Adenocarcinoma ; metabolism ; Adenoma ; metabolism ; Breast Neoplasms ; metabolism ; Carcinoma, Papillary ; metabolism ; Carcinoma, Small Cell ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; Central Nervous System Neoplasms ; metabolism ; Diagnosis, Differential ; Digestive System Neoplasms ; metabolism ; Female ; Genital Neoplasms, Female ; metabolism ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; metabolism ; Liver Neoplasms ; metabolism ; Lung Neoplasms ; metabolism ; Neuroendocrine Tumors ; metabolism ; Nuclear Proteins ; metabolism ; Pituitary Neoplasms ; metabolism ; Small Cell Lung Carcinoma ; metabolism ; Thyroid Neoplasms ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

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

OBJECTIVETo provide inspiration and ideas for clinical treatment of coronary heart disease (CHD) by data mining technology based frequency analysis and cluster analysis of medical records, prescriptions and herbs in treating CHD by distinguished veteran doctors of traditional Chinese Dedicine (TCM).

METHODSTotally 386 medical cases were retrieved from Wanfang Data, Chinese Scientific Journals Database (VIP medical information resources system, China National Knowledge Infrastructure (CNKI), and Typical Collections of Medical Cases by Contemporary Distinguished Veteran Doctors of Traditional Chinese Medicine. They input into database trimmed after unified standard. Medication laws of CHD by distinguished veteran doctors of TCM were analyzed using frequency analysis and cluster analysis, and so on.

RESULTSDistinguished veteran doctors of TCM frequently used top ten herbs in treatment of C D as Salvia miltiorrhiz , Ligusticum wallichii, Trichosanthes kirilowi, Pinellia ternat, Angelica sinensis, Poria coco stragalu , Panax ginseng, Allium macrostemon, and Radix Ophiopogonis. Cluster analysis summarized that there were 16 herb pairs commonly used, 7drug assemblies consisting of 3 herbs and 5 drug assemblies consisting of multiple herbs.

CONCLUSIONSDistinguished veteran doctors of TCM mainly used herbs assemblies capable for invigorating Pi to resolve phlegm, and promoting qi and activating blood circulation in treating CHD. Meanwhile, they concurrently used herbs combination of nourishing Xin and tranquilization, and regulating yin and yang.

China ; Cluster Analysis ; Coronary Artery Disease ; therapy ; Data Mining ; Databases, Factual ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Medicine, Chinese Traditional

ObjectiveTo explore the prevalence and spectrum of β-thalassemia mutations in Fujian province,and to provide a reference for prenatal diagnosis and genetic counseling in this population.Methods Two thousand three hundred and one blood samples were randomly selected from 9 different areas of Fujian province from May 2008 to December 2010.PCR and reverse dot blot hybridization (RDB) were adopted for detection of the 17 common types of mutation,and the frequency of each genotype of β-thalassemia mutations was calculated.The β-globin gene of unknown positive samples were analyzed directly with DNA sequencing.Results Three hundred and fifty-nine cases were detected with β-thalassemia mutations of the 2301 copy blood samples submitted,and the detection rate was 15.60％ (359/2301).Of the mutated genes,12 different mutations were identified,namely IVS-2-654(C→T),CD41-42(-TCTT),CD17(A→T),-28(A→G),CD27-28(+C),CD26(G→A),CD71-72(+A),IVS-1-1(G→T),CD43(G→T),-29(A→G),initiation codon ATG→AGG and CD36(-C).Mutation frequencies were 46.54％ (175/376),33.24％ (125/376),9.31％ (35/376),5.05％ (19/376),2.13％(8/376),1.33％(5/376),0.80％(3/376),0.27％(1/376),0.27％(1/376),0.27％(1/376),0.53％(2/376),and 0.27％(1/376),respectively.The most common mutations were IVS-2-654 (C→T) and CD41-42 (-TCTT),which accounted for 79.78％(300/376) of total genetic mutations.In addition,a novel β-globin gene mutation CD36 (-C) allele was detected for the first time,the deletion of a nucleotide C at code 36 within exon 2 lead to a frameshift mutation that could result in a premature termination at code 60.Conclusions β-thalassemia mutations in Fujian province are complex with significant genetic heterogeneity.We present for the first time the detection of a new β-thalassemia mutation in the population:CD36(-C),which provides valuable information for genetic counseling and prenatal diagnosis in Fujian province.

OBJECTIVETo explore clinical outcomes and advantages of anterior small-incision focus debridement with posterior internal fixation through muscle spa ring in treating patients with lumbar spinal tuberculosis.

METHODSFrom February 2010 to February 2014, totally 82 patients with lumbar spinal tuberculosis were treated by posterior individual fixation with small-incision focus debridement,including 50 males and 32 females with an average of 50.5 years old. All patients were divided into two groups according to different procedures. Forty-nine patients in group A were treated with anterior small-incision focus debridement with posterior internal fixation through muscle spa ring at stage I ; and 33 patients in group B were treated with focus debridement with posterior internal fixation by extraperitoneal approach at stage I . Postoperative mechanical ventilation time, preoperative and postoperative Cobb angle, visual analogue scale (VAS), erythrocyte sedimentation rate (ESR) and Frankel grading were observed and compared. Postoperative complications, stability of internal fixation and bone union were compared.

RESULTSAll patients were followed-up from 15 to 36 months with an average of 23.7 months. Psoas abscess of three patients in group A and 1 patient in group B on the opposite side increased and were healed by the secondary apocenosis. The other 78 cases were healed at stage I, and no sinus tract formation, incisional hernia, leakage of cerebrospinal and occurrence of spinal tuberculosis were occurred. Fracture healing time ranged from 3 to 7 months with an average of 4.6 months. Postoperative mechanical ventilation time and VAS score in group A was better than group B. There were no statistical differences in Cobb angle, ESR and Frankel grading at the final following-up between two groups.

CONCLUSIONAnterior small-incision focus debridement with posterior internal fixation through muscle spa ring in treating patients with lumbar spinal according to degree of damage is a safe and effective method.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Debridement ; methods ; Female ; Fracture Fixation, Internal ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Treatment Outcome ; Tuberculosis, Spinal ; surgery ; Young Adult

OBJECTIVETo study the clinicopathologic features, immunohistochemical findings, diagnosis and differential diagnosis of atypical teratoid/rhabdoid tumors (AT/RT) of central nervous system in childhood.

METHODSThe clinicopathologic data, morphologic features and immunophenotypes were reviewed in 6 cases of AT/RT. EnVision method was applied. Antibodies include cytokeratin (CK), epithelial membrane antigen (EMA), vimentin, smooth muscle actin (SMA), muscle specific actin (MSA), glial fibrinary acid protein (GFAP), desmin, placental alkaline phosphatase (PLAP) and INI1.

RESULTSFive of the six cases of AT/RT occurred in infancy and early childhood. Histologically, the predominant component was rhabdoid cells. Cytoplasmic inclusions were present in all cases. Primitive neuroectodermal tumor (PNET) component was also identified in 5 of the 6 cases studied. Immunohistochemically, the tumor cells were positive for cytokeratin, epithelial membrane antigen and vimentin. The staining for INI1, desmin and PLAP was negative. Smooth muscle actin was expressed in 2 cases and glial fibrillary acidic protein in 5 cases. The proliferative index as demonstrated by Ki-67 staining was high.

CONCLUSIONSAT/RT is not a particularly uncommon malignancy in childhood. The histologic hallmark is the presence of rhabdoid cells with cytoplasmic inclusions. The tumor cells are positive for cytokeratin, epithelial membrane antigen and vimentin, and negative for INI1. Differential diagnosis includes PNET, medulloblastoma and medullomyoblastoma.

Brain Neoplasms ; metabolism ; pathology ; surgery ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Infant ; Keratins ; metabolism ; Male ; Medulloblastoma ; metabolism ; pathology ; Mucin-1 ; metabolism ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; Rhabdoid Tumor ; metabolism ; pathology ; surgery ; Teratoma ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Background The diagnosis of central serous chorioretinopathy (CSC) is mainly dependent onfluorescine fundus angiography (FFA). However, the combination of optical coherence topography (OCT) with FFA offers a new approach to the research of the pathogenesis of CSC. Objective This clinical study was designed to study the combined application of the FFA and OCT for the research of the pathogenesis of central serous chorioretinopathy (CSC). Methods Forty-four eyes of 44 patients with CSC were included in this study with 36 cases of males and 8 cases of female. The patients were aged 39.3 ± 5.3 years and the visual acuity was 0. 64 ±0. 27. FFA and OCT examinations were performed in all patients and the FFA images were imported into the Topcon 3D OCT 1000 device to locate the conformity of OCT lesions with the leakages of FFA. The neuroepithelial layer thickness at the fovea and the height of the neuroepithelial layer detachment were measured using 3-D OCT. Results OCT showed serous REP detachment in 34 eyes (77.3%) and rough surfaces of RPE in 10 eyes (22. 7% ). In thirtyfour eyes with RPE detachment, the OCT lesions and FFA leakage spots conformed to the same locations in 31 eyes, but the other three eyes did not. The mean foveal neuroepithelial thickness was (138.5±19.4) μm in CSC eyes and that of normal eyes was ( 131.35±5. 01 ) μm ,showing a significant difference between them( t=0. 39 ,P＞0. 05 ). The mean height of neuroepithelial detachment was (263.3 ± 126.7 ) μm in CSC eyes. Conclusion RPE detachment occurs in CSC eyes and further induces macular neuroepithelial detachment. Leakage lesion of fluorescine corresponds to RPE detachment. CSC without RPE detachment may be related to the increase in RPE permeability. OCT can accurately measure the thickness of the macular neuroepithelial layer and the height of the neuroepithelial detachment.

OBJECTIVETo investigate the effect of heme oxygenase/carbon monoxide (HO-1/CO) system on lipid deposition at aortic intima and the mechanism involved in hyperlipidemic rabbits.

METHODSTotally 32 rabbits, were divided into four groups. One group as control. Three groups for the following treatments: 1.5% cholesterol ration (Ch group, n = 8); 1.5% cholesterol ration plus HO-1 inducer hemin (Hm group, n = 8); and instead of hemin, the HO-1 inhibitor, zinc protoporphyrin IX (Zn group, n = 8) was given by injection into the abdominal cavity. Experiments were lasted for 12 weeks. Rabbit aortas were then isolated as the samples for histopathologic and ultrastructural examination. The protein expressions of HO-1 and endothelin-1 (ET-1) were investigated by immunohistochemical staining and Western blot analysis.

RESULTSComparing with the Ch group, rabbits of the Hm group showed a remarkably less extent of lipid deposition at the aortic intima [(17.9 ± 3.0)% vs (54.0 ± 4.2)%], and rabbits of the Zn group had a marked extent of lesion development [(61.1 ± 3.5)%]. Lipid deposition, endothelial damage and neo-intimal formation were less severe in rabbits of the Hm group than those in the Zn or Ch group, respectively. Comparing with the control group, rabbits of the Ch group showed a significant decrease of aortic NO production and cNOS activity. However, there were an enhancement of CO production and HO-1 activity (P < 0.01). Compared with Ch group, rabbits of the Hm group showed a remarkable elevation of aortic HO activity and CO production, whereas rabbits of the Zn group showed a marked decrease of both parameters. Compared with the Ch group, rabbits of the Hm group demonstrated a marked reduction of aorta ET-1 expression, whereas Zn group had a significantly higher ET-1 expression.

CONCLUSIONSModulation of HO-1/CO system may improve vascular endothelial function and inhibit smooth muscle cell proliferation in hypercholesterolemic rabbits, likely through a compensatory mechanism and a reduction of ET-1 expression, eventually leading to an inhibition of atherosclerotic plaque development.

Animals ; Aorta ; metabolism ; pathology ; Carbon Monoxide ; metabolism ; Cholesterol ; pharmacology ; Endothelin-1 ; metabolism ; Enzyme Inhibitors ; pharmacology ; Heme Oxygenase-1 ; antagonists & inhibitors ; metabolism ; Hemin ; pharmacology ; Hyperlipidemias ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Plaque, Atherosclerotic ; metabolism ; pathology ; prevention & control ; Protoporphyrins ; pharmacology ; Rabbits ; Tunica Intima ; metabolism ; pathology

OBJECTIVETo determine the role and related mechanisms of heme oxygenase-1/carbon monoxide (HO-1/CO) on VSMCs proliferation induced by insulin-like growth factor-I (IGF-I).

METHODSVSMCs isolated from rabbit aorta were cultured in vitro and proliferation was induced by IGF-I. Hemin (a substrate and inducer of HO-1) or zinc protoporphyrin-IX (Znpp-IX, an inhibitor of HO-1) was added to stimulate or inhibit the expression of HO-1. The mRNA and protein expressions of HO-1 were detected by RT-PCR and Western blot analysis. CO released into the culture media was quantitated by measuring carbon monoxide hemoglobin (COHb), VSMCs proliferation and cell cycle were determined by (3)H-TdR incorporation assay and flow cytometry, respectively.

RESULTSThe HO-1 mRNA and protein expressions in VSMCs and the amount of COHb in the culture media were significantly increased and the IGF-I-induced (3)H-TdR incorporations of VSMCs significantly reduced by hemin in a dose-dependent manner (P < 0.01). Furthermore, VSMCs in the G(0)/G(1) phase were increased and in the S and G(2)/M phase decreased by hemin (P < 0.01). Opposite results were observed in VSMCs treated with Znpp-IX.

CONCLUSIONSEndogenous HO-1 and CO are important mediators for inhibiting IGF-I induced VSMCs proliferation by reducing VSMCs DNA synthesis and decelerating cell cycle progression.

Animals ; Carbon Monoxide ; metabolism ; Cell Proliferation ; Cells, Cultured ; Heme Oxygenase-1 ; metabolism ; Insulin-Like Growth Factor I ; pharmacology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; metabolism ; RNA, Messenger ; genetics ; Rabbits

OBJECTIVETo determine the effects of berberine hydrochloride on the expressions of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in periodontal tissues in rat periodontitis model.

METHODSBased on the successful rat periodontitis model, the experimental rats were randomized into different groups followed by oral treatment with berberine hydrochloride for 1, 2, 3, 4 weeks and then the rats were sacrificed and analyzed. Pathological assay and HE staining were used to detect the general conditions and pathological changes of rat periodontal tissues. And immunohistochemical staining was conducted to determine the expressions of IL-1beta and TNF-alpha in rats periodontitis model periodontal tissues.

RESULTSThe levels of IL-1beta and TNF-alpha in the periodontitis tissues were significantly higher than that in the control group. Treatment with berberine hydrochloride decreased the levels of IL-1beta and TNF-alpha in periodontitis tissues (P<0.05). Moreover, the general conditions and pathological changes in the control group and groups treated with berberine hydrochloride were much better than that in periodontitis groups.

CONCLUSIONBerberine hydrochloride inhibited the expression of IL-1beta and TNF-alpha in periodontal tissues in rats periodontitis model and promoted the regeneration of the periodontal tissues. This study suggested that berberine hydrochloride may have potential clinical application.

Animals ; Berberine ; Interleukin-1beta ; Male ; Periodontitis ; Rats ; Tumor Necrosis Factor-alpha