OBJECTIVE：To stud y the pharmacok inetics of PELGE-crebanine nanopartic les （PELGE-Cre-NPs） in rabbits. METHODS：Totally 6 rabbits were collected ，and injected with PELGE-Cre-NPs （3.5 mg/kg）via ear vein. 1 mL of blood samples were collected at 5，15，30，60，90，120，150，180，240，300 min after administration from the ear vein. After the plasma were isolated and Cre were extracted with ethyl acetate ，HPLC method was adopted to determine the plasma concentration of Cre by using verapamil hydrochloride as internal standard. The plasma concentration-time curve was drawed and pharmacokinetic parameters were calculated by using DAS 2.0 software. Chromatographic conditions such as the chromatographic column was Agilent ZORBAX Extend-C 18；the mobile phase consisted of methanol- 0.01％ triethylamine solution （75 ∶ 25，V/V）；the flow rate was 1 mL/min；the detection wavelength was 280 nm；the column temperature was 30 ℃；the injection volume was 20 μL. RESULTS：The linear range of Cre were 45.0-3 600 µg/L（R2＝0.999 9）. RSDs of inter-day and intra-day precision and stability tests were all lower than 5％（n＝6 or n＝12）；the accuracies were （97.44±2.41）％-（98.45±3.87）％（n＝6）. PELGE-Cre-NPs was in a two-compartment model in rabbits. Main pharmacokinetic parameters included that t1/2 was（109.357±33.917）min；CL was（0.016±0.001）L/（min·kg）；MRT was （76.733±7.502）min；cmax was（3 699.458±287.713）μg/L. CONCLUSIONS：The half-life period of PELGE-Cre-NPs in rabbits is longer than that of Cre injection；its retention time in the body is prolonged ，and sustained-release effect is obvious.

Objective:Based on the degradation of skeletal muscle protein MuRF mediated by pFoxO1 when insulin resistance occurs, this paper explores the content change of skeletal muscle protein and the effect of Jianpi Qinghua formula when insulin resistance occurs.Methods:C57 mice were fed with high-fat food and made as the model of obesity accompanied by insulin resistance. Then they were divided into model group, Jianpi Qinghua formula group and metformin group according to random number table method with 10 mice in each group. Jianpi Qinghua formula group was orally administered with water decoction 20.961 g/kg, and the metformin group was orally administered with metformin suspension 18.498 g/kg, once a day for 12 consecutive weeks. Intraperitoneal Glucose Tolerance Tests (IPGTT) was used after the model was established and intervened respectively. The relative protein content of pFoxO1, FoxO1, MuRF, MyoD and myosin were detected by Western blot method, and the localization of MyoD and myosin was detected by immuno-histochemistry.Results:Compared with the model group, the blood glucose of IPGTT at 0 min, 60 min and 120 min of both Jianpi Qinghua formula group and Metformin group decreased ( P<0.05). Compared with model group, the ratio of pFoxO1/FoxO1 protein expression level (0.27±0.07, 0.24±0.14 vs. 0.05±0.03) of both Jianpi Qinghua formula group and Metformin group increased ( P<0.05), and the relative expression of MuRF protein (1.22±0.42, 1.15±0.32 vs. 3.21±0.35) of both Jianpi Qinghua formula group and Metformin group decreased ( P<0.05). The relative protein expression of MyoD (1.42±0.45 vs. 0.40±0.11) and myosin (0.80±0.11 vs. 0.51±0.08) relative protein expression of Jianpi Qinghua formula group was significantly higher than that of model group ( P<0.05). Immunohistochemical staining showed that MyoD (5.06±1.72 vs.2.28±0.83) and myosin (60.28±7.47 vs. 39.77±3.34) of Jianpi Qinghua formula group significantly increased compared with model group ( P<0.05). Conclusion:Jianpi Qinghua formula could effectively increase the content of skeletal muscle protein, enhancing the phosphorylation of FoxO1 in skeletal muscle and the inhibition of MuRF degradation pathway.

Objective To investigate if the ratio of pulmonary valve annulus, which is the proportion of pulmonary valvular annulus size to total size of aortic valvular annulus and pulmonary valvular annulus, can better guide the choice of surgical approach than the value of z. Methods A retrospective analysis was made for 254 patients who underwent total correction of tetralogy of Fallot in Guangdong General Hospital between January 2016 and January 2018. There were 154 males and 100 females with an average age of 14.60±18.76 years. The patients were categorized into two groups, a transannular patch group (TAP, n=164) and a non-TAP group (n=90). The sizes of pulmonary and aortic valvular annulus were evaluated in each group, and the cutoff value of proportion of pulmonary valvular annulus for TAP was calculated. Results Both proportion of pulmonary valvular annulus and z-scores were smaller in the TAP group than those in the non-TAP group (0.29±0.06 vs. 0.36±0.06, P<0.001; –4.04±2.13 vs. –2.06±1.84, P<0.001, respectively). In receiver operating characteristics analyses, proportion of pulmonary valvular annulus and the z-score cutoff values were 0.353 (area under the curve 0.781, 95%CI 0.725–0.831) and –2.13 (area under the curve 0.766, 95%CI 0.709–0.817), respectively, demonstrating that the proportion of pulmonary valvular annulus was a more powerful diagnostic tool as a predictor of TAP. Conclusion Our results suggest that the proportion of pulmonary valvular annulus is an effective predictor for TAP and can be easily applied to clinical practice.

Objective     To analyze the use of modified pericardial oblique sinus approach in surgical repair for total anomalous pulmonary venous connection in neonates. Methods     Between May 2005 and December 2015, 67 consecutive neonates with supracardiac or infracardiac type total anomalous pulmonary venous connection who underwent surgical repair in our institute were included in this study. The patients are divided into three groups according to the different approaches including a sulcus approach group (6 patients), a superior approach group (14 patients), and a modified pericardial oblique sinus approach group (47 patients). There were 53 males and 14 females at median age of 12.5 (7.0, 20.5) d.  Results     The time of cardiopulmonary bypass [88 (80.0, 107.0) min vs. 135 (121.0, 157.0) min, P<0.05] and aortic cross clamping of the modified pericardial oblique sinus approach group was significantly shorter than that of the sulcus approach group [45 (39.0, 53.0) min vs. 80 (73.0, 85.0) min, P<0.05]. Perioperative mortality (2.1% vs. 28.6%, P<0.05) was significantly lower in the modified pericardial oblique sinus approach group than that in the superior approach group. The long-term mortality (4.3% vs. 60.0%, P<0.05) was significantly lower in the modified pericardial oblique sinus approach group than that in the sulcus approach group or the superior approach group . The rate of pulmonary venous stenosis was significantly lower in the modified pericardial oblique sinus approach group than that in the sulcus approach group (2.1% vs. 50.0%, P<0.05) or superior approach group (2.1% vs. 35.7%, P<0.05).  Conclusions     In surgical correction of neonatal supracardiac and infracardiac total anomalous pulmonary venous, compared with the traditional surgical approach, the modified pericardial oblique sinus pathway can provide excellent surgical space and has a good surgical prognosis.