Objective To study the best titer of recombinant adeno-associated virus serotype 2 (rAAV2) delivered to myocardium by targeted ultrasound microbubbles. Methods Twenty one adult SD rats were divided into seven groups. SonoVue attached with different titer [1.5 × 109~ 3.0 × 1011 vg/ml (virus genome/ml)] of rAAV2-EGFP was infused into the tail vein of rats, following ultrasound mediated microbubbles destruction,as experiment groups. Normal saline was infused into the tail vein of rats as the control group (without rAAV2). Rats were killed after 14 days and hearts were harvested. GFP protein expression which showed rAAV2 transfer was observed under fluorescence microscope in frozen section and integrate optical density(IOD) was measured by Image Pro Plus software. Results When the titer of rAAV2 was 1.5 × 1011 vg/ml infused into the tail vein of rats there was much more GFP expression in myocardium than lower titers (P <0.01). Conclusions The best titer of rAAV2 delivered to myocardium by targeted ultrasound microbubbles is 1.5 × 1011 vg/ml in the tail vein infusion of rats.

Objective A retrospective analysis were conducted to identify the effect of bypassing the emergency department on 30-days outcomes of patients with acute myocardial infarction undergone primary percutaneous coronary intervention ( PPCI) . Methods From June 2014 to April 2015, 187 patients underwent PPCI in Kunming General Hospital were included. 13 patients were excluded owing to their incomplete follow-up data. The total 174 patients were divided into two groups: the control group (n =59) who did not bypass the emergency department, and the bypass group ( n = 115) who bypassed the emergency department and directly received PPCI. The data of all patients were collected and analyzed. Results There were no significant differences in baseline characteristics and PPCI related data (including percentage of thrombus aspiration catheter used, length or diameter of stents applied between two groups (all P ﹥ 0. 05) . The bypass group had shorter door-to-ballon ( D2B) than the control group [ (67. 7 ± 21. 5) min vs. (89. 4 ± 23. 6) min, P ﹤ 0. 001] . There were no significant differences in 30-days all-cause mortality, re-myocardial infacrtion and target ressel revascularization (TVR) between the two groups (P ﹥ 0. 05) . Total MACEs rate in the bypass group was lower than in the control group (10. 2% vs. 1. 7% , P = 0. 012) . Logistic regression analysis showed that age, diabetes, pain-to-door (PTD) time and CK peak value were the main influencing factors for 30-day MACEs rate of patients receiving PPCI ( P ﹤0. 05) . Conclusions Bypassing the emergency department can shorten D2B time and reduce 30-days MACEs post-PPCI, but reducing the total ischemic time will be more beneficial to patients with acute myocardial infarction.

Objective To investigate the relationship between the content of stromal cell-derived factor-1 (SDF-1) in myocardium in different period of myocardial infarction and left ventricular function.Methods Twenty three Chinese miniature pigs were randomly divided into the experimental group and the control group.The swines in experimental group were prepared as acute myocardial infarction model by ligating anterior descending coronary artery and were randomly divided into 6 subgroups according to the different time points after infarction.The left ventricular end-diastolic diameter (LVDd),left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were measured respectively.Global circumferential strain (GCS) and global radial strain (GRS) of left ventricle were measured.The content of SDF-1 were also measured by real-time quantitative PCR.Results Compared with the control group,SDF-1 levels were significantly elevated,and LVEF,LVFS,GCS and GRS were reduced.However,LVDd were significantly increased.The content of SDF-1 and GCS has a negative correlation (r =-0.580,P =0.000).Conclusions The content of SDF-1 in myocardial tissue have a certain relationship with GCS of left ventricular myocardium.

BACKGROUND:The measure and prediction of the shape of optic nerve head are the key issues for early diagnosis and duration prediction of glaucoma. Therefore, it is significant to research the shape variation of optic nerve head under high intraocular pressure.
OBJECTIVE:To establish three-dimensional finite element model of optic nerve head and to analyze the deformation of optic nerve head and the change in retina thickness after acute high intraocular pressure.
METHODS:Animal model of acute ocular hypertension was established by methods of anterior chamber perfusion. The tomographic images of the optic nerve head of a cat were obtained at the normal intraocular pressure and 5 320 Pa, 7 980 Pa, 10 640 Pa, 13 300 Pa, 15 960 Pa intraocular pressures using optical coherence tomography. Then, we measured the variation of retinal thickness at typical location. Basing on the tomographic images of optic nerve head of a cat at normal intraocular pressure, we obtained three-dimensional structure of retina and choroid using software MIMICS. Then three-dimensional model of optic nerve head was established by assembling the retina and choroid. The deformation of optic nerve head and the change in retinal thickness under high intraocular pressure were observed using software ABAQUS. The effectiveness of the model was verified by the experimental result.
RESULTS AND CONCLUSION:With the increase of intraocular pressure, the retinal thickness is thinner, the optic nerve head depth, width and the ratio of the depth to width are gradual y increased. It suggests that the acute high intraocular pressure causes retinal thinning, optic nerve head widening and deepening. It is feasible to establish optic nerve head modeling in vivo by using optical coherence tomography, mechanical analysis can be applied to predict the shape variation of optic nerve head, which is significant to further deduce the pathological process of glaucoma.

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

Objective To investigate the association of HLA-DRB31*03,*04 and *11 alleles with alopecia areata(AA)in Han Nationality in East China.Methods Polymerase chain reaction-sequence specific primer(PCR-SSP)method was conducted in 158 Chinese Han patients with AA as well as in 172 healthy human controls in East China.The relationships of HLA-DRB1 polymorphism to age of onset,episode frequency,clinical course,family history,and severity of AA were evaluated.Results No significant differences were observed for the frequency of HLA DRB1*03,*11 alleles between the patients and human controls,while increased frequency of HLA-DRB1*04 was observed in patients(OR=1.99,Pc=0.01).Multiple logistic regression analysis revealed that HLA-DRB1*04 was more prevalent in patients with an onset after 16 years of age(OR=1.94,Pc=0.02),those without family history(OR=1.97,Pc=0.02),those with recurrent AA(OR=2.49,Pc=0.02),those with a clinical course of more than 1 year(OR=2.94,Pc=0.01),those with severe AA(OR=3.53,Pc=0.00)and tbose with single episode of AA(OR=1.83,Pc=0.04)in comparison with the normal human controls.Conclusion This study demonstrates that HLA-DRB1*04 allele is associated with the occurrence and clinical types of AA in Han Nationality in East China.

OBJECTIVETo investigate the safety and efficiency of the disposable circumcision suture device (DCSD) in the surgical treatment of phimosis and redundant prepuce.

METHODSWe randomly assigned 249 outpatients with phimosis or redundant prepuce to be treated with DCSD (n = 129) and by conventional circumcision (CC, n = 120), respectively. Then we compared the safety and efficiency of the two strategies.

RESULTSComparisons between DCSD and CC showed that the operation time was (4.02 +/- 0.69) vs (30.8 +/- 4.05) min, blood loss was (1.07 +/- 1.29) vs (8.72 +/- 2.15) ml, intraoperative pain score was 0.81 +/- 0.81 vs 2.42 +/- 1.15, 24-hour postoperative pain score was 1.84 +/- 1.02 vs 4.99 +/- 1.36, postoperative complication rate was 13. 95% (18/129) vs 9.17% (11/120), wound healing time was (13.99 +/- 9.06) vs (17.48 +/- 3.49) d, satisfaction with the penile appearance was 98.4% (127/129) vs 95% (109/120), and treatment cost was (2215.62 +/- 17.67) vs (576.47 + 15.58) Y RMB. DCSD exhibited obvious superiority over CC for shorter operation time, less blood loss, milder intraoperative pain, sooner wound healing, and better penile appearance, but it also had a higher rate of postoperative complications (P > 0.05) and involved more treatment cost than the latter (P < 0.05).

CONCLUSIONThe disposable circumcision suture device affords ideal clinical effects and therefore deserves clinical popularization.

Circumcision, Male ; instrumentation ; Disposable Equipment ; Follow-Up Studies ; Humans ; Male ; Phimosis ; surgery ; Surgical Staplers ; Treatment Outcome

OBJECTIVETo study the efficacy of interleukin-10 (IL-10) in the treatment of experimental autoimmune prostatitis (EAP) and its effect on the expressions of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1 ) in EAP rat models.

METHODSThirty Wistar rats were equally and randomly divided into a control, an EAP and an IL-10 group. The controls were treated with normal saline, the EAP models were made by injection of purified prostate protein twice with immune adjuvant, and the IL-10 group included the EAP models subjected to IL-10 intervention. The infiltration of the inflammatory cells of the prostate tissue was detected by HE staining, the ultrastructure of the prostate cells and their surrounding cells observed by electron microscopy, and the levels of TNF-alpha and TGF-beta1 in the three groups determined by semi-quantitative RT-PCR assay.

RESULTSThe EAP group showed significantly severer inflammation and higher levels of TNF-alpha and TGF-beta1 in the prostate tissue than the controls (P < 0.05). The IL-10 group exhibited significantly lessened inflammatory infiltration of the prostate tissue and decreased levels of TNF-alpha and TGF-beta as compared with the EAP group (P < 0.05).

CONCLUSIONIL-10 could relieve inflammatory infiltration of the prostate tissue and inhibit the expressions of TNF-alpha and TGF-beta1 in EAP rats, which is suggestive of its therapeutic efficacy for autoimmune prostatitis.

Animals ; Autoimmune Diseases ; complications ; drug therapy ; metabolism ; Disease Models, Animal ; Interleukin-10 ; therapeutic use ; Male ; Prostatitis ; drug therapy ; etiology ; metabolism ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo explore the effect of transforming growth factor (TGF) beta1/Smad signaling pathway on the expression and enzymatic activity of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in cultured rat mesangial cells (MsC).

METHODSLipofectin method was used to transfect Smad 2, Smad 3 and Smad 7 vectors into MsC; and immunofluorescence, RT-PCR and Western blot analysis were used to detect their transfection efficiency. The expression and enzymatic activity of MMP-2 and TIMP-2 were determined by Western blot, zymography or reverse zymography assay.

RESULTSMsC transfected with Smad 2 gene showed slightly increased expression and enzymatic activity of both MMP-2 and TIMP-2, which was more obvious upon stimulation by TGF-beta1. MsC transfected with Smad 3 gene showed a slight upregulation of TIMP-2 expression and its enzymatic activity, which was enhanced after TGF-beta1 stimulation. There was however no change in MMP-2 expression and its enzymatic activity. On the other hand, MsC transfected with Smad 7 gene showed a decrease in MMP-2 and TIMP-2 expression and enzymatic activity, which was especially obvious after stimulation by TGF-beta1.

CONCLUSIONSTGF-beta1/Smad signaling pathway may play an important role in the pathogenesis of glomerulosclerosis, probably via MMP-2 and TIMP-2 expression and the associated enzymatic activity.

Animals ; Blotting, Western ; Cells, Cultured ; DNA-Binding Proteins ; genetics ; physiology ; Fluorescent Antibody Technique ; Gene Expression ; Genetic Vectors ; genetics ; Glomerular Mesangium ; cytology ; drug effects ; metabolism ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Smad2 Protein ; Smad3 Protein ; Smad7 Protein ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; metabolism ; Trans-Activators ; genetics ; physiology ; Transfection ; Transforming Growth Factor beta ; pharmacology ; Transforming Growth Factor beta1

Objective ToexplorethevalueofMRIiterativedecompositionofwaterandfatwithechoasymmetryandleastsquares estimationquantificationsequence(IDEALIQ)techniquetoevaluatemyelosuppressionduringradiotherapyandchemotherapyincervicalcancer. Methods 25femalesubjectswereenrolledinthisstudy,whowereclinicallydiagnosedascervicalcancerandacceptedtheradiotherapyand chemotherapy.AllthesubjectswereperformedwithsagittalMRIIDEALIQscansineachweek’streatmentandattheendofwhole fiveweeks’therapy,soeachpatienthad6timesMRIscans.ROIweremanuallyplacedonL4,L5andS1vertebralbodyandsubcutaneousfatto measurethefatfraction.ThefatfractioncolorimageswerereconstructedonaAW (AdvantageWorkstation)4.6workstation.Results Asthe radiationandchemotherapyprocess,thevaluesoffatfractionincreasedprogressivelyonL4,L5andS1vertebralbody(P<0.001), whilethefatfractionvaluesinsubcutaneousfatappearedstableallthetime(P=0.987).Conclusion MRIIDEALIQtechniquecan evaluatethereal-timefatfraction,andradiotherapyandchemotherapyplansmaybeoptimizedaccordingtothefatfractionresult.