High performance liquid chromatography-time-off-flight mass spectrometer (HPLC-TOFMS) technology coupled with partial least squares discriminant analysis (PLS-DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.05) at fourth week. The metabolic profiling significantly changed and four metabolites involved in G protein-coupled pathway were identified. Metabolomics is able to detect holistic and microcosmic alternations in organism, so as to elucidate therapeutic mechanism of drugs.
Animals ; Biomarkers ; blood ; Blood Pressure ; Chromatography, High Pressure Liquid ; Discriminant Analysis ; Least-Squares Analysis ; Mass Spectrometry ; Metabolome ; Metabolomics ; Rats ; Rats, Inbred SHR ; Valsartan ; pharmacology

Acupuncture Therapy ; Adult ; Aged ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Needles ; Periarthritis ; therapy ; Punctures ; Treatment Outcome

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Intraoperative Complications ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Tracheotomy ; adverse effects ; methods ; Young Adult

Child ; Chronic Disease ; Cough ; diagnosis ; etiology ; therapy ; Humans ; Practice Guidelines as Topic

Objective To investigate the anatomic feature and exposing methods of recurrent laryngeal nerve(RLN) in thyroid surgery. Methods The data of 327 cases of thyroid tumor were analyzed retrospectively. The anatomic feature, injury and prevention of RLN were discussed. Of all the cases, 293 RLNs (242 cases) were anatomically exposed. Results The temporary injury rates of RLN was 1.65% (4/242) in the exposed group and 8.23% (7/85) in the unexposed group with a persistent injury rate of 2.35%(2/85). The differences of temporary injury rates and persistent injury rates between the two groups were statistically significant (P<0.05). 67.23% (197/293) of the RLNs had two branches before entering larynx, 61.09%(179/293) of RLNs were posterior to the inferior thyroid artery and 31.39% (92/293) anterior to the inferior thyroid artery, 4.09% (12/293) passed through the bifurcation of inferior thyroid artery, and 4. 13% (10/293) were not related to the inferior thyroid artery. The incidence of non-recurrent laryngeal nerve (inferior laryngeal nerve) was 0.68% (2/293). Conclusions The anatomic relation of RLN is relatively complicated along its journey. The injury of RLN could be reduced with designed exposal during the thyroid surgery.

Objective To study the relationship between peripheral blood hemoglobin (HB) and blood pres- sure.Methods We performed a cross-sectional analysis in 1153 subjects aged 29-83 years.Waist circumfer- ence,HB,blood pressure,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL- C),triglycerides (TG),total cholesterol (TC) were determined.Results ①With the increasing of blood pres- sure,HB had a clearly increasing trend (HB,normotensive:137.5?14.7 vs prehypertension:143.4?14.4 vs hy- pertension:144.3?13.8 g/L,P

2', 3', 5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (WS070117) is a derivative compound of natural product cordycepin. It has significant lipids regulating activity and low toxicity which has been proved by in vitro and in vivo experiments. In this study, 1H NMR-based metabolomics was used to investigate the dose-related effects of WS070117 on hyperlipidemia of high-fat-fed hamsters. The hyperlipidemic hamsters were administrated with six different doses of WS070117, including 3, 12, 50, 100, 200 and 400 mg x kg(-1) x d(-1). 1H NMR spectra of hamster serum were visually and statistically analyzed using two multivariate analyses: principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). As a result, WS070117-treated groups showed dose-related regulation of metabolites associated with lipid metabolism, choline metabolism and glucose metabolism. The dose of 3 mg x kg(-1) x d(-1) of WS070117 only exhibited a little lipids regulating activity. However, the doses of 12 and 50 mg x kg(-1) x d(-1) of WS070117 both regulated the contents of metabolites to reverse significantly toward normal levels. When the dose of WS070117 reached 100 mg x kg(-1) x d(-1), it was more effective than positive control drugs. The work suggested that NMR-based metabolomics might be a valuable approach to evaluate dose-related effects of lipids regulating compounds.
Adenosine ; analogs & derivatives ; pharmacology ; Animals ; Cricetinae ; Hyperlipidemias ; metabolism ; Least-Squares Analysis ; Lipid Metabolism ; drug effects ; Magnetic Resonance Spectroscopy ; Metabolomics ; Multivariate Analysis ; Principal Component Analysis

BACKGROUND:Adenovirus, expressing within a limited period, can limit the expression time and amount of target genes that is not conducive to ongoing experiments. Here, we select adenovirus as vectors for genetic recombination with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Trail) gene fragment.
OBJECTIVE:To explore the construction of recombinant lentiviral vector carrying Trail in rats
METHODS:The Trail gene was obtained:according to GenBank in rat Trail gene sequence (NM_145681.1), we designed the gene specific primers of Trail-Age I-F and Trail-AgeI-R, and used AgeI as enzyme cutting site. PCR was applied to amplify Trail gene from rat cDNA Library and construct recombinant plasmids after cutting Trail gene to be cloned into expression vector GV218 by AgeI. Recombinant plasmids were transfected into 293T cells by Lipofeetamine2000 encapsulated recombinant plasmid and auxiliary packaging carrier. The Trail protein of lentiviral plasmids was expressed. Fol owing virus col ection, we identified virus titer and extracted protein from cells to detect Trail expression by western blot assay.
RESULTS AND CONCLUSION:Screened positive Escherichia coli DH5a competent cells were sequenced with 861 bp, which was consistent with Trail nucleotide sequence in GenBank. After transfection 2 days, virus liquid was col ected and confirmed as recombinant plasmid including Trail gene by PCR and Trail proteins expressed in 293T cells by western blot assay. Hole dilution method and real-time fluorescent quantitative PCR determination showed that the virus titer was 2×109 TU/mL. In this study, recombinant lentiviral vector carrying Trail is successful y constructed by homologous recombination in Escherichia coli.

Follow-Up Studies ; Forearm ; Humans ; Infant, Newborn ; Male ; Melanoma ; congenital ; surgery ; Skin Neoplasms ; congenital ; surgery

OBJECTIVETo investigate the role of endogenous hydrogen sulfide (H2S) in erectile dysfunction (ED) induced by androgen deficiency.

METHODSWe randomly divided 30 eight-week-old healthy male SD rats into six groups: 2-week control (A), 4-week control (B), 2-week castration (C), 4-week castration (D), 2-week castration + androgen replacement (E), and 4-week castration + androgen replacement (F), those in groups E and F subcutaneously injected with testosterone propionate (TP) at the physiological dose of 3 mg/kg per day after castration, while those in the other groups with isodose oil instead. At 2 and 4 weeks after operation, we determined the level of serum testosterone (T) , intracavernous pressure (ICP) , mean carotid arterial pressure (MAP) of the rats, measured the concentration of H2S in the plasma and corpus cavernosum tissue, and detected the expressions of cystathionine-P3-synthase (CBS) and cystathionine-gamma-lyase (CSE) by immunohistochemistry and Western blot.

RESULTSThe serum T level was significantly lower in group C ([0.63 +/- 0.15] nmol/L) than in A ( [ 16.55 +/- 4.17] nmol/L) and E ( [ 18.99 +/- 4.62] nmol/L) (P <0.05), as well as in group D ([0.70 +/-0.22] nmol/L) than in B ([15.44 +/-5.18] nmol/L) and F ([20.99 +/-6.41] nmol/L) (P <0. 05) , and so were ICP/MAP after 5 and 7 V electrical stimulation of the pelvic ganglia (P <0. 05) , H2 S concentration (P <0.05), and the expressions of CBS and CSE (P <0.05). The expressions of CBS and CSE proteins were also significantly decreased in group C as compared with D (P <0.05).

CONCLUSIONThe reduced expressions of CBS and CSE may inhibit the H2 S signaling pathway, which might be one of the mechanisms underlying androgen deficiency-induced ED in rats.

Androgens ; deficiency ; Animals ; Cystathionine beta-Synthase ; metabolism ; Cystathionine gamma-Lyase ; metabolism ; Erectile Dysfunction ; metabolism ; Hydrogen Sulfide ; metabolism ; Male ; Orchiectomy ; Penis ; metabolism ; Rats ; Rats, Sprague-Dawley