Adult ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Peripheral Vascular Diseases ; drug therapy ; Phytotherapy ; Takayasu Arteritis ; drug therapy

Objective To investigate the relationship between human leukocyte antigen-G( HLA-G) gene Exon 8 14 bp deletion polymorphism and the pathogenesis of severe pre-eclampsia.Methods Forty-two pregnant women with severe pre-eclampsia,who admitted to the Third Affiliated Hospital of Zhengzhou University from October 2008 to February 2009,and their newborns were chosen as the severe pre-eclampsia group.Another 45 healthy gravidas at the third trimester and their newborns were chosen as the control.All gravidas in both groups were Han Nationality.HLA-G Exon 8 genotyping was detected by PCR in both groups and the allele frequencies and genotype frequencies were compared between the two groups.The genotype frequencies of maternal-neonatal pairs were also analyzed.Results ( 1 ) In the severe pre-eclampsia group,14% of the maternal-neonatal pairs were homozygote of 14 bp deletion,and significantly higher frequency 33% (15/45) was found in the control group (P =0.038).(2) No significant difference was found in the allele frequencies and genotype frequencies of HLA-G 14 bp deletion polymorphism among all the mothers between the two groups (P >0.05).(3) The + 14 bp and-14 bp allele frequencies of HLA-G 14 bp deletion polymorphism in newborns in the severe pre-eclampsia group were 44% (37/84) and56% (47/84),respectively,and 30% (27/90) and 70% (63/90) in the control group.Although there was no significant difference between the two groups,but differences in trends was identified (χ2= 3.678 P = 0.055) ; The genotype (-14 bp/-14 bp) frequency of neonates in the severe pre-eclampsia group showed no difference compared with that in the control group[29% (12/42) vs 49% (22/45)],but differences in trends was also found (P =0.052).Conclusions HLA-G 14 bp deletion polymorphism is associated with the susceptibility of severe pre-eclampsia in Chinese Han nationality.Maternal-fetal genotype pairs of-14 bp/-14 bp may have reduced risk of severe pre-eclampsia.

Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Drug Therapy, Combination ; Female ; Hearing Disorders ; chemically induced ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Middle Aged ; Recombinant Proteins ; adverse effects ; therapeutic use ; Ribavirin ; adverse effects ; therapeutic use

OBJECTIVETo construct a single-chain human anti-EGFR antibody (scFv) and truncated protamine (tP) fusion protein, ScFv/tP, carrying small interfering (si)RNA directed against the heat shock protein Hsp47, a collagen-binding glycoprotein, in order to evaluate the role Hsp47 in apoptosis of hepatic stellate cells.

METHODSA single chain of the human variable fragment was obtained by phage display and fused with the tP gene and with or without (negative control) the Hsp47 siRNA sequences. Following expression and purification of the scFv/tP fusion protein and the scFv/tPHsp47 siRNA fusion protein, internalization capabilities were tested in isolated human hepatic stellate cells and the QSG-7701 human hepatocyte cells with visualization by immunofluorescent staining. The DNA binding ability of the fusion proteins were verified by gel shift assay.Following ScFv/tP-Hsp47 siRNA fusion protein transfection into the human hepatic stellate cells, the levels of Hsp47 mRNA and protein expression were tested by RT-PCR and Western blotting; in addition, effects of siRNA-mediated silencing of Hsp47 on cell proliferation and apoptosis were analyzed by the cell counting kit (CCK)-8, flow cytometry and Western blot detection of the apoptosis marker poly (ADP-ribose) polymerase (PARP).

RESULTSIndirect immunofluorescence revealed that the ScFv/tP fusion proteins were internalized into human hepatic stellate cells but not into the QSG-7701 cells.The ScFv/tP-Hsp47 siRNA fusion protein caused reduced expression of Hsp47 mRNA and protein expression in the human hepatic stellate cells, as well as increased the cells' apoptosis remarkably.

CONCLUSIONThe ScFv/tP fusion protein can be used as a transfection reagent to deliver Hsp47 siRNA into hepatic stellate cells and to mediate apoptosis via blockade of Hsp47 expression.

Apoptosis ; Cell Proliferation ; HSP47 Heat-Shock Proteins ; genetics ; Hepatic Stellate Cells ; cytology ; Humans ; Protamines ; metabolism ; RNA, Messenger ; RNA, Small Interfering ; Receptor, Epidermal Growth Factor ; immunology ; Single-Chain Antibodies ; Transfection

AIMTo investigate the pharmacokinetics of hylotelephin in Beagle dogs and obtain the main pharmacokinetic parameters.

METHODSAn HPLC method with UV detection was developed to study the pharmacokinetics of hylotelephin in dogs by joining an internal standard (anthracene). Benzoyl chloride was used to the pre-column derivatization of hylotelephin and methanol-water (64:36) was used as the mobile phase. According to the 3P97 pharmacokinetic program, the main parameters were calculated.

RESULTSThe hylotelephin pharmacokinetics conforms to a two-compartment open model after a single iv dose of hylotelephin 10.6 or 21.3 mg x kg(-1) in Beagle dogs. The parameters of two groups were as follows: T(1/2) alpha were 2.3 and 2.1 min, T(1/2) beta were 1.9 and 2.0 h, K12 were 0. 12 and 0.11 min, K21 were 0.17 and 0.21 min, K10 were 0.011 and 0.0094 min, Vc were 0.54 and 0.54 L x kg(-1), AUC were 1.8 and 4.1 g x min x L(-1), CL were 0.0048 and 0.0056 L x kg(-1) x min(-1), MRT were 2.10 and 2.4 h, respectively.

CONCLUSIONThe pharmacokinetics of hylotelephin after iv administration showed a rapid distribution and elimination process in Beagle dogs and was of first order kinetics.

Animals ; Antiviral Agents ; chemistry ; isolation & purification ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; Crassulaceae ; chemistry ; Dogs ; Female ; Heterocyclic Compounds, 3-Ring ; chemistry ; isolation & purification ; pharmacokinetics ; Male ; Molecular Structure ; Plants, Medicinal ; chemistry ; Spectrophotometry, Ultraviolet

Newcastle disease virus (NDV) and Salmonella Pullorum have significant damaging effects on the poultry industry, but no previous vaccine can protect poultry effectively. In this study, a recombinant-attenuated S. Pullorum strain secreting the NDV hemagglutinin-neuraminidase (HN) protein, C79-13ΔcrpΔasd (pYA-HN), was constructed by using the suicide plasmid pREasd-mediated bacteria homologous recombination method to form a new bivalent vaccine candidate against Newcastle disease (ND) and S. Pullorum disease (PD). The effect of this vaccine candidate was compared with those of the NDV LaSota and C79-13ΔcrpΔasd (pYA) strains. The serum hemagglutination inhibition antibody titers, serum immunoglobulin G (IgG) antibodies, secretory IgA, and stimulation index in lymphocyte proliferation were increased significantly more (p < 0.01) in chickens inoculated with C79-13ΔcrpΔasd (pYA-HN) than with C79-13ΔcrpΔasd (pYA) but were not significantly increased compared with the chickens immunized with the LaSota live vaccine (p > 0.05). Moreover, the novel strain provides 60% and 80% protective efficacy against the NDV virulent strain F48E9 and the S. Pullorum virulent strain C79-13. In summary, in this study, a recombinant-attenuated S. Pullorum strain secreting NDV HN protein was constructed. The generation of the S. Pullorum C79-13ΔcrpΔasd (pYA-HN) strain provides a foundation for the development of an effective living-vector double vaccine against ND and PD.
Animals ; Antibodies ; Bacteria ; Chickens ; Hemagglutination ; HN Protein ; Homologous Recombination ; Immunoglobulin A, Secretory ; Immunoglobulin G ; Lymphocytes ; Methods ; Newcastle disease virus ; Newcastle Disease ; Plasmids ; Poultry ; Salmonella ; Suicide ; Vaccines

Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.
Animals ; Gastric Mucosa ; Methylnitronitrosoguanidine/toxicity* ; Precancerous Conditions/chemically induced* ; Rats ; Stomach Neoplasms/drug therapy*

Objective:To investigate the efficacy and safety of SIMI mouthguard paint(test group) in the treatment of enamel demineralization during orthodontic therapy with fixed applince.Methods:152 cases underwent orthodontic therapy with fixed applince were included in a randomized,open,positive control trial,and were treated by SIMI and Duraphant fluoride toothpast (control group) respectively(n =76).The enamel opaque spot was observed before and 3 months after using the products.The oral mucosa reactions,asthma attacks or stomach nausea and other adverse events were recorded.Results:150 cases (n =75) completed the trial.The results showed that the test group was non-inferior compared with the control group.No adverse event was found in both groups.Conclusion:SIMI mouthguard paint is effective in control of enamel demineralization during orthodontic therapy with fixed applince.

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.