Objective To establish the clinical pharmacokinetics research method for Bawei Jiangu Tablet.Methods Drug blood concentration was estimated through analyzing the ingredients and preclinical pharmaceutical research results of Bawei Jiangu Tablet.Results Corresponding cardiac glycoside value in serum of animals treated with oral use of Bawei Jiangu Tablets and cortex periplocae extracts can be detected by drug monitor system of digoxin immunoreaction, which was similar to that in animals treated with digoxin.Corresponding cardiac glycoside value had also been detetected in serum of subjects in phaseⅠclinical tolerance trial,which was related to the time and dosage of administration.Clini- cal negative control trial showed that the reaction was specific.Conclusion Pharmacokinetics study on target of toxic components with cross-reaction of periplocoside is feasible through drug monitor system of digoxin immunoreaction.

To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets, a randomized cross-over study was conducted in 18 healthy volunteers. A single oral dose of 1,000 mg Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high-performance liquid chromatography. The main parameters of T were: for Clavulanate Potassium and Amoxicillin, Cmax: 2.46 +/- 1.11 micrograms/ml and 18.81 +/- 7.26 micrograms/ml, Tmax: 1.12 +/- 0.23 h and 1.30 +/- 0.34 h, AUC(0-6 h): 5.18 +/- 2.24 micrograms.h/ml and 45.09 +/- 14.53 micrograms.h/ml, t1/2: 1.43 +/- 0.44 h and 1.09 +/- 0.22 h., respectively. The relative bioavailability of T to R were 96.5 +/- 19.2% and 98.4 +/- 26.1%, respectively. Statistical analysis showed that the two formulations were bioequivalent.
Amoxicillin-Potassium Clavulanate Combination/*pharmacokinetics ; Drug Therapy, Combination/*pharmacokinetics ; Tablets ; Therapeutic Equivalency

Objective To discuss the optimal radiation dose in the treatment of the late course accelerated hyperfractionation(LCAH) radiotherapy for esophageal carcinoma by using two different treatment doses,focusing on the difference of the short term results,local control rates,treatment tolerance and long term survival rates between the two groups.Methods One hundred patients with esophageal carcinoma were randomly divided by the envelope method into two groups:the 60Gy group and the 75Gy group.Patients in 60Gy group received conventional fraction radiation for the first 3 weeks,and then hyperfractionation radiation(1.5Gy per fraction,two fractions a day with 6 hour interval,10 fractions per week) to the total dose of 60Gy/35 fractions/5 weeks.The radiation schedule of the 75Gy group was the same as the 60Gy group: conventional fractionation of radiation for the first 3 weeks and then hyperfractionation radiation for the rest 3 weeks to the total dose of 75Gy/45 fractions/6 weeks.Results There was no significant difference between the two groups in short term results.The 1-,3-,5-year local control rates were 86%,42%,32% in 60Gy group and 88%,52%,48% in 75Gy group,respectively.The 1-,3-,5-year survival rates were 86%,40%, 28% in 60Gy group and 72%,34%,16% in 75Gy group,with no significant difference(P= 0.283).The median survival time was 25 months for the 60Gy group and 19 months for the 75Gy group.Patients suffered from heavy radiation-induced esophagitis in the 75Gy group were significantly more than those in the 60Gy group(28% vs 10%,P= 0.022).But it was similar for patients who died of side effects in the two groups.Conclusions It is not suitable to pursue high dose in treating esophageal carcinoma with late course accelerated hyperfractionation radiotherapy as high incidence of side effects are unadvoidable if the dose is increased without changing the radiation fields and techniques.When escalating the dose to the esophagus,the radiated lung volume as well as the other normal tissues should be first subjected to meticulous and careful consideration.

Objective To study the correlation between time of fever onset in the course of patients'illness and etiologies of fever of unknown origin (FUO).Methods A total of 1 570 patients with FUO admitted from January 2013 to December 2014 were retrospectively analyzed, and clinical data ( sex, age, time of fever onset) of 348 patients meeting FUO diagnosis criteria with definite etiology diagnosis and time of fever onset were collected for multivariate logistic regression analysis after bias check.Results No statistically significant bias was found between 348 selected cases and 1 570 overall cases in gender (χ2 =0.029, P=0.903) and age (t=-1.040, P=0.299), and multivariate logistic regression analysis showed positive correlation between fever onset during 13: 00-18: 00 and infection (P=0.044, B=1.275), 18:00-24: 00 and connective tissue diseases ( P =0.029, B =0.838 ) , and showed negative correlation between age and miscellaneous (P =0.010, B =-0.042).Conclusions Characteristics of fever onset time may have significant value in preliminary diagnosis and guiding the correct direction of final definite diagnosis by means of targeted examinations or diagnostic treatments.It is worth to be further studied and discussed.

Objective To measure the setup errors of patients with esophageal carcinoma during the treatment of three dimensional conformal radiotherapy (3DCRT), and to analyze the impact of setup errors on dose distribution of GTV,CTV and normal tissues around. Methods Forty-two patients with esophageal cancer treated by 3DCRT were included. The setup errors of each patient were measured once a week for 6 times by electronic portal imaging device (EPID). The setup errors were integrated into the treatment plan-ning system by moving the isocenter. Then the dose distribution of GTV, CTV and normal tissues were recal-culated. Results The systematic setup errors of the 42 patients were - 2.31 mm, - 0.55 mm and - 0.16 mm, and the random errors were 4.42 mm, 4.35 mm and 4.48 mm in the directions of lef-fight, anterior-posterior,and superior-inferior, respectively. The dose covered 95% GTV( D95 ) was reduced by 32 cGy and by 88 cGy for CTV D95. The lung V20 in the original plan and the integrated plan was 22.49% and 22.02%, respectively. The average dose of the heart in the two plans was 2077.62 cGy and 2036.23 cGy, respectively. In the original plan, no patient had maximum dose of spinal cord over 4500 cGy; While in the intergrated plan there were 18 patients had the spinal cord dose more than 4500 cGy, with a maximum dose of 5503.90 cGy. Conclusions The setup errors cause significant dose reduction of GTV and CTV, but not of the lung and heart . The maximum dose of the spinal cord may exceed 4500 cGy due to the setup errors.

To investigate the roles of apoptosis and the Fas system (Fas, Fas ligand, soluble Fas) in the process of liver cirrhosis (LC) converting into hepatocellular carcinoma (HCC), expression of Fas and Fas ligand (FasL) in 49 LC and 36 HCC samples was detected by immunohistochemical method. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. Serum soluble Fas (sFas) levels in 28 cases of LC and 27 cases of HCC were measured by enzyme-linked immunosorbent assay (ELISA) method. Compared with LC, apoptotic indices (AI) in HCC tissues were significantly reduced (P<0.001), expression of Fas was decreased (P<0.05), and that of FasL was increased (P<0.05). Serum sFas levels in HCC patients were significantly higher than those in normal controls. Down-regulation of Fas expression, up-regulation of FasL expression in hepatocytes and elevation of sFas level in serum might contribute to tumor escape from immune surveillance of the body. Apoptosis and the Fas system are significantly involved in the process of liver cirrhosis converting into hepatocellular carcinoma.

To investigate the roles of apoptosis and the Fas system (Fas, Fas ligand, soluble Fas) in the process of liver cirrhosis (LC) converting into hepatocellular carcinoma (HCC), expression of Fas and Fas ligand (FasL) in 49 LC and 36 HCC samples was detected by immunohistochemical method. Apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. Serum soluble Fas (sFas) levels in 28 cases of LC and 27 cases of HCC were measured by enzyme-linked immunosorbent assay (ELISA) method. Compared with LC, apoptotic indices (AI) in HCC tissues were significantly reduced (P<0.001), expression of Fas was decreased (P<0.05), and that of FasL was increased (P<0.05). Serum sFas levels in HCC patients were significantly higher than those in normal controls. Down-regulation of Fas expression, up-regulation of FasL expression in hepatocytes and elevation of sFas level in serum might contribute to tumor escape from immune surveillance of the body. Apoptosis and the Fas system are significantly involved in the process of liver cirrhosis converting into hepatocellular carcinoma.

ObjectiveTo investigate the long term clinical result of three-dimensional radiotherapy for esophageal carcinoma,discuss the effect of correlative factors to survival and local control.Methods From July 2003 to December 2008,792 patients with esophageal cancer were eligible.Patients were treated with three-dimensional radiotherapy (672 patients) or intensity-modulated (120 patients) radiotherapy.The radiotherapy was delivered in 1.8-2.0 Gy per fraction,5 fractions per week,total dose of 50-70 Gy,(median,60 Gy).142 patients were treated by concurrent radiochemotherapy,and the other 650 patients radiotherapy alone.The local control rate and survival rate were calculated by Kaplan-Meier method.Logrank method was used for univariate analyses.Cox regression model was used for multivariate analyses.ResultsThe follow-up rate was 95.8％.The number of patients with 5 years time followed-up was 133.The 1-year,3-year and 5-year local control rates were 76.6％,53.2％,48.6％,and the 1-year,3-year and 5-year overall survival rates were 70.1％,36.7％ and 28.0％,respectively.There were significant influence on the prognosis of T stage,N stage,TNM stage,tumor volume ( x2 =20.58-55.60,all P =0.000).The Cox multivariate model showed that N stage and tumor volume were independent prognostic factors (x2 =6.35,29.23,P =0.012,0.000).For the two groups of concurrent chemo-radiotherapy and radiotherapy alone,5-year local control rates were 57.0％ and 46.8％ ( x2 =7.34,P =0.007 ),the 5-year overall survival rate 32.8％ and 27.6％ ( x2 =3.42,P =0.064.ConclusionsThree-dimensional radiotherapy is effective for esophageal carcinoma.It might improve the local control rate and overall survival rate to some extent.T staging,N staging,TNM staging and tumor volume were important prognostic factors for long-term survival.The addition of concurrent radiochemotherapy could improve local control rates.

To study the bioequivalence of Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets, a randomized cross-over study was conducted in 18 healthy volunteers. A single oral dose of 1,000 mg Clavulanate Potassium and Amoxicillin (1:7) dispersible tablets (Tested formulation, T) or Augmentin syrup (Reference formulation, R). Concentrations in plasma were determined with high-performance liquid chromatography. The main parameters of T were: for Clavulanate Potassium and Amoxicillin, Cmax: 2.46 +/- 1.11 micrograms/ml and 18.81 +/- 7.26 micrograms/ml, Tmax: 1.12 +/- 0.23 h and 1.30 +/- 0.34 h, AUC(0-6 h): 5.18 +/- 2.24 micrograms.h/ml and 45.09 +/- 14.53 micrograms.h/ml, t1/2: 1.43 +/- 0.44 h and 1.09 +/- 0.22 h., respectively. The relative bioavailability of T to R were 96.5 +/- 19.2% and 98.4 +/- 26.1%, respectively. Statistical analysis showed that the two formulations were bioequivalent.
Adult ; Amoxicillin-Potassium Clavulanate Combination ; pharmacokinetics ; Drug Therapy, Combination ; pharmacokinetics ; Humans ; Male ; Tablets ; Therapeutic Equivalency

Objective To study the pattern of lymphatic metastasis in patients with thoracic esopha-geal carcinoma, and to determine the indication and the target volume for post-operative radiotherapy. Meth-ods 229 patients with thoracic esophageal carcinoma who had undergone radical esophagectomy and two-field lymph node dissection were included in this study. The pattern and ratio of lymph node metastasis were analyzed. The effect of the tumor length and pathology stage on lymph node metastasis was studied. Then the indication and target of post-operative radiotherapy for the thoracic esophageal carcinoma was determined. Results Regional lymph node metastasis was found in 57.1% patients with upper thoracic esophageal car-cinoma. For the middle thoracic esophageal carcinoma, the ratio of regional metastasis, skip, upward, down-ward and two-way spread were 39.0%, 19.5% ,5.2% ,28.6% and 7.8% ,respectively. For lower thoracic esophageal carcinoma,downward spread was found in 77.2% patients. For upper thoracie esophageal carci-noma,the proportions of patients with lymph node metastasis were 19.0% ,6.7% ,9.8% and 14.3% in the superior mediastinum, middle mediastinum, inferior mediastinum and abdominal cavity ( x2 = 2.75, P = 0.433). The corresponding figures were 26.1% ,7.4% ,11.8% and 11.9% (x2 = 17.98,P =0.000) for middle thoracic esophageal carcinoma,and 0%, 1.6% ,5.3% and 10.0% (x2= 5.96 ,P = 0. 051 ) for low-er thoracic esophageal carcinoma. The lymph node metastasis ratios were 9.1%, 11.6% and 11.7% in pa-tients with tumor ≤3 cm,3-5 cm and ≥5 cm,respectively (x2 =3.93,P=0. 140), and were much higher in stage Ⅲ disease than those in stage 0 to Ⅱ (19.3% vs4.8% ;x2 =131.06,P=0.000). Conclusions he pattern of lymph node metastasis is complex and extensive in patients with thoracic esophageal carcinoma. For upper and middle thoracic esophageal carcinoma, the extended prophylactic portal is suggested and the superior mediastinum is an important target area. For the lower thoracic esophageal carcinoma,it seems that regional fields could be applied. Post-operative radiotherapy should be performed in stage Ⅲ disease because of the high lymph node metastasis ratio.