Objective To study the characteristics of pharmacokinetics and pharmacodynamics of insulin dry powder inhalation and its relative bioavailability as compared with subcutaneous injection of regular insulin. Methods In this open,single-center,randomized,two-period,cross-over,euglycemic glucose clamp study,18 healthy volunteers(14 men and 4 women),aged(24.9?1.7)years,with body mass index(20.6?1.2)kg/m~2, received the insulin dry powder inhalatin(80 U)or regular insulin(15 U)subcutaneous administration.The blood samples of this study at 0,20,30,40,50,60,70,80,90,100,110,120,135,150,165,180,195, 210,225,240,270,300,330,360,390,420,450 and 480 rain were taken for serum insulin measurement, meanwhile,glucose infusion rates(GIR)were determined per 5 minutes over a period of 8 hours.Results The C_(max)were(57.9?17.8 vs 114.5?29.7)mU/L(tested vs reference preparation),T_(max)were(46.7?45.6 vs 107.8?33.7)min,GIR_(max)were(3.35?0.98 vs 5.17?1.75)mg?kg~(-1)?min~(-1)and T_(GIRmax)were(88.3?17.0 vs 151.9?34.6)min.The relative bioavailability was(10.26?2.25)%,and the relative bioefficacy was(14.33?7.26)%.Conclusion The study shows that insulin dry powder inhalation is absorbed via lungs and its action sets in earlier than that of the regular insulin injected subcutaneously.These pharmacokinetie and pharmacodynamic data may provide a reliabe guide for further clinical trial.

Antineoplastic Agents ; administration & dosage ; therapeutic use ; Child ; Female ; Humans ; Injections, Intralesional ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Neoplasms ; drug therapy ; Recombinant Proteins ; Treatment Outcome

OBJECTIVETo evaluate the clinical efficacy of autologous semitendinosus and gracilis tendon grafting with anchor repair for the treatment of chronic achilles tendon rupture and severe scarring.

METHODSFrom April 2010 to October 2012,26 patients with chronic achilles tendon rupture(with Myerson type III ) and severe scarring were treated with autologous semitendinosus and gracilis tendon grafting with anchor repair. There were 19 males and 7 females,with an average age of 32 years old (ranged, 22 to 47 years). The time from injury to surgery was from 3 to 12 months (7 months on average). The plantar flexion strength of all injuried feet attenuated and single heel rise test were positive in 26 cases before operation. Plaster immobilization and routine rehabilitation therapy were performed after operation. Clinical effects were evaluated by Arner-lindholm criterion and complications were observed after operation.

RESULTSAll the patients were followed up from 12 to 24 months with a mean of 16 months. No complications such as achilles tendon re-rupture, wound infection, etc were found during follow-up period. According to the Arner-Lindholm standard, 15 cases got excellent results and 11 good.

CONCLUSIONUsing autologous semitendinosus and gracilis tendon grafts with anchor repair to treat chronic achilles tendon rupture and severe scarring is a perfect surgical procedure.

Achilles Tendon ; injuries ; surgery ; Adult ; Chronic Disease ; Cicatrix ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Rupture ; Young Adult

A novel targeting drug carrier (FA-BO-PAMAM) based on the PAMAM G5 dendrimer modified with borneol (BO) and folic acid (FA) molecules on the periphery and doxorubicin (DOX) loaded in the interior was designed and prepared to achieve the purposes of enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. 1H NMR was used to confirm the synthesis of FA-BO-PAMAM; its morphology and mean size were analyzed by dynamic light scattering (DLS) and transmission electron microscope (TEM). Based on the HBMEC and C6 cells, cytotoxicity assay, transport across the BBB, cellular uptake and anti-tumor activity in vitro were investigated to evaluate the properties of nanocarriers in vitro. The results showed that the nanocarrier of FA-BO-PAMAM was successfully synthesized, which was spherical in morphology with the average size of (22.28 ± 0.42) nm, and zeta potential of (7.6 ± 0.89) mV. Cytotoxicity and transport across the BBB assay showed that BO-modified conjugates decreased the cytotoxicity of PAMAM against both HBMEC and C6 cells and exhibited higher BBB transportation ability than BO-unmodified conjugates; moreover, modification with FA increased the total uptake of DOX by C6 cells and enhanced the cytotoxicity of DOX-polymer against C6 cells. Therefore, FA-BO-PAMAM is a promising nanodrug delivery system in employing PAMAM as a drug carrier and treatment for brain glioma.
Biological Transport ; Blood-Brain Barrier ; Bornanes ; chemistry ; Cell Line, Tumor ; Dendrimers ; Doxorubicin ; pharmacology ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Folic Acid ; chemistry ; Glioma ; Humans

OBJECTIVETo study changes of left ventricular remodeling (LVR) in hypertension patients with carotid atherosclerosis (CAS) of phlegm-dampness syndrome (PDS).

METHODSDoppler ultrasonography data of CAS were observed in 223 hypertension patients with CAS (as the hypertension group, including 119 patients of the PDS group and 104 of the non-PDS group), 81 CAS patients with non-hypertension, and 19 non-hypertension non-CAS patients (as the control group). The difference in the degree of LVR was compared among the above groups.

RESULTSThe left ventricular posterior wall thickness (LVPWT), inter ventricular septum thickness (IVS), E/A were higher in the hypertension group than in the non-hypertension group (P < 0.05). The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), stroke volume (SV) were higher in the soft plaque hypertension group and the soft plaque non-hypertension group than in the hard plaque group, the thickening intimal group, and the normal intimal group (P < 0.01 , P < 0.05). The LVEDD, LVESD, and SV were higher, and the ejection fraction (EF) was lower in the PDS hypertension group than in the non-PDS hypertension group (all P < 0.05). Of them, LVEDD, LVESD, and SV were higher in the soft plaque group than in the hard plaque group (P < 0.01), the thickening intimal group (P < 0.01) and the normal intimal group (P < 0.05). There was no statistical difference in PDS hypertension between the soft plaque group and the hard plaque group (P > 0.05).

CONCLUSIONThe hypertension patients with CAS of PDS might be correlated to LVR, and LVR was more obviously in the soft plaque patients.

Aged ; Aged, 80 and over ; Carotid Artery Diseases ; diagnosis ; diagnostic imaging ; physiopathology ; Case-Control Studies ; Female ; Humans ; Hypertension ; diagnosis ; diagnostic imaging ; physiopathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Ultrasonography ; Ventricular Remodeling

OBJECTIVETo observe the proliferation inhibition, apoptosis, and cell proliferation cycle of human lung carcinoma cell line A549 treated with Inotodiol extracts from Inonotus obliquus and explore the possibility of Inotodiol extracts from Inonotus obliquus as a new tumor chemopreventive drug.

METHODSHuman lung cancer cell line A549 was treated with different concentrations of Inotodiol, the effects of Inotodiol on cell apoptosis, the expression of Ki-67, Bcl-2, Bax, and p53 and cell cycle were detected by TUNEL assay, immunohistochemistry, and flow cytometry assay respectively.

RESULTSInotodiol extracts had antiproliferation effect on human lung carcinoma cell line A549. The expression of Ki-67 decreased with the increase of Inotodiol concentration and exposure time (P<0.05), in a dose-dependent and time-dependent manner. The typical characteristics of the apoptosis of A549 cells treated with Inotodiol were observed, and the apoptotic rate of A549 cell at 48 h was the highest by TUNEL assay. Inotodiol arrested A549 cells in the S phase, and apoptotic peak was observed by flow cytometry. Immunocytochemistry indicated that the expression of Bcl-2 protein decreased, while the expression of p53 and Bax proteins increased in A549 cells treated with Inotodiol, compared with the control cells (P<0.05).

CONCLUSIONInotodiol can inhibit proliferation and induce the apoptosis of A549 cells, and its molecular mechanism may be associated with the up-regulating expression of p53 and bax proteins and down-regulating expression of Bcl-2 protein, which arrested A549 cells in S phase.

Adenocarcinoma ; drug therapy ; genetics ; metabolism ; pathology ; Apoptosis ; drug effects ; genetics ; Basidiomycota ; chemistry ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Gene Expression Regulation, Neoplastic ; drug effects ; Genes, bcl-2 ; drug effects ; Genes, p53 ; drug effects ; Humans ; Ki-67 Antigen ; metabolism ; Lanosterol ; analogs & derivatives ; pharmacology ; therapeutic use ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Phytotherapy ; bcl-2-Associated X Protein ; genetics

OBJECTIVETo investigate the relationship among oxygen concentration, quorum sensing system, type secretion system, and biofilm production of Pseudomonas aeruginosa.

METHODSA total of 23 clinical strains of Pseudomonas aeruginosa were cultured at different levels of environmental oxygen for three days. Then biofilm mass and alginate were quantified. The expression levels of LasI and RhlI were detected by real time polymerase chain reaction (PCR). The secretion of exoenzyme S was examined by Western blot.

RESULTSBoth the biofilm mass (R=0.455, P=0.000) and alginate (R=0.367, P=0.000) were positively correlated with oxygen concentration. Real time PCR showed that the expression levels of LasI and RhlI were not significantly correlated with oxygen concentration (R=0.025, P=0.794; R=-0.044, P=0.653), the production of biofilm (R=0.001, P=0.990; R=0.011, P=0.909), or alginate(R=0.029, P=0.770; R=0.193, P=0.064). Western blot showed that the optimal oxygen concentration range for exoenzyme S secretion of Pseudomonas aeruginosa ranged 10% to 30%.

CONCLUSIONSHyperoxia can promote the production of biofilm and alginate by Pseudomonas aeruginosa. Las/Rhl system may not participate in biofilm production at the early stage due to the low bacteria amount. The increased production of biofilm may inhibit the expression of Type Secretion system and thus inhibit bacterial virulence.

Alginates ; metabolism ; Biofilms ; drug effects ; Oxygen ; metabolism ; Pseudomonas aeruginosa ; metabolism ; physiology ; Quorum Sensing ; drug effects ; physiology

Objective To investigate the effects of smad7 on transdifferentiation and collagenⅠsynthesis in advanced glyeosylation end-products(AGE)-stimulated NRK52E cells.Methods NRK52E cells were transferred by pTet-on plasmid system and the cell lines of doxycycline(Dox)-regulated Smad7 expression were selected for the study.Transnuclear location of p-Smad2/3 was examined with immunocytochemistry.The mRNA and protein expressions of Smad7,?-SMA,E-cadherin,collagenⅠwere detected with RT-PCR and Western blot. Results AGE-induced expressions of Smad7 mRNA and protein were further increased in NRK52E cells by the addition of Dox in a dose-dependent manner.Overexpression of Smad7 caused a marked inhibition of p-Smad2/3 transnuclear location at 30 min(68.3% vs 31.2%,P

Objective To understand health seeking behavior and its influential factors to reproductive tract infections (RTIs) on women at reproductive age in the rural areas. Methods 54 540 fertile women aged 15-49 were surveyed by a stratified-cluster-random sampling method and gynecological examination were conducted in two steps: converging at the clinics, and then visiting their households, later, 31 624 women who had at least one RTI symptom were chosen. Results Among all the women at reproductive age, the rate of having at least one RTI symptom was 59.8% with the means of RTI symptom as 1.66±0.89. 15 989 women went to see doctors out of the 31 624 women who had RTI symptoms, with a proportion of 50.6 %. The results of logistic regressy showed that those women whose husbands having higher education level, higher income, more RTI symptoms and better knowledge on RTI were more easily to go to the hospitals. However, those women whose husbands working out of the county, having older first bearing age and more numbers of pregnancy were less likely to go to the hospitals. Reasons that refrained them from going to see a doctor would include: 2137(13.7%) did not know that RTI was a disease; 7443(47.6%) of them thought that every woman were bound to have at least one symptom and it did not matter; 1629 (10.4%) of them felt shameful; 349 (2.2%) learned that the diseases were incurable; 975 (6.2 % ) felt the cost of treatment was too expensive; 2101 (13.4 %) had no time; 1001 (6.4 %) would treat themselves through buying medicines over the counter. Conclusion RTI symptoms were quite prevalent among women at reproductive age but the rate of seeing a doctor was low and caused by multi-factors. Health education and gynecological census in increasing the curable rate of RTIs should to be strengthened.

BACKGROUNDThe dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria are two major types. While clinical and histological presentations are similar in these two diseases, genetic diagnosis is critical in the differential diagnosis of these entities.

METHODSThree patients initially diagnosed with DUH were included. The gene test was carried out by targeted gene sequencing. All mutations detected on ADAR1 and ABCB6 genes were analyzed according to the frequency in control database, the mutation types, and the published evidence to determine the pathogenicity.

RESULTSFamily pedigree and clinical presentations were reported in 3 patients from two Chinese families. All patients have prominent cutaneous dyschromatoses involving the whole body without systemic complications. Different pathogenic genes in these patients with similar phenotype were identified: One novel mutation on ADAR1 (c. 1325C>G) and one recurrent mutation in ABCB6 (c. 1270T>C), which successfully distinguished two diseases with the similar phenotype.

CONCLUSIONTargeted gene sequencing is an effective tool for genetic diagnosis in pigmentary skin diseases.

ATP-Binding Cassette Transporters ; genetics ; Adenosine Deaminase ; genetics ; Adolescent ; Asian Continental Ancestry Group ; Child ; Diagnosis, Differential ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Pedigree ; Pigmentation Disorders ; congenital ; diagnosis ; genetics ; RNA-Binding Proteins ; genetics ; Skin Diseases, Genetic ; diagnosis ; genetics