Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.
Cell-Penetrating Peptides ; chemistry ; Drug Delivery Systems ; Enzymes ; chemistry ; Humans ; Neoplasms ; drug therapy

Objective To evaluate the correlation between thin-section CT morphologic features and pathological vascular invasion in the clinical stage ⅠA peripheral lung adenocarcinoma.Methods The preoperative thin-section CT images,clinical and pathological characteristics of 102 nodules in 98 patients were retrospectively analyzed and divided into two groups according to pathological vascular invasion.Variables including the diameter of tumor(T) and consolidation part (C) in the mix ground glass nodule (mGGN),C/T ratio,morphology and pathological classification were analyzed by two-independent samples Mann-Whitney U test or t test and x2 test or Fisher exact probability test.Variables with significant difference in the univariate analyses were entered into multivariate analysis to explore predictors for vascular invasion.The correlation between these measurements and vascular invasion was evaluated by a ROC analysis.Results All of 102 nodules,36 had pathological vascular invasion and 66 without.The numbers of two groups with speculation,air bronchogram,abnormal vein,vascular convergence,pleural indentation were 30,30;26,26;35,3;35,39;32,39 and the mediandiameter of tumors were 2.1(1.0-3.0),1.2(0.5-3.0) cm respectively.By univariateanalysis,spiculation,air bronchogram,abnormal vein,vascular convergence,pleural indentation,and diameter of tumor were significantly associated with pathological vascularinvasion (P＜0.01).By multivariate logistic analysis,the statistically significant difference were found in speculation and abnormal vein (OR=33.867,8 161.063,P＜0.05).The ROC analysis showed the area under curve,cut-off value,sensitivity and specificity ofthe diameter of tumor and consolidation part of mGGN and C/T ratio were 0.784,2.05 cm,66.7％,78.8％;0.886,1.08 cm,82.4％,90.0％ and 0.861,0.65,79.4％,85.0％ respectively in differentiating tumors with pathological vascular invasion.Conclusion The spiculation sign and abnormal vein are independent predictors for vascular invasion in stage ⅠA peripheral lung adenocarcinoma.

?AIM: To observe the clinical curative effect of the intravitreal injection of anti-VEGF antibody combined with the implantation of Ex-press glaucoma drainage device for neovascular glaucoma ( NG) .?METHODS:A retrospective analysis of 20 patients with NG, who got the intravitreal injection of anti -VEGF antibody combined with the implantation of Ex-press. The visual acuity, intraocular pressure ( IOP ) , iris neovascularization fade and intraoperative and postoperative complications were observed at 1wk, 1, 3 and 6mo postoperatively.?RESULTS:The average IOPs of 20 patients were 47 ± 5.6mmHg, 13.4 ±3.6mmHg, 15.3 ±4.2mmHg, 16.9 ± 5.3mmHg and 18.7 ±6.9mmHg preoperatively and postoperatively 1wk, 1mo, 3mo and 6mo with statistical difference (P<0.05).The intraoperative and postoperative complications of the implantation of Ex-press mainly included early shallow anterior chamber, drainage tube obstruction, filtering bleb scarring. There were 8 eyes with filtering bleb scarring with normal IOP.?CONCLUSION: The intravitreal injection of anti-VEGF antibody combined with implantation of Ex -press is effective for NG, which can significantly reduce the IOP.

OBJECTIVETo explore the correlation between early postoperative tumor relapse with lymph node micrometastasis in the patients with pN(0) esophageal cancer.

METHODSUsing reverse transcriptase-polymerase chain reaction (RT-PCR), one hundred and sixty-six regional lymph nodes obtained from forty-three patients with esophagus cancer without invasion of the tumor confirmed by histopathologic analysis (pN(0)) were studied for further detecting mRNA of Mucin1 (MUC1) gene and determining nodal micrometastasis. All the patients underwent radical resection and regional lymph node dissection. Patients were followed up for one year to detect early tumor relapse. Difference in relapse was compared by chi(2) test.

RESULTSMUC1 mRNA expression was identified for twenty-six lymph nodes (15.7%), in eighteen patients (42%) who were diagnosed as having nodal micrometastasis. TNM staging for these patients was up-regulated from stages I-II(A) to stages II(B)-III. Relapse disease was found in nine patients with lymph nodes micrometastasis and three patients without nodal micrometastasis (P < 0.05).

CONCLUSIONEarly tumor relapse after radical surgery in the patients with pN(0) esophageal cancer might be correlated with nodal micrometastasis.

Esophageal Neoplasms ; surgery ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; genetics ; Male ; Middle Aged ; Mucin-1 ; genetics ; Neoplasm Staging ; Postoperative Period ; RNA, Messenger ; genetics ; metabolism ; Recurrence ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo assess the clinical value of digitalized minimally invasive technique in the treatment of the hepatolithiasis.

METHODSThe 64-slice spiral CT data were acquired from 4 hepatolithiasis patients for three-dimensional reconstruction and simulation operation using abdominal medical image-3D visualization system (MI-3DVS). Three-dimensional reconstruction was performed for the liver, hepatic arteries, hepatic veins, portal veins, intrahepatic bile ducts and calculi. Based on the size and position of the calculi and the distribution of the dilated or stenotic biliary ducts, several simulation operations such as partial hepatectomy and hepaticojejunstomy were performed. With guidance by the findings in the simulation operation, the actual minimally invasive operation was performed.

RESULTSThe three-dimensional models of the liver, hepatic arteries, hepatic veins, portal veins, intrahepatic bile ducts and calculi were reconstructed successfully, which clearly visualized the site and the number of calculi and the condition of the involved intrahepatic bile ducts. Guided by the three-dimensional models and the simulation operations, partial hepatectomy and hepaticojejunstomy were performed and the calculi were removed completely in all the 4 cases with maximum preservation of the residual liver volume.

CONCLUSIONThree-dimensional reconstruction and simulation operation allows digital minimally invasive treatment of hepatolithiasis, which can be a new approach to hepatobiliary surgery.

Adult ; Aged ; Bile Ducts, Extrahepatic ; diagnostic imaging ; surgery ; Bile Ducts, Intrahepatic ; diagnostic imaging ; surgery ; Computer Simulation ; Female ; Gallstones ; diagnostic imaging ; surgery ; Hepatectomy ; methods ; Humans ; Image Processing, Computer-Assisted ; Imaging, Three-Dimensional ; methods ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Tomography, Spiral Computed

Objective: To identify the functional domain of ?-Synuclein in affecting mitochondrial function and how the function to be impaired,especially,the mitochondrial membrane potential and the release of Cytochrome c.Methods: Harvest of ?-Syn-N and ?-Syn-△N by PCR,then subcloned into the pCMV-Myc mammalian expression vector.The recombinant plasmids were transfected into HEK293T cells by Lipofectamine 2000.After detecting the protein expression by Western blot,the functional domain was detected by co-immunoprecipitation.The mitochondrial membrane potential through flow cytometry and immunofluorescence,at the same time,the release of Cytochrome c through flow cytometry to detect.Results: The recombinant plasmids were constructed successfully.CO-IP has proved that N-terminal may be the functional domain of ?-Synuclein in affecting mitochondria.Over-expression of N-terminal could depolarize the mitochondrial membrane potential and induce the Cytochrome c releasing in MN9D cells.Conclusion: N-terminal may be the functional domain of ?-synuclein and over-expression of N-terminal could decrease mitochondrial activity.

This study was performed to explore the mechanism of myocardial injury attenuation by honokiol via the inhibition of immuno-inflammatory response in ischaemic heart disease(IHD).Twenty of 60 specific-pathogen-free(SPF)male mice were set as sham-operated group,and the remaining mice were subjected to IHD modeling.After model establishment,mice were classified into model group and honokiol group using a random number table method,with 20 mice in each group.Honokiol group was injected intraperitoneally with 0.2 mg/kg of honokiol,and the sham-operated group and model group were given equal volume of 0.9%sodium chloride solution.Cardiac function parameters,including left ventricular end-diastolic pressure(LVEDP),left ventricular systolic pressure(LVSP),maximum rate of left ventricular pressure rise/decline(LV±dp/dtmax),were measured using electrocardiography.Flow cytometry was used to detect the number of Th17/Treg lymphocytes in blood and calculate the Th17/Treg ratio.The levels of IL-1β,IL-6 and TNF-α were detected by enzyme-linked immunosorbent assay.The pathological morphology of myocardium was observed by immunohistochemical staining,the count of myocardial cells was observed under microscope,and the apoptosis rate of myocardial cells was detected by terminal deoxyribonucleotide transferase-mediated dUTP nick end labelling(TUNEL).Compared with sham-operated group,model group and honokiol group demonstrated a reduction in LVSP and LV±dp/dtmax and an increase in LVEDP(P<0.05).Compared with model group,LVSP and LV±dp/dtmax increased and LVEDP decreased in honokiol group(P<0.05).As for Th17/Treg ratio,model group demonstrated the highest level,followed by honokiol group,and sham-operated group showed the lowest level,with statistical difference(all P<0.05).An increase in serum levels of IL-1β,IL-6 and TNF-α were observed in model group and honokiol group when compared to sham-operated group(P<0.05).Levels of IL-1β,IL-6 and TNF-α in serum showed a reduction in honokiol group when compared to model group(P<0.05).The pathological changes including disordered myocardial cell arrangement,severe myocardial necrosis and structural damage,and massive infiltration of inflammatory cells were found in model group and honokiol group,while those changes were alleviated in honokiol group when compared to model group(P<0.05).The cell apoptosis rate showed an increase in model group and honokiol group when compared to sham-operated group(P<0.05),while the cell apoptosis rate was decreased in honokiol group when compared to model group(P<0.05).In conclusion,honokiol pretreatment can improve cardiac function and diminish myocardial injury in IHD.

OBJECTIVETo investigate and evaluate the clinical features, diagnostic methods, surgical management of trachea tumors in order to improve patients outcome.

METHODSClinical data of 32 patients with trachea tumors surgically treated from June 1986 to June 2005 were retrospectively analyzed. There were 22 male and 10 female patients. The age ranged from 14 to 63 years old with a median of 48 years old. The surgical procedures performed were resection and reconstruction of trachea in 10 cases, right or left pneumonectomy and carinal resection and reconstruction in 8 cases, right sleeve upper lobectomy, carinal resection and reconstruction of trachea and carina in 8 cases, and carina resection and reconstruction with tumor removal through tracheal windows 6 cases. The tracheal defect was repaired with a Teflon flap in two patients. Cardiopulmonary bypass was used in 2 patients during surgery.

RESULTSThe histological examination of resected lesions revealed squamous cell carcinoma in 19 cases, adenoid cystic carcinoma in 8 cases, adenocarcinoma in 2 cases, carcinoid in 2 cases, leiomyosarcoma in 1 case and adenoma in 1 case. One case had infection of thoracic cavity and 3 cases experienced temporary cardiac arrhythmia. There was no operative death. The follow-up periods were from 5 months to 3 years. The 1, 2 and 3 year survival rates were 93.7%, 59.4% and 50.0% respectively.

CONCLUSIONSSquamous cell carcinoma adenoid cystic carcinoma are the most common in trachea tumors. Preoperative bronchoscope examination and chest CT scan can provide valuable diagnostic data. Proper choice of surgical procedure is important for improved patients' outcome.

Adolescent ; Adult ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Tracheal Neoplasms ; diagnosis ; surgery ; Treatment Outcome ; Young Adult

BACKGROUNDThe studies of the natural progression of Parkinson's disease (PD) in Chinese populations have been lacking. To address this issue and obtain a preliminary data, we conducted a PD progression assessment in 15 adults with de novo PD from a nutritional intervention trial (NIT) cohort in Lin County China.

METHODSUsing the Copiah County screening questionnaire and United Kingdom Parkinson's Disease Society Brain Bank diagnostic criteria, we surveyed the available NIT cohort members in 2000 and diagnosed 86 patients as PD. In 2010, we resurveyed all PD patients and confirmed definite PD diagnosis in 15 cases with the rest of them being dead (54); having probable (10) PD or vascular Parkinsonism (3); refusing to participate (2); or being away (2). In both surveys, we used Hoehn and Yahr (HY) scale and assessed the disease progression. Unified Parkinson's Disease Rating Scale (UPDRS) was added to the second survey.

RESULTSIn 2010, the average disease duration for 15 definite PD patients was 13.6 ± 7.3 years. Over a 10-year time span, 9 out of 15 patients remained at the same HY stage while the remaining 6 progressed. Rigidity (47% vs. 100%; P = 0.002) and postural instability (7% vs. 47%; P = 0.005) worsened significantly. The mean UPDRS motor scores in 2010 were 39.4 ± 23.7.

CONCLUSIONSOverall worsening of motor function in PD seems to be the rule in this untreated cohort, and their rate of progression seemed to be slower than those reported in the western populations.

Aged ; Aged, 80 and over ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease ; pathology ; Severity of Illness Index

AIMTo study the effect of curcumin on pulmonary arterial pressure and type I collagen of pulmonary arterioles in pulmonary hypertensive rats induced by chronic hypoxia and hypercapnia.

METHODSThirty six rats were randomly divided into three groups: normal control group (NC), hypoxic hypercapnic group (HH) and hypoxic hypercapnia + curcumin group (HC). Collagen I in pulmonary arterioles was observed by the technique of immunohistochemistry.

RESULTS(1) The findings from hemodynamics showed that the mPAP in group HH was significantly higher than that in group NC and HC. Differences of mCAP among groups were not significant (P > 0.05). (2) Light microscopy showed the value of WA/TA (vessel wall area/total area), SMC (the density of medial smooth muscle cells) and thickness of pulmonary arterial media smooth cell layer(PAMT) were significantly higher in group HH than group NC (P < 0.01) and group HC (P < 0.01). (3) Electron microscopy showed that structure of the endothelial cells in pulmonary arterioles in group HC was near to normal, and the proliferation of medial smooth muscle cells and collagen fibers in adventitia was much lighter than those of group HH. (4) Expression of collagen I in pulmonary arterioles was significantly higher in group HH than group NC (P < 0.01) and group HC (P < 0.01).

CONCLUSIONCurcumin can decrease pulmonary arterial pressure, improve pulmonary vessel remodeling and inhibit the deposition of collagen I in pulmonary arterioles.

Animals ; Arterioles ; drug effects ; metabolism ; Collagen Type I ; metabolism ; Curcumin ; pharmacology ; Extracellular Matrix ; metabolism ; Hypercapnia ; metabolism ; physiopathology ; Hypertension, Pulmonary ; metabolism ; physiopathology ; Hypoxia ; metabolism ; physiopathology ; Male ; Pulmonary Artery ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley