OBJECTIVETo study the effects of Tongxinluo on the expressions of matrix metalloproteinase-3 (MMP-3), MMP-9 and peroxisome proliferators-activated receptor gamma (PPARgamma) in atherosclerotic rabbits and explore the mechanism of its anti-atherosclerotic effect.

METHODSTwenty-four rabbits were randomized equally into control group, atherosclerotic model group (fed with high-fat diet for 14 weeks) and Tongxinluo group. The expressions of MMP-3, 9 and PPARgamma in the 3 groups were observed by means of immunohistochemistry.

RESULTSThe expressions of MMP-3, 9 and PPARgamma in the model group and Tongxinluo group were significantly higher than those in the control group (P<0.01). After high-fat diet feeding for 14 weeks, Tongxinluo group showed significantly lower expressions of MMP-3 and 9 but higher expression of PPARgamma than the model group (P<0.01).

CONCLUSIONTongxinluo can inhibit the expression of MMP-3 and 9 and increase the expression of PPARgamma, which might be the mechanism of its anti-atherosclerotic effect.

Animals ; Atherosclerosis ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Male ; Matrix Metalloproteinase 3 ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; PPAR gamma ; genetics ; metabolism ; Rabbits ; Random Allocation

BACKGROUNDNon-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however, the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined. The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy, low-intensity warfarin therapy, and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF).

METHODSA total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups: standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group, low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group. All patients were evaluated by physicians at 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after randomization to obtain a patient questionnaire, physical examination and related laboratory tests.

RESULTSThe annual event rates of ischemic stroke, transient ischemic attack (TIA) or systemic thromboembolism were 2.6%, 3.1% and 6.9% in the standard-intensity warfarin, low-intensity warfarin and aspirin groups, respectively (P = 0.027). Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P = 0.018, P = 0.044), and there was no significant difference between the two warfarin groups. Severe hemorrhagic events occurred in 15 patients, 7 (2.6%) in the standard-intensity warfarin group, 7 (2.4%) in the low-intensity warfarin group and 1 (0.4%) in the aspirin group. The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group, but the difference did not reach statistical significance (P = 0.101). The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10.2%, 7.6% and 2.2%, respectively, in the 3 groups (P = 0.001). Furthermore, there was no significant difference in all cause mortality among the three study groups.

CONCLUSIONIn Chinese patients with NVAF, the warfarin therapy (INR 1.6 - 2.5) for the prevention of thromboembolic events was superior to aspirin.

Aged ; Aged, 80 and over ; Anticoagulants ; administration & dosage ; therapeutic use ; Aspirin ; administration & dosage ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Warfarin ; administration & dosage ; therapeutic use

Qigui Tongfeng tablet (QLTFT) is a traditional Chinese medicine with good effect for treating gout. Here, network pharmacology method and molecular similarity analysis were utilized to study the effective substance basis and molecular mechanism of the QLTFT on the gout. The similarity to the medicinal compounds is reflected in the Tanimoto coefficient that gives the structural similarity of two compounds. Operationally, similar modifiers were described as pairs of concepts with a similarity score of 0. 500. The results of the molecular similarity analysis suggested that the flavonoids in QLTFT could be new leads for gout. Furthermore, complex biological systems may be represented and analyzed as computable networks. Two important properties of a network were degree and betweenness. Nodes with high degree or high betweenness may play important roles in the overall composition of a network. And the results of network analysis showed that dongbeinine, verticinone-N-oxide, verticine N-oxide, peimine, peiminine, isobaimonidine, dongbeirine, peimisine and simi-arenol which with high degree acted on xanthine dehydrogenase/oxidase, matrix metalloproteinase-9, an arachidonate 5-lipoxygenase-activating protein, tyrosine-protein kinase and etc. Inhibition of these targets can prevent the formation of uric acid, reduce inflammation by uric acid and regulate the body's immune response. Thus, these compounds may be the main effective substance basis. The research results not only reveals its molecular mechanism, but also provide a theoretical basis for the quality control of drugs and clinical application.
Gout ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Pharmacology ; methods ; Tablets ; Technology, Pharmaceutical ; methods

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

AIMTo study bioequivalences of bambuterol and its metabolites terbutaline in 20 healthy male volunteers.

METHODSA single oral dose of domestic bambuterol capsule or imported bambuterol tablet was given according to a randomized 2-way cross-over design. The plasma bambuterol and terbutaline concentrations were determined by high performance capillary zone electrophoresis (HPCZE).

RESULTSThe pharmacokinetic parameters of the capsule and tablet of bambuterol: AUC0-1 were (72 +/- 18) and (72 +/- 13) microgram.h.L-1, Cmax were (8.1 +/- 1.8) and (9.2 +/- 2.3) microgram.L-1, Tmax were (3.6 +/- 1.3) and (3.7 +/- 1.0) h, respectively; terbutaline: AUC0-t were (129 +/- 32) and (130 +/- 34) microgram.h.L-1, Cmax were (7.8 +/- 2.2) and (8.5 +/- 2.9) microgram.L-1, Tmax were (5.4 +/- 0.8) and (5.6 +/- 1.1) h, respectively. The bioavaiability of the capsule was (100 +/- 16)% (bambuterol) and (101 +/- 13)% (terbutaline).

CONCLUSIONThe results demonstrated that the two preparations of bambuterol and terbutaline were bioequivalent by analysis of variance, with two-one sided test at 90% confidential level.

Administration, Oral ; Adult ; Area Under Curve ; Biological Availability ; Capsules ; Chromatography, High Pressure Liquid ; Cross-Over Studies ; Electrophoresis, Capillary ; Humans ; Male ; Tablets ; Terbutaline ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Therapeutic Equivalency

This study is to investigate the antitumor activity of CIP-36 on multidrug resistant human oral squamous carcinoma cell line (KBV200 cells) in vitro and the possible anticancer mechanisms. MTT assay, Hoechst fluorescein stain, RT-PCR and immunohistochemistry were carried out on KBV200 and KB cells. The growth of many tumor cells was obviously inhibited by CIP-36, especially the multidrug resistant cells KBV200. Obvious apoptosis could be observed in the Hoechst 33342 staining experiments. The results of RT-PCR showed that the levels of p53, p21, caspase-3 and bax mRNA increased, and meanwhile the expression of mdr-1 and bcl-2 mRNA decreased in a dose-dependent manner. The data were significantly different from that of vehicle. The expression of P-gp significantly decreased with the increasing dosage of CIP-36 examined by immunohistochemistry. It can be concluded that CIP-36 could change resistance-related genes and proteins to overcome multidrug resistance in the KBV200 cell line.
ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Caspase 3 ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; KB Cells ; Mouth Neoplasms ; metabolism ; pathology ; Podophyllotoxin ; administration & dosage ; analogs & derivatives ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Proto-Oncogene Proteins p21(ras) ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; bcl-2-Associated X Protein ; genetics ; metabolism

·AIM: To study the mechanism and effect of Qingxuan decoction on evaporative dry eye in rabbit model. ·METHODS: Totally 25 healthy male Japanese white rabbits were randomly divided into 5 groups: control group, model group, western medicine group, high dose of Qingxuan decoction group, low dose of Qingxuan decoction group. The blank control group did not do any treatment. The improved dry eye model of rabbit was prepared by the improved method of glandular burning of the eyelid plate. The high and low dose group were given daily 27. 2mg/kg, 6. 8mg/kg Qingxuan decoction by gavage. The model group was intragastric with the same amount of normal saline every day. The western medicine group with tobramycin and dexamethasone ophthalmic ointment 1 drops, once a day. The treatment were administered continuously for 28d. At 14d before the experiment, 7d before the experiment, 7d after the model, and 14d after the model, all the rabbits were tested by Schirmer Ⅰ test ( SⅠt) and break-up time (BUT). On the 15d after modeling, the animals were sacrificed by excessive anaesthesia. Rabbit ocular surface tissue sections were prepared. Hematoxylin - eosin staining method was used to observe the corneal morphological changes in each group. The concentrations of TNF-α, IL-1 and IL-6 in the ocular surface of rabbits were detected by ELISA. ·RESULTS: (1) BUT, SⅠt: 7d after the model had been prepared, BUT and SⅠt of the model group and the western medicine group, high dose and low dose of Qingxuan decoction group was improved ( P< 0. 05 );Those of western medicine group, high dose and low dose of Qingxuan Decoction group compared with the model group, were significantly different (P<0. 05). (2) TNF-α, IL-1, IL-6: The ELISA assay showed that TNF-α and IL-1, IL-6 concentration in the model group rabbits was significantly higher than those of the control group, TNF-α and IL-1, IL-6 concentration in western medicine group and high dose group of rabbits was significantly lower than those in the model group, the differences were statistically significant (P<0. 05), and in high dose group the effect was better than that of Western medicine group. ( 3 ) Histopathological examination: on the 14d after the model, the corneal epithelium in the blank control group was stratified well. The cells in the base were columnar, near the surface, the cornea epithelium showed a squamous change. Conjunctiva showed complete epithelial layer and subconjunctival tissue layer, and goblet cells arranged closely. The number of corneal epithelial cells in model group was reduced or even stripped, and the matrix layer was disorder; Irregular loss of conjunctival epithelial cell layer and a large decrease in goblet cells. The corneal morphology of the rabbits in the western medicine group and the high dose group was close to the normal group, and the number of conjunctival goblet cells was not significantly different from that in the blank control group. ·CONCLUSION: The expression of Qingxuan decoction can inhibit the inflammatory reaction through down -regulation of TNF-α and IL-1, IL-6 and in evaporative dry eye rabbit cornea and conjunctiva, so as to improve the ocular symptoms, increase tear secretion, prolong the time of BUT.

AIMTo study the chemical constituents of Dryopteris sublaeta Ching et Hsu.

METHODSFresh plant of Dryopteris sublaeta Ching et Hsu was extracted twice with boiling water, the extract was concentrated to small volume under reduced pressure at 50 degrees C. The concentrated material was partitioned with ether, ethyl acetate, and n-butanol. The fraction of ether extract was chromatographed over silica gel column. The compounds were identified on the basis of their physiochemical and spectral data.

RESULTSFour compounds were obtained and identified as 2 (S)-5, 7, 3'-trihydroxy-6, 8-dimethyl-5'-methoxyflavanone (1), matteucinol (2), desmethoxymatteucinol (3) and 5, 7, 2'-trihydroxy-6, 8-dimethylflavanone (4).

CONCLUSIONCompound 1 is a new one, the others were isolated from Dryopteris for the first time.

Chromones ; chemistry ; isolation & purification ; Dryopteris ; chemistry ; Flavanones ; chemistry ; isolation & purification ; Molecular Conformation ; Molecular Structure ; Plants, Medicinal ; chemistry

OBJECTIVETo construct a function model that can be used in the diagnosis bladder outlet obstruction (BOO) resulting from benign prostatic hyperplasia, and to develop a diagram allowing the judgement of bladder outlet for patients with different detrusor contractility, especially with impaired one.

METHODSUrodynamic and clinical data of 131 men were analyzed retrospectively. By Logistic analysis, a function model was constructed. Based on the model, a diagram allowing the evaluation of bladder outlet was drawn. The cutoff point for diagnosing BOO with the function model and the curve was confirmed by ROC curve analysis.

RESULTSThe function model (BOOI) was obtained by the formula 5.03 x residual fraction + 0.04 x PdetatQmax - 0.20 x Qmax - 0.91 + alpha (alpha = 0 for those with low pressure-low flow on P-FS, alpha = 1.42 for high pressure-low flow, alpha = -7.30 for high pressure-high flow). The cutoff point for BOOI diagnosing BOO was 0.36. When validated, the sensitivity, specificity, positive predictive value, and negative predictive value were 85.7%, 91.7%, 96.0% and 73.3% respectively.

CONCLUSIONThe BOOI, with an easy calculation mode, could predict the probability of BOO. The sensitivity and specificity of the criterion for the diagnosis of BOO were satisfactory. The curve we drew could help to differentiate the obstructed men with low pressure-low flow and thus benefit them by surgical relief of their obstruction.

Aged ; Aged, 80 and over ; Humans ; Logistic Models ; Male ; Middle Aged ; Prostatic Hyperplasia ; complications ; ROC Curve ; Retrospective Studies ; Urinary Bladder Neck Obstruction ; diagnosis ; etiology ; Urodynamics

AIMTo study the chemical constituents of Dryopteris sublaeta Ching et Hsu.

METHODSFresh plant of Dryopteris sublaeta ching et hsu was extracted twice with boiling water, concentrated to small volume under reduced pressure at 50 degrees C. The concentrated material was partitioned with ether, ethyl acetate, and n-butanol. The fraction of ethyl acetate extract was chromatographed over macroporous adsorption resin (Diaion HP-20) eluted with a mixture of H2O and MeOH in increasing MeOH content. Their fractions from resin were repeatedly chromatographed over Toyopearl HW-40, Sephadex LH-20 and silica gel column chromatography. The compounds were identified on the basis of their physiochemical and spectral data.

RESULTSFour compounds were obtained and identified as 3,5-dihydroxy-stilbene-3-O-neohesperidoside (1), 3,5-dihydroxy-stilbene-3-O-beta-D-glucoside (2), polydotin peceid (3) and 3,5,4'-trihydroxy-bibenzyl-3-O-beta-D-glucoside (4).

CONCLUSIONCompound 1 is a new compound, the others were isolated from Dryopteris for the first time.

Dryopteris ; chemistry ; Glycosides ; chemistry ; isolation & purification ; Molecular Structure ; Plants, Medicinal ; chemistry ; Stilbenes ; chemistry ; isolation & purification