OBJECTIVE: To develop an UHPLC-MS/MS method for the determination of R-/S-2-(2-hydroxypropanamido) benzoic acid (R-/S-HPABA) in rat urine, feces and bile and apply the method to study the excretion of R-/S-HPABA in rats. METHODS: After liquid-liquid extraction by ethyl acetate,the separation was achieved on a Thermo Syncronis C18 column (2.1 mm×50 mm, 1.7 μm) using mobile phase consisting of solvent A (methanol) and solvent B (0.1% formic acid) at a flow rate of 0.4 mL•min-1. The concentration of R-/S-HPABA after single dose oral administration of 50 mg•kg-1 R-/S-HPABA to rats was detected by UHPLC-MS/MS method. RESULTS: The calibration curve was linear over the range of 0.002-5 μg•mL-1 and the lower limit of quantification (LLOQ) was 0.002 μg•mL-1. The intra-and inter-day RSDs were less than 13.0% and the accuracy (relative error) of R-/S-HPABA was within -7.5%-4.2%. The average recoveries were (87.3±3.4)%-(104.4±7.0)%. After intragastric administration of R-HPABA and S-HPABA at a dose of 50 mg•kg-1, the cumulative amounts of R-HPABA and S-HPABA excreted in the urine (0-48 h) were (536.1±29.7) and (771.7±38.6) μg, the urinary excretion amounted to 4.9% and 7.0% of the dosage, respectively; the cumulative amounts of R-HPABA and S-HPABA excreted in feces (0-48 h) were (3 963.0±345.2) and (4 771.8±355.0) μg, the fecal excretion amounted to 36.0% and 43.4% of the dosage, respectively; the cumulative amounts of R-HPABA and S-HPABA excreted in bile (0-12 h) were (150.6±30.3) and (747.7±89.2) μg, the biliary excretion amounted to 1.4% and 6.8% of the dosage, respectively; the summation of urinary, fecal and biliary excretion amounted to 42.3% and 57.2% of the dosage in rats for R-HPABA and S-HPABA, respectively. The cumulative amounts of S-HPABA excreted in the urine, feces and bile were higher than those of R-HPABA. CONCLUSION: This UHPLC-MS/MS method is suitable for the study of the excretion of R-/S-HPABA in rats. The excretion of the two enantiomers in rats shows significant stereoselectivity difference.

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.

Background Asthma is a complex disease involving genetic and environment interactions.Atopy is a strong risk factor for asthma.The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials.To explore the effects of airway epithelium on asthma,we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier,which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma.Methods Thirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group:control group,asthma group,ovalbumin (OVA)+OVA group,lipopolysaccharide (LPS) group and LPS+OVA group.In the control group,0.9％ saline was injected intraperitoneally on day 1.Fourteen days later,the rats were exposed to aerosolized 0.9％ saline.In the asthma group,the rats were sensitized with an injection of 10 mg of OVA,followed by an aerosolized 2％ OVA challenge14 days later.The OVA+OVA group was sensitized by an inhalation 2％ OVA,20 minutes a day,from day 1 to day 7,and then OVA challenged in the same way as the asthma group.In the LPS group,LPS (200 μl,1 μg/μl) was given by airway on day 1 and day 3,with a simultaneous aerosol inhalation of 2％ OVA for 20 minutes a day from day 1 to day 7.Fourteen days later,the rats were challenged with saline as in the control group.While in the LPS+OVA group,LPS (200 μl,1 μg/μl) was given by airway on day 1 and day 3,with a simultaneous aerosol inhalation of 2％ OVA for 20 minutes a day from day 1 to day 7.Fourteen days later,the rats were challenged with OVA as in the asthma group.The expression of interleukin (IL)-4,interferon-gamma (IFN-y) and thymic stromal lymphopoietin (TSLP) in the lungs was detected by reverse transcription polymerase chain reaction (RT-PCR) and the pulmonary pathological changes were also observed.The level of IL-4,IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay (ELISA).Bronchoalveolar lavage fluid (BALF) was collected to conduct differential cell counts.Flow cytometry analysis was also used to count Th1 and Th2 cells.Results The pathological changes in the LPS+OVA group were similar to the asthma group,while in other groups,the pathological changes were not obvious.The ratio of lymphocytes in BALF,IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS+OVA groups were higher than in the control group and the OVA+OVA group (P ＜0.05).The level of IgE was higher in the asthma,LPS and LPS+OVA groups than in the control group and the OVA+OVA group (P ＜0.05).By flow cytometry analysis,the Th1/Th2 ratio was lower in the LPS+OVA and asthma groups than in other groups (P ＜0.05).Conclusions The experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses.This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.

OBJECTIVETo study the durability of expanded polytetrafluoroethylene artificial heart valve (ePTFE AHV).

METHODSSix ePTFE AHVs were tested for 400 million times against accelerated fatigue using TH-2200 artificial heart valve exosomatic accelerated fatigue instrument. Hydromechanical parameters of fore-and-aft accelerated fatigue test of the 6 AHVs were obtained by TH-1200 artificial heart valve exosomatic pulsatile stream instrument.

RESULTS AND CONCLUSIONThe mean gradient pressure spanning the valve and the effective orific area of ePTFE AHVs did not undergo significant changes after fore-and-aft the fatigue test, but the regurgitation volume and regurgitation rate of ePTFE AHVs were reduced after the accelerated fatigue test, suggesting good durability of ePTFE AHV.

Biocompatible Materials ; chemistry ; Heart Valve Prosthesis ; standards ; Materials Testing ; methods ; Polytetrafluoroethylene ; chemistry ; Tensile Strength

Objective To explore the setting of logos on tobacco control information at outlets for retails and restaurants in 12 selected cities of China.Methods For all the shops for retail of tobacco,alcohol,food and restaurants under survey in 333 blocks of 12 cities (Beijing,Tianjin,Shanghai,Qingdao,Hangzhou,Shaoxing,Suzhou,Nantong,Zhenjiang,Chengdu,Xining and Harbin),setting and contents of logos on tobacco control information,inside and outside them were examined.Results 45 700 objectives were included in the study.Among all types of retail shops,the identification rate of tobacco control information at the entrance and inside were 3.6％ and 4.4％,with an overall identification rate as 7.0％.The overall rate at the entrance of all the restaurants was 4.6％ which was larger than the ones at the retail shops.Our result showed that there were differences between cities and types of establishments and higher rates seen in the larger ones.Of all the places that having had placement of information on tobacco control,only 18.5％ of them had put them both inside and outside.Slogans or images on "No Smoking" were the main forms of information but less than 10％ of them would show signs as ‘exclusive non-smoking'.Conclusion Data from our survey showed that the identification rate of tobacco control information was at a low level in 12 cities,and differences were seen between cities,size of establishment,that called for improvement of the existing tobacco control policies in China.

The new edition of Pharmacology of Chinese Materia Medica has broken through the previous mode of the teaching materials. It classified traditional Chinese medicinal herbs into three categories: the herbs for radical cure depending on syndrome differentiation, the herbs for etiological treatment aimed at pathogenesis, and the herbs for symptomatic treatment, combined diseases differentiation with syndrome differentiation, showing active significance in enlightening, guiding the Chinese medicine theory of combining traditional Chinese and Western medicine's compiling, teaching, learning and research applications.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Pharmacology, Clinical ; education ; Plants, Medicinal ; Teaching Materials

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; metabolism ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Fallopia multiflora ; chemistry ; HMGB1 Protein ; metabolism ; Hepatocytes ; drug effects ; Interleukin-1beta ; metabolism ; Liver ; drug effects ; pathology ; Plant Extracts ; pharmacology ; Rats ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the inhibitory effect of artesunate on human endometrial carcinoma RL95-2 cell line proliferation in vitro and the possible mechanisms.

METHODSThe inhibitory effect of artesunate on the cell proliferation was assessed with MTT assay. Transmission electron miscrosopy was used to observe the morphological change of the cells after the treatment. Flow cytometry was performed to examine the changes in the cell cycle, reactive oxygen species (ROS) levels (with DCFH-DA labeling) and mitochondrial membrane potential (rhodamine123 staining), and caspase-3 activity was detected by immunohistochemistry.

RESULTSArtesunate inhibited the proliferation of RL95-2 cells with an IC(50) of 26.29 microg/ml. Transmission electron microscopy revealed early apoptotic changes of the cells with obvious chromatin fragmentation. The cell cycle arrest at G(0)/G(1) phase was observed by flow cytometry, and immunohistochemistry demonstrated caspase-3 positivity in cytoplasm. ROS generation in the cells increased obviously after treatment with artesunate for 72 h, which also resulted in lowered mitochondrial membrane potential.

CONCLUSIONArtesunate suppressed the proliferation of RL95-2 cells in vitro possibly by inducing cell apoptosis.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Artemisinins ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Endometrial Neoplasms ; pathology ; Female ; Humans

OBJECTIVETo investigate the expression levels of nm23, P53, and S100A4 in gastric carcinoma and their relationships with clinicopathologic parameters and metastasis potential.

METHODSPathological specimens from gastric carcinoma,matched para-tumor tissues, metastatic lymph node and distant metastatic tissues were examined for the expression levels of nm23, P53, and S100A4 proteins by tissue microarray technique and immunohistochemistry.

RESULTSThe expression levels of P53 and S100A4 were upregulated (P< 0.01), while the expression of nm23 downregulated (P< 0.05) in gastric carcinoma compared with non-tumor tissues. S100A4 expression was significantly higher in distant metastatic tissues, while nm23 lower in metastatic lymph nodes than those in cancer tissues. Upregulating expression levels of nm23, P53, and S100A4 were significantly correlated with some malignant behaviour of gastric cancer. The expression rates of nm23+/P53+, P53+/S100A4+, and nm23+/S100A4+ immunohistochemical phenotypes were 48/74 (64.9%), 50/74 (67.6%), and 39/74 (52.7%). P53+/S100A4+, nm23+/S100A4+, and nm23+/P53+/S100A4+ phenotypes were associated with high metastasis potential of gastric cancer.

CONCLUSIONSAlteration of nm23, P53, and S100A4 expression may contribute to the development of gastric carcinoma. Nm23 and S100A4 proteins play a critical role in tumor metastasis. Co-detection of the expression of P53, nm23, and/or S100A4 can be used to evaluate high metastasis potential of gastric cancer.

Female ; Gene Expression ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Neoplasm Invasiveness ; Neoplasm Staging ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo observe the effect of electroacupuncture (EA) on cytokines in the cardiac surgical patient and to evaluate the application of combined acupuncture anesthesia to cardiac surgery.

METHODSThirty patients with atrial septal defect were divided into 3 groups, general anesthesia group (A), acupuncture anesthesia group (B) and combined general anesthesia and EA group (C). Peripheral blood samples were collected before anesthesia, before cardiopulmonary bypass (CPB), 30 min after CPB and 24 h after operation to determine the levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-6 and IL-10.

RESULTSThe levels of IFN-gamma and IL-2 decreased in the 3 groups after CPB and further decreased 24 h after operation, and in the group C were higher than those in the group B. The levels of IL-6 and IL-10 significantly increased 24 h after operation in the 3 groups with no significant difference among the 3 groups.

CONCLUSIONThe general anesthesia combined with EA can not completely improve the decrease of IFN-gamma and IL-2 induced by CPB, indicating that the good response of the general anesthesia combined with EA to stress can partially improve the immunosupression induced by CPB. Acupuncture does not have significant effect on inflammatory cytokine reaction induced by cardiac surgery.

Acupuncture Analgesia ; Adult ; Cardiac Surgical Procedures ; Electroacupuncture ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Interleukin-6 ; blood ; Male ; Middle Aged