This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avβ3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 ± 4.2) nm and (259.5 ± 3.3) nm. Electric potential of those two nanoparticles were (33.5 ± 0.8) mV and (25.7 ± 1.6) mV. Encapsulation efficiencies were (76.0 ± 2.2) % and (74.4 ± 2.0) %. Drug loading efficacies were (50.1 ± 2.1) % and (26.1 ± 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs.
Biological Transport ; Caco-2 Cells ; Caveolae ; Chitosan ; chemistry ; Clathrin ; Endocytosis ; Humans ; Integrin alphaVbeta3 ; chemistry ; Nanoparticles ; Particle Size ; Pinocytosis

Objective To study effects of different degree of hypothyroidism in severe preeclampsia (S-PE) pregnant women on renal function and the correlation between them.Methods 46 S-PE patients with subclinical hypothyroidism (SCH) registered for treatment in the Shengjing Hospital of China Medical University from May 2011 to March 2013 were selected into SCH group,and 23 S-PE with overt hypothyroidism (OH) were selected into OH group,and 109 S-PE with normal thyroid stimulating hormone (TSH) levels were selected into simple group.Thyroid hormone and kidney function tests were analyzed in pregnant women with S-PE.We made an analysis of the relative risk of the detection rate of abnormal renal function and also the relationship between the levels of thyroid hormone and serum uric acid,serum urea and creatinine in patients with S-PE.Results (1) In SCH group serum TSH was (6.1±3.2) mU/L,free triiodothyronine (FT3) was (4.0±0.6) pmol/L,free thyroxine (FT4) was (11.8± 1.5) pmol/L; in OH group serum TSH was (5.2± 1.3) mU/L,FT3 was (3.7±0.6) pmol/L,FT4 was (9.3±0.5) pmol/L; in simple S-PE group serum TSH was (1.9±0.8) mU/L,FT3 was (4.0±0.8) pmol/L and FT4 was (11.9±1.9) pmol/L.TSH in SCH group was significantly higher than that in simple S-PE group (P＞0.01),the difference of in SCH and OH group were not statistically significant (P＞0.05).The difference of FT3 in three groups were not statistically significant (P＜0.05) ;FT4 in OH group was significantly lower than thoes in SCH and simple groups (P＜0.05).(2)Serum uric acid,creatinine and urea levels in OH group was (436± 114),(75± 15) μmol/L and (6±3)mmol/L,in simple S-PE group they were (378± 114),(65 ±22) μmol/L and (5±3) mmol/L.In comparison,the differences was statistically significant(P＜0.05).The differences were not statistically significant in SCH and OH groups (P＞0.05).(3)The abnormal detection rate of uric acid was significantly higher in SCH than that in OH group [46％ (21/46) versus 22％ (5/23),OR=3.0,P＜0.05].The comparison of remaining index has no statistical significance(P＞0.05).(4)In SCH group there was a significant inverse correlation of serum FT3 with serum urea levels,serum creatinine and serum uric acid (r=-0.32,-0.58,-0.35,P＜0.05).There was not a correlation of serum TSH,FT4 with indicators of renal function (P＞0.05).In OH group there was a negative correlation between FT3 and serum creatinine concentrations (r=-0.40,P＜0.05).In OH group there was not a correlation of FT3 with serum uric acid and urea (P＞0.05).There was a positive correlation between TSH and serum creatinine in simple S-PE group (r=0.20,P=0.04).There was not a correlation between TSH and serum urea(r=0.04,P=0.65),and serum uric acid (r=0.12,P=0.20).Conclusions There was effect of different hypothyrosis state in pre-eclampsia patients on renal function.Serum uric acid,urea and creatinine concentrations in S-PE pregnant women with OH were significantly higher than those in simple S-PE group with normal TSH.There was a negative correlation between FT3 and serum creatinine in S-PE.Hence the thyroid function should be regularly monitored in S-PE patients to find damage of renal function and management hypothyrosis.

This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avβ3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 ± 4.2) nm and (259.5 ± 3.3) nm. Electric potential of those two nanoparticles were (33.5 ± 0.8) mV and (25.7 ± 1.6) mV. Encapsulation efficiencies were (76.0 ± 2.2) % and (74.4 ± 2.0) %. Drug loading efficacies were (50.1 ± 2.1) % and (26.1 ± 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs.

Objective To investigate the com and pepper fluorine in Zhenxiong county of Yunnan province, as well as the change of com and pepper fluorine after baked by coal, clay-mixed with cual for a relatively long-term, in order to provide a scientific basis for reducing fluorine intake. Methods The endemic areas of Yile, Wufeng's Songlinwan, Tangfang and Wufeng's Wugu in Zhenxiong county, and a non-endemic area Xiaguan in Dali city were selected as study sites. Ten samples of fresh corn and pepper were collected in each region, and fluorine was determined using acid leaching/potentiometry freshly and after baking or drying for 10 days or 4 months, respectively. Results The fluorine content of local fresh corn in Xiaguan of Dali city and Yile,Wufeng's Songlinwan, Tangfang, Wufeng's Wugu in Zhenxiong county were (1.31 ± 0.13),(1.65 ± 0.64),(1.92 ±0.37), (2.32 ± 0.49), (1.98 ± 0.66)mg/kg, respectively, and there were statistically significant differences across the regions(H = 27.871, P ＜ 0.05). The fluorine content of corn samples after baking or drying for 4 months were ( 1.82 ± 0.17), (26.43 ± 12.03), (39.27 ± 8.09), ( 14.27 ± 4.37), ( 14.33 ± 1.73)mg/kg, respectively, which were significantly higher than that of the fresh com in the corresponding region(all P ＜ 0.05 ), and there were statistically significant differences across the regions(H = 42.512, P＜ 0.05). The fluorine content of the local fresh chili were (3.34 ± 1.08), (3.44 ± 0.55), (3.47 ± 0.74), (3.46 ± 0.93)mg/kg, respectively, in the 4 observed places in Xiaguan of Dali city and Yile, Wufeng's Songlinwan, Tangfang in Zhenxiong county, and there were no statistically significant differences across the regions (F = 0.052, P ＞ 0.05 ). The fluorine content of pepper samples after baking or drying for 4 months were (7.01 ± 1.64), (226.07 ± 83.69), (179.36 ± 148.37), (54.51 ± 34.67)mg/kg,respectively, which were significantly higher than that of the fresh pepper in the corresponding region(all P ＜ 0.05 ),and there were statistically significant differences across the regions(H = 28.822, P ＜ 0.05). Conclusion Corn and chili fluorine is significantly increased after baked with coal and clay-mixed with coal by farmers in Zhenxiong county, a coal- burning borne endemic fluorosis area of Yunnan province.

Objective To study such clinical characteristics as number of circulating endothelial progenitor cells (EPCs), cerebral blood flow velocity (CAFV) and platelet count in patients with Alzheimer' s disease (AD). Methods A total of 78 patients were recruited from the outpatient and inpatient departments of our hospital. Patients with AD (n=23), patients with vascular dementia (VaD,n=25) and healthy elderly controls with normal cognition (n=30) were enrolled after matching for clinical data, carotid intima-media thickness (IMT) and Mini Mental State Examination (MMSE). The CAFV was examined with transcranial Doppler (TCD). Peripheral blood EPCs were counted by flow cytometry.Results No statistical significant differences were noted between patients with AD and VaD, and controls on gender, age, body mass index, blood pressure, total cholesterol, triglycerides, platelet and IMT (P＞0.05). Compared with those in control group, the number of circulating EPCs and scores of MMSE and CAFV in patients with AD and VaD were significantly decreased (P＜0.05). After the adjustment of traditional risk factors, thc number of circulating EPCs had a positive correlation with the scores of MMSE (r=0.541, P=0.000). Liner regression analyses showed that body mass index, diastolic pressure,platelet and scores of MMSE were positively correlated to the circulating EPCs number in patients with AD (P＜0.05). Conclusion The reduction of number of circulating EPCs, decreasing the repair capability of cerebrovasculars and inducing poor cerebral perfusion, plays important roles in the cognitive dysfunction of patients with AD.

OBJECTIVETo investigate the effects and mechanism of intranasal interferon gamma (IFN-gamma) in the treatment of allergic rhinitis.

METHODSOvalbumin (OVA) absorbed to aluminum hydroxide was used to construct the allergic rhinitis model (group C), and the normal control group (group A), the allergic rhinitis model group (group B) and beclomethasone dipropionate group (group D) consisted of 8 rats for each. PBS 50 microl was absorbed to group B, IFN-gamma 1 microg was absorbed to group C and beclomethasone dipropionate 3.5 microg was absorbed to group D on day 31 to day 38 once daily once nasal cavity. The nasal lavage fluid was collected on day 39, and the cellular constituents, levels of interleukin-4 (IL-4), interleukin-5 (IL-5) and IgE were determined, together with the pathologic changes and expression of GATA-3 were observed.

RESULTSDecrease of eosinophils [(0.005 +/- 0.003) x 10(4)/ml, x +/- s] was seen in nasal lavage fluid of group C as comparing with group B [(0.225 +/- 0.060) x 10(4)/ml, (P < 0.01)], and the levels of IL-4 (7.8 +/- 3.5) pg/ml and IL-5 (12.5 +/- 4.3) pg/ml decreased significantly in comparing with group B (P < 0.01). The serum levels of total IgE (38.5 +/- 9.6) microg/ml and ovalbumin-specific IgE (19.8 +/- 5.4) IU/ml decreased significantly in comparing with those of group B (P < 0.01). In group B, mucosal congestion and edema thickening with inflammatory cells infiltration mainly of eosinophils; in group C, the above mentioned changes were much more ameliorated. Immunohistochemistry showed significant increase of GATA-3 expression in the nasal tissue of group B but much lesser than that in group C.

CONCLUSIONSIFN-gamma can inhibit the composition of IL-4 and IL-5, and inhibit the airway inflammation with eosinophilic infiltration and the serum levels of total IgE and ovalbumin specific IgE, probably through the mechanism of restraining the Th2 reaction by blockade of GATA-3 expression in the nasal tissue.

Animals ; Eosinophils ; immunology ; Female ; Immunoglobulin E ; blood ; Interferon-gamma ; administration & dosage ; therapeutic use ; Interleukin-4 ; immunology ; Interleukin-5 ; immunology ; Male ; Nasal Cavity ; immunology ; Rats ; Rats, Wistar ; Rhinitis, Allergic, Perennial ; drug therapy ; metabolism

Objective To compare the diagnostic value of ultrasonography and CT in acute appendicitis.Methods A retrospective analysis was conducted on 279 patients who were diagnosed with acute appendicitis and followed emergency surgery.Patients were divided into different subgroups based on postoperative pathological results and body mass index(BMI),and the pathological results were used as the gold standard to analyze whether there were differences in the diagnostic accuracy of ultrasonography and CT examination for acute appendicitis.Results A total of 279 patients with confirmed acute appendicitis,with 64 cases of simple appendicitis,127 cases of suppurative appendicitis,and 88 cases of gangrenous appendicitis according to pathological classification.The diagnostic accuracy of ultrasonography was 68.75%(44/64),73.22%(93/127),and 81.81%(72/88),respectively.The diagnostic accuracy of CT was 71.87%(46/64),82.67%(105/127),and 90.90%(80/88),respectively.There was no statistically significant difference in diagnostic accuracy between the two examinations(P>0.05).Subgroup analysis based on patient BMI showed that there was no difference in diagnostic accuracy of the two examinations for patients with normal BMI(P>0.05),while for overweight and obese patients,the diagnostic accuracy of CT was better than that of ultrasonography,with a statistical difference(P<0.05).Conclusion There is no difference in the diagnostic accuracy of ultrasonography and CT examinations for acute appendicitis of different pathological types.But for overweight and obese acute appendicitis patients,the diagnostic accuracy of CT examination is superior to ultrasonography.

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ²=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ²=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ²=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ²=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ²=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ²=0.230, P=0.891; χ²=2.628, P=0.269; χ²=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ²=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.
Adolescent ; Anemia, Aplastic/therapy* ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Retrospective Studies ; Treatment Outcome ; Unrelated Donors

OBJECTIVETo study the effects of combination of angiopoietin-1 (ANG-1) and vascular endothelial growth factor₁₆₅ (VEGF₁₆₅) gene transfer mediated by recombinant adeno-associated viral vector on the neovascularization in chronic ischemic porcine myocardium.

METHODSAn ameroid constrictor was implanted around the left circumflex coronary artery (LCX) via endoscopy. Six weeks later, coronary angiography revealed that the myocardial ischemia was established by gradual occlusion of the left circumflex coronary artery (LCX). Sixteen swine with the total occlusion or partial stenosis (> 85 %) of the LCX were divided into 4 groups (4 in each group): group I, group II and group IV (control) received direct myocardium injection of rAAV₂ VEGF₁₆₅, rAAV₂ ANG-1 or PBS alone, respectively; group III received rAAV₂ VEGF₁₆₅ and rAAV₂ ANG-1. Selective coronary angiography and ultrasonography were performed perioperatively to evaluate the cardiac function and the formation of collateral circulation. The expression of VEGF₁₆₅ and ANG-1 proteins were assessed using ELISA or Western blot. The degree of angiogenesis was assessed by use of immunohistochemical analysis.

RESULTAngiography showed that the occlusion of all LCX was completed or exceeded 95% 6 weeks after ameroid constrictor implantation, indicating the successful establishment of animal model. The expression levels of VEGF₁₆₅ in group I and III and ANG-1 in groups II and III began to increase at d7 after transfection and reached the peak at d14; then decreased gradually to the normal level after 3 months. The expression levels of VEGF₁₆₅ in group II and group IV or that of ANG-1 protein in group I and group IV had no markedly changes at different time after transfection. There were significant increase in capillary density and arteriole density and more side branch vessels formed in group III compared with other groups. Echocardiographic measurements showed that the left ventricular systolic function of animals in groups I, II and III increased significantly after gene transfection, especially in group III; but there was no changes in group IV.

CONCLUSIONMyocardial perfusion and the left ventricular systolic function are improved after rAAV₂ VEGF₁₆₅ or rAAV₂ ANG-1 transfection, which is associated with the angiogenesis in porcine model of chronic myocardial ischemia.

Adenoviridae ; genetics ; Angiopoietin-1 ; genetics ; Animals ; Collateral Circulation ; Coronary Vessels ; physiopathology ; Disease Models, Animal ; Genetic Therapy ; Genetic Vectors ; Male ; Myocardial Ischemia ; physiopathology ; therapy ; Neovascularization, Physiologic ; Swine ; Swine, Miniature ; Transfection ; Vascular Endothelial Growth Factor A ; genetics

Objective To explore the characteristics of gene sequence of mtDNA-COⅠof Culex pipiens pallens from differ-ent geographical regions in Shandong Province and different resistant strains from the lab and five common mosquito species, and analyze the genetic diversity of these mosquitoes.Methods Adult mosquitoes were collected from Jinan,Jining,Qingdao cities and other places in Shandong Province.The sensitive,dichlorvos-resistant,pyrethroid-resistant and propoxur-resistant strains were reared in the lab.Five species of mosquito(Cx.pipiens pallens,Cx.tritaeniorhynchus,Anopheles sinensis,Aedes al-bopictus,and Armigeres subalbatus)were collected from Jining City and identified in the lab.mtDNA-COⅠwas specifically am-plified by PCR and sequenced.The gene sequences were compared and analyzed by the biological information systems,and the phylogenetic tree was constructed.Results The amplified mtDNA-COⅠfragments of Cx.pipiens pallens from eight different cit-ies and four different resistant strains were 528 bp in length,with 67.4% A+T contents and two mutation sites.The nucleotide se-quence homology among the different geographic strains was 99.95% and the gene sequences of the four resistant strains were the same,showing a high homogeny.The amplified mtDNA-COⅠfragments of the five species of mosquitoes were 528 bp with 408 conserved sites,120 variable sites,42 parsimony informative sites and 78 singleton sites. The A+T contents were between 65.7% and 68.0%.The nucleotide sequence homology among the different mosquito species was between 86.17% and 92.05%,and the molecular identification was consistent with the traditional morphological identification. The molecular phylogenetic study showed that the different species were clustered at their own branch at the species and genus levels,while genera Armiger-es was distantly related to the others.Conclusion mtDNA-COⅠcould not serve as the molecular marker to analyze the popula-tion genetic variation and phylogenesis of Cx.pipiens pallens from different geographical regions and different resistant strains, but it has species and genus specificities,which could be used for the identification of the mosquito species and genus.