Premature ejaculation is a common but incompletely understood male sexual dysfunction. Recent years have witnessed fruitful researches on NO in the mechanism of male ejaculation and successful application of selective PDE5 inhibitor in the treatment of male sexual dysfunction. And now the researches on the etiopathogenesis, mechanism, diagnosis and therapy of premature ejaculation have achieved great development. Selective serotonin re-uptake inhibitors (SSRIs) have been widely applied to clinical practice, but with increasing adverse effects. The purpose of the review is to introduce the updated development of the epidemiology, definition, etiopathogenesis, mechanism and therapy of premature ejaculation, and to provide some reference for the diagnosis and management of the problem.
Adult ; Aged ; Ejaculation ; Humans ; Male ; Middle Aged ; Serotonin Uptake Inhibitors ; therapeutic use ; Sexual Dysfunction, Physiological ; diagnosis ; drug therapy ; epidemiology

OBJECTIVETo study the mechanism of uPA improving sperm capacitation by investigating the effect of uPA on the mitochondrial function of mouse capacitated-sperm in vitro.

METHODSMitochondrial function of mouse capacitated-spermatozoa was evaluated through the assessment of mitochondrial membrane potential using JC-1 performed by flow cytometer and fluorescent microscope respectively. The experiment and the control groups were designed according to the presence or absence of uPA, each divided into 5 subgroups based on the different time of uPA treatment (or BWW in the control groups) at 0, 5, 15, 30 and 60 min respectively.

RESULTS(1) Compared with that at 0 min, the mean fluorescence intensity of JC-1 within the spermatozoal body and the percentage of orange-red colored spermatozoa in the experiment group were increased significantly at 5 and 15 min respectively after uPA incubation (P < 0.05). (2) The mean fluorescence intensity of JC-1 within the spermatozoal body at 15, 30 and 60 min and the percentage of orange-red colored spermatozoa at 5 and 15 min in the group were significantly higher than those in the control group (P < 0.05).

CONCLUSIONuPA could increase the mitochondrial membrane potential of mouse capacitated-spermatozoa in vitro, and maintain it at a high level for a certain period of time. By enhancing sperm mitochondrial function, uPA may provide sufficient energy for capacitated-spermatozoa to increase their motility and change their motor pattern, which might be one of the therapeutic mechanisms of uPA on male infertility.

Animals ; Flow Cytometry ; Fluorescent Dyes ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Mice ; Mice, Inbred Strains ; Sperm Capacitation ; Sperm Motility ; Spermatozoa ; drug effects ; physiology ; Urokinase-Type Plasminogen Activator ; pharmacology

To study the effects and possible mechanism of Vitamin K(2) (VK(2)) in the treatment of MDS-JSN04 cells, the changes of morphologic features of MDS-JSN04 cells were investigated by cytomorphology, the apoptosis of MDS-JSN04 cells was observed by transmission electron microscope; cellular proliferation was determined by the MTT assay; cell apoptosis, cell cycle shift and expression of myeloid-specific differentiation antigen (CD11b, CD13) were analyzed by flow cytometry (FCM). The expression of apoptosis-related genes bcl-2, survivin and bax were detected by retrotranscriptase polymerase chain reaction (RT-PCR); the activity of caspase-3 was determined by chemiluminescence assay. The results showed that the typical apoptotic morphological features appeared in cells treated with VK(2) for 72 hours; VK(2) induced apoptosis of MDS-JSN04 cells and in a dose-and-time-dependent manner, G(0)/G(1) cell arrest and significantly down-regulated the expression of bcl-2 and survivin, but had no effect on the expression of bax; the activity of caspase-3 significantly increased. It is concluded that VK(2) induces apoptosis of MDS-JSN04 cells through activating caspase-3 pathways and the apoptosis-related genes bcl-2, survivin may play an important role in this process.
Apoptosis ; drug effects ; CD11b Antigen ; analysis ; CD13 Antigens ; analysis ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Inhibitor of Apoptosis Proteins ; Luminescent Measurements ; methods ; Microscopy, Electron, Transmission ; Microtubule-Associated Proteins ; genetics ; Myelodysplastic Syndromes ; genetics ; metabolism ; pathology ; Neoplasm Proteins ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Vitamin K 2 ; pharmacology ; bcl-2-Associated X Protein ; genetics

OBJECTIVETo study the clinicopathologic features, diagnosis and differential diagnosis of sinonasal teratocarcinosarcoma (SNTCS) and olfactory neuroblastoma (ONB), and to discuss the histogenesis and possible relationship between SNTCS and ONB.

METHODSSeven cases of SNTCS and 34 cases of ONB were retrieved from the pathological archives together with one case each of malignant teratoma and immature embryonic tissue at 8 weeks were collected from Beijing Tongren Hospital. The clinicopathologic features were analyzed and immunohistochemical staining was performed on paraffin sections.

RESULTSSix of the SNTCS patients were male and one was female. The patients age range was 25 to 69 years (mean age 46). Four cases were initial presentation and three were recurrences. Histologically, the tumor shows multiple tissue components derived from three germ layers. There were mixture of teratoma-like tissue and carcinosarcoma. The components include fetal clear cell squamous epithelium derived from ectoderm. Glandular and tubular structures and ciliated columnar epithelium derived from endoderm. Fibroblasts, striated muscle, smooth muscle, cartilage and osteoid matrix derived from mesoderm. The carcinoma component exhibited mostly adenocarcinoma and squamous cell carcinoma, whereas the sarcoma component mostly exhibited rhabdomyosarcoma, leiomyosarcoma, and fibrosarcoma. In addition, carcinoid, and primitive mesenchymal tissue and the ONB component were also seen. The morphological characteristics of SNTCS comprised fetal clear cell squamous epithelium, carcinosarcoma and the ONB component. By immunohistochemistry, the epithelial component and cells with epithelium differentiation were positive for cytokeratin (pan) and EMA. The ONB component was positive for Syn, NSE, CD99, NF and CgA to different degrees. Neurofibril bundles were positive for S-100, and Flexner-Wintersteiner rosettes expressed cytokeratin (pan) and EMA. The spindle cells expressed vimentin, SMA, desmin, myosin and myoglobin. The primitive mesenchymal tissue expressed vimentin, and the mucoid materials and glycogen were positive for PAS. GFAP was negative in all cases. The 34 cases of ONB, included 18 men and 16 women, the age ranged from 12 to 72 years (mean 42.8 years). Microscopically, the tumor shows epithelial nests, net of angioma-like fibrous connective tissues, small round and spindle cells, glandular, squamous-like cells, and cells of rhabdomyoblastic differentiation, Homer-Wright and Flexner rosette, bundles of neurofibrils, etc. NSE and CgA were expressed in small cells. S-100 protein was positive in the areas of bunches of neurofibril. Cytokeratin (pan) was positive in epithelial cells. Myoglobin was positive in the cells of rhabdomyoblastic differentiation. The single case of immature malignant teratoma exhibited primitive nerve tissue, but fetal clear cell squamous epithelium was not found. In the immature embryonic tissue, rudimentary organs were formed, with fetal clear cell squamous epithelium lining present on the nasal and oral cavities surface.

CONCLUSIONSSNTCS is a rare and aggressive malignant neoplasm. Most of ONB are low-grade malignant tumors. Morphological differences are the most important basis to make differentiate SNTCS from ONB. As SNTCS may demonstrate a multiplicity of structures and pleomorphism, inadequate sampling at biopsy, therefore, may lead to errors in diagnosis. No evidence show that SNTCS are derived from germ cells and sinonasal teratoid carcinosarcoma may be a more proper name. SNTCS probably arises from primitive totipotential cells of olfactory/sinonasal membrane, and the relationship between SNTCS and ONB needs further study.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Carcinosarcoma ; pathology ; Diagnosis, Differential ; Esthesioneuroblastoma, Olfactory ; pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Nasal Cavity ; pathology ; Nose Neoplasms ; pathology ; Paranasal Sinus Neoplasms ; pathology ; Phosphopyruvate Hydratase ; Rhabdomyosarcoma ; pathology

In the context of internationalization of education,the military graduate education concepts and models also come to change,and opportunities and challenges coexist.In this article,the challenges and problems of army medical college graduate education were mentioned and analyzed,and the exploration and attempt of graduate education in the process of international were summarized.

Objective: To compare the effects of propofol combined with sevoflurane on maintenance of general anesthesia with sevoflurane alone for maintenance of anesthesia for patients’ recovery .Methods:160 patients scheduled for gastrointestinal surgery under epidural block combined with general anesthesia were randomly divided into sevoflurane group (group S ,n= 80) and sevoflurane/propofol group (group SP ,n= 80) .After induction ,anesthesia was maintained with sevoflurane in group S and sevoflurane combined with propofol (1 .2 μg/mL) in group SP .Bispectral Index (BIS) values were maintained at 40-60 during the maintenance of anesthesia .The time to extubation ,the incidence of serious cough and agitation during emergence ,and other related events were recorded .Results:The recovery time and the time to extubation in the SP group were (7 .2 ± 2 .0) min and (8 .0 ± 1 .8) min ,respectively ,the recovery time and the time to extubation of the S group were (12 .3 ± 1 .5) min and (12 .8 ± 1 .6) min ,and the difference was statistically significant (P< 0 .05) .The incidence of serious coughing and agitation in SP group (30% and 25% ) were significantly lower than that of group S (68% and 53% ,P<0 .05) .There was no significant difference in BIS value ,the dosage of fentanyl and muscle relaxants during anesthesia between the two groups .Conclusions:Compared with sevoflurane maintenance , sevoflurane combined with propofol for anesthesia maintenance shortens the recovery time and leads to lower incidence of emergence coughing and agitation .

This study was aimed to establish a cytokine-independent human myelodysplastic cells line from bone marrow of a patient with MDS-CMML. This cell line was incubated in mixed culture of RPMI 1640 and DMEM with 15% bovine serum, but without cytokines; its biological characteristics were identified by morphology, surface marker profiles, cell proliferation, differentiation and apoptosis. The results showed that the established cell line could not depend on cytokines for long-term survival and growth, and could differentiate into colony-forming unit-macrophage, colony-forming unit-megakaryocyte. In conclusion, a cytokine-independent human myelodysplastic syndrome cell line, named MDS-JSN04 (MDS Nanjing Jiansu 04), was established. Its partial biological characteristics were identified and clarified.
Antigens, CD19 ; analysis ; Antigens, CD20 ; analysis ; Apoptosis ; drug effects ; Bone Marrow Cells ; metabolism ; pathology ; ultrastructure ; CD79 Antigens ; analysis ; Cell Differentiation ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Culture Media ; pharmacology ; Cytokines ; pharmacology ; Flow Cytometry ; HLA-DR Antigens ; analysis ; Humans ; Lewis X Antigen ; analysis ; Male ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Middle Aged ; Myelodysplastic Syndromes ; metabolism ; pathology ; Sialic Acid Binding Ig-like Lectin 2 ; analysis ; Time Factors

OBJECTIVETo investigate the reversible effect of nilotinib, BrTet (5-bromotetrandrine) and their combination on multidrug resistance cell line K562/A02 and its mechanism.

METHODSCell proliferation inhibition was assessed by MTT method and cell apoptosis by flow cytometry (FCM). The expression of mdr1 mRNA was determined by RT-PCR, and the expression of P-gp was assessed by Western blot.

RESULTSAfter 48 h 5 nmol/L nilotinib or 0.5 µmol/L BrTet treatment, IC(50) of daunorubicin (DNR) to K562/A02 was 4.52 mg/L or 5.41 mg/L respectively; While on combinative treatment, its IC(50) decreased to 2.98 mg/L. Nilotinib or BrTet alone was not able to increase the DNR induced apoptosis rate of K562/A02 cell (P > 0.05), while on combination treatment the apoptosis rate increased remarkably. After 48 h 5 nmol/L nilotinib or 0.5 µmol/L BrTet treatment alone, gray-scale value of mdr1 mRNA was 0.48 ± 0.04 or 0.64 ± 0.01, respectively; while on combinative treatment the value decreased to 0.35 ± 0.04. The P-gp expression level in K562/A02 cells was 0.61 ± 0.05, or 0.52 ± 0.02 when treated with 5 nmol/L nilotinib or 0.5 µmol/L BrTet alone for 48 h, but on combination treatment, the level decreased to 0.44 ± 0.03.

CONCLUSIONNilotinib or BrTet alone can partially reverse drug resistance of K562/A02 cells. The mechanism may be associated with the decrease of mdr1 mRNA and P-gp expression and increase of the apoptosis rate. And there is a synergistic action with these two agants in combination.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Daunorubicin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; K562 Cells

To explore whether the complete donor chimerism could be achieved and graft-versus-host disease could be alleviated by donor lymphocyte infusion which was sensitized by the skin of the recipient, female C57BL/6 mice (H-2(b), B6) as recipients received total body irradiation (TBI) of 5.5 Gy ((60)Co gamma-ray) on day 0 followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The allo-grafts consisted of 2 x 10(7) peripheral hematopoietic stem cells from mobilized male BALB/c (H-2(d)) donor mice with the granulocyte colony-stimulating factor (G-CSF). Day 2 after allo-HSCT, the recipient mice were given 200 mg/kg cyclophosphamide intraperitoneally. Afterwards these recipient mice were infused 2 x 10(6) sensitized or unsensitized-donor lymphocytes at the 28 days after transplantation. The results showed that the mice receiving sensitized-donor lymphocyte infusion did not suffer from GVHD and the phenotypic character of the recipient mice (black color) converted to that of the donor mice (white color), and to become full-donor chimerism. It was found that the ratio of CD4(+)/CD8(+) T lymphocytes of them decreased at the earlier period and increased after half month, but which were also lower than that of the normal value. While various grades of acute GVHD was observed in that of the control group and the mixed-chimeras were maintained, though it increased a little, and the ratio of CD4(+)/CD8(+) T lymphocytes increased at first, then decreased to the normal level half month later. It is concluded that sensitized DLI converted mixed to complete donor chimerism without GVHD, and the rate of CD4(+)/CD8(+) has close relation to the incidence of GVHD.
Animals ; CD4-CD8 Ratio ; Chimerism ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Leukemia Effect ; Lymphocyte Transfusion ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Stem Cell Transplantation ; adverse effects ; methods ; Transplantation Conditioning ; methods ; Whole-Body Irradiation

OBJECTIVEPhosphorylation of myosin light chain (MLC) is one of the most important steps for vascular smooth muscle contraction and Rho-kinase is involved in this process. We investigated the role of Rho-kinase in a porcine coronary artery spasm model with interleukin-1beta.

METHODSSegments of left coronary artery adventitia were surrounded by normal saline (n = 8) or IL-1beta agarose microne (n = 8) for 2 weeks. Vasospastic responses to intracoronary serotonin or histamine then studied at the saline or IL-1beta-treated site. The Rho-kinase mRNA expression in the treated site was measured by reverse transcription-polymerase chain reaction analysis (RT-PCR). The extent of phosphorylation of myosin-binding subunit of myosin phosphates (MBS, one of the major substrates of Rho-kinase) were quantified by Western blot analysis.

RESULTSIntracoronary serotonin or histamine repeatedly induced coronary artery spasm and coronary arterial stenosis was evidenced at IL-1beta-treated site. Expression of Rho-kinase mRNA in IL-1beta-treated site was significantly increased compared to saline treated site (98.20% +/- 7.66% vs. 63.70% +/- 4.26%, P < 0.05). Western blot analysis showed that during the serotonin-induced contractions the extent of phosphorylation of MBS was also significantly increased in the spastic site (25,485 +/- 4745 vs. 6510 +/- 779, P < 0.05).

CONCLUSIONRho-kinase upregulation at the spastic site and increased phosphorylation of myosin-binding subunit of myosin phosphates are key players in inducing vascular smooth muscle hypercontraction in this porcine model.

Animals ; Coronary Vasospasm ; metabolism ; pathology ; Disease Models, Animal ; Interleukin-1beta ; adverse effects ; metabolism ; Male ; Myosin Light Chains ; metabolism ; Phosphorylation ; RNA, Messenger ; metabolism ; Swine ; rho-Associated Kinases ; metabolism