Objective:To establish a nicotine-treatment and-withdrawal rat model and to evaluate its characteristics and application through analyzing 3 parameters.Methods:Male Sprague-Dawley rats,aged 10-11 weeks old,were randomly divided into normal saline group(subcutaneous injection of saline [0.5 ml/kg] for 6 weeks),nicotine-treated group(injection with nicotine [0.5 ml/kg,3 mg/(kg?d)] for 6 weeks),and nicotine-withdrawn group(injection with nicotine [0.5 ml/kg,3 mg/(kg?d)] for 3 weeks and followed by saline injection for additional 3 weeks).Body weight,food intake,and water intake of animals were recorded during the treatment in 3 groups.The model was evaluated through analyzing body weight,serum parameters and adipose tissue weights.Results:The body weight of rats,as well as the serum levels of triglyceride and insulin,were all decreased after nicotine treatment;the weights of subcutaneous fat,visceral fat and periaortic fat were also decreased.The above indicators increased after withdrawal of nicotine.Conclusion:The established model can be used to study multiple pharmacological effects of nicotine;it can also be used for smoking and smoking cessation related studies.

Objective To explore the role of long noncoding RNA ( lncRNA) CTD-2012K14. 6 in the development of gestational diabetes mellitus (GDM) related macrosomia. Methods The quantitative real-time PCR ( qRT-PCR) was performed to measure the expression of CTD-2012K14.6 in placentas of women with or without GDM, and the quantity of CTD-2012K14. 6 expression and its association with fetal weights were analyzed; Bioinformatic analysis was performed to predict the downstream molecules. CTD-2012K14. 6 over-expressing lentiviral and siRNA was constructed in human trophoblastic cell line HTR-8/SVneo cells, qRT-PCR and Western blot (WB) were used to invest its effect in modulating the expression of downstream molecules. Results The expression of CTD-2012K14.6 in GDM placentas was significantly higher than that in normal controls (1.70 ± 0.63 vs 1.00 ± 0.56,t=3.68,P＜0.01), and positively correlated with fetal weight (r=0.8501, P＜0.01); on-line analysis showed that CTD-2012K14.6 was located at chr16:67,549,214-67,563,958, which was located in the intron of CCCTC-binding factor( CTCF); Up-regulating CTD-2012K14.6 could significantly reduce the expression of CTCF mRNA and protein, and increase the expression of insulin-like growth factor-Ⅱ( IGF-Ⅱ) mRNA and protein, while down-regulating CTD-2012K14.6 could significantly increase the expression of CTCF mRNA and protein, and reduce the expression of IGF-ⅡmRNA and protein. Conclusion The CTD-2012K14. 6 may play an important role in the pathogenesis of GDM related macrosomia by upregulating the expression of CTCF and IGF-Ⅱ.

Objective To observe the clinical efficacy of Shen Shuai Ⅱ Granules combined with integrated Western medicine therapy in patients with primary chronic kidney disease(CKD)in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis,and its effects on expression of serum autophagy related proteins.Methods Totally 88 patients were randomly divided into treatment group and control group,with 44 cases in each group.Both groups were given an integrated Western medicine therapy.On this basis,the treatment group was given Shen Shuai Ⅱ Granules,while the control group was given Shen Shuai Ⅱ placebo,1 bag at a time,twice a day,orally.The treatment for both groups lasted for 24 weeks.The clinical efficacy of the two groups was observed.The TCM symptom scores,serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),blood calcium(Ca2+),blood phosphorus(P3-),parathyroid hormone(PTH),and 24-hour urinary protein quantification(24 UPro)before and after treatment were compared in the two groups.The serum levels of autophagy related protein Beclin-1,Atg7,and LC3-Ⅱ were detected by ELISA before and after treatment in the two groups.Safety indexes of both groups were monitored.Results During the treatment,4 cases fell off in the treatment group and 4 cases in the control group.The total effective rate in the treatment group was 55％(22/40),while that in the control group was 30％(12/40).The therapeutic effect in the treatment group was better than that in the control group(P<0.01).Compared with before treatment,the TCM symptom scores in the treatment group decreased after treatment(P<0.01),the levels of Scr,BUN,UA,P3-,PTH,and 24 UPro decreased(P<0.05,P<0.01),while eGFR increased(P<0.01).The levels of Scr in the control group increased(P<0.05),while eGFR decreased(P<0.01).After treatment,the treatment group had lower various TCM symptom scores,Scr,BUN,UA,P3-,PTH,and 24 UPro levels than the control group(P<0.01,P<0.05),and higher eGFR than the control group(P<0.01).Compared with before treatment,the serum levels of Beclin-1,Atg7,and LC3-Ⅱ increased in the treatment group after treatment(P<0.01,P<0.05),while the serum level of Beclin-1 decreased in the control group after treatment(P<0.01).After treatment,the improvement of the above indicators in the treatment group were better than those in the control group(P<0.01,P<0.05).Correlation analysis showed that Beclin-1,Atg7,and LC3-Ⅱ were negatively correlated with Scr and BUN(P<0.05),and positively correlated with eGFR(P<0.05).There was no obvious adverse reaction in both groups.Conclusion The combination of Shen Shuai Ⅱ Granules and integrated Western medicine therapy for the treatment of primary CKD in stages 3-4 with the syndrome of spleen and kidney qi deficiency,dampness turbidity and blood stasis has confirmed efficacy,which can effectively alleviate clinical symptoms,improve renal function,and delay the progression of CKD.The mechanism may be related to improving the level of autophagy in renal.