Aged ; Chondrosarcoma ; Humans ; Laryngeal Neoplasms ; Male ; Middle Aged

Objective To evaluate the clinical efficacy of transcatheter renal sympathetic denervation(RDN)in the treatment of resistant hypertension.Methods Clinical data of 10 patients with resistant hypertension treated by transcatheter renal sympa-thetic denervation were retrospectively analyzed.The blood pressure and complications were analyzed.Results In all of the 10 pa-tients,systolic and diastolic blood pressure decreased significantly after two weeks compared with preoperative,and further de-creased after 3 months (P <0.05 ).There were no statistical difference of systolic and diastolic blood pressure between 3 and 6 months(P >0.05).Before the RDN,the mean number of antihypertensive drugs was 5.3±0.9.After 6 months which was 3.2±0. 6,and which was decreased significantly compared with the preoperative (P <0.05).No adverse reactions were found.Conclusion The RDN can be quickly and sustained decrease the blood pressure in patients with resistant hypertension.

OBJECTIVE TNF- related apoptosis- inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors. However, most breast cancer cells are resistant to TRAIL- induced apoptosis. Our objectives are to investigate the underlying molecular mechanisms and to develop strategies to overcome such resistance. METHODS To identify modulators of TRAIL-induced apoptosis, we carried out a genome wide siRNA screen. To validate the screening result, we either silenced or overexpressed the identified genes in various breast cancer cells and changes in growth and TRAIL-induced cell apoptosis were determined in vitro and in an orthotopic xenograft mouse model. Finally, we investigated whether small molecules targeting the identified genes improve the effectiveness of TRAIL-therapy. RESULTS We unexpectedly identified androgen receptor (AR) to be responsible for TRAIL resistance. While AR is classically viewed as the key factor in prostate cancer progression, we found that AR expression levels were markedly elevated in human invasive breast cancer specimens including triple- negative breast cancers (TNBC) that are highly aggressive with poor prognosis. Importantly, breast cancer cell lines express different levels of AR that correlated with their TRAIL resistance. AR overexpression in MDA- MB- 231 and MDA- MB- 436 cells suppressed the TRAIL sensitivity whereas knockdown of AR rendered MCF-7 and MDA-MB-453 cells sensitive to TRAIL-induced apoptosis. AR overexpression also induced TRAIL resistance in breast tumors in vivo. Further, we observed an upregulation of the TRAIL receptor, death receptor 5 (DR5) in breast cancer cells, following the removal or inhibition of AR by its antagonists Casodex and MDV3100. Treatment with AR antagonists also enhanced TRAIL- induced breast cancer cell apoptosis. CONCLUSION AR signaling suppresses TRAIL-induced breast cancer cell apoptosis, in part, by suppressing DR5 expression, and a combination of AR antagonists together with TRAIL may be a novel and effective therapy for TNBC.

· AIM: To explore the effects of C3F8 tamponade on hypotony on or after primary operation and the prognosis of severe ocular trauma.· METHODS: Twenty-six cases (26 eyes) of severe ocular trauma were treated with pure C3F8 tamponade on or after primary operation. IOP was observed, and the curative effect of C3F8 tamponade was observed on secondary operation with prognosis evaluated.· RESULTS: Hypotony improved in 23 eyes postoperatively,in which 18 eyes with edematous and cloudy cornea, 15 eyes had clear cornea after gas tamponade. Retina was reattached under the gas action in 21 eyes during the secondary operation. Visual acuity improved in 22 eyes, remained unchanged in 3 eyes and decreased in 1 eye during the follow-up of 3-12months.· CONCLUSION: Application of pure C3F8 tamponade on or after primary operation can effectively improve hypotony after severe ocular trauma and benefit a better prognosis.

Objective To research the combined prognostic utility of NT-proBNP and hs-CTNI in NSTE-ACS risk stratification and early intervention therapy .Methods A total of 245 NSTE-ACS patients were divided to 4 groups(Aa ,Ab ,Ba ,Bb groups) ac-cording to immediate admission NT-proBNP and hs-CTNI .Patients were accepted percutaneous coronary intervention (PCI) ,coro-nary artery bypass grafting and conservative treatment were taken 6 months follow-up .Results The heart failure incidence of Aa group was significantly higher than Ba group(P<0 .05) .6 patients happened left main lesion or multivessel lesion in Aa group were obviously higher than other groups .The incidence of Bb group accepted PCI was obviously higher than Aa group (P<0 .05) .Bb group patients were accepted PCI earlier than other groups ,there was no significance(P>0 .05) .In 6 months follow-up ,5 patients died and 10 patients accepted revascularization again because of severe angina and AMI .Conclusion In NSTE-ACS patient ,NT-proBNP and hs-CTNI elevation was closely related with severe coronary lesions and worse prediction ,which could undergo early in-tervention therapy .

Objective:To detect the effect of microRNA-7 ( miR-7 ) knockdown on pathology in murine acute lung injury ( ALI) model,and preliminarily explore its significance.Methods:Murine ALI model was performed by intraperitoneal injection of Li-popolysaccharide (LPS) (10 mg/kg) into miR-7KD mice and wild-type (wild type,WT) mice respectively.Then,the pathologic injury of lung tissue were observed by HE staining.And total cell count of bronchoalveolarlavage(BAL) was calculated.The relative expression of related cytokines in lung tissue was analyzed by Real-time PCR assay.Furthermore,the changes on proportion of innate immune cells (γδT cell and F4/80 macrophages cell) and adaptive immune cell ( CD4+T cell and CD8+T cell) were analyzed by FACS.Meanwhile, the expression of CD62L and CD69,as well as the absolute number,in CD4+T cell were also analyzed.Results: Compared with WT mice,pathological damage in lung tissues was significantly alleviated in miR-7KD mice.Real-time PCR analysis showed that the relative expression of IL-6 was obviously reduced (P<0.01),conversely,relative expression of IL-4 and TGF-βwere obviously increased (P<0.05).Furthermore,the total cell number in BAL also reduced significantly (P<0.05).Importantly,FACS analysis showed that the proportion and the absolute number of F4/80+Mφcells obviously reduced (P<0.05);however,the proportion of γδT cells increased (P<0.05).Moreover,the proportion and the absolute number of CD4+T cells and CD8+T cells were significantly reduced (P<0.05). Finally, the proportion and the absolute number of CD62L+in CD4+T cells were upregulated vigorously,contrastly,the proportion and the absolute number of CD69+in CD4+T cells were notably up-regulated (P<0.05).Conclusion:miR-7 defeciency could significantly ameliorate the pathology of murine ALI,suggesting that it may play an important regulatory role in the development of ALI.

Objective:To detect the change of proportions of αβT lymphocytes in mesenteric lymph nodes of miR-7 knockdown (miR-7KD)mice,and preliminarily explore its importance.Methods: The volume,weight index and total cells number of mesenteric lymph node in miR-7KD mice were measured.The pathologic morphology change of mesenteric lymph nodes was observed by HE stai -ning.And the changes on proportion of αβT lymphocytes in mesenteric lymph nodes of miR-7KD mice were analyzed by Flow cytometry.Results:Compared with those of WT (wild type) mice,the volume,weight index,and the total cells number of mesenteric lymph node were significantly increased ( P<0.05 ).Moreover ,the pathologic morphology was significantly changed.The proportion and numbers of T lymphocyte were significantly increased;however,the proportion of B lymphocyte were significantly decreased (P<0.05). Notably,the proportion and number of CD4+T cells and CD8+T cells were significantly increased (P<0.05).Meanwhile,CD62L+T cell proportion were vigorously reduced and CD 69+T cell and IFN-γ+T cell proportion were notably up-regulated,which belong to CD4+and CD8+T cell(P<0.05).Conclusion:There was significant influence in the proportion of αβT lymphocytes in mesenteric lymph nodes of miR-7KD mice,suggesting that miR-7 might play an important role in the composition and function of lymphocytes in mesenteric lymph nodes.

Objective To determine the effecting factors for diagnosis of binign or malignant in cystic lesions of pancreas(CLP).Methods One hundred twenty-six patients undergoing operations for CLP or suspected CLP in this hospital from January 1984 to June 2008 were reviewed.Patients were divided into two groups according to lesion's histological features after operation.The predictive effect of various preoperative factors on the malignant potential of CLP was evaluated.Results One hundred twenty-six patients underwent operations for suspected pancreatic cystic neoplasms.There were 89 benign and 37 malignant CLPs.The univariate analysis showed that gender, clinical symptoms(jaundice and weight loss), elevated serum CA199, and presence of one or more of three morphologic features such as solid component, nodule or septation were significantly different between benign and malignant cystic neoplasm of pancreas.The multivariate analysis indicated that imaging features and gender were independent predictors of malignancy.Conclusion In patients with suspected pancreatic cystic neoplasms, elevated serum CA199, clinical symptoms(jaundice and weight loss)and presence of suspicious morphologic features on imaging are predictors of malignant potential of CLP.Patients with a high likelihood of a potentially malignant or malignant lesion based on these three factors should undergo operation without additional investigations.

Female ; Humans ; Neoplasms ; physiopathology ; Thoracic Neoplasms ; pathology ; physiopathology ; Thoracic Wall ; pathology ; Young Adult

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.