This study aims to investigate the synergistic antimicrobial effect of demethylzeylasteral meropenem against NDM-1-positive Escherichia coli.Firstly,the nitrocefin hydrolysis assay and molecular docking assay were used to determine the inhibitory effect and mechanism of demethyl-zeylasteral on the hydrolytic activity of the NDM-1 protein.Secondly,the synergistic bacteriostatic effect of demethylzeylasteral with the carbapenem antibiotic meropenem was confirmed by the checkerboard minimum inhibitory concentration assay,growth curve assay,and inhibition zone as-say.The synergistic bactericidal effect of the combination was further determined by the time-kill-ing assay,live/dead bacterial staining assay,and membrane integrity assay.Finally,the G.mellonel-la infection model demonstrated the protective effect of demethylzeylasteral and meropenem.The results indicated that demethylzeylasteral significantly inhibited the hydrolytic activity of NDM-1(IC50=0.32 mg/L)and competitively affected the binding of NDM-1 to meropenem.In vitro tests showed that demethylzeylasteral had good a synergistic antibacterial effect with meropenem and could exert a synergistic bactericidal effect by enhancing the membrane damage of bacteria caused by meropenem.In vivo assays demonstrated that demethylzeylasteral increased the protective effect of meropenem from 67％to 80％.The results obtained in this study provide a therapeutic strategy and antibacterial synergist for treating NDM-1-positive bacterial infections.

Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell(ADMSC)exosomes(Exo)on adverse ventricular remodeling after myocardial infarction(MI).Methods The chan-ges of autophagy and inflammasomes phenotype of cardiac fibroblasts after H2O2 treatment were observed.MI rats were in-jected with an equal volume of normal saline,adipose derived mesenchymal stem cell exosomes(MSC-Exo)or fibroblast exosomes(MEF-Exo)via a tail vein.The expression of autophagy related 16 like protein 1(ATG16L1),autophagy re-lated protein 7(ATG7)and NOD-like receptor protein 3(NLRP3),inflammatory response,the degree of myocardial fi-brosis,and the cardiac function were observed in different groups.Results After treatment with H2O2 on cardiac fi-broblasts,the expressions of ATG16L1 and ATG7 were significantly decreased(P＜0.001),NLRP3 was significantly in-creased(P＜0.001),and the levels of inflammatory cytokines interleukin-1β(IL-1β)and IL-18 were significantly elevated(P＜0.001).After MI rats were intervened with MSC-Exo,the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated(P＜0.001),NLRP3 was significantly down-regulated(P＜0.001),serum IL-1β and IL-18 levels were significantly decreased(P＜0.001),fibrosis-related proteins collagen Ⅰ and Ⅲ were significantly reduced(P＜0.001),myocardial fibrosis was significantly relieved(P＜0.001),and cardiac function was sig-nificantly improved(P＜0.001).Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes.

In 2016, the median of 24-hour urinary sodium, sodium-to-potassium ratio, and sodium intake per capita of residents in Jiaodong area of Shandong Province were 161.7 ( IQR:120.5, 218.9) mmol/d, 3.4 ( IQR: 2.4, 5.0) and 9.5 ( IQR:7.1, 12.8) g/d, all were lower than that of 2011[193.3( IQR:149.2,243.3)mmol/d, 4.5( IQR:3.3,5.9), 11.3( IQR:8.7, 14.2)g/d] ( P<0.05); the median of 24-hour urinary potassium was 47.2 ( IQR:34.4, 66.5) mmol/d, higher than that of 2011[42.9( IQR:33.6,56.0)] ( P<0.05); the proportion of salt intake per capita per day exceeding 5 g (89.9%) was lower than that in 2011 (90.0%). The results of the generalized linear regression model showed that the 24-hour urinary sodium was positively correlated with systolic and diastolic blood pressure [β values were 0.04 (95% CI: 0.00, 0.07), 0.03 (95% CI 0.01, 0.05), respectively], and the sodium-to-potassium ratio was positively correlated with diastolic blood pressure [β(95% CI): 0.78 (0.09, 1.47)].

In 2016, the median of 24-hour urinary sodium, sodium-to-potassium ratio, and sodium intake per capita of residents in Jiaodong area of Shandong Province were 161.7 ( IQR:120.5, 218.9) mmol/d, 3.4 ( IQR: 2.4, 5.0) and 9.5 ( IQR:7.1, 12.8) g/d, all were lower than that of 2011[193.3( IQR:149.2,243.3)mmol/d, 4.5( IQR:3.3,5.9), 11.3( IQR:8.7, 14.2)g/d] ( P<0.05); the median of 24-hour urinary potassium was 47.2 ( IQR:34.4, 66.5) mmol/d, higher than that of 2011[42.9( IQR:33.6,56.0)] ( P<0.05); the proportion of salt intake per capita per day exceeding 5 g (89.9%) was lower than that in 2011 (90.0%). The results of the generalized linear regression model showed that the 24-hour urinary sodium was positively correlated with systolic and diastolic blood pressure [β values were 0.04 (95% CI: 0.00, 0.07), 0.03 (95% CI 0.01, 0.05), respectively], and the sodium-to-potassium ratio was positively correlated with diastolic blood pressure [β(95% CI): 0.78 (0.09, 1.47)].

Objective To understand the pathogenicity and multilocus sequence typing (MLST) characteristics of the pathogenic strain of Burkholderia pseudomallei (Bp) in Hainan,and provide a reference for studying the structural characteristics and phylogenetic characteristics of pathogenic Bp in Hainan.Methods The data of patients with melioidosis in Hainan,who were treated in Hainan General Hospital from 2011 to 2018,and Bp pathogenic strains isolated from patient infected specimens were collected.The Bp pathogenic strains were genotyped by MLST method,and the distribution characteristics of the sequence type (ST) were analyzed.The ST of all Bp pathogenic strains was analyzed by eBURST v3 software to establish the evolutionary relationship map.Results A total of 91 cases of melioidosis patients were studied,including 76 males and 15 females;the ages were mainly concentrated in 40-70 years old;clinical manifestations included sepsis,pulmonary infection and local abscess;and the most common diseases were diabetes.A total of 91 Bp pathogenic strains were observed,of which 85 Bp pathogenic strains were distributed in coastal areas of Hainan,accounting for 93.41％;identified by MLST method,39 ST were discovered,the most common were ST46 (13 strains),ST55 (12 strains),STS0 (8 strains) and ST58 (7 strains),accounting for 14.29％,13.19％,8.79％ and 7.69％,respectively;except ST46 was widely distributed in the coastal areas of Hainan,the ST55,ST50 and ST58 were concentrated in the southwest,northeast and southeast regions of Hainan.Compared with the MLST database,ST30 (3 strains) was currently found only in Hainan,ST562 (4 strains) had been reported in northern Australia,and the remaining ST models had been reported in southeast Asia.The eBURST v3 software divided the 39 ST into 3 subtypes and 18 individual types.Among them,the subtypes with ST300 as the original type had the most number of ST,including 17 ST,57 Bp pathogenic strains;compared with the MLST database,the ST300 was mainly distributed in southeast Asian regions such as Thailand.Conclusions The ST of Bp pathogenic strains in Hainan has high regional diversity and genetic diversity,and is closely related to Bp in southeast Asian regions such as Thailand.

Objective To study the missed diagnosis of colorectal polyps during colonoscopy and its risk factors.Methods Data of 655 patients who underwent repeated co]onoscopy in 3 months (90 days) were analyzed in three endoscopy centers in Shenzhen.Miss rates of polyps and patients were calculated.Logistic regression analysis was used to identify the suspected risk factors associated with the miss rate including gender,age,symptoms of patient and number,shape,location of polyps.Results A total of 459 polyps(20.47％,459/2 242) in 224 patients(34.20％,204/655) were missed in overall 1 783 polyps within 655 patients.The patient miss rate increased with the polyp count increasing from 1 to 4,but with no significant differences.Polyp count of more than 5 was the independent risk factor for patient miss rate during colonoscopy(OR=4.98,P=0.00).Polyps in males were easier to be missed than those in females (OR =1.76,P =0.00).Size less than 5 mm was the independent risk factor for missed diagnosis during colonoscopy(OR=2.94,P=0.00).The flat type(Yamada Ⅰ,Ⅱ) was also the independent risk factor(OR=2.72,P=0.01;OR=3.23,P=0.00 respectively).Conclusion The miss rate of polyps is related to gender,basic polyp count,the size and shape of polyp.Male with multiple polyps and polyps with flat type and small size tend to be missed.

Objective To compare and analyze clinical effects of Bipolar transurethral plasma kinetic enucleation of prostate (PKEP) and transurethral resection of the prostate(TURP) on the treatment huge benign prostatic hyperplasia.Methods Nine-six cases of huge benign prostatic hyperplasia were selected in this hospital from March 2012 to March 2015.All the patients were divided into two groups according to different operation method,namely PKEP group and TURP group.Then the operative time,bleeding amount,bladder washing time,hospital stay,complications between two groups were compared,and the international prostate symptom score (IPSS),quality of life score (QOL),maximal urinary flow rate (Qmax),residual urine volume 6 months before and after operation were compared between the two groups.Results The operative time [(100.0 ± 3.5)min],bleeding amount [(161.0 ± 9.2) mL],bladder washing time[(15.2 ± 1.2) h],hospital stay[(10.8 ± 2.6) d],complications (6 cases) in PKEP group were less than that in the TURP group,which were(132.0±4.2)min,(198.0±12.1)mL,(36.8±1.3)h,(13.6±2.9)d,complications (18 cases)respectively(P＜0.05).The IPSS,QOL,Qmax,residual urine volume in both group were significantly improved compared with surgery before(P＜0.05),and there were no significant differences between the two groups(P＞0.05).Conclusion PKEP and TURP both are effective surgeries for the treatment of huge BPH,while PKEP has short operation time,less intraoperarive bleeding and low incidence of complications,it is worthy of further clinical promotion.

Objective To research the clinical effect of transurethral plasmakinetic enucleation of prostate (PKEP) in the treatment of high-risk huge benign prostate hyperplasia(BPH).Methods Fifty-two cases of high-risk huge(＞120 g) BPH in this hospita1 from May 2010 to May 2015 were selected and performed PKEP.International prostate symptoms score(IPSS),quality of life(QOL) score,residual urine(RUV) and biggest urine flow rate(Qmax) were observed after operation.Results The mean operation time was (130.12 ± 12.14) min,the mean intraroperation bleeding amount was (120.24±9.81) mL,the mean hospital stay was (14.52 ± 1.82)d,the mean weight of resected prostate tissues was (113.42 ± 12.53)g.Follow-up lasted for 6 months without serious complications.IPSS、QOL,RUV and Qmax after operation were improved obviously,the difference was statistically significant compared with before operation(P＜0.05).Conclusion PKEP is safe and effective in the treatment of high-risk huge BPH.

Background Researches showed that CD4+CD25+ natural regulatory T cells (nTregs) play an important role in maintaining peripheral immune tolerance, while immunotherapy using in vitro-expanded induced regulatory T cells (iTregs) suppresses allograft rejection in multiple organ transplantation.The inducing method of iTregs still needs to be optimized.Furthermore,the effect of iTregs on grafts of keratoplasty is unclear.Objective This study was to investigate the inducing and expansion method of iTregs and explore its inhibitory effects on corneal allograft rejection.Methods Bone marrow-derived dendritic cells (BMDCs) were isolated from C57BL/6 mice femora and cultured.CD4+ CD25+ T cells and CD4+ CD25-T cells were isolated from mouse spleen and separated using flow cytometry.The CD4+CD25-T cells were divided into negative control group (CD4+CD25-T cells), CD3/ 28 antibody bead group (CD4+CD25-T cells+CD3/28 antibody bead) ,2.5 ng/ml transforming growth factor (TGF)-β1 induced group and 10.0 ng/ml TGF-β1 induced group.The iTregs was formed after induction of different concentrations of TGF-β1 and CD3/CD28 antibody bead (1 : 1).CD3/CD28 antibody bead (1 : 2) , interleukin-2 (IL-2) and TGF-β1 were used to expand iTregs.The phenotype and proliferation of iTregs were assayed by flow cytometry,and the inhibitory effect of iTregs on effector T cells (Teffs) was analyzed by mixed lymphocyte reaction.Allogenic keratoplasty model (C57BL/6→BALB/c) was build,and 0.1 ml iTregs or nTregs suspension or PBS was injected via posterior venous plexus of fellow eyes to assess the graft survival time.The use and care of the mice followed the ARVO statement.Results The CD4+CD25+ T cell proportions were (6±3)％ ,(91±4)％ ,(91±3)％ and (86± 6) ％ in the negative control group,CD3/CD28 antibody bead group, 2.5 ng/ml TGF-β1 induced group and 10.0 ng/ml TGF-β1induced group, showing significant increases in the CD3/CD28 antibody bead group, 2.5 ng/ml TGF-β1 induced group and 10.0 ng/ml TGF-β1 induced group compared with the negative control group (all at P＜0.01).The Foxp3+ T cell proportions of the CD3/CD28 antibody bead group,2.5 ng/ml TGF-β1 induced group and 10.0 ng/ml TGF-β1 induced group were (1.18 ±0.20) ％ , (8.70± 1.80) ％ and (21.80±3.36) ％ , showing significant increases in the 2.5 ng/ml TGF-β1 induced group and 10.0 ng/ml TGF-β1 induced group compared with the CD3/CD28 antibody bead group (both at P＜0.01).Compared with the nTregs, the expression of CD69 was lower, and the expressions of PD-1 and Foxp3 were raised in the iTregs (all at P＜0.01).The proliferation of Teffs were decreased when cocultured with iTregs in comparison with nTregs at 1 : 1,1 : 2,1 : 4,1 : 8,1 : 16 Tregs/Teffs rations (all at P＜ 0.01).The survival time of mouse corneal grafts was 4 weeks with the permanent tolerance of 50％ in the iTregs injected group,which was superior to the 3 weeks survival time and 17％ permanent tolerance in the nTregs injected group(P＜0.05).Conclusions TGF-β1 can induce CD4+ CD25-T cells to form iTregs, which highly express Foxp3.iTregs show a stronger inhibitory effect on the growth of lymphocytes than nTregs, and therefore suppress the graft rejection after keratoplasty.

This paper introduces the history of Ilizarov technology,led to the design and application of Bone Lengthening Growth Diary,and describes the specific application effect.On this basis,to think about Bone Lengthe-ning Growth Diary’ clincial application:constantly improve the nurses’ professional level; follow the basic princi-ples of medical ethics;strengthen the doctor-patient communication and humanstic care.