1.Contrast-enhanced computed tomography radiomics for the preoperative prediction model of microvascular invasion in intrahepatic cholangiocarcinoma
Zheyu ZHOU ; Shuya CAO ; Chunlong ZHAO ; Qiaoyu LIU ; Xiaoliang XU ; Chaobo CHEN
International Journal of Surgery 2024;51(8):511-516
		                        		
		                        			
		                        			Objective:To predict the status of microvascular invasion (MVI) in intrahepatic cholangiocarcinoma (ICC) patients preoperatively based on the radiomics analysis of contrast-enhanced CT to provide imaging evidence for early identification of patients at high risk of recurrence.Methods:Clinical data of 40 ICC patients who underwent radical hepatectomy at Nanjing Drum Tower Hospital from January 2021 to May 2024 were retrospectively collected. Patients were divided into the MVI group ( n=8) and the non-MVI group ( n=32) according to the MVI status of the postoperative pathology report. Whether there were differences in each pathological index between the groups and the efficacy of radiomics analysis of contrast-enhanced CT for the preoperative prediction of MVI were analyzed. The regions of interest (ROI) were outlined on the arterial and venous phase images using the 3D Slicer software. Then, radiomics features were extracted from each ROI based on Python. Finally, the LASSO regression and glm function were used to screen radiomics features and establish a prediction model based on the R language. The established predictive model′s diagnostic efficacy, calibration, and net clinical benefit were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), respectively. Normally distributed measurement data were expressed as mean±standard deviation ( ± s) and compared using the t-test. Count data were expressed as frequency and compared using the chi-square test. Results:Patients in the MVI group had more poorly differentiated tumors and a significantly higher proportion of lymph node metastases ( P<0.05). The established radiomics prediction model included six features, 1 first-order statistical feature and 5 gray texture features. The area under the ROC curve was 0.87, the sensitivity was 75.0%, and the specificity was 90.6%. The calibration curve showed good agreement between the predicted MVI and actual MVI status, and the decision curve demonstrated that the model could provide a large net clinical benefit. Conclusion:Radiomics analysis of contrast-enhanced CT can identify the MVI status of ICC patients preoperatively and aid in clinical decision-making, providing vital evidence for individualized and precise treatment of ICC.
		                        		
		                        		
		                        		
		                        	
2.Effects of Danshensu on Myocardial Mitochondrial Function in Diabetes Cardiomyopathy Rats Based on PPARγ/PGC-1α Pathway
Jie CHEN ; Qiaoyu YUAN ; Bin LIU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1329-1336
		                        		
		                        			
		                        			Objective To explore the effect of Danshensu on myocardial mitochondrial function in diabetes cardiomyopathy(DCM)rats based on peroxisome proliferator-activated receptor γ(PPARγ)/peroxisome proliferator-activated receptor γ co-activator-1α(PGC-1α)pathway.Methods Rats were randomly separated into normal group,model group,low-(5 mg·kg-1),medium-(10 mg·kg-1)and high-(20 mg·kg-1)dose Danshensu groups,metformin group(140 mg·kg-1),as well as high-dose Danshensu+GW9662 group(20 mg·kg-1 Danshensu+1 mg·kg-1 GW9662),with 12 rats in each group.Except for the normal group,rats in other groups were fed with high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin to construct a DCM model.After successful modeling,the rats were administered corresponding drug once a day for six weeks.Fasting blood glucose values were detected by blood glucose meter.Echocardiography was applied to evaluate cardiac function of rats including left ventricular fractional shortening(LVFS)and left ventricular ejection fraction(LVEF).HE staining was applied to detect pathological changes in myocardial tissue.Transmission electron microscopy was applied to observe mitochondrial structure of myocardial tissue.JC-1 staining was applied to detect mitochondrial membrane potential in rat cardiomyocytes.The kit was applied to detect adenosine triphosphate(ATP)content and reactive oxygen species(ROS)expression in myocardial tissue.Western Blot was applied to detect the protein expression of PPARγ and PGC-1α in myocardial tissue.Results Compared with normal group,fasting blood glucose in model group was significantly increased(P<0.05),LVFS and LVEF were significantly decreased(P<0.05).It was found that myocardial tissue was obviously damaged and myocardial mitochondria became swollen.The percentage of non-deleted cardiomyocyte mitochondrial membrane potential was significantly decreased(P<0.05).ATP content in myocardial tissue was significantly decreased(P<0.05),ROS expression was significantly increased(P<0.05).The protein expressions of PPARγ and PGC-1α in myocardial tissue were significantly downregulated(P<0.05).Compared with model group,fasting blood glucose levels in Danshensu and metformin groups were significantly decreased(P<0.05),while LVFS and LVEF were significantly increased(P<0.05).It was found that myocardial tissue damage and mitochondrial structure damage were alleviated.The percentage of non-deleted cardiomyocyte mitochondrial membrane potential was significantly increased(P<0.05).ATP content in myocardial tissue was significantly increased(P<0.05),ROS expression was significantly decreased(P<0.05).The protein expressions of PPARγ and PGC-1α in myocardial tissue were significantly upregulated(P<0.05).Compared with high-dose Danshensu group,fasting blood glucose level in high-dose Danshensu+GW9662 group was significantly increased(P<0.05),LVFS and LVEF levels were significantly decreased(P<0.05).Damage of myocardial tissue and myocardial mitochondria structure became serious and myocardial mitochondria was obviously swollen.The percentage of non-deleted cardiomyocyte mitochondrial membrane potential was significantly decreased(P<0.05).ATP content in myocardial tissue was significantly decreased(P<0.05),ROS expression was significantly increased(P<0.05).The protein expressions of PPARγ and PGC-1α in myocardial tissue were significantly downregulated(P<0.05).Conclusion Danshensu improves mitochondrial function in DCM rats,which may be related to the activation of the PPARγ/PGC-1α pathway.
		                        		
		                        		
		                        		
		                        	
3.Effect of intensive blood pressure control after successful endovascular therapy on outcomes in patients with anterior circulation stroke: a multicentre, open-label, blinded-endpoint, randomized controlled trial
Chengfang LIU ; Qiwen DENG ; Hongchao SHI ; Feng ZHOU ; Yukai LIU ; Meng WANG ; Qiaoyu ZHANG ; Bingqi ZHANG ; Min LI ; Lei PING ; Tao WANG ; Haicun SHI ; Wei WANG ; Jiankang HOU ; Shi HUANG ; Jinfeng LYU ; Rui SHEN ; Yingdong ZHANG ; Junshan ZHOU
International Journal of Cerebrovascular Diseases 2023;31(6):401-408
		                        		
		                        			
		                        			Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.
		                        		
		                        		
		                        		
		                        	
4.The preliminary study of extracorporeal carbon dioxide removal in acute respiratory distress syndrome for a pediatric patient
Shuang LIU ; Yi HUI ; Qiaoyu WANG ; Pengkun YANG ; Dong QU
Chinese Pediatric Emergency Medicine 2023;30(1):40-45
		                        		
		                        			
		                        			Objective:Extracorporeal carbon dioxide removal(ECCO 2R) is a technique that aims to decarboxylate the blood and thus to correct hypercapnia and respiratory acidosis in acute respiratory failure, but is rarely used in children.We successfully completed the ECCO 2R treatment for a pediatric case with adenovirus pneumonia, severe acute respiratory distress syndrome(ARDS) and hypercapnia in PICU, which provided clinical references for the use of ECCO 2R in acute respiratory failure for children. Methods:A patient with adenovirus pneumonia and severe ARDS was successfully treated with ECCO 2R-continuous renal replacement therapy(CRRT)combined system after weaning from extracorporeal membrane oxygenation(ECMO). We reported the treatment process, ECCO 2R treatment effect and side effects, so as to provide clinical reference for ECCO 2R treatment of children with ARDS. Results:One-year and four-month-old boy was treated with mechanical ventilation and venous-arterial ECMO due to adenovirus pneumonia and severe ARDS.After ECMO treatment for 25 days, he developed severe hypercapnia after weaning from ECMO.ECCO 2R was initiated.The pH value increased by 11.2%(from 7.222 to 7.303) 1 hour after ECCO 2R treatment, partial pressure of blood carbon dioxide(PCO 2)decreased by 29.1%(from 72.6 mmHg to 51.5 mmHg, 1 mmHg=0.133 kPa) and the average airway pressure of high-frequency ventilation decreased by 5 cmH 2O(from 20 cmH 2O to 15 cmH 2O, 1 cmH 2O=0.098 kPa) after 6 hours of ECCO 2R.The CO 2 removal rate of ECCO 2R system was 29.1 mL/min.It was stopped because of ECCO 2R-membrane clotting after 72 h. There was no increase of PCO 2.Extubation was successfully after undergoing invasive mechanical ventilation for 39 days and with noninvasive ventilation for 5 days.The boy was hospitalized in PICU for 54 days, improved and discharged from the hospital.Followed up for 2 years after discharge, the growth and development were good, but the strenuous exercise endurance was still poor. Conclusion:ECCO 2R is effective in improving gas exchange, reducing PCO 2 and lowering ventilator pressure in children with ARDS and hypercapnia, which allow more protective ventilation.ECCO 2R provide transitional treatment for ECMO weaning and provide meaningful clinical reference for the use of ECCO 2R as part of respiratory support in children with respiratory failure.
		                        		
		                        		
		                        		
		                        	
5.Research progress in developmental toxicity and mechanism of letrozole in juvenile animals
Lili FU ; Liping WEI ; Chuqiao LIU ; Qiaoyu TAO ; Peng ZHANG ; Yunliang QIU
Chinese Journal of Pharmacology and Toxicology 2023;37(12):959-965
		                        		
		                        			
		                        			Letrozole,a third generation non-steroidal aromatase inhibitor,has been approved for the treatment of breast cancer in women.In recent years,it has been used in the field of growth and development in children,such as childhood dwarfism,somatic delayed pubertal growth and precocious puberty,but the long-term effects on liver and kidney function,lipid metabolism,reproductive function and bone metabolism are unclear.Studies have shown that letrozole can cause abnormal testicular morphology,changes in seminiferous tubules and interstitial tissues,reduce bone density,affect the bal-ance of bone metabolism,and cause cognitive impairment and apoptosis of nerve cells.The mecha-nism of reproductive toxicity of letrozole may be related to its influence on the development and matura-tion of testicular cells,the expression of sex hormones and gonadotropins in vivo,and the distribution and expression of estrogen receptors in testicular tissues.The mechanism of bone metabolic toxicity is related to its increase in the proliferation and differentiation of osteoclasts induced by receptor activator of NF-κB ligand,as well as the increase of apoptosis,oxidative stress and NF-κB activity of osteo-blasts.The mechanism of cognitive toxicity is related to its regulation of classical and nonclassical effects of the hippocampus,reduction of glutamate uptake by astrocytes,and reduction of L-type calcium channel blockade of caspase 3 activation.This article is to provide reference for safe and effective use of letrozole in clinical pediatrics.
		                        		
		                        		
		                        		
		                        	
6.Effect of general anesthesia under guidance of bispectral index on postoperative fatigue syndrome in elderly patients undergoing laparoscopic resection of gastrointestinal tumor
Qiaoyu LONG ; Yali GE ; Yongjie TENG ; Zhi LIU ; Ju GAO ; Youjing SHEN
Chinese Journal of Anesthesiology 2022;42(4):394-398
		                        		
		                        			
		                        			Objective:To evaluate the effect of general anesthesia under the guidance of bispectral index (BIS) on postoperative fatigue syndrome (POFS) in elderly patients undergoing laparoscopic resection of gastrointestinal tumor.Methods:A total of 90 patients of both sexes, aged 65-80 yr, with body mass index of 18-25 kg/m 2, of American Society of Anesthesiology physical status Ⅰ-Ⅲ, undergoing elective laparoscopic resection of gastrointestinal tumor, were divided into 3 groups ( n=30 each) using a random number table method: control group (C group), BIS value 40-49 group (B1 group), and BIS value 50-60 group (B2 group). Combined intravenous-inhalational anesthesia was used.The intraoperative BIS value was maintained at 40-49 in group B1, the intraoperative BIS value was maintained at 50-60 in group B2, and the fluctuation range of heart rate and mean arterial pressure was maintained within 20% of the baseline value during operation, and vasoactive drugs were given when necessary in group C. Patient-controlled intravenous analgesia was performed with sufentanil plus dezocine plus palonosetron after surgery, when the VAS score > 3 points, oxycodone/acetaminophen tablets 5 mg were administered orally or flurbiprofen axetil 50 mg was intravenously injected for rescue analgesia.The Christensen′s Fatigue Scale (CFS) scores were recorded at 1 day before operation and 1, 3, 7 and 30 days after operation, and the development of POFS (CFS score ≥ 6) was recorded.The intraoperative consumption of propofol, remifentanil and sufentanil was recorded.The serum C-reactive protein concentration was determined by immunoturbidimetry at 1 day before operation and 1 day after operation.The requirement for rescue analgesia within 48 h after operation was recorded.The time to the first flatus, the first ambulation time, length of hospital stay, and occurrence of fever, vomiting and delirium within 3 days after operation were recorded.The Quality of Recovery-15 (QoR-15) scores were measured at 1, 3 and 7 days after operation. Results:Compared with group C, CFS scores were significantly decreased at 1, 3 and 7 days after surgery, the incidence of POFS was decreased at 7 days after surgery, QoR-15 scores were increased at each time point after operation, the length of hospital stay was shortened, and the intraoperative consumption of propofol was reduced in B1 and B2 groups ( P<0.05). Compared with group B1, the intraoperative consumption of propofol was significantly reduced, QoR-15 scores were increased at each time point after operation ( P<0.05), and no significant change was found in CFS scores, incidence of POFS at each time point after operation, or length of hospital stay in group B2 ( P>0.05). There were no significant differences in serum C-reactive protein concentration, postoperative requirement for rescue analgesia, time to first flatus, first ambulation time, and incidence of fever, vomiting and delirium at each time point among the three groups ( P>0.05). Conclusions:General anesthesia under BIS guidance can reduce POFS and promote early postoperative recovery in elderly patients undergoing laparoscopic resection of gastrointestinal tumor.
		                        		
		                        		
		                        		
		                        	
7.Clinical value of split domino donor auxiliary liver transplantation
Wenjie ZHANG ; Qingxiang XU ; Guoqiang LI ; Decai YU ; Yang YUE ; Xinhua ZHU ; Qiaoyu LIU ; Heng CUI ; Beicheng SUN
Chinese Journal of Digestive Surgery 2022;21(2):287-294
		                        		
		                        			
		                        			Objective:To investigate the clinical value of split domino donor auxiliary liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinco-pathological data of 3 liver transplantation recipients who were admitted to Nanjing Drum Tower Hospital affiliated to Nanjing University Medical School and 1 liver transplantation recipient who was admitted to external hospital in September 2018 were collected. The first case was male, aged 22 years, who was diagnosed as type II citrullinemia (CTLN2). The second case undergoing liver transplantation in external hospital was male, aged 59 years, who was diagnosed as decompensated alcoholic cirrhosis. The third case was female, aged 52 years, who was diagnosed as hepatocellular carcinoma of right lobe of liver. The fourth case was female, aged 51 years, who was diagnosed as hepatocellular carcinoma of right lobe of liver. The donor liver from a brain and cardiac death donor was split in vitro into the left liver and the right liver, in which the right liver without middle hepatic vein, and the modified piggyback liver transplantation using the left liver and the classical orthotropic liver transplantation using the right liver was conducted on the first and the second case, respectively. The original liver of the first case was split in vivo into the left liver and the right liver, and the piggyback auxiliary liver transplantation using the left liver and the piggyback auxiliary liver transplantation using the right liver was conducted on the third and the fourth case who underwent extended right hemihepatectomy, respectively. Observation indicators: (1) intraoperative situations; (2) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect liver function, liver imaging, complication and survival of recipients up to October 2021.Results:(1) Intraoperative situations. Liver transplantation was conducted successfully on the first, third and fourth case, with the operation time, the volume of intraoperative blood loss, the donor liver cold ischemia time, the graft-to-recipient weight ratio were 400 minutes, 370 minutes, 390 minutes, 600 mL, 1 300 mL, 1 600 mL, 230 minutes, 152 minutes, 135 minutes, 1.2%, 0.8%, 1.1%. (2) Follow-up. B-ultrasound examination of the first, third and fourth case after liver transplantation showed that the blood flow was normal, and all the 3 cases discharged and were followed up at postoperative 1, 6 and 12 month. The liver function, the level of blood ammonia and citrulline were normal of the first, third and fourth case at postoperative 1 week. Imaging examina-tion showed normal liver morphology of the first and third case, and a transplanted liver atrophy caused by portal vein steal of the fourth case. ① The level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil) of the first case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 22.8 U/L, 404.1 U/L, 355.5 U/L, 289.6 U/L, 31.0 U/L, 23.1 U/L, 42.1 U/L and 25.8 U/L, 31.5 U/L, 517.7 U/L, 327.6 U/L, 172.9 U/L, 15.9 U/L, 21.4 U/L, 47.5 U/L and 29.7 U/L, 3.8 μmol/L, 92.1 μmol/L, 87.4 μmol/L, 79.7 μmol/L, 90.1 μmol/L, 130.6 μmol/L, 33.8 μmol/L and 25.4 μmol/L, 2.3 μmol/L, 47.0 μmol/L, 44.1 μmol/L, 47.1 μmol/L, 57.4 μmol/L, 70.9 μmol/L, 24.7 μmol/L and 9.7 μmol/L, respectively. The level of citrulline and blood ammonia of the first case before and after liver transplantation were 999.0 μmol/L, 196.0 μmol/L and 14.6 μmol/L, 9.0 μmol/L, respectively. The first case was followed up for 3 years and survived without any liver transplantation related complication. ② The level of ALT, AST, TBil, DBil of the third case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 21.3 U/L, 143.9 U/L, 182.0 U/L, 132.0 U/L, 17.2 U/L, 10.1 U/L, 17.6 U/L and 16.8 U/L,20.0 U/L, 291.0 U/L, 227.5 U/L, 106.4 U/L, 15.8 U/L, 10.8 U/L, 17.1 U/L and 19.4 U/L, 6.8 μmol/L, 50.9 μmol/L, 45.0 μmol/L, 34.0 μmol/L, 32.4 μmol/L, 22.3 μmol/L, 12.8 μmol/L and 14.9 μmol/L, 2.5 μmol/L, 18.4 μmol/L, 17.2 μmol/L, 14.9 μmol/L, 14.8 μmol/L, 12.1 μmol/L, 3.6 μmol/L and 4.4 μmol/L. The level of citrulline and blood ammonia of the third case after liver transplantation were 24.9 μmol/L and 16.0 μmol/L. The third case was followed up for 3 years and survived without any liver transplantation related complication. ③ The level of ALT, AST, TBil, DBil of the fourth case before liver transplantation, at postoperative 1 day, 2 day, 3 day, 7 day, 10 day, 6 month and 1 year were 35.0 U/L, 268.7 U/L, 682.0 U/L, 425.8 U/L, 57.5 U/L, 34.0 U/L, 29.4 U/L and 18.1 U/L, 37.0 U/L, 419.1 U/L, 436.2 U/L, 139.5 U/L, 35.2 U/L, 32.4 U/L, 54.7 U/L and 32.8 U/L, 7.1 μmol/L, 64.2 μmol/L, 41.4 μmol/L, 17.6 μmol/L, 34.2 μmol/L, 48.7 μmol/L, 14.1 μmol/L and 21.8 μmol/L, 2.8 μmol/L, 18.9 μmol/L, 16.1 μmol/L, 6.0 μmol/L, 14.6 μmol/L, 26.7 μmol/L, 3.9 μmol/L, 11.8 μmol/L. The level of citrulline and blood ammonia of the fourth case after liver transplantation were 8.4 μmol/L and 47.0 μmol/L. One week after surgery, the transplanted right liver of the fourth case occurred atrophy due to blood stealing from the right branch of the portal vein. B-ultrasound examination showed that the reflux of the hepatic artery and hepatic vein was unobstructed. Immunosuppressants were discontinued 3 months after operation on the fourth case and there was no complication such as rejection, bile leakage, biliary stricture, thrombosis and vascular stricture during follow-up. The fourth case died of lung metastasis 19 months after operation.Conclusion:Split domino donor auxiliary liver transplantation can be used for the treatment of metabolic liver disease and advanced hepatocellular carcinoma.
		                        		
		                        		
		                        		
		                        	
8. Elemental and isotopic determination of lead in whole blood by ISIS-ICP-MS
Jianpei YUN ; Aihua ZHANG ; Fen LIU ; Tiandi LI ; Yiran LIN ; Qiaoyu PAN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2019;37(8):619-622
		                        		
		                        			 Objective:
		                        			To establish a method for determination of lead and istope ratios in the blood by ISIS-ICP-MS.
		                        		
		                        			Methods:
		                        			After wet digestion, the blood sample was on-line addition of thallium as internal standard and analyzed by ISIS-ICP-MS.
		                        		
		                        			Results:
		                        			The limit of detection was 0.03 μg/L and the lower limit of quantification was 0.08 μg/L. The detection concentration was 0.45 μg/L and the minimum quantitative concentration was 1.49 μg/L. The relative standard deviations (
		                        		
		                        	
9.Purification of Total Flavonoids from Tripterospermi Chinensis Herba by Macroporous Resin
Chinese Journal of Information on Traditional Chinese Medicine 2015;(3):94-97
		                        		
		                        			
		                        			Objective To optimize the purification technology of total flavonoids from the Tripterospermi Chinensis Herba by macroporous resin. Methods The purification abilities of six kinds of macroporous adsorption resins for total flavonoids from Tripterospermi Chinensis Herba were studied with the adsorption and desorption rates as the index by static adsorption and desorption experiments. The column liquid concentration, adsorption rate, and the loaded amount were studied by using dynamic adsorption experiments. The optimal desorption technology was examined by orthogonal experiment. Results AB-8 macroporous resin was found to have good adsorption and desorption effects. The optimal purification conditions were as follows:the column liquid concentration was 5.285 mg/mL, adsorption rate was 2 BV/h;the loaded amount was 17.62 mg/mL. The sample was eluted by 10%ethanol with 4 BV and 50%ethanol of 5 BV at a flow rate of 4 BV/h. The purity of total flavonoids increased to 61.95% after the purification, and the yield was 87.28%. Conclusion This optimized process was stable, feasible and suitable for separation and purification of total flavonoids from Tripterospermi Chinensis Herba.
		                        		
		                        		
		                        		
		                        	
10.Optimization and in vitro characterization of resveratrol-loaded poloxamer 403/407 mixed micelles.
Jinfeng LI ; Mingyue GAO ; Huimin WANG ; Qiaoyu LIU ; Shirui MAO
Acta Pharmaceutica Sinica 2015;50(8):1045-51
		                        		
		                        			
		                        			The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.
		                        		
		                        		
		                        		
		                        	
            
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