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.

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

OBJECTIVETo present a new mini-invasive surgery for compressive optic neuropathy (CON) in Graves' ophthalmopathy (GO) by adequately decompressing the orbital apex and correcting proptosis, and to analyze its results.

METHODSA retrospective chart was reviewed in 29 patients receiving orbital decompression for the treatment of CON secondary to GO from October 2006 to May 2011. All patients diagnosed CON were in stable and inactive phase of GO at least for 6 months. All patients received endoscopic transethmoid medial orbital wall decompression to reduce the compression on the orbital apex. In the meanwhile, an endoscopic transethmoid intraconal fat-removal orbital decompression was performed to remove parts of intraconal fat with a special aspiration/cutting instrument to further reduce the proptosis. All patients were followed up periodically.

RESULTSof improvement of visual acuity (VA), color vision, and amount of proptosis reduction and incidence of induced diplopia 9 months after surgery was recorded for analysis its feasibility.

RESULTSForty-five orbits of 29 patients were included in the study. At the 9 months review, 44 of 45 eyes (97.8%) improved their VA from -0.65±0.30 (x±s) preoperatively to -0.24±0.22, with a mean improvement of 0.55±0.17 (t=-13.012, P<0.001), 23 of 29 eyes (79.3%) had improved color vision (P<0.001), and the mean reduction in proptosis was (7.07±1.59) mm (range 4-11 mm). Postoperative symmetry to within 2 mm were achieved in all patients. Except 1 patient complaining of deterioration in diplopia following surgery, no patients presented new on-set diplopia postoperatively.

CONCLUSIONThe endoscopic transethmoid medial orbital wall decompression combined with the endoscopic transethmoid intraconal fat-removal orbital decompression is an effective treatment with minimal morbidity for both visional recovery and improvement of proptosis for CON in GO.

Adipose Tissue ; surgery ; Adult ; Decompression, Surgical ; methods ; Endoscopy ; Ethmoid Bone ; surgery ; Female ; Graves Ophthalmopathy ; surgery ; Humans ; Male ; Middle Aged ; Orbit ; surgery ; Retrospective Studies ; Treatment Outcome

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

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

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

Animals ; Carcinoma, Hepatocellular ; genetics ; metabolism ; virology ; Genes, p53 ; Hepatitis B ; genetics ; metabolism ; virology ; Hepatitis B virus ; Humans ; Inhibitor of Growth Protein 1 ; Intracellular Signaling Peptides and Proteins ; metabolism ; Liver Neoplasms ; genetics ; metabolism ; virology ; Loss of Heterozygosity ; Nuclear Proteins ; metabolism ; Point Mutation ; Signal Transduction ; Trans-Activators ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Tumor Suppressor Proteins ; 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