Background Researches demonstrated that avastin-assisted vitrectomy for serious proliferative diabetic retinopathy can decrease intra-operation complication and bring down difficulty of surgery.It is speculated that this is associated with suppression of avastin on neovascularization.However,the evidence of its pathology is lack.Objective The aim of this study was to evaluate the application and mechanism of avastin in vitrectomy for severe proliferative diabetic retinopathy. Methods Twenty-four eyes from consecutive 24 patients with vitrectomy for severe proliferative diabetic retinopathy were enrolled in this study.Fourteen eyes received all intravitreal injection of 0.06 ml avastin(1.5 mg)14 days prior to vitrectomy。And the other 10 eyes underwent only vitrectomy without avastin injection as controls,Preretinal membranes were collected during vitrectomy for histopathologic examination by hemotoxylin and eosin staining.The differences in the density of the neovessels and micro-neovessels between the two groups were observed by detecting the expression of CD34 in vesse]endothelial cells using immunohistochemistry.Written informed consent was obtained from each patient before surgery. Results No statistically significant differences were found in the demography and eye manifestations between only vitreetomy group and avastin+vitrectomy group(P＞0.05).The neovessels with grade three was in 10 eyes in only vitrectomy group and 1 eye in avastin+vitrectomy group(P＜0.01).More capillary-like neovascularization with single vascular endothelial cells,obvious hemorrhage and inflammatory cells infiltration were observed on preretinal membranes in vitrectomy group.However,there were less hemorrhage,ceUular components and few capillary-like neovascularization but more hyaline degeneration of fibrous tissue were observed in avastin+vitrectomy group under the light microscope.Immunochemistry revealed that CD34 was positively expressed in vascular endothelial cells on preretinal membrane in both two groups.The neovessels density and miero-neovessels density were 15.40±7.42/field and 1.88±1.70/field in avastin+vitrectomy group and those in vitreetomy group were 18.00±3.80/field and 0.45±0.56/field respectively,showing significant differences between these two groups(neovessels density:Z=-4.102,P＜0.01;micro-neovessels density:Z=-4.137,P＜0.01).Conclusion As an adjunct drug during the vitrectomy for proliferative diabetic retinopathy, avastin can improve the successful rate of surgery by inhibiting the neovascular formation and alleviating retinal edema.

Purpose To study the mechanism of NLRP3 inflammasome activation caused by albumin in renal tubulointerstitial cells.Methods Cathepsin B was detected by immunohistochemistry in renal biopsy tissue of 30 membranous nephropathy patients which had different levels of proteinuria.HK-2 cells were stimulated by albumin,and then were treated by high concentration KCl,CA 074 Me and DPI,which was Cathepsin B inhibitor and ROS inhibitor.Finally,IL-1β and IL-18 were detected by Western blot and real time PCR,respectively.Results The expression of Cathepsin B in tubulointerstitial cells was significantly higher in patients with severe proteinuria than that in patients with mild proteinuria (P ＜ 0.05).CA 074 Me and DPI significantly reduced IL-1β and IL-18 secretion in HK-2 cells stimulated by albumin (P ＜ 0.05),but high concentration KCl did not result in this change (P ＞ 0.05).Conclusion NLRP3 inflammasome is activated via Cathepsin B release and increases ROS production caused by proteinuria,but not via K + efflux.

Objective To investigate the expression of TRIM28 and p16 in esophageal squamous cell car-cinoma(ESCC)and explore the possible correlation with them and clinicopathological characteristics. Methods The expression level of TRIM28 and p16 were measured by immunohistochemistry S-P in 136 cases with ESCC and 37 cases with normal esophageal mucosa,selected from the First Affiliated Hospital of Hebei North University De-partment of Pathology.The relationship between them and the clinical-pathological features was also analyzed.The localization of TRIM28 and p16 protein in ESCC was detected by immunofluorescence. Results(1)The positive rates of TRIM28 and p16 in ESCC were 91.2%and 32.4%,respectively,whereas in normal esophageal mucosa the corresponding rates were 24% and 57%,respectively.(2)Immunofluorescence results showed that TRIM28 and p16 protein were all mainly distributed in the nucleus of ESCC.(3)The abnormal expression of TRIM28 and p16 protein were all related to the invasion depth,TNM staging and lymph node metastasis in ESCC(P < 0.05).(4) The expression of TRIM28 was negatively correlated to the expression of p16 in ESCC(r =-0.284,P = 0.001). Conclusions The abnormal expression of TRIM28 and p16 may have synergistic effect on the initiation and devel-opment of ESCC.Co-detection of the expression of them may be useful for diagnosis of ESCC and guiding the clini-cal therapy.

Objective To report a new approach,endoscopic transoral approach for the resection of jugular foramen schwannoma.Methods Nine patients with jugular foramen schwannoma ( three males and six females,ranging in age from 15 to 61 years old ) were treated by direct surgery via a pure endoscopic transoral approach to the jugular foramen. Eight patients complained of hypoglossal nerve palsy with hemiatrophy of the tongue; six cases complained of vagus nerve palsy. Three cases complained of glossopharyngeal nerve palsy,one case complained of facial nerve palsy and hearing loss.Results The nerves in this area were preserved and radical intracapsular removal of the tumor was performed via endoscopic transoral approach in the nine cases.Tumor removal,as assessed by intraoperative endoscopic inspection,postoperative magnetic resonance imaging and clinical evaluation,revealed all tumors were completely removed.One patient suffered from temporary swallowing difficulties and temporary right vagus palsy Ⅰ day after surgery.There were no others intraoperative and postoperative complications.All patients were followed up for 4 -29 months,no recurrences were occured in all these patients and the muscle bulk,motor and the pre-postoperative swallowing fuction,the vagus palsy,the facial nerve palsy and hearing loss had improved in these patients.Conclusion The endoscopic transoral approach and intracapsular removal of the tumor provided for successful minimally invasive surgery in the jugular foramen schwannomas.

Objective To analyze the related pathogenicity gene mutations in a sudden death of hypertrophic cardiomyopathy (HCM) on whole exome level.Methods Whole exome sequencing (WES) was been performed on a sudden death case sample with pathological features of HCM by Illumina(R) Hiseq 2500 platform.Using hgl9 as the reference sequences,the sequencing data were analyzed.Suspicious single nucleotide variants (SNV) were screened,and the conservatism and function were analyzed by the software such as PhyloP,PolyPhen-2,SIFT,etc.Results After screening,a heterozygous mutation C719R was finally identified in the gene MYBPC3 of this case.Conclusion The molecular anatomy on whole exome level by second generation sequencing technology can help to define the molecular mechanism of HCM and provide a new mothed and thought for analysis of death cause.

Objective Dyslipidemia and chronic inflammation are risk factors of cardiac fibrosis.This study was aimed to investigate their possible synergetic effects and underlying mechanisms on progression of cardiac fibrosis in apolipoprotein E knockout (ApoE-/-) mice.Methods Twenty-four ApoE-/-mice were divided into normal chow diet (control),high fat diet (HFD group),and HFD plus subcutaneously injection of 10％ casein (inflammation group) for 8 weeks.Lipid profile and serum amyloid A (SAA) were examined by clinical biochemical assays and Enzyme-Linked Immunosorbent Assay,respectively.Hematoxylin-eosin staining (HE) and Masson staining were used to evaluate the myocardial accumulation of lipid and collagen.Collagen Ⅰ protein expression was detected by immunohistochemical staining.Endothelial-to-mesenchymal transition related protein expressions were determined by Western blot.Results Serum SAA level was significantly higher in inflammation group [(127.42 ± 26.99) ng/ml] than in control [(15.40 ± 7.62) ng/ml] and HFD [(8.17 ± 0.72) ng/ml] group (all P ＜ 0.01).However serum levels of triglyceride,total cholesterol,and low density lipoprotein (LDL) cholesterol were significantly higher in HFD group than in inflammation and control groups[TG (7.53 ± 2.05) mmol/L vs.(3.43 ± 0.79) mmol/L ; TC (27.80 ± 3.99) mmoL/L vs.(14.94 ± 1.92) mmol/L ; LDL-C (11.56 ±2.56) mmol/L vs.(9.46 ± 1.31) mmol/L,all P ＜ 0.05).Foam cell formation in cardiac vessels.myocardial collagen deposit,protein expressions of collagen Ⅰ,CD31,and alpha-smooth muscle actin (α-SMA) were all significantly higher in inflammation group than in HFD group (all P ＜ 0.05) suggesting that inflammation contributes to the phenotype endothelial-to-mesenchymal transition in heart.Conclusion Inflammation exacerbates dyslipidemia mediated cardiac fibrosis in ApoE-/-mice partly through enhancing myocardial endothelial-to-mesenchymal transition.

Background Acute lung injury (ALI) and end-stage acute respiratory distress syndrome (ARDS) were among the most common causes of death in intensive care units.The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS.Recent studies had demonstrated the importance of mesenchymal stem cells (MSCs) in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury.Here,our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS.Methods Bone marrow derived MSCs were obtained from Sprague-Dawley (SD) rats and their differential potential was verified.ALl was induced in rats byoleic acid (OA),and MSCs were transplanted intravenously.The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours,24 hours and 48 hours after OA-injection.Results The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs.The concentration of tumor necrosis factor-α and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs,whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours,24 hours and 48 hours after OA-challenge.Conclusions Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS.Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.

Objective To investigate the morphological characteristics and types of ventricular wall with dysplastic development and their associations to primary cardiomyopathy.Methods Ninety-two hearts from heart transplant patients were studied soon after explanation from 2004 to 2007.Gross examination/measurement,histopathology and photography were performed.Results Dysplastic development of ventricular wail could be evidenced in patients with various heart diseases but more often in patients with primary cardiomyopathy,though the extension and distribution of dysplastic development of ventricular wall varied between patients with or without primary cardiomyopathy.Severe dysplastic development of ventricular wall is associated with clinical dysplastic cardiomyopathy.The range of extension and degree of dysplasia in the ventricular wall correlated positively to heart dilation/failure and time point of heart failure development.The incidence of severe vantricular wall dysplasia was 27.17% in all transplanted hearts and was 43.1%(25/58) in hearts diagnosed as primary cardiomyopathy (P＜0.05).The main pathological changes of dysplastic hearts were:(1) extensive proliferative hypertrophy of the heart wall,(2) fibrous/fat or fat/fibrous tissue replacement of normal myocardium,(3) disarrangement of myocardial fibers,(4)dysplastic change in the medium-sized intramural arteries.Dysplastic cardiomyopathy was presented mainly as a combination of several forms of dysplasia.The same clinical manifestations of dysplastic cardiomyopathy patients did not always show the same pathologic changes.Fibrous-fat tissue replacement was commonly found in dilated cardiomyopathy and arrhythmogenic right ventricular eardiomyopathy.Disarrangement of myocardium was often accompanied by hypertrophic cardiomyopathy.Dysplasia of intramural arteries could result in heart dilatation due to myocardial ischemia.Conclusion Dysplasia of ventricular wall is a common variation of heart structure.Only severe or diffuse types of dysplasia is associated with cardiomyopathy,especially primary cardiomyopathy.

Objective Acute lung injury induced by variety causes can be reduced by mesenchymal stem cells.Some studies have shown that mesenchymal stem cell-derived exosomes have similar features with mesenchymal stem cell,but its role in acute lung injury is less studied.The study was to investigate the protective role and underlying mechanisms of bone marrow mesenchymal stem cell-derived exosomes (BMSC-DEs) on smoke inhalation injury (SⅡ) in rats.Methods Thirty Wistar rats were randomly divided into 3 equal groups:normal control group,smoke inhalation injury (SⅡ) model group and bone marrow mesenchymal stem cell-derived exosomes (BMSC-DEs) treated group.12 h after establishing the SⅡ model,BMSC-DEs treated group was injected with 0.5 mL BMSC-DEs (derived from 4× 106 BMSCs),and normal control group and SⅡ model group were injected with equivalent volume of normal saline.7 days later,samples were collected.The histopathologic changes of lung were observed after HE staining;BCA was used to test the amounts of total protein in bronchoalveolar lavage fluid (BALF);Enzyme linked immunosorbent assay was used to test the levels of tumor necrosis factor-α (TNF-α) and keratinocyte growth factor (KGF) in the lung tissue;Immunohistochemical was used to test the levels of pulmonary surfactant protein C(SP-C).Results The BALF levels of total protein of SⅡ group was significantly higher than those of normal control group (P＜0.01) and BMSC-DEs groups(P＜0.05);Compared with normal group [(0.164±0.021) ng/L],the levels of tumor necrosis factor-α of SII and BMSC-DEs groups [(0.355±0.106)、(0.234±0.024) ng/L] (P＜ 0.05) were significantly higher,and SⅡ group was higher than that of BMSC-DEs group(P＜0.01);Compared with normal group,the KGF protein expression level in lung tissue of SⅡ group was significantly lower (P＜0.05),but BMSC-DEs group was higher (P＜0.05).BMSC-DEs group was higher than SⅡ group (P＜0.01);Immunohistochemistry showed that the SP-C expression level in lung tissue of SⅡ group was significantly lower than those of other groups (P＜0.05).There was no statistically difference between BMSC-DEs group and control group (P＞0.05).Conclusion BMSC-DEs has a protective effect of smoke inhalation injury rats,the underlying mechanism may be related to BMSC-DEs to reduce inflammation and promote restoration of the alveolar epithelial type Ⅱ.

Objective To investigate the value of the cardiac CT examination for decision making in middle-aged and elderly patients before planned transcatheter atrial septal defect (ASD) closure. Methods Cardiac CT was performed in 63 adult patients [18 males, aged from 50 to 77 years, mean age (56. 87 ±5.79) years]with ASD before planned transcatheter ASD closure. Coronary CT angiography was made for detection of associated cardiovascular diseases, followed by 3D reconstruction of ASD for determination of the defect size in the GE-workstation, results were compared between transthoracic echocardiography measurement, CT measurement, and atrial septal defect occluder waist diameter. Results Cardiac CT identified additional cardiovascular diseases in 14 patients and decision making was changed based on cardiac CT results. Coronary artery stenosis was detected in 8 patients by cardiac CT, and proved by coronary angiography, and all of them were given comprehensive management: percutaneous coronary intervention and thanscatheter ASD closure were successively performed in 2 cases, and 1 case was referred to surgery for both coronary artery bypass graft and surgical ASD repair, and 5 patients were given pharmacological management for coronary artery disease besides thanscatheter ASD closure. Cardiac CT identified large ASD with insufficient rim tissue in 2 cases and transcatheter closures were abandoned.Cardiac CT screened out 1 case from those with insufficient posterior inferior rim by transthoracic echocardiography, and transcatheter ASD closure was successfully pedormed. Cardiac CT ruled out ASD in 1patient. In addition, cardiac CT detected 1 partial abnormalous pulmonary vein connection and 1 ductus arteriosus in this cohort. A correlation on ASD measurements was found between CT size and TTE size(r =0. 80,P ＜ 0. 01 ; Y =0. 84X + 8. 85, R2 =0. 63, P ＜ 0. 05 ), and between ASO size and CT size ( r =0. 92,P ＜ 0. 01 ; Y =0. 93X + 4. 78, R2 =0. 84,P ＜ 0. 05 ). Conclusion In middle-aged and elderly patients with ASD for possible transcatheter closure, cardiac CT is valuable on determing ASD size and morphology and could provide incremental information for optimizing clinical management for ASD patients.