Objective:To study the effect of Lycium Barbarum Polysaccharide(LBP) on the activity and gene expression of hepatocyte cytochrome P4503A(CYP3A) in rat model with alcoholic fatty liver (AFL). Methods:The AFL rats models were established by ethanol intragastric infusion for ten weeks. Then,those AFL model rats were treated with 5% and 10% LBP and 10% GSH intragastric infusion. Liver pathologic changes were observed and the activity of CYP3A and its gene expression as well as the contents of malondialdehyde(MDA) and glutathione(GSH) in liver were detected and compared among the control group,treatment group and abstinence treatment group. Results:Fatty degeneration in liver recovered normally in the LBP treatment groups. LBP could inhibit the expression of CYP3A gene,reduce the activity of CYP3A and the content of MDA,and increase the content of GSH. The curative effect of LBP was not significantly different from that of GSH,but greater than that of abstinence treatment. Conclusion:LBP can prevent AFL through markedly inhibiting the hepatocyte CYP3A activity and gene expression.

Objective: To establish an experimental animal model of chromic alcoholic fatty liver.Methods: Fifty three Wister rats were divided into four groups: control group and model groups(lower dose ethanol group?medium dose ethanol group and higher dose ethanol group).The rats in model groups were induced by ethanol intragastric infusion of 40%(v/v)ethanol orally [7g/(kg?d) for lower group?8 g/(kg?d) for medium group and 9 g/(kg?d) for higher group],two times a day for the first 4 weeks.Ethanol intragastric infusion of 50%(v/v)ethanol orally [8 g/(kg?d) for lower group,9 g/(kg?d) for medium group and 10 g/(kg?d) for higher group],two times a day for the second 4 weeks.Then,the liver was examined by Ultrasonography.The pathologic changes were observed and the amount of ALT?AST??-GT in serum were detected at the end of the eighth week.Results: At the end of eighth week,serum AST and ?-GT levels were increased significantly in model groups.The typical fatty liver pathologic changes of chronic alcoholism were observed in rats in medium and higher dose model groups.Conclusions: Experimental model of chronic alcoholic fatty liver can be established in rats with ethanol intragastric infusion.

Objective:To study the effect of Lycium Barbarum Pclysaccharide(LBP)on the expression of hepatocyte cytochrome P4502E1(CYP2E1) in rat model of alcoholic fatty liver(AFL).Methods: The AFL rats models were established by ethanol intragastric infusion in ten weeks,then,5% and 10% LBP and 10% GSH intragastric infusions were adopted to treat those AFL model rats.Liver pathologic changes were observed and CYP2E1 gene and protein expressions as well as the contents of malondialdehyde(MDA) and glutathione(GSH) in liver were detected and compared with those in the control group,treatment groups and abstinence treatment group.Results: Fatty degeneration in liver recovered normally in the LBP-treated groups.LBP could inhibit the expressions of CYP2E1 gene and protein,reduce the content of MDA,and increase the content of GSH.The curative effect of LBP was of no significant difference compared with GSH,but had more effect than abstinence treatment.Conclusion: LBP can prevent AFL though inhibiting the hepatocyte CYP2E1 expression markedly.

Objective:To evaluate the effect of hydrotalcid combined with Tibolone,a compound with the effects of estrogen,progestogen and androgen on the menopause patients with bile-reflux gastritis and 24-hour intragastric bile.Methods:Nineteen menopause women with bile-reflux gastritis proven by gastroscope and 24-hour intragastric bile monitoring were divided into 2 groups at random, which were treated with hydtotalcid 1.0g three times a day and the same dose of hydrotalcid combined with Tibolone 2.5mg one time a day.The severity of the symptoms including heartburn,epigastric distention,nausea and bile vomiting was investigated before and after 2,4 weeks treatment.Twenty-four hour intragastrie bile monitoring was also reexamined.Results:The severity of all the symptoms in the two groups decreased greatly after 2 weeks treatment.After 4 weeks treatment,the severity of all the symptoms decreased further.The total fraction time of bile reflux,the time of the longest bile reflux in two groups decreased greatly after treatment ( P

Objective:To investigate the effect of tibolone on the symptoms of functional dyspepsia in menopausal women.Methods:143 menopausal patients with functional dyspepsia were divided into 3 groups at random.They were treated with tibolone or cisapride or both drugs respectively for 4 weeks.The scores of symptoms including epigastric pain and fullness,abdominal distention after meal,early satiety and belching were recorded before and after 2 or 4 weeks' treatment.From the 3 guoups we drew out 20 patients at random.The gastric emptying was measured before and after 4 weeks' treatment respectively.Results:The symptoms of epigastric pain and fullness,abdominal distention after meal were improved after 2,4 weeks' treatment in three groups.Either tibolone or tibolone combined with cisapride remarkably relieved early satiety and belching,but no response was observed in the treatment of cisapride.The combination of tibolone and cisapride did not show better effect than tibolone treatment alone.The 30-min gastric emptying rates of all groups were significantly improved ( P 0.05).Conclusion:Compared with cisapride,tibolone can increase gastric emptying and show better relief for the symptoms of functional dyspepsia in menopausal patients.

Objective To investigate the expression of long non-coding RNA FRAPT(lncRNA FRAPT) in triple-negative breast cancer(TNBC) cells and analyze its effects on proliferation,cell cycle and drug resistance of TNBC cells.Methods Using scRNASeqDB and TCGA on-line bioinformatics database,the expression of lncRNA FRAPT in TNBC and its correlation with prognosis were detected;TNBC cell line MDA-MB-231 was transfected with si-lncRNA FRAPT and si-Ctrl(negative control) by using Lipofectamine~(TM) 2000 respectively,of which the proliferation and cell cycle changes after transfection were detected by SRB test and flow cytometry,and the drug resistance to chemotherapy drug paclitaxel(PTX)was detected.Results The expression of lncRNA FRAPT was up-regulated in TNBC tissues and cells,and its high expression was positively correlated with the poor prognosis of TNBC patients(Hazard Ratio=1.66,P=0.047).Silencing lncRNA FRAPT significantly inhibited the proliferation of TNBC cells,with the cell cycle arrested in G1 phase,while increased the sensitivity of TNBC cells to PTX.Conclusion LncRNA FRAPT was highly expressed in TNBC and related to tumor prognosis-Silencing lncRNA FRAPT inhibited proliferation and cell cycle of TNBC,and increased the sensitivity to chemotherapy drug PTX.

With the continuous improvement of China's drug regulatory laws and regulations, Life-cycle regulatory management has become a key means and an inevitable development trend to ensure the safety of public drug use. The management of post-approval changes to biological products is gradually shifting towards the risk-based model from the item-based model.In recent years, there has been a significant increase in supplementary applications for manufacturing site changes of marketed therapeutic recombinant protein drugs. However, the risks associated with manufacturing site changes vary under different circumstances. Therefore, the research that needs to be carried out is also different. This paper provides an in-depth discussion on three key aspects: risk assessment and grading, general requirements and special considerations for pharmaceutical research, and common application issues. It outlines general requirements for manufacturing site change, aiming to offer valuable insights for industry needs. Through the collaborative efforts between regulatory authorities and the industry, patient rights and interests can be effectively protected, and high-quality drugs can be made available to the public.

Objective To investigate the relationship between helicobacter pylori(HP)eradication and curative effect of gastroe-sophageal reflux disease(GERD) .Methods Two hundred and fifty four patients with GERD were prospectively recruited for endo-scope and acid reflux evaluation .According to the results of gastroscope ,the eligible patients were divided into non-erosive reflux disease (NERD) and erosive esophagitis (EE) group ,and each divided into HP positive and HP negative group ,the HP positive group were randomly divided into the anti HP treatment group and not .These patients were assigned to rabeprazole triple therapy (the anti HP treatment group) or rabeprazole(20 mg ,twice per day) single(other groups) for 10 d ,then rabeprazole (20mg ,twice per day) was given to all patients until two months .Then all patients underwent acid reflux evaluation ,EE group underwent endos-copy ,and all patients underwent a 13 C urea breath test 4 weeks after cessation of rabeprazole to determine HP status .Results One hundred and seventy nine GERD patients were included in the study(NERD group 119 cases ,including anti HP treatment group 47 cases ,not anti HP treatment group 32 cases ,HP negative group 40 cases ;EE group 60 cases ,including anti HP treatment group 24 cases ,not anti HP treatment group 15 cases ,HP negative group 21 cases) .HP was eradicated in 76 .6% of the NERD anti HP treatment group and in 75 .0% of the EE anti HP treatment group .Overall ,there is no difference between the anti HP treatment group and other groups on these aspects ,including symptom、esophagitis and acid reflux improvement .Conclusion There are no significant correlation between HP eradication and GERD .

Objective To observe the long-term smokers with primary hypertension patients characteristics and changes in the circadian rhythm of blood by non-invasive 24-hour ambulatory blood pressure monitoring (ABPM),so as to long-term smokers with primary hypertension the prevention and treatment of patients provide a theoretical reference.Methods A total of 200 cases with essential hypertension from February to October 2012 were divided into 2 groups,group A of 100 patients with longterm smoking (smoked ＞ 10 years the daily smoking 30-40 sticks) with primary hypertension crowd;group B of primary hypertension in 100 patients with non-smoking.All patients underwent 24-hour ABPM the patient's consent,were disabled antihypertensive drugs 1 week,its non-invasive 24-hour ABPM,two groups were compared for 24 h average systolic blood pressure (24 h SBP),24-hour average diastolic pressure (24 h DBP),diurnal mean systolic blood pressure (dSBP),mean nighttime systolic blood pressure (nSBP),daytime average diastolic blood pressure (dDBP),night mean diastolic blood pressure (nDBP)and nighttime systolic blood pressure decreased percentage.Results 24 h SBP,24 h DBP,dSBP,nSBP,dDBP,nDBP in group A were higher than those in group B [(139.60 ± 11.69) mmHg (1 mmHg =0.133kPa) vs.(133.90 ± 12.73) mmHg,(82.03 ± 7.44) mmHg vs.(72.58 ± 8.97) mmHg,(152.50 ± 9.79)mmHg vs.(141.30 ±8.92) mmHg,(84.97 ±7.65) mmHg vs.(76.24 ±8.06) mmHg,(138.20 ±8.73)mmHg vs.(127.00 ±9.74) mmHg,(78.52 ± 10.49) mmHg vs.(68.45 ± 11.01) mmHg,and there were statistically significant differences (P ＜ 0.05); hypertension percentage at night systolic blood pressure in group B was lower than that in group A [(6.23 ± 1.79)％ vs.(10.14 ±2.46)％],there was significant difference (P ＜ 0.05).Conclusions Long-term smoking can make the average blood pressure of essential hypertension crowd 24 h,daytime blood pressure and elevated blood pressure at night,and the long-term smoking population in essential hypertension circadian adjustment feature to affect larger,so as soon as possible to promote smoking cessation and long-acting antihypertensive drugs,thereby reducing the incidence of heart,brain,kidney and other target organ damage.

Objective To observe the apoptosis and expression of Toll-like receptor (TLR)-4's mRNA in ischemia-reperfusion injured rat renal tubular epithelia cells (NRK-52E) in vitro, and effect of Cordyceps Sinensis (CS) extractant.Methods Cultured NRK-52E cells were divided into a control group, a model group, and a CS preincubated group. All first removed media and incubated with antimycin A for 1 h, and then recovered the media to simulate the ischemia-reperfusion injury in vitro. We detected the apoptosis ratio of cells by flow cytometer and the mRNA expression of TLR-4, Bax, Bcl-2 gene by reverse transcription-polymerase chain reaction at different time points.Results In ischemia-reperfusion injured NRK-52E, the apoptosis ratio rose as time passed (P＜0.05). We also observed increased mRNA expression of TLR-4, Bax (P＜0.05) and deceased expression of Bcl-2 (P＜0.05). Compared with the model grpup, the CS preincubated NRK-52E cells showed apparent tolerance to ischemia-reperfusion injury, which manifestated lower apoptosis ratio (P＜0.05), decreased expression of mRNA of TLR-4, Bax and increased expression of Bcl-2 (All Ps＜0.05). Conclusion The number of apoptosis cells and the expression of TLR-4 mRNA inceased with ischemia-reperfusion injury of NRK-52E in vitro. CS can prevent the NRK-52E cells from ischemia-reperfusion injury by downregulating TLR-4 gene.