[Surveillance of key parasitic diseases in Baise City from 2006 to 2015].

OBJECTIVE: To understand and master the infection status of key parasitic diseases in Baise City from 2006 to 2015, so as to provide evidence for the development and adjustment of the control strategy for parasitic diseases. METHODS: The relevant information of the final evaluation of the key parasitic diseases in 12 counties (cities and districts) of Baise City from 2006 to 2015 was collected, and analyzed. RESULTS: During the period of 2006-2015, a total of 20 654 person-times were investigated for parasitic diseases in Baise City and 1 147 persons were infected, with an average infection rate of 5.55%. In 2006, the infection rate was the highest (28.67%, 362/1 254), while the lowest was in 2013 (2.08%, 44/2 113). The infection rate of Clonorchis sinensis was the highest, and the infection rate of Ascaris lumbricoides was the second. The infection rates of the males and females were 5.35% (631/11 795) and 5.82% (516/8 859) respectively, with no significant difference between them (χ2 = 2.175, P > 0.05). The highest infection rate existed in the 40-49 years group, the rural residents, the farmers and the crowd with the educational level of senior high middle school or above. CONCLUSIONS: The infection rate of parasitic diseases presents a decline trend overall in Baise City from 2006 to 2013, however it rebounded in 2014 and 2015. The next step is to strengthen the prevention and control of parasitic diseases by promoting health education, regular insect repellent, and fecundity management.

Adenoviral-mediated transfer of the human endothelial nitric oxide synthase gene reduces acute hypoxic pulmonary vasoconstriction in rats.

Nitric oxide (NO), a vasodilator involved in the regulation of pulmonary vascular tone, is synthesized by a family of enzymes, nitric oxide synthases (NOS). To investigate whether adenoviral-mediated overexpression of constitutive endothelial NOS (ceNOS) would attenuate hypoxic pulmonary vasoconstriction, we aerosolized 3 X 10(9) plaque forming units of a recombinant adenovirus containing the ceNOS gene (AdCMVceNOS) into rat lungs. Four days after infection, transgene expression was confirmed using immunoblot techniques. Diffuse ceNOS immunostaining was detected in alveoli and medium-sized and small pulmonary vessels of AdCMVceNOS-transduced lungs. AdCMVceNOS-transduction was associated with an 86% increase in [3H]arginine to [3H]citrulline conversion and a rise in pulmonary cGMP levels from 7 +/- 1 to 59 +/- 9 pmol/mg protein in lungs from AdCMVceNOS versus control rats, (P < 0.05). During acute hypoxia (FIO2 = 0.10) for 25 min, mean pulmonary artery pressure (PAP) increased significantly from 17 +/- 1 to 27 +/- 1 mmHg in rats aerosolized with saline (n = 4) and from 18 +/- 1 to 28 +/- 1 mmHg in rats given an adenoviral vector expressing a nuclear-targeted beta-galactosidase gene (AdCMV beta gal, n = 8). In contrast, in AdCMVceNOS-transduced rats (n = 8) the hypoxia-induced increase in PAP was significantly attenuated (18 +/- 1 to 23 +/- 2 mmHg). Systemic blood pressure was not affected by aerosol gene transfer. Thus, adenoviral-mediated ceNOS gene transfer to rat lungs increases ceNOS expression and activity, and reduces acute hypoxic pulmonary vasoconstriction. Aerosolized recombinant adenovirus overexpressing vasodilatory proteins can act as a selective pulmonary vasodilator and may hold promise as a future therapeutic strategy for pulmonary hypertension.

[Establishment of response system to emergency parasitic disease affairs in China].

China's prevention and control of parasitic diseases has made remarkable achievements. However, the prevalence and transmission of parasitic diseases is impacted by the complicated natural and social factors of environment, natural disasters, population movements, and so on. Therefore, there are still the risks of the outbreak of emergency parasitic diseases affairs, which may affect the control effectiveness of parasitic diseases and endanger the social stability seriously. In this article, we aim at the analysis of typical cases of emergency parasitic disease affairs and their impacts on public health security in China in recently years, and we also elaborate the disposal characteristics of emergency parasitic disease affairs, and propose the establishment of response system to emergency parasitic disease affairs in China, including the organizational structure and response flow path, and in addition, point out that, in the future, we should strengthen the system construction and measures of the response system to emergency parasitic disease affairs, so as to control the risk and harm of parasitic disease spread as much as possible and to realize the early intervention and proper disposal of emergency parasitic disease affairs.

Soluble guanylate cyclase alpha(1) and beta(1) gene transfer increases NO responsiveness and reduces neointima formation after balloon injury in rats via antiproliferative and antimigratory effects.

In vascular smooth muscle cells, NO stimulates the synthesis of cGMP by soluble guanylate cyclase (sGC), a heterodimer composed of alpha(1) and beta(1) subunits. NO/cGMP signal transduction affects multiple cell functions that contribute to neointima formation after vascular injury. Balloon-induced vascular injury was found to decrease sGC subunit expression and enzyme activity in rat carotid arteries. The effect of restoring sGC enzyme activity on neointima formation was investigated using recombinant adenoviruses specifying sGC alpha(1) and beta(1) subunits (Adalpha1 and Adbeta1). Coinfection of cultured rat aortic smooth muscle cells with Adalpha1 and Adbeta1 increased NO-stimulated intracellular cGMP levels 60-fold and decreased DNA synthesis and migration by 16% and 48%, respectively. Immunoreactivity for alpha(1) and beta(1) subunits colocalized in carotid arteries infected with Adalpha1 and Adbeta1. Molsidomine-stimulated carotid tissue cGMP levels were greater after coinfection with Adalpha1 and Adbeta1 than after infection with a control virus, AdRR5 (0.53+/-0.09 pmol/mg protein, mean+/-SEM, versus 0.23+/-0.09, P<0.05). Mean intima/media ratio, 2 weeks after balloon injury and twice-daily administration of 5 mg/kg molsidomine, was less in rats coinfected with Adalpha1 and Adss1 than in rats infected with AdRR5 or in uninfected rats (0.36+/-0.11 versus 0. 81+/-0.13 and 0.75+/-0.25, respectively, P<0.05). Thus, Adalpha1 and Adbeta1 gene transfer to balloon-injured rat carotid arteries increases NO responsiveness and attenuates neointima formation via a direct antiproliferative and antimigratory effect on vascular smooth muscle cells.

Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma.

Previous investigations have supported or indicated a stimulatory role of the insulin-like growth factor II gene (IGF2) in hepatocarcinogenesis. We have studied the transcript levels, promoter usage, and imprinting status of the ICF2 gene and its relationship to H19 in human hepatocellular carcinomas (HCCs) and liver tumor cell lines. The activity of the IGF2 promoter P1 was lost in about 70% of the cases (18 of 25). This is the most prominent abnormality regarding the IGF2 regulation in this study. Total IGF2 as well as promoter P3 transcription were up-regulated in a small group of the tumors. Twenty genetically informative cases were obtained from 26 cases, thus excluding the probability of loss of heterozygosity of the IGF2 gene. Among these, nine showed abnormal monoallelic expression of IGF2. One HCC and one HCC cell line proved loss of functional imprinting of IGF2. H19 and IGF2 were regulated in parallel, and expression levels were variable. Taken together, the disruption of the IGF2 promoter regulation, particularly the loss of P1 activity, is a common feature of human HCCs. The loss of P1 activity explains the frequent loss of biallelic IGF2 expression and may potentially be used as a diagnostic or monitoring marker for human HCC.

Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats.

BACKGROUND: Nitric oxide (NO) is a potent vasodilator with an important role in the regulation of pulmonary vascular tone. The effects of NO synthase (NOS) gene transfer on pulmonary vascular remodeling associated with hypoxic pulmonary hypertension are unknown. METHODS AND RESULTS: We aerosolized 3 x 10(9) pfu of an adenoviral vector containing inducible NOS gene (AdNOS2), constitutive NOS3 gene (AdNOS3), or no transgene (AdRR5) into rat lungs. Exhaled NO levels, monitored with chemiluminescence, were higher in AdNOS2-infected rats than in AdNOS3- and AdRR5-infected rats (at 3 days, 33+/-6 ppb, n=9, versus 17+/-4, n=9, and 6+/-2 ppb, n=3, P:<0.05 for both). Exposure to FIO(2) 0.10 for 7 days increased pulmonary artery pressure from 19+/-4 mm Hg (baseline) to 27+/-1 and 26+/-2 mm Hg in AdNOS3- and AdRR5-infected rats, respectively, but only to 21+/-1 mm Hg in AdNOS2-infected animals (P:<0.05). After 7 days of hypoxia, total pulmonary resistance in AdRR5- and AdNOS3-infected rats was significantly higher than in AdNOS2-infected animals (0.41+/-0.05 and 0.39+/-0.07 versus 0.35+/-0. 03 mm Hg. mL(-)(1). min(-)(1), respectively, P:<0.05). Right ventricular hypertrophy was reduced in AdNOS2-infected rats [right ventricular/(left ventricular+septal) weight, 0.19+/-0.10 versus 0. 28+/-0.10 and 0.32+/-0.10 in AdRR5- and AdNOS3-infected rats, respectively, P:<0.05]. The percentage of muscularized precapillary pulmonary resistance vessels was also significantly decreased (18+/-4% versus 25+/-8% and 30+/-5% in AdRR5- and AdNOS3-infected rats, P:<0.05). CONCLUSIONS: Aerosol NOS2 gene transfer increases pulmonary NO production and significantly reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Aerosol NOS2 gene transfer may be a promising strategy to target pulmonary vascular disorders.

L-arginine administration reduces neointima formation after stent injury in rats by a nitric oxide-mediated mechanism.

The clinical outcome of vascular stenting is limited by in-stent stenosis. Increased nitric oxide (NO)/cGMP signaling by L-arginine (L-Arg) supplementation, the substrate for NO synthase (NOS), or NOS gene transfer may reduce in-stent neointima formation. After stenting, vascular cell proliferation in rat carotid arteries, as measured by 5'-bromodeoxyuridine (5'-BrdU) incorporation, indicated 15+/-8%, 28+/-5%, and 33+/-7% 5'-BrdU-positive vascular cells at 4, 7, and 14 days, respectively. Reporter beta-galactosidase gene transfer efficacy was evidenced by 30% beta-galactosidase-expressing medial smooth muscle cells at 14 days. The intima-to-media ratio (I/M) progressively increased to 2.32+/-0.24 at 14 days. To target in-stent neointima formation, animals were infected with adenoviral vectors (4x10(10) plaque-forming units per mL) expressing NOS2 (AdNOS2) or no transgene (AdRR5), or they received daily doses of L-Arg (500 mg. kg(-1). (d-1) IP). The neointima at 14 days was smaller in L-Arg-treated than in untreated rats (I/M 1.25+/-0.35 vs 2.32+/-0.24, P<0.05, n=7 each) or in AdRR5- and AdNOS2-infected rats (I/M 2.57+/-0.43, n=7 and 1.82+/-0.75, n=8, respectively; P<0.05 for both). The effect of L-Arg was abolished by simultaneous administration of N(G)-nitro L-arginine methyl ester, an NOS inhibitor (2.03+/-0.39, P<0.05, vs L-Arg). Inflammation was markedly less in L-Arg- and AdNOS2-treated than in AdRR5-infected rats. Supplemental L-Arg reduces neointima formation after stenting by way of an NOS-dependent mechanism and may be a valuable strategy to target in-stent stenosis.

Hepatocyte-targeted delivery using ph-sensitive liposomes loaded with lactosylnorcantharidin phospholipid complex: preparation, characterization, and therapeutic evaluation in vivo and in vitro.

Liposomes loaded with lactosyl-norcantharidin phospholipid complex (LPC) were prepared, in which soybean phosphatidylcholine was used to improve the liposolubility of lactosyl-norcantharidin (Lac-NCTD). The pH-sensitive LPC liposomes (pH-LPC-lips) were obtained by electrostatic adsorption of the carboxymethyl chitosan onto the surface of the liposomes. The in vitro drug release of pH-LPC-lips and LPC-lips was investigated in dissolution media with pH ranging from 1.0 to 8.0. The in vitro antitumor activity and cellular uptake of Lac-NCTD and its liposomes to HepG2 cells were studied. The pH-LPC-lips demonstrated strong cytotoxicity against the cells and easily permeated the cell membrane. The in vivo antitumor activities of Lac-NCTD and its liposomes were evaluated in mice bearing H22 liver tumors. The pH-LPC-lips displayed the best tumor inhibitory effect. The optical imaging results indicated that Cy7- labeled pH-LPC-lips showed excellent hepatocyte specificity in H22 tumor-bearing mice. Therefore, pH-LPC-lips can be regarded as liver-targeting agents that combine targeting and active releasing.

Adeno-associated virus-mediated gene transfer into rat carotid arteries.

Gene transfer into the arterial wall may allow study of the role of specific genes in vascular pathophysiology and development of local gene therapies for vascular disorders. The feasibility of adeno-associated virus (AAV)-mediated gene transfer into isolated segments of normal and balloon-injured rat carotid arteries was studied using a recombinant AAV carrying CMVlacZ as a reporter gene. Approximately 10(6) and 10(7) infectious units (IU) of AAV were infused into 1 cm isolated segments of the carotid artery of 14 animals with the aid of a Silastic catheter and allowed to remain for 20 min. Animals were killed at different time-points after infection and arteries stained for beta-gal activity. Microscopic examination demonstrated comparable gene transfer into medial and adventitial cells, with significantly higher efficiency of transduction in injured as compared with normal vessels. High levels of in vivo beta-gal expression persisted for at least 30 days after gene transfer. Thus, AAV is capable of transducing media and adventitia of rat carotid arteries, suggesting that it may constitute a useful vector for arterial gene transfer and gene therapy protocols.

Inhibition of tissue angiotensin-converting enzyme with quinapril reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling.

BACKGROUND: Angiotensin II may contribute to hypoxic pulmonary hypertension via its vasoconstrictor and growth-stimulatory effects on vascular smooth muscle cells (VSMCs). Therefore, the use of ACE inhibitors might reduce hypoxic pulmonary hypertension by decreasing pulmonary vasomotor tone or vascular remodeling. METHODS AND RESULTS: Pulmonary hemodynamics and vascular remodeling were compared in chronically hypoxic (FIO2 = 0.10) rats treated with 0, 1, and 10 mg.kg-1.d-1 quinapril, a potent tissue ACE inhibitor, both during and after the development of pulmonary hypertension. Quinapril reduced the development of pulmonary hypertension after 12 days of hypoxia from 26 +/- 1 to 19 +/- 1 mm Hg (P < .05). When started in established pulmonary hypertension, quinapril reduced pulmonary artery pressure and total pulmonary resistance index from 29 +/- 1 to 25 +/- 1 mm Hg and from 0.136 +/- 0.01 to 0.101 +/- 0.005 mm Hg .mL-1.min-1 per kg, respectively (P < .05). Chronically hypoxic rats showed a small pulmonary vasoconstrictor response that was not affected by quinapril. In contrast, percent medial thickness in alveolar duct blood vessels was reduced by quinapril treatment both in developing and in established pulmonary hypertension (10.0 +/- 0.2% versus 8.9 +/- 0.1% [P < .05] and 11.2 +/- 0.2% versus 9.1 +/- 0.2% [P < .05], respectively). 5'-Bromo-deoxyuridine-positive VSMCs were detected in 56 +/- 3% of hypoxic control pulmonary resistance vessels versus 41 +/- 3% of vessels after quinapril treatment (P < .05). CONCLUSIONS: Pulmonary ACE and angiotensin II contribute to the development and maintenance of hypoxic pulmonary hypertension in rats. ACE inhibition with quinapril reduces the development of hypoxic pulmonary hypertension and in part reverses established pulmonary hypertension, most likely via inhibition of pulmonary VSMC proliferation and/or growth.

Nitric oxide inhalation inhibits platelet aggregation and platelet-mediated pulmonary thrombosis in rats.

Endothelium-derived nitric oxide (NO) inhibits in vitro platelet aggregation via a cGMP-dependent mechanism. The effect of inhaled NO on platelet-mediated pulmonary thrombosis following intravenous thrombotic challenge with collagen was examined in rats and compared with the effect of G4120, a cyclic Arg-Gly-Asp-containing synthetic pentapeptide that binds to the platelet glycoprotein IIb/IIIa receptor. Intraplatelet cGMP dose-dependently increased from 39 +/- 6 fmol/10(8) platelets in control to 46 +/- 6, 68 +/- 13, and 81 +/- 13 fmol/10(8) platelets after inhalation with 20, 40, and 80 ppm NO, respectively (P < .05 for 40 and 80 ppm). Ex vivo platelet aggregation of platelet-rich plasma induced by 1 microgram/mL collagen was reduced from 75 +/- 4% in control rats to 22 +/- 10% and 20 +/- 7% in rats ventilated with 40 and 80 ppm NO, respectively, and to 30 +/- 9% in G4120-treated rats (each P < .05 versus control). Circulating platelet counts 3 minutes after collagen injection were significantly higher in the inhaled NO and G4120 groups compared with control rats (250,000 +/- 18,000 and 223,000 +/- 10,000/microL versus 160,000 +/- 18,000/microL, each P < .05). The rise in pulmonary arterial pressure after collagen injection was significantly reduced in NO- and G4120-treated rats (26 +/- 1 and 27 +/- 1 versus 32 +/- 1 mm Hg in control rats, each P < .05). The number of pulmonary resistance vessels containing platelet thrombi was significantly smaller after inhaled NO and G4120 treatment compared with control (56 +/- 3% and 50 +/- 3% versus 68 +/- 3%, respectively; P < .05). Thus, NO inhalation reduces in vivo activation of circulating platelets and platelet-rich thrombosis in thromboembolic pulmonary hypertension. Inhalation of NO may be useful in cardiovascular diseases associated with platelet activation.

Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats.

BACKGROUND: Loss of endothelial NO production after arterial injury may contribute to restenosis, characterized by neointima formation and elastic recoil. Adenovirus-mediated transfer of the gene encoding NO synthase (NOS) in balloon-injured arteries may restore NO production and inhibit neointima formation. METHODS AND RESULTS: After balloon injury, rat carotid arteries were transduced with 3x10(10) pfu/mL recombinant adenovirus carrying the human endothelial constitutive NOS cDNA (AdCMVceNOS, n=8) or no cDNA (AdRR5, n=8). ceNOS expression was confirmed by immunoblot analysis of vascular extracts and was localized by immunostaining in 30% of medial smooth muscle cells (SMCs) and in the adventitia of AdCMVceNOS-transduced arteries. Vascular cGMP levels were reduced from 3.9 pmol/g wet wt in uninjured arteries to 0.7 pmol cGMP/g after AdRR5 but were restored after ceNOS gene transfer (3.8 pmol cGMP/g wet wt, P<.05 versus AdRR5). Intima-to-media ratio 2 weeks after injury was significantly reduced (0.19+/-0.02 in AdCMVceNOS-infected versus 0.69+/-0.07 in AdRR5-infected arteries, P<.05). In vitro, BrdU incorporation of AdCMVceNOS-infected SMCs was reduced by 28% compared with AdRR5-infected SMCs. Transduced cells from injured carotid arteries subjected to FACS sorting showed a significantly lower BrdU labeling index in ceNOS-infected rats (29+/-6% versus 43+/-5% and 45+/-4% in control, injured, and AdRR5-infected rats, respectively, P<.05). CONCLUSIONS: AdCMVceNOS gene transfer to balloon-injured rat carotid arteries restores vascular NO production and reduces neointima formation, at least in part because of an antiproliferative effect on medial SMCs. Adenovirus-mediated ceNOS gene transfer might reduce arterial restenosis after balloon angioplasty.

Effect of inhaled interleukin-4 on airway hyperreactivity in asthmatics.

lnterleukin-4 (IL-4) has been shown to play a crucial role in the pathogenesis of allergic disease including bronchial asthma. In order to investigate the role of IL-4 in airway hyperreactivity, we investigated the effect of inhaled recombinant human IL-4 on airway responsiveness to methacholine and eosinophil numbers in induced sputum in eight patients with allergic asthma using a placebo-controlled study design. Our results demonstrated that in the control experiments receiving vehicle inhalation, methacholine PC20 values did not change nor did the numbers of eosinophils in sputum change from baseline values. In contrast, after IL-4 inhalation, methacholine PC20 fell from baseline (0.43 +/- 1.81 mg/mI) to 0.22 +/- 1.73 mg/mI (p < 0.01) at 24 h, and to 0.21 +/- 1. 74 mg/ml (p < 0.01) at 48 h. Accompanying this increased airway sensitivity was a significant eosinophilia in sputum. Our data indicated that IL-4 increases airway responsiveness by recruiting eosinophils into the airway in patients with allergic bronchial asthma.