Objective To elucidate the mechanism of angiotensin (Ang) Ⅱ in regulation of renin synthesis and secretion in primary cultured juxtaglomerular granular cells (JGCs). Methods Mice JGCs were isolated and cultured as described before. Real-time PCR was used to demonstrate the expression of angiotensin converting enzyme (CE) and angiotencin receptor (AT1, AT2) in JGCs. Ang Ⅱ was co-cultured with JGCs stimulated by PGE2 and isoproternol or not. Renin activity in supernatant was detected by radioimmunoassay and renin mRNA expression was examined by real-time PCR. Different concentrations of Ang Ⅱ were co-cultured with JGCs with different time (1 h, 4 h and 24 h), cAMP in cell lysate and supernatant was measured by Cayman Cyclic AMP EIA Kit. The cytoplasmic calcium was decreased by BAPTA-AM, and increased by thapsigargin and cyclopiazonic acid, which could be used to observe the cAMP concentration affected by calcium. Adenylyl cyclase type 5, 6 (AC5, AC6) mRNA expression of JGCs co-cultured with Ang Ⅱ was measured by real-time PCR. Results Real-time PCR confirmed the expression of ACE and AT mRNA in JGCs of WT mice. Angiotensin Ⅱ reduced renin secretion in primary cultures of JGCs [(370.6±36.9) vs (299.6±25.7) ng AngI'ml~(-1)·h~(-1), P=0.014]. Angiotensin Ⅱ dose-dependently down-regulated forskolin-stimulated cAMP production in JGCs. Thapsigargin and cyclopiazonic acid decreased cAMP level. BAPTA-AM increased cAMP production obviously [(11.09±0.48) vs (3.55±0.47) nmol/L, P<0.01]. Ang Ⅱ inhibited AC5 mRNA expression by 42.12%, but did not inhibit AC6 mRNA expression. Conclusions Angiotensin Ⅱ can directly inhibit renin synthesis and secrestion maybe through reducing AC-stimulated cAMP levels. Crosstalk between calcium and cAMP system may exist in precise regulation of renin in JGCs.

Objective To observe the effect of Tangluotong Decoction(Decoctions of removing obstruction of meridians for treating diabetes)based on the principle of reinforcing kidney,activating blood and removing obstruction of meridians on the early diabetic nephropathy(DN)patients.Methods Totally 68 DN patients were randomized into two groups.In addition to the routine treatment for diabetes,the treatment group(38 patients)was administered Tangluotong Decoction while the control group(30 patients)was giv- en Lossartan Potassium Tablets.The clinical symptoms and signs and lab indices before and after treatment were observed.Results The comprehensive total effective rate of the treatment group was 89.47% while that of control group was 60.00%,the difference was significant(P

A total of 104 marine bacterial strains were isolated from Stelletta tennui around Sanya area of South China Sea by dilution-plate method and were screened for anti-microbial activity on Escherichia coli, Staphylococcus aureu, Pseudomonas fluorescens, Bacillus subtilis, Aspergillus niger, Candida albicans and Pacecilomyces variotii by agar diffusion, paper disc diffusion assay and cell concentration counts methods. It was found that 23 strains, which are 22.2% of the total isolated strains, have anti-microbial activities. Among the 23 strains, A05, A08, A72 and A75 were morphologically, physiologically and biochemically characterized and identified to be the genus Bacillus. At the same time, it was proved that there are positive and negative synergistic effects between or among active strains, e.g., as for A72-75 combination, an obvious enhanced anti-microbial activities on inhibiting Candida albicans and Pseudomomas fluorescens growth was observed than A72 or A75.

Medicine, Chinese Traditional

Objective: To investigate the relationship of murine fibrinogen-like protein 2(mfgl2) / fibroleukin with pulmonary impairment in the murine model of severe acute respiratory syndrome(SARS).Methods: The Balb/cJ mice infected with murine hepatitis virus strain 3(MHV-3) through the trachea were observed for the pathological features and virus distribution in different organs.The expressions of both mfgl2 and fibrino in the lungs were determined by in situ hybridization and immunohistochemistry.Results: The MHV-3 infected mice developed typical interstitial pneumonia with extensive hyaline membrane formation in the alveoli,presented micro-vascular thrombosis in the pulmonary vessels and died within 5 days.MHV-3 virus replication was identified in all the organs observed.The specific expression of mfgl2 prothrombinase was noted in the terminal and respiratory bronchioles,alveolar epithelia and infiltrating cells.Conclusion: The characteristics of the pulmonary impairment of SARS in human can be properly simulated by the MHV-3 induced murine model of SARS.The up-regulation of the specific gene mfgl2 in the lungs involved in fibrino deposition and microvascular thrombosis may be largely responsible for SARS-associated pulmonary damages.

Objective To investigate the effect of ginkgolide B(BN52021) on the NF-?B expression in pulmonary tissue of mice with LPS-induced acute lung injury.Methods Fifty Kunming mice were divided into 2 groups at random: LPS group(L group) and BN52021 pretreated group(B group),and then each group was subsequently divided into 5 subgroups according to different time point(0,1,3,9 and 12 h).The mice from corresponding groups received an intraperitoneal injection of normal saline or 20 mg/kg BN52021 followed by an injection of 15 mg/kg LPS 5 min later.The mice were sacrificed in 0,1,3,9 and 12 h after LPS injection.The wet/dry ratio(W/D) was recorded for pulmonary function and the pathological changes of lung tissues stained by HE were examined by light microscopy.The expression of NF-?B p65 was detected by Western blotting,and the levels of tumor necrosis factor-?(TNF-?) and interleukin-10(IL-10) were determined by ELISA.Results The significant increase of W/D was found after LPS injection in L group,which indicated the existence of pulmonary edema;while the W/D in B group was lower(P

AIM　To improve the treatment efficacy of anti-tumor drug mitoxantrone, the conjugation of mitoxantrone-loaded nanospheres and anti-C-erbB-2 monoclonal antibodies were prepared. METHODS Mitoxantrone-loaded nanospheres were prepared with emulsion-heating solidification technique. A heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP), was used as the crosslinker of mitoxantrone-loaded nanospheres and anti-C-erbB-2 monoclonal antibodies; pharmaceutical properties of immunonanocapsuls were studied; the conjugates of nanospheres and monoclonal antibodies was confirmed with immunological methods such as slide agglutination test, fluorescent immunossay and rosset formation test, fluorescent staining and scanning electron microscope. RESULTS　Mitoxantrone-loaded nanospheres were spherical, with smooth surface and median diameter of 0.665 micron. When stored at 3-5, 20-25 and 37℃, RH 75% for three months, the appearance, morphology, size distribution, drug loading and in vitro release characteristics showed no significant change and the stability was satisfactory. The size analysis demonstrated that there was no obvious increase in the particle size of nanoparticles after conjugation. Immunological tests indicate highly selective binding of antibody-targeted nanospheres to C-erbB-2-overexpressing cells SK-BR-3. CONCLUSION　The conjugation of mitoxantrone-loaded nanospheres and anti-C-erbB-2 monoclonal antibodies can keep the activity of anti-C-erbB-2 and increase the therapeutic efficacy of anti-mammary cancer drugs.

OBJECTIVETo evaluate the efficacy and safety of high dose dexamethasone combined with recombinant human thrombopoietin (rhTPO) in adults with severe newly diagnosed immune thrombocytopenia (ITP).

METHODSForty-eight adult patients with severe ITP were randomized into two groups, experimental group and control group. The patients in experimental group were given high-dose dexamethasone combined with rhTPO treatment, the patients in control group were given single high-dose dexamethasone treatment. Platelet count, platelet increase, as well as the overall response rate were strictly observed in the process. At the same time, the patient's drug tolerance and any adverse drug reactions were observed.

RESULTSThe platelet counts and platelet increase of the patients in experimental group were significantly higher than that in control group (P<0.05) at day 3, 7, 14, 30. There was no significant difference in overall response rates between the two groups (34.8% vs 36.0%, 56.5% vs 48.0%, P>0.05) at day 3, 7. The overall response rates of experimental group at day 14, 30 were significantly higher than that of control group (91.3% vs 68.0%, 82.6% vs 52.0%, P<0.05). The muscle aches occurred in one patient in experimental group which was self-recovery without special treatment.

CONCLUSIONrhTPO combined with high-dose dexamethasone could rapidly increase the platelet count, reduce the risk of bleeding, and prolonge the effect with a low incidence of tolerable adverse events compared to single high-dose dexamethasone. rhTPO combined with high-dose dexamethasone could be a new therapeutic choice for severe primary ITP.

Adult ; Blood Platelets ; Dexamethasone ; administration & dosage ; therapeutic use ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Thrombopoietin ; administration & dosage ; therapeutic use ; Treatment Outcome

Educational Measurement ; Humans ; Inservice Training ; Pneumoconiosis ; diagnosis ; Reference Standards

Objective To evaluate the cytogenetic, molecular responses and safety of generic imatinib in newly diagnosed patients with chronic myelogenous leukemia in chronic phase (CML-CP) in 1-year at different stages. Methods From January 2014 to November 2014, 50 CML-CP patients received oral generic imatinib 400 mg/d. The cytogenetic examinations, bcr-abl transcript levels and safety were monitored after 3, 6, 9 and 12 months respectively. Results 46 of 50 patients insisted on oral generic imatinib and followed up 1 year. At 3-month, 52.0 % (26/50) patients reached the complete hematologic responses (CHR) rate, and patients at least achieved minor cytogenetic response (mCyR) and bcr-ablIS≤10 % were 84.0 % (42/50) and 42.0 % (21/50). At 6-month, patients at least achieved part cytogenetic response (PCyR) and bcr-ablIS≤10 %were 73.5 % (36/49) and 59.2 % (29/49). At 12-month, patients achieved complete cytogenetic response (CCyR), bcr-ablIS≤1 % and bcr-ablIS≤0.1 % were 60.9 % (28/46), 63.1 % (29/46) and 45.7 % (21/46). The grade 3 leukopenia, thrombocytopenia and anemia rates were 34 % (17/50), 40 % (20/50) and 30 % (15/50), respectively. No grade 4 hematologic toxicity occurred. The common non-hematologic toxicities included edema [84 % (42/50)], nausea [46 % (40/50)], muscle pain [20 % (10/50)], rash [16 % (8/50)], and impaired liver function [8 % (4/50)]. Conclusion Generic imatinib has a favorable effect in treatment of patients with CML-CP, and without serious adverse reactions.