The pharmacokinetics and pharmacodynamics of famotidine were investigated in 10 healthy male volunteers after single intravenous administration of 20 mg. The blood drug levels were determined by a high performance liquid chromatography. The 1gC of famotidine in plasma vs time curve were found to be twcncompartment open model in healthy volunteers. The terminal half-life averaged 3.16h; the total distribution volume 99.40L; the total plasma clearance 392.12ml/min; the area under the plasma concentration curve 1057.45 h?ng/ml. A mathematic equation describing the whole course of blood drug levels in relation to inhibitory effects on intragastric acid output is as follows: E= 100?C2.60/(C2.60+14.712.60). The constant 14.71 is EC50 (ng/ml), the blood drug concentration producing 50% of maximal pharmacological effects. Prediction of pharmacodynamic effects from blood drug level and vice versa becomes possible by using the mathematic equation.

Objective To study the biological effect of different dose of satereotactic body radiation therapy (SBRT) on hepatoma Hep G2 Cells.Methods Hep G2 hepatumor cells vitality of 0,2,4,6,8,and 10 Gy doses of SBRT were determined by methyl thiazolyl tetrazolium (MTT) method.The cell colony formation rate and the cell survival fraction were detected.The cell apoptosis was detected by flow cytometry.The expressions of cyclin D1,Bax,Bcl-2,and caspase-3 protein were detected by Western blot.Results Hep G2 cells vitality was obvious inhibitory effect in different doses of SBRT,increasing with the SBRT dose,the cell vitality inhibition [2 Gy group (4.29 ± 0.63) ％,4 Gy group (19.37 ± 4.54) ％,6 Gy group (41.35 ±4.51)％,8 Gy group (86.34 ±5.68)％,10 Gy group (97.24 ±5.41)％] was increased,compared to 0 Gy group [(2.94 ± 0.52) ％],the difference was statistically significant (all P ＜ 0.01 or P ＜0.05).The cell colony formation rate and survival score in different doses of SBRT were statistically lower than the control group,increasing with the SBRT dose,the cell colony formation rate [4 Gy group (83.15 ± 4.71),6 Gy group (65.23 ± 5.47),8 Gy group (41.28 ± 5.36),10 Gy group (8.14 ± 5.22)] and survival score [2 Gy group (95.49 ±3.21),4 Gy group (84.23 ±3.45),6 Gy group (66.08 ± 3.71),8 Gy group (41.82 ± 3.82),10 Gy group (8.25 ± 3.56)] were decreased,compared to 0 Gy group [(98.72 ± 1.23),(100.00 ±0.00)],the differences were statistically significant (all P ＜0.01 or P ＜ 0.05).The cell apoptosis in different doses of SBRT was increased,increasing with the SBRT dose,the Hep G2 cells apoptosis [4 Gy group (13.67 ±4.62),6 Gy group (28.71 ±5.13),8 Gy group (54.16 ±5.24),10 Gy group (76.31 ± 5.17)] were significantly increased,compared to 0 Gy group (1.35 ±0.46),the difference was statistically significant (all P ＜ 0.01).The expressions of cyclinD1,Bax,Bcl-2,and caspase-3 protein in different doses of SBRT were decreased,increasing with the SBRT dose,the cyclin D1 [6 Gy group (1.94 ± 0.57),8 Gy group (1.38 ± 0.41),10 Gy group (0.52 ± 0.34)],Bax[6 Gy group (2.67 ±0.59),8 Gy group (1.73 ±0.45),10 Gy group (0.63 ±0.37)],Bcl-2 [4 Gy group (1.78 ±0.41),6 Gy group (1.03 ±0.35),8 Gy group (0.76 ±0.28),10 Gy group (0.38 ± 0.21)],Caspase-3 [6 Gy group (0.76 ± 0.31),8 Gy group (0.42 ± 0.24),and 10 Gy group (0.24 ± 0.21)] were obviously decreased,compared to 0 Gy group [(3.41 ± 0.75),(4.36 ± 0.87),(2.57 ± 0.46),(1.67 ± 0.55)],the difference was statistically significant (all P ＜ 0.05).Conclusions Different dose of SBRT can reduce Hep G2 cell vitality,enhance radiation sensitivity,have a dose dependent,maybe related to promote cell apoptosis and inhibit the proliferation of protein expression.

To explore the relationships between traditional Chinese medicine (TCM) constitutional types and overweight or obesity so as to provide evidence for adjusting constitutional bias and preventing and treating obesity.

Objective To construct a nucleic acid vaccine expressing H.pylori HpaA and inter- leukin-2 gene and to identify the immunogenicity of the vaccine proteins in vitro and protection in vivo. Methods The H paA gene fragment was amplified by polymerase chain reaction(PCR) from the genomic DNA of the standard H.pylori strain 17874.Mouse interlukin(IL)-2 gene was amplified from pClneo- IL-2.The HpaA and IL-2 were cloned into pUCmT vector.After DNA sequences of the amplified HpaA gene and IL-2 were confirmed,both were cloned into the eukaryotic expression vector pIRES through a serial of enzyme digestion and ligation reactions.The recombinant plasmids were screened by PCR and restriction enzyme digestion.Then,recombinant pIRES-HpsA-IL-2 was transfected to COS-7 cells using Lipofectamine~(TM)2000.The immunogenicity of HpaA and IL-2 protein was detected by SDS- PAGE and Western blot.The recombinant plasmids were transformed to LB5000 and then to final host SL7207.The recombinant strains were passaged repeatedly.The mice were challenged with H.pylori after 4 weeks of inoculation of nucleic acid vaccine.H.pylori infection was detected by rapid urease test.Results The amplified HpaA gene fragment and IL-2 were confirmed by sequence analysis.The eukaryotic expression vector plRES and the pIRES-HpaA-IL-2 construction were confirmed by PCR and restriction digestion.The expressions of HpaA(30 000) and IL-2(14 000)protein by pIRES-HpaA-IL- 2 were detected by Western blot.The in vivo study showed that 75.0% and 58.4% of mice vaccinated by HpaA-IL-2 and HpaA,respectively,were protected anaigst H.pylory infection,which was signifi- cant different in comparison with PBS control (P

Objective : To investigate the prevalence of comorbid chronic obstructive pulmonary disease (COPD) and osteoporosis (OP) and its influencing factors among residents aged 40 years and older in Zhangjiagang City, Jiangsu Province, so as to provide insights into prevention of comorbid COPD and OP. Methods: Permanent residents aged 40 years and older were sampled using a multi-stage stratified cluster random sampling method in Zhangjiagang City in 2019, and their pulmonary functions and bone mineral density were measured. The prevalence of comorbid COPD with OP was estimated. The demographic features, smoking, diet, exercises and physical examinations were collected, and factors affecting the prevalence of comorbid COPD with OP were identified using a logistic regression model. Results: Totally 3 140 subjects were enrolled, including 1 315 men (41.88%) and 1 825 women (58.12%), and a mean age of (62.89±9.13) years. A total of 137 subjects were detected with comorbid COPD and OP, with prevalence of 4.36%. The patients with COPD alone included 19 cases with mild, 133 cases with moderate, 87 cases with severe and 26 cases with very severe COPD, and the patients with comorbid COPD and OP included 10 cases with mild, 56 cases with moderate, 56 cases with severe and 15 cases with very severe COPD. The grade of pulmonary functions was higher in patients with comorbid COPD and OP than in patients with COPD alone (Z=-12.304, P<0.001). Multivariable logistic regression analysis identified ages of 65 years and older (OR=2.703, 95%CI: 1.862-3.923), women (OR=2.897, 95%CI: 1.915-4.384) and physical labor (OR=1.540, 95%CI: 1.083-2.189) as factors affecting the development of comorbid COPD and OP. Conclusion The prevalence of comorbid COPD and OP was 4.36% among residents at ages of 40 years and older in Zhangjiagang City, and moderate and severe degree was the predominant grade of pulmonary functions. The elderly, women and physical labors are at a high risk of developing comorbid COPD and OP.

Objective To investigate characteristics and alternation of cerebral evoked potentials (CEP) response to esophageal mucosal acid exposure and distention in patients with non-erosive gastro-oesoph- ageal reflux disease (NERD) and in healthy subjects,and to study the mechanism of visceral hypersensitivity in NERD.Methods Twenty-one NERD patients and 10 volunteers were recruited.Mechanical distention stimulation and acid perfusion of the esophagus were performed using the balloon-affixed and polyvinyl multi- lumen catheter.First,maximally tolerated pain thresholds of all subjects were recorded,then esophageal mechanical stimulation with a 75% of maximal tolerated intensity and a frequency of 0.2 Hz was performed altogether 64 times by means of a computer-controlled barostat.The alternation of esophageal CEP was recorded before and after acid perfusion with a multichannel international 10-20 system of electroencephalography. Experimental data was analyzed by student's t-test and one way analysis of variance.Results Esophageal mu- cosal distention may evoke recognizable and reproducible and multi-peak CEP.The latencies for N1,P1 and N2 in volunteers were (246?77),(388?84)and (502?78) ms,CEP morphology of NERD patients was charac- terized by randomly distributed patterns,and the latencies for N1 ,P1 and N2 were (192?46),(293?76) and (440?79)ms,significantly shorter for mechanical stimulation compared with those of control group respectively (all P value

Retinopathy of prematurity (ROP) is a disease which the retinal vascular system is not mature at birth, leading to cessation of development and abnormal proliferation of blood vessels, in a relatively high oxygen environment.Adiponectin (APN) is an endogenous bioactive protein secreted by adipocytes.It has functions of regulating Glucose and lipid metabolism, inhibiting atherosclerosis and protecting the cardiovascular system.APN can inhibit angiogenesis which may be involved in the occurrence and development of ROP in recent research.APN may be regulating the serum level of tumor necrosis factor α (TNF-α), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) A to prevent the development of ROP.The expression of APN is also affected by fibroblast growth factor 21 (FGF-21) and long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) at the same time.Understanding the role of APN in ROP can provide new ideas for further study of the pathogenesis and prevention and treatment of ROP.

Objective:To investigate the clinical application value of serum carcinoembryonic antigen (CEA) level in predicting lymph node metastasis of resectable medullary thyroid carcinoma (MTC) .Methods:140 patients of resectable MTC from Zhejiang Cancer Hospital and Hangzhou First People’s Hospital from Jan. 2009 to Feb. 2019 were included. The relationship of serum CEA and lymphatic metastasis was retrospectively analyzed in 140 patients of resectable MTC, and the clinical significance of serum CEA for predicting total lymph node, central lymph node, lateral lymph node and upper mediastinal lymph node metastasis was also evaluated.Results:The positive rate of serum CEA in resectable MTC was 77.14%. The expression level of serum CEA in resectable MTC with lymph node metastasis was significantly higher than those without lymph node metastasis ( P<0.001) . Spearman correlation analysis further indicated that the level of serum CEA expression was positively correlated with the number of lymph node metastases of resectable MTC patients ( P<0.001) . The area under curve of predicting lymphatic metastasis of total lymph node, central lymph node, lateral lymph node and upper mediastinum was 0.773, 0.768, 0.827 and 0.847. When the cut-off value of serum CEA was 6.58, 11.43, 15.74 and 30.45 ng/ml, respectively, the sensitivity of serum CEA to predict total, central, lateral neck and upper mediastinal lymph node metastasis was 88.46%, 81.43%, 85.00%, 95.00%, and the specificity was 56.45%, 60.00%, 71.25%, and 69.17%, respectively. Conclusion:Serum CEA has a high positive expression rate in resectable MTC, and its expression level has important clinical significance in evaluation of lymphatic metastasis.

Objective To study the clinical impact of microvascular invasion (MVI) on patients with intrahepatic cholangiocarcinoma (ICC) after R0 resections.Methods The clinicopathological data of 359 patients with ICC who underwent R0 resection in the Zhongshan Hospital,Fudan University between January 2000 and December 2008 were retrospectively studied.Univariate analysis and multivariate analysis were carried out to study factors related to postoperative survival outcomes and recurrence.The impact of MVI on patients with ICC after R0 resection was studied.Results The incidence of MVI was 13.6％ in the study cohort.MVI was correlated with HBV infection (P ＜ 0.05),liver cirrhosis (P ＜ 0.05) and tumor differentiation (P ＜ 0.05).The 1-,3-,5-year overall survival (OS) between the MVI positive and negative groups were 50.0％,20.9％,12.2％ and 63.9％,33.1％,22.0％ respectively (P ＜ 0.05),and the median survival time was 13 months and 18.5 months (P ＜0.05).The 1-,3-,5-year recurrence free survival (RFS) rates between the MVI positive and negative groups were 29.7％,12.7％,8.5％ and 50.6％,26.9％,18.4％,respectively (P ＜0.05),and the median recurrence free survival time was 8 months and 12.5 months (P ＜ 0.05).Multivariate analysis showed that MVI was an independent risk factor affecting recurrence after R0 resection (HR 1.852,95％ CI:1.075 ～ 3.195,P ＜ 0.05).Conclusions The occurrence of MVI in ICC patients was associated with hepatitis B infection.MVI was an independent risk factor affecting recurrence in ICC patients after R0 resection.However,it was not an independent risk factor of overall survival in patients after R0 resection.The clinical impact of MVI on patients with ICC was not as strong as for hepatocellular carcinoma.

OBJECTIVETo observe the regional homogeneity (ReHo) of resting-state brain function in the healthy subjects of gastric distention treated with acupuncture at the back- and front- points of the stomach, Weishu (BL 21) and Zhongwan (CV 12) and the correlation with gastric motility so as to explore the mechanism on the central integration of the front- and back- points of the stomach.

METHODSThe crossover test design was adopted. Twenty-four healthy subjects were assigned to a Weishu group, a Zhongwan group and a combined-point group separately, 8 cases in each one in each of the three times. Totally, 24 subjects were included in each group. Under the water load condition, the subjects received acupuncture at Weishu (BL 21), Zhongwan (CV 12) and the combined Weishu (BL 21) and Zhongwan (CV 12). Before and after each acupuncture, the resting-state brain functional magnetic resonance imaging (fMRI) scan and electrogastrogram (EGG) test were applied. The ReHo value was calculated in the collected fMRI imaging data. The changes in ReHo values were analyzed and compared before and after acupuncture in each group, as well as among the groups. The gastric motility was analyzed before and after acupuncture. Additionally, the correlative analysis was conducted between the gastric motility and ReHo changes before and after acupuncture.

RESULTS(1) After acupuncture, EGG amplitudes in the subjects of each group were lower remarkably as compared with those before acupuncture (all <0.01). The EGG frequencies were not different significantly as compared with those before acupuncture (all >0.05). The EGG amplitudes in the Weishu group and the Zhongwan group were higher than those in the combined-point group (both <0.05). (2) As compared with the conditions before acupuncture, acupuncture at the combined front- and the back- points as well as Weishu (BL 21) and Zhongwan (CV 12) separately all induced the changes in the brain ReHo. Acupuncture at the combined front- and the back- points significantly increased Reho values in the right inferior temporal gyrus, the left thalamus, the precuneus and the posterior cingulate gyrus (all <0.05) and remarkably reduced the ReHo values in the the middle temporal gyrus of the right temporal pole, sulcus calcarinus and precuneus (all <0.05). Compared with the single point groups, acupuncture at the combined front- and the back- points induced the increase of ReHo value in the posterior cingulate gyrus and the decrease of ReHo in the temporal pole (all <0.05). (3) The correlative analysis showed that the changes in the ReHo values in the posterior cingulate gyrus, the thalamus and the precuneus were positively correlated to the changes of the gastric motility amplitudes. The changes in the ReHo values in the temporal pole was negatively correlated to the changes of the gastric motility amplitudes.

CONCLUSIONAcupuncture at the combined back- and front- points of the stomach, as well as acupuncture at single Weishu (BL 21) and Zhongwan (CV 12) induce the ReHo changes in the different brain regions. Acupuncture at the combined back- and front- points of the stomach may induce the ReHo changes in some new brain regions as compared with the acupuncture at the single point. The thalamus, the posterior cingulate gyrus and the precuneus may be the the important integrated brain regions for acupuncture at the back- and the front- points in regulating the gastric motility. The effects of acupuncture at the back- and the front- points for the regulation of the gastric motility are closely related to the thalamus, the limbic system and the default network of the brain regions.

Acupuncture Points ; Acupuncture Therapy ; Brain ; diagnostic imaging ; physiology ; Cross-Over Studies ; Electroencephalography ; Gastrointestinal Motility ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Stomach ; physiopathology