OBJECTIVETo observe mainfestations of syndrome and biochemical indices of hypertensive model rats with excessive accumulation of phlegm-dampness syndrome (EAPDS), and to explore its possible pathological mechanism.

METHODSEAPDS rat model was prepared in 50 Wistar rats by feeding with high fat forage. Meanwhile, a normal control group consisting of 10 Wistar rats was set up by feeding with normal forage. After 25-week continuous feeding, 22 rats with body weight (BW) and blood pressure (BP) exceeding 25% those of the control group were selected as a model group. BW, BP, blood lipids, and related serological indicators were detected in all rats. Morphological changes of target organs were observed. mRNA expression levels of leptin receptor (LepR), Janus kinase2 (Jak2), signal transducer and activator of transcription 3 (Stat3), suppressor of cytokine signaling-3 (Socs3), angiotensin II receptor type 1 (AT1), angiotensin II receptor type 2 (AT2), phosphatidylinositol 3 kinase (P13K), serine threonine kinase (Akt), nuclear factor of kappa B (NF-κBp65), inhibitor of nuclear factor kappa-B kinase α (IKKα), NF-kappa-B inhibitor β (lKKβ), NF-kappa-B inhibitor α (IKBα), and AMP-activated protein kinase (AMPK) were detected by quantitative real-time PCR (qPCR). Expression levels of AT1 and LepR in aorta were detected by immunohistochemical assay and Western blot respectively.

RESULTSCompared with the control group, BW, BP, and blood lipids increased; serum levels of leptin (Lep) , Ang II, Hcy, ET-1, TNF-α, IL-6, and p2-MG increased, but NO decreased in the model group (P < 0.05, P < 0.01). Aortal endothelial injury and smooth muscle cell proliferation occurred in the model group, accompanied with heart and renal injury. Compared with the control group, mRNA expression levels of LepR, Jak2, Stat3, Socs3, AT1 , PI3K, Akt, NF-κB p65, IKKβ, IKBα, and AMPK in aorta were up-regulated significantly (P < 0.05), while the expression of IKKa decreased (P < 0.05). Immunohistochem- ical staining showed, brownish yellow deposit of AT1 and LepR was obviously increased, with more extensively positive distribution. Western blot results showed, as compared with the control group, protein expression levels of AT1 and LepR obviously increased in the model group (P < 0.05).

CONCLUSIONSModel rats exhibited typical syndromes of EAPDS. They put up weight with fat abdomen, gloomy hair, poor appetite, hypersomnia, lowered activities , reduced food intake, loose stool, dark red tongue, white tongue with white, thick, greasy fur. Lep could be taken as one of objective indicators for evaluating hypertension rat model with EAPDS.

Animals ; Aorta ; Cell Proliferation ; Disease Models, Animal ; Hypertension ; physiopathology ; I-kappa B Proteins ; Interleukin-6 ; Leptin ; blood ; NF-KappaB Inhibitor alpha ; NF-kappa B ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Wistar ; Suppressor of Cytokine Signaling Proteins ; Transcription Factor RelA ; Tumor Necrosis Factor-alpha

Objective To optimize the supercritical carbon dioxide(SC-CO2)extraction of lipids from tempeh(TE-C)and further improve the lipid classes ratio. Methods The experimental parameters of SC-CO2 extraction including extraction temperature, pressure,and moisture content of tempeh were optimized using a Box-Behnken design combined with response surface methodology (RSM),according to the weighted extraction ratio of TE-C and lipid classes after the experimental results of single factors. Detailed chemical compositions of TE-C obtained by optimum conditions of SC-CO2 extraction were analyzed by high performance liquid chroma?tography with an evaporative light-scattering detector(HPLC-ELSD)and high performance liquid chromatography-atmospheric pres?sure chemical ionization mass spectrometry(HPLC-APCI-MS). Results TE-C was composed of three lipid classes:fatty acids(Ⅰ), diacylglycerols(Ⅱ)and triacylglycerols(Ⅲ). The optimum SC-CO2 extraction conditions of TE-C were 50℃extraction temperature, 25 MPa pressure,1.99%moisture content of tempeh and 1.5 hour extraction time. Conclusion The optimum value of RSM for SC-CO2 extraction was(5.97±0.15)g/100 g.

Objective To investigate the effects of gonadotropin releasing hormone agonist (GnRH- a) and antagonist (GnRH-ant) on cyclophosphamide (CTX)-induced ovarian damage in rats.Methods Seventy-two Sprague-Dawley female rats were divided randomly into six groups,which received normal saline (NS),CTX,GnRH-a+NS,GnRH-a+CTX,GnRH-ant+NS,and GnRH-ant+CTX respectively.Levels of serum follicle-stimulating hormone (FSH),luteinizing hormone (LH) and estradiol (E_2) were measured successively by the enzyme-linked immunosorbent assay method,and half of the rats were killed in the first week and between the fourth and the fifth week after stop of medication,respectively to compare the weight of the ovaries and the number of the primordial follicles and the growth follicles.Results (1) Throughout experiment,the serum levels of FSH,LH and E_2 of the control group fluctuated slightly,while those in the CTX group kept rising.During medication treatment,compared with the control group[(118?16) ?g/L, (350?35) ?g/L] and the CTX group[(113?15) ?g/L,(289?42) ?g/L],the concentrations of LH [(42 ?8)-(47?7) ?g/L,(31?5)-(36?7) ?g/L] and FSH [(124?45)-(136?32)?g/L,(178 ?54)-(198+27)?g/L] in the GnRH-a groups and the GnRH-ant groups were maintained at low levels significantly and the levels of LH in the GnRH-ant groups were significantly lower than that in the GnRH-a groups,but the levels of FSH in the GnRH-ant groups were significantly higher than that in the GnRH-a groups(P0.05),but the levels of FSH,LH and E_2 of the GnRH-ant+CTX group rose obviously and were similar to the levels of the CTX group,especially the FSH,and the levels of LH and FSH of the GnRH- ant + CTX group [(156?12) ?g/L,(520?44) ?g/L] and the CTX group [(178?18) ?g/L,(546?36) ?g/L] were significantly higher than that of the other four groups [(121?15)-(132?13) ?g/L,(335 ?35)-(359?26) ?g/L] at the 4~(th)-5~(th) week after stop of treatment(P0.05),but the number of all kinds of follicles declined significantly in the GnRH-ant+CTX group[(195?15),(36?12)] and the CTX group [(212?11),(36?9)] compared to the other four groups[(302?15)-(690?43),(44?12)-(58?11),P

This study was aimed to investigate the effect of chemokine-like factor superfamily 8 (CKLFSF8) on proliferation and expression of epidermal growth factor receptor (EGFR) of HL-60 cells. Expression of CKLFSF8 mRNA on HL-60 cell line was assayed by RT-PCR; the target gene was transfected into the cells by lipid vector, cell proliferation was determined by MTT assay, while expression of EGFR in HL-60 was determined by immunocytochemical technique. The results indicated that expression of CKLFSF8 existed in HL-60 cells. After transfection, cell proliferation was inhibited (P < 0.05) and the expression of EGFR in HL-60 cells was also discovered to be inhibited (P < 0.05). It is concluded that the proliferation and expression of EGFR in HL-60 cells can be inhibited by transfection of CKLFSF8. The novel chemokine may provide a new approach in the treatment of leukemia.
Cell Proliferation ; Chemokines ; metabolism ; Gene Expression Regulation, Neoplastic ; HL-60 Cells ; Humans ; MARVEL Domain-Containing Proteins ; RNA, Messenger ; metabolism ; Receptor, Epidermal Growth Factor ; metabolism ; Transfection

In recent studies some urea derivatives have been identified as potent anti-tuberculosis agents by targeting mycobacterial membrane protein large 3 (MmpL3). However, this compound series as exemplified by AU1235 exhibited poor in vitro pharmacokinetic profile. With AU1235 as the lead, we have identified a novel benzimidazole series as potential anti-tuberculosis agents by using scaffold hopping approach. Among these synthesized compounds, 2-aminobenzimidazole derivative 8b showed the potent anti-tuberculosis activity with the MIC value of 0.03 microg x mL(-1). This compound also showed improved metabolic stability compared to AU1235. Our investigation indicated that benzimidazole derivatives are the promising lead for further optimization as anti-tuberculosis agents.
Antitubercular Agents ; pharmacology ; Benzimidazoles ; chemistry ; pharmacology ; Drug Design ; Humans ; Structure-Activity Relationship ; Tuberculosis ; drug therapy

To investigate the specific anti-leukemia effect of cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) activated by exosomes alone or in combination with CpG ODN in vitro and the feasibility of exosomes as remedial vaccine, the DCs induced from normal volunteer PBMNCs were divided into 7 groups. Three groups of them were added with the exosomes: Kexo (exosomes derived from K562 cells) or DCexo (exosomes derived from DCs induced from K562 cells) or FTexo (exosomes derived from DCs induced from K562 cells and pulsed by freeze-thawing antigen of K562 cells) as experimental groups (Kexo, DCexo and FTexo). The other three groups were added with CPG ODN while added the exosomes (Kexo, DCexo and FTexo), and were used as experimental groups also (Kexo+CpG, DCexo+CpG and FTexo+CpG). The seventh group DCs was added with nothing as blank control. These DCs above mentioned were cultured continuously for 72 hours. The T lymphocytes were co-cultured with DCs for another 72 hours to generate CTL. Then, the killing effects of them on K562 cells were determined by MTT assay. The results showed that all experimental groups pulsed by exosomes displayed stronger killing effect, compared with control group (p<0.05). DCexo and FTexo displayed stronger killing effect too, compared with Kexo (p<0.05). CPG ODN as an adjuvant could enhance the killing effect (p<0.05). It is concluded that the special killing effect on K562 cells can be induced by exosomes, CPG ODN as an adjuvant can enhance the killing effect. Exosome is hopeful as a remedial vaccine to be used for the leukemia therapy.
Adjuvants, Immunologic ; pharmacology ; Cancer Vaccines ; immunology ; Dendritic Cells ; immunology ; Exosomes ; immunology ; Humans ; K562 Cells ; Oligodeoxyribonucleotides ; immunology ; T-Lymphocytes, Cytotoxic ; immunology

OBJECTIVETo investigate the proper anticoagulation intensity in patients after mechanical heart valve replacement in china.

METHODSThe anticoagulation therapy intensity and the complications in 480 patients after mechanical heart valve replacement were studied.

RESULTSThe follow-up rate was 89.17%, the total patient-years (Pty) was 2,110.04 years, the mean oral import warfarin dosage was (2.81 +/- 0.95) mg/day, and native warfarin dosage (2.38 +/- 0.46) mg/day. The mean PTR value of 2 116 samples was 1.43 +/- 0.26, and the INR value of 1 195 samples was 1.63 +/- 0.49. The total hemorrhage rate was 4.60% Pty, and the hemorrhage death rate was 0.38% Pty. The PTR and INR values were higher in the hemorrhage group than in the no-hemorrhage group. (t = 1.816, P < 0.05; t = 2.407, P < 0.01). The thromboembolism rate was 0.66% Pty, and the thromboembolism death rate was 0.05% Pty. There were 15 pregnancies in 14 women patients and no malformed newborns were found.

CONCLUSIONSThe most important complication of anticoagulation therapy after mechanical heart valve replacement is hemorrhage in china; The proper anticoagulation intensities of this group are INR 1.5-2.0 and PTR 1.3-1.5. It is beneficial to adopt the low intensity anticoagulation therapy for decreasing the death rate from hemorrhage, protecting pregnant women and newborns from hemorrhage and malformation, and improving the life qualities of the patients.

Adolescent ; Adult ; Aged ; Anticoagulants ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Heart Valve Prosthesis Implantation ; adverse effects ; methods ; Hemorrhage ; chemically induced ; prevention & control ; Humans ; Male ; Middle Aged ; Postoperative Care ; Postoperative Complications ; etiology ; prevention & control ; Pregnancy ; Thromboembolism ; chemically induced ; prevention & control ; Warfarin ; administration & dosage ; adverse effects ; therapeutic use ; Young Adult

Objective To explore whether autoreactive antibody presents in patients with sporadic idiopathic hypoparathyroidism(sIHP).Methods The subjects including 26 patients with sIHP and 112 genealogical members as well as 60 age-and sex-matched healthy controls.Anti-parathyroid antibodies in the sera were assayed by indirect immunofluorescence.The levels of calcium,phosphorus and magnesium as well as intact parathyroid hormone(iPTH)in the sera were tested.Results Positive autoantibodies against parathyroid tissue were demonstrated in 10 patients(38%)with sIHP,significantly higher than that of in genealogical members(10%,?~2=13.42,P

Essential hypertension (EH) is affected by both genetic and environmental factors.The polymorphism of connexin (Cx) genes is found associated with the development of hypertension.However,the association of the polymorphism of Cxs with EH has not been investigated.This study aimed to investigate the association of the polymorphism of connexin (Cx) genes Cx37,Cx40,and Cx43 with EH in Kazak and Han Chinese in Xinjiang,China.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to analyze the polymorphism of Cx genes in Kazak and Han EH patients as well as their normotensive controls.The results showed that there were no significant differences in the frequencies of different three genotypes (A/A,A/G,and G/G) and A and G alleles of Cx40 rs35594137 and rs11552588 between EH patients and normotensive controis.However,in Kazak EH patients,the frequencies of three genotypes (A/A,A/G;and G/G) of Cx37 rs1630310 were 24.8％,47.2％ and 28.0％,respectively,which were significantly different from those in Han EH patients.In Han EH patients,the frequencies of the three genotypes (C/C,C/G and G/G) of Cx43 rs1925223 were 6.4％,35.6％ and 58.0％,respectively.Frequencies of the other four genotypes had no statistical differences among Kazak and Hart EH patients and their normotensive controls.These results suggest polymorphisms of Cx37 rs 1630310 and Cx43 rs 1925223 genes may be associated with the pathogenesis of EH.Carrying Cx37 rs1630310-A or Cx43 rs1925223-G genotypes may protect against the development of EH.

A L9 (3(4)) orthogonal design table to be used to get nine combinations of extraction of three herbs of Wuji pill: Coptis chinensis, Tetradium ruticarpum and Paeonia lactiflora Pall., and nine extraction of single herbs correspondingly, altogether eighteen combinations. Quantification of five representative bioactive ingredients: berberine, palmatine, evodiamine, rutaecarpine, paeoniflorin in rat liver by ultra high liquid chromatography-tandem mass spectrometry after oral administration at 2 h time point of eighteen combinations. The result shows the bioactive ingredients have different concentrations betweem different combinations and the single herb with the same dosage significantly as well as the same dose combinations. C. chinensis with evodiamine concentration of low and high dose T. ruticarpum was positively correlated. T. ruticarpum with berberine concentration of low dose C. chinensis was negatively correlated and of meddle dose C. chinensis was correlated positively. T. ruticarpum with paeoniflorin concentration of middle dose P. lactiflora was correlated positively. P. lactiflora with palmatine concentration of middle dose C. chinensis was negatively correlated and with evodiamine and rutaecarpine concentration of middle dose T. ruticarpum was negatively correlated. These shows the three single herbs interactions resulted in the differences of each ingredients concentration in rat liver. The orthogonal analysis indicates the combination 12: 6: 6 make the maximum concentration in rat liver.
Administration, Oral ; Animals ; Biological Availability ; Biomedical Research ; methods ; Chromatography, High Pressure Liquid ; methods ; Drug Stability ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Liver ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Temperature