Shanghanlun contains the theory of stagnation,though which is concealed among the treating system.This theory is great important to clinical practice.When we have a whole understanding to the theory of stagnation,it is easy to analyze the obstruction-removing therapy.Though this principle hasn't clearly definition,it is connected closely with other regular treating methods.Based on it,the dissertation analyzes all kinds of obstruction-removing therapy in Shanghanlun.That will be very helpful for readers to understand this theory and its significance in clinical practice.

This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in rat > in dog > in human > in monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

Objective To evaluate the feasibility and safety of double-lumen balloon catheter applied in patients with achalasia of cricopharyngeal muscle. Method Fifty patients with achalasia of cricopharyngeal muscle were randomly divided into experimental group and control group. All the patients received routine drug treatment,swallowing function training,feeding training and low frequency VitalStim electric stimulation. In addition,double-lumen balloon catheter and #14 urinary catheters were applied to patients in the experimental group and control group,respectively. The swallow water tests and video fluoroscopy swallowing study(VFSS) were used to evaluate the treatment effects,the electron-nasopharyngolaryngoscope was used to assess bleeding and swelling of mucous membrane,and VRS-5 was used to assess pain. Result After treatment,the scores of swallow water tests and VFSS were significantly better than those before treatment in both groups(P<0.05). There was no significant difference between the two groups(P>0.05). However,the incidence of complications was significantly higher in the control group than that of experimental group(P<0.05). Conclusion Both treatment methods can effectively relieve the achalasia of cricopharyngeal muscle,but modified double-lumen balloon catheter can reduce the incidence of complications.

Objective To develop a sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of forsklin in rat plasma.Methods After extraction with methyl tert-butyl ether,chromatographic separation was performed on a C18 column with the mobile phase consisting of water ( 0.1％ formic acid)-acetonitrile in a gradient elution mode.A tandem mass spectrometer equipped with electrospray ionization (ESI) source was used as detector in the positive ion mode.Quantification was performed using multiple reaction monitoring (MRM) with the precursor product combination ions of m/z 411→375.3 and 285→193 for forsklin and diazepam.Results Good linearity was obtained in the 0.5-1000 ng/ml range for the analyte and the analytical method was validated in terms of specificity,precision,accuracy,recovery,stability and matrix effect.These assays gave RSD values always lower than 14.4％ and RE values between -3.5 ％ and 3.8％.In addition,the specificity,extraction recovery,stability and matrix effect were satisfactory.Conclusion Due to its high sensitivity,specificity and simplicity,the method could be used for pharmacokinetic studies of forsklin.

Objective To study the effect of ganoderma lucidum polysaccharides combined with metformin on oxidative stress of type 2 diabetic rats. Methods SD rats were fed with high fat diet for 4 weeks and injected with streptozotocin (30 mg·kg-1 ) to produce type 2 diabetic model. The diabetic rats were randomly divided into diabetes model group, ganoderma lucidum polysaccharides group (600 mg·kg-1 ), metformin group (600 mg·kg-1 ), combination group (ganoderma lucidum polysaccharides 300 mg·kg-1+ metformin 300 mg·kg-1 ), After 12 weeks of treatment, the level of fasting blood glucose was determined, and the activity of superoxide dismutase ( SOD), malondialdehyde ( MDA), catalase ( CAT), glutathione peroxidase (GSH-Px), total cholesterol (TC) and triglyceride (TG) were detected. Results The levels of fasting blood glucose in the treatment groups were significantly lower than that in the diabetes model group (P<0. 01). Furthermore, fasting blood glucose in the combination group was significantly lower than that in ganoderma lucidum polysaccharides group and metformin group (P<0. 01). Compared with diabetes model group, serum TC and TG in the treatment groups were significantly lower (P<0. 05, P<0. 01). Serum TC and TG were significantly lower in the combination group than in ganoderma lucidum polysaccharides group and metformin group (P<0. 05, P<0. 01). Compared with diabetes model group, serum SOD levels in the treatment groups were significantly higher (P<0. 01). Compared with ganoderma lucidum polysaccharides group and metformin group, serum SOD levels in the combination group was significantly higher (P<0. 05). Compared with diabetes group, serum MDA levels in the treatment groups were significantly lower (P<0. 01). Serum MDA in the combination group was significantly lower than that in ganoderma lucidum polysaccharides group and metformin group ( P<0. 05). Compared with diabetes model group, serum CAT and GSH-Px in the treatment groups were significantly higher (P<0. 05, P<0. 01). Serum CAT and GSH-Px in the combination group were significantly higher than those in ganoderma lucidum polysaccharides group and metformin group (P<0. 05). Conclusion Ganoderma lucidum polysaccharides combined with metformin could effectively inhibit oxidantion stress in type 2 diabetic rats. The effect was better than ganoderma lucidum polysaccharides or metformin used alone. The possible mechanism may be related to increased activity of SOD, CAT, GSH-Px in vivo and regulation of dyslipidemia.

Aim To investigate the effects and mecha of ganoderma lucidum polysaccharides and metformin on pathological changes of thoracic aorta in diabetic ratsandthemechanisms.Methods SDratswerefed with high fat diet for 4 weeks and injected with strepto-zotocin ( 30 mg · kg-1 ) to replicate type 2 diabetic model. The diabetic rats were randomly into diabetes group, ganoderma lucidum polysaccharides group ( 600 mg·kg-1 ) ,metformin group(600 mg·kg-1 ) ,combi-nation group ( ganoderma lucidum polysaccharides 300 mg· kg-1 + metformin 300 mg · kg-1 ) and normal control group. After 12 weeksˊ treatment, the levels of fasting serum glucose, the activity of catalase(CAT), glutathione peroxidase ( GSH-Px ) , total cholesterol (TC)and triglyceride(TG) in serum were detected. Pathological changes of thoracic aorta were observed by HE staining. Immunohistochemy and Western blot were used to detect thoracic aorta VEGF protein expression. Results Combination group could lower fasting serum glucose and blood fat significantly, meanwhile the ac-tivity of CAT and GSH-Px in serum was improved. The expression of VEGF in thoracic aorta was repressed. The result of HE staining suggested that the lipid de-posits in aortic endothelium in combination group were lessthanthoseinthemodelgroup.Conclusions Ga-noderma lucidum polysaccharides combined with met-formin has an obvious prevention on pathological chan-ges of thoracic aorta in diabetic rats. The possible mechanism may be related to repressing oxidative stress of thoracic aorta, regulating the dyslipidemia, and the down regulation of the expression of VEGF in thoracic aorta.

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

Aim To study the effects of ganoderma lu-cidum polysaccharides and metformin on myocardial fi-brosis of type 2 diabetic rats and its mechanism. Methods SD rats were fed with high fat diet for 4 weeks, and then were injected with streptozotocin (30mg·kg-1 ) to replicate type 2 diabetic model. The diabetic rats were randomized into normal control group,diabetes group, ganoderma lucidum polysaccha-rides group ( 600 mg · kg-1 ) , metformin group ( 600 mg·kg-1 ) , and combination group( ganoderma lucid-um polysaccharides 300 mg·kg-1 +metformin 300 mg ·kg-1 ) . After 12 weeks’ treatment,the levels of fast-ing serum glucose were determined and the extent of myocardial fibrosis was observed by Picro-sirius red staining. The contents of AGEs in serum were deter-mined by fluorescence spectrophotometer. The activities of CAT and GSH-Px in myocardium were detected. Im-munohistochemical method and Western blot were used to detect myocardial tissue AGEs and CTGF protein ex-pression. Results Combination group could repress patho-proceeding of myocardial fibrosis efficiently, im-prove the activity of CAT and GSH-Px in myocardium and lower the concentration of AGEs in serum, as well as reduce the expression of AGEs and CTGF in myo-cardium. Conclusions Ganoderma lucidum polysac-charides and metformin could prevent myocardial fibro-sis. The possible mechanism may be related to repress-ing oxidative stress of myocardium, lowering serum AGEs and down regulating AGEs and CTGF of myocar-dium.