotrexate (HD-MTX) chemotherapy and 29 related factors including SLCO1B1 521T ＞ C genovariation,and to enhance drug safety.Methods Eighty-two children with acute lymphoblastic leukemia (ALL) received HD-MTX chemotherapy.The regimen was MTX 3-5 g/m2 continuous infusion for 24 hours.The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the patients' genotypes of SLCO1B1 T521C polymorphism,which was the coding gene of organic anion transporting polypeptide 1 B1 (OATP1 B1).Haematological,gastrointestinal and hepatic toxicities in 1-10 days after HD-MTX administration were observed and graded according to Common Terminology Criteria for Adverse Events (CTCAE,version 4.02).The patients were divided into two groups based on toxicity grades:case group (grades Ⅲ-Ⅴ) and normal group (grades 0-]]).The differences of 29 variates including biology features,biochemical indicators,SLCO1B1 T521 C polymorphism and etc.were compared between the two groups by univariate analysis,and the significant factors were found out.The final predictive model of severe HD-MTX-related toxicity was set up through Logistic regression analysis.Receiver operating characteristic (ROC) curve of predictor was drawn based on final model in order to evaluate its predictive ability.Results There were only 4 significant different variates between case group and normal group (P ＜ 0.05),including SLCO1B1 T521C polymorphism,serum MTX concentrations at 72 hours after starting MTX infusion (C72h),the ratios of 7-hydroxy-MTX (the metabolin of MTX) to MTX concentrations at 48 hours (k48 h),and frequency of k48 h ≤2.Based on a multivariate logistic regression analysis,only SLCO1B1 521T＞ C genovariation (odds ratio 18.489,95％ confidence interval 5.413-63.157)was the significant independent predictor for severe HD-MTX-related toxicity.The area under ROC (95％ confidence interval) of SLCO1B1 521T ＞ C genovariation as the predictor for severe HD-MTX-related toxicity was 0.776 (0.653-0.899),which had significant diagnositic value (P ＜ 0.05).Conclusions There is higher risk of severe HD-MTX-related toxicity while patients having SLCO1B1 521T ＞ C genovariation.Clinician should consider it and take some protective measures.

Objective To evaluate the changes of the activation and proliferation of rat cardiac fibroblasts in infarcted and non-infarcted regions.Methods The model of myocardial infarction (AMI)was developed through the ligation of anterior descending branch of left coronary artery.After 24 hours,the survived 114 rats were randomly assigned to the following 2 groups:(1)AMI group (n=57);(2)telmisartan treatment group(n=57).And a sham-operated group(n=32)was used asa control.All groups were terminated at day 4,7,14,28,respectively(n=10,12,15,20).At the end of the study,heart rate(HR),blood pressure (BP),ventricle relative weight (ventricle weight/body weight,VW/BW) and survival rate were measured,and the activation and proliferation of fibroblast and collagen volume fraction (CVF) were assessed.Results (1)The 28 day accumulated survival rate for treatment group was lower than that for AMI group (P

Objectives To investigate the clinical features,prognosis and risk factors of patients with cryptococcal meningitis.Methods Totally 146 patients with cryptococcal meningitis who were hospitalized in Huashan Hospital from January 2000 to December 2006 were enrolled in this study.The clinical data including diagnosis and misdiagnosis,experimental and etiology tests,treat- ments and prognosis from all the patients were analyzed retrospectively.Results Among the 146 patients enrolled in the study,78 patients(53.4%)had concomitant diseases.The misdiagnosis rate of all patients was 72.6%(106/146).The positive rate of cerebrospinal fluid(CSF)India ink smear was 59.6%(87/106),while 43.2%(63/146)cases of cryptococcus neoformans culture in CSF was positive.The positive rate of Latex agglutination test(LAT)was 91.7%(134/146)in CSF among all patients.The treatments were as follows:combination of Amphotericin B(AmpB)or its lipid formula- tions with flucytosine(5-FC)(98 cases),including combination with Fluconazole initally(62 cases), single therapy of Fluconazole(13 cases).Ommaya implanted for lateral cerebral ventricle drainage(53 cases)and AmpB intrathecal injection(53 cases).The average dose of AmpB is 3.06 g.The course of treatment lasted from 12 weeks to 20 months.There were 104 patients(71.2%)cured,27(18.5%) improved,15(10.3%)died and 34(23.3%)relapsed.Conclusions High misdiagnosis rate is common in patients with cryptococcal meningitis.Immunodeficiency is the major risk factor for cryp- tococcal meningitis.CSF LAT is the most sensitive diagnostic test.Early diagnosis,combination of AmpB with 5-FC antifungal therapy and control of acute intracranial hypertension are the keys to im- prove prognosis of cryptococcal meningitis.

Objective To investigate the expression of Toll-like receptor 3 (TLR3) on dendritic cells(DCs) derived from peripheral blood mononuclear cells(PBMCs) of chronic hepatitis B(CHB) patients and to explore the mechanism of sustained infection of hepatitis B virus (HBV). Methods Twenty CHB patients were randomly screened in the study,and ten healthy persons were recruited as controls.The monocytes isolated from peripheral blood of candidates were incubated with recombinant human granuloeyte macrophage colony-stimulating factor (rhGM-CSF) and rhIL-4 to induce the DCs generation and proliferation.Then the phenotype of DCs was identified by micro- scope.The expressions of the phenotypes[histocompatibility leukocyte antigen(HLA)-DR,CD80, CD86,CD83]of immature and mature DCs were measured by flow cytometer.Furthermore,the ex- pression of TLR3 on mature DCs(mDC) and immature DCs(imDC) was determined by flow cytometry and Western blot analysis respectively.Results As for healthy volunteers,the expressions of CD80, CD86,HLA-DR and CD83 on DCs at the 7th day,which were(82.35?8.67)%,(79.61?10.08)%, (92.79?8.48)% and (83.76?5.47)% respectively,were significantly higher than those at the 5th day which were(28.31?8.79) %,(31.17?11.23)%,(27.61?10.28)% and (23.46?11.53)% respec- tively(P0.05).The expression of TLR3 on imDC was significantly higher than that on mDC at control group (P0.05).And the expression of TLR3 on imDC in CHB patients group was significantly lower than that of control group(P

Objective:To preliminarily evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for pulmonary oligometastatic tumors from head and neck carcinoma.Methods:Clinical data of 24 patients with pulmonary oligometastasis from head and neck carcinoma undergoing SBRT in Zhejiang Cancer Hospital from January 2014 to May 2019 were retrospectively analyzed. Survival analysis was performed by Kaplan- Meier method. Results:Among the 24 patients, 12 cases were diagnosed with nasopharyngeal origin and 12 cases of non-nasopharyngeal origin. A total of 34 pulmonary metastatic lesions were treated with SBRT. The median follow-up time was 19.5 months. Thirteen cases developed new lesions after SBRT, and 9 of them occurred within 1 year after SBRT treatment. The actual 1-year local control rate was 95%. The median progression-free survival was 15.2 months, and the 1-and 2-year progression-free survival were 59% and 46%, respectively. The 2-and 3-years overall survival rate at were 71% and 51% fter lung metastasis, respectively. Univariate analysis showed that the patients with primary lesions located in nasopharynx and disease-free interval of more than 1 year had survival advantage. No more than grade 3 radiation-induced injury was observed in the whole cohort after SBRT, and the incidence of mild radiation-induced injury was 13%.Conclusions:SBRT is safe and effective in the treatment of pulmonary oligometastatsis from head and neck carcinoma, and it may be more effective for patients with primary tumors located in nasopharynx.

OBJECTIVETo collect evidence in diagnosis and treatment of oral mucosal diseases.

METHODSThe Cochrane library (Issue 3, 2009) was searched to get the full texts of published related Cochrane systematic reviews. The results were summarized for recommendation to dentists. The current status of evidence based medicine in this field was analyzed.

RESULTSReliable evidence for management of oral submucous fibrosis is still limited; amifostine, hydrolytic enzymes, ice chips and Chinese medicine may be effective in preventing oral mucositis for patients with cancer receiving radiotherapy or chemotherapy; the evidence in treating oral mucositis with allopurinol mouthwash, granulocyte macrophage-colony stimulating factor, immunoglobulin or human placentral extract for patients with cancer receiving treatment is weak and unreliable yet; there is evidence that acyclovir is efficacious in prevention and treatment of herpes simplex virus infections in patients being treated for cancer; there is strong evidence that drugs absorbed or partially absorbed from the gastrointestinal tract prevent oral candidiasis in patients receiving treatment for cancer; relapses and adverse effects are common in using beta carotene, lycopene, vitamin A or retinoids to treat oral leukoplakia; only some weak evidence is provided in using cyclosporines, retinoids, steroids or phototherapy for treating oral lichen planus; the evidence about acyclovir for treating primary herpetic gingivostomatitis is insufficient; there is little research evidence for treatment of burning mouth syndrome.

CONCLUSIONIt is essential to raise the quality of design and conduction of clinical trials in the field of oral mucosal disease to provide solid bases for systematic review, so that to improve evidence based treatment of these diseases.

Objective To investigate the effect induced by specific inducible nitric oxide synthase (iNOS) inhibitor 1 400 W on nasopharyngeal carcinoma CNE-2 cells lines and its mechanism.Methods CNE-2 cells were treated by different concentrations of 1 400 W,diamminedichloroplatinum (DDP),and both chemicals.Cell counting kit-8 (CCK-8) was used to examine the viability of cells.Quantitative realtime polymerase chain reaction (qRT-PCR) was applied to detect the iNOS mRNA expression.Results The expression of iNOS mRNA was down-regulated by 1400W and was positively correlated with inhibitionrate of cell proliferation.1 400 W inhibits proliferation of CNE-2 cell in a concentration-dependent manner.The proliferation inhibition rate of CNE-2 cells treated by 1 400 W combined with DDP was not enhanced.Conclusions Specific inducible nitric oxide synthase inhibitor 1 400 W can exerts anti-tumor effect though inhibiting the expression of iNOS mRNA;The mechanism of chemosensitization induced by iNOS inhibitor on CNE-2 cells may be closely related level of down-regulation of iNOS expression.

Objective To investigate the clinical value of acoustic radiation forcs impulse (ARFI)in quantitative evaluating placental elasticity.Methods The study population included 487 normal pregnant women,and ARFI generated shear wave velocity (SWV)was measured.On the basis of gestational ages, placental sites and sampling depths in region of interest (ROI),the normal population was divided into different groups.One-way analysis of variance was used to compare the discrepancy on the SWV values amomg the nomal placental sites or the sampling depths in ROI.Pearson correlation coefficient were used to assess the possible relationships between the normal placental SWV values and the different gestational ages or the placental grades.A total of 5 1 cases were diagnosed with severe preeclampsia,among them 25 cases were categorized as severe preeclampsia with fetal growth restriction (FGR).The placental SWV values were measured and compared with those of the normal population.The pathological examinations were performed on 50 normal and 5 1 abnormal placentas.Results Basing on the placental sites,the normal population were divided into three groups:anterior wall,lateral wall and posterior wall groups.Compared with the posterior wall group,the placental SWV values in the anterior wall or lateral wall group significantly decreased (P <0.05).No statistical significant difference was found between the anterior wall group and the lateral wall group.Basing on the distance from the sampling depths to the probe (range from 2 to 7.99 cm,and each additional 1 cm corresponding a group),the normal population were divided into six groups.There was statistical significant difference for the placental SWV values between the two groups of distance in the range of 2.0 to 5.99 cm and 6.0 to 7.99 cm (P <0.05).There was no statistical significant difference between the other two groups.The mean SWV value was (0.78±0.08 m/s)in the normal group. No significant relationships were found between the placental SWV values and the gestational ages of the normal population.However the placental SWV values were significantly related to the placental grades.For the placental SWV values,there was statistical significant difference between the normal group and the abnormal group (P <0.05).No statistical significant difference was found between the severe preeclampsia group and the severe preeclampsia with FGR group.The pathological examinations also showed significant changes in the abnormal group.Conclusions ARFI may quantitatively analyze the placental elasticity and make a difference between nomal and abnormal placenta.