1.Effect of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis
Jide A ; Hongshuai PAN ; Kechang ZHAO ; Yongzhen WANG ; Linxun LIU ; Ying ZHANG ; Jingni ZHANG ; Jinping CHAI
Chinese Journal of Hepatobiliary Surgery 2025;31(6):453-457
Objective:To observe the effects of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis.Methods:One hundred healthy female Kunming mice weighing (20±4) g were used to establish a model of alveolar echinococcosis infection by intraperitoneal injection of alveolar echinococcosis protoscoleces. After 6 weeks of feeding, the rats were divided into 5 groups, 15 rats in each group, which were given warm saline, albendazole (100 mg/kg), and sorafenib at high-dose (100 mg/kg), middle-dose (50 mg/kg) and low-dose (30 mg/kg) by gavage for 6 weeks, respectively. Eyeball blood and hepatic alveolar echinococcosis tissue were collected from the mice after the last administration, and the body weight of the mice and the lesion weight were weighed. The concentrations and expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) in serum and lesion tissues were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results:There was no statistically significant difference in the body weight of mice among the saline group, albendazole group and low-dose, medium-dose and high-dose sorafenib groups ( F=0.43, P=0.784). The ratios of lesion weight to body weight in the above groups were (0.057±0.009), (0.031±0.005), (0.033±0.005), (0.031±0.005), and (0.031±0.005), respectively. The saline group had a higher ratio than the other four groups, and the differences were statistically significant (all P<0.05). The relative expression levels of HIF-1α, VEGF-A, VEGFR-2, CD31 and CD34 detected by Western blotting in the saline group were all higher than those in the albendazole group and the high-dose, medium-dose and low-dose sorafenib groups, and the differences were statistically significant (all P<0.05). The relative expression levels of the above proteins in the medium-dose and high-dose sorafenib groups were lower than those in the albendazole group, and the relative expression levels of the above proteins in the high-dose sorafenib group were also lower than those in the medium-dose sorafenib group, and the differences were statistically significant (all P<0.05). The concentration levels of HIF-1α, VEGF-A and VEGFR-2 in serum of mice in each group detected by ELISA were consistent with those detected by Western blotting. Conclusion:Sorafenib inhibits the proliferation of alveolar echinococcosis in mice by suppressing the expression of angiogenic factors in alveolar echinococcosis lesions.
2.Effect of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis
Jide A ; Hongshuai PAN ; Kechang ZHAO ; Yongzhen WANG ; Linxun LIU ; Ying ZHANG ; Jingni ZHANG ; Jinping CHAI
Chinese Journal of Hepatobiliary Surgery 2025;31(6):453-457
Objective:To observe the effects of sorafenib on the lesions and vascular growth factors in the mouse model of hepatic alveolar echinococcosis.Methods:One hundred healthy female Kunming mice weighing (20±4) g were used to establish a model of alveolar echinococcosis infection by intraperitoneal injection of alveolar echinococcosis protoscoleces. After 6 weeks of feeding, the rats were divided into 5 groups, 15 rats in each group, which were given warm saline, albendazole (100 mg/kg), and sorafenib at high-dose (100 mg/kg), middle-dose (50 mg/kg) and low-dose (30 mg/kg) by gavage for 6 weeks, respectively. Eyeball blood and hepatic alveolar echinococcosis tissue were collected from the mice after the last administration, and the body weight of the mice and the lesion weight were weighed. The concentrations and expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor receptor-2 (VEGFR-2) in serum and lesion tissues were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results:There was no statistically significant difference in the body weight of mice among the saline group, albendazole group and low-dose, medium-dose and high-dose sorafenib groups ( F=0.43, P=0.784). The ratios of lesion weight to body weight in the above groups were (0.057±0.009), (0.031±0.005), (0.033±0.005), (0.031±0.005), and (0.031±0.005), respectively. The saline group had a higher ratio than the other four groups, and the differences were statistically significant (all P<0.05). The relative expression levels of HIF-1α, VEGF-A, VEGFR-2, CD31 and CD34 detected by Western blotting in the saline group were all higher than those in the albendazole group and the high-dose, medium-dose and low-dose sorafenib groups, and the differences were statistically significant (all P<0.05). The relative expression levels of the above proteins in the medium-dose and high-dose sorafenib groups were lower than those in the albendazole group, and the relative expression levels of the above proteins in the high-dose sorafenib group were also lower than those in the medium-dose sorafenib group, and the differences were statistically significant (all P<0.05). The concentration levels of HIF-1α, VEGF-A and VEGFR-2 in serum of mice in each group detected by ELISA were consistent with those detected by Western blotting. Conclusion:Sorafenib inhibits the proliferation of alveolar echinococcosis in mice by suppressing the expression of angiogenic factors in alveolar echinococcosis lesions.
3.Clinical efficacy of three-dimensional laparoscopic surgery in treatment of hepatic cystic echinococcosis
Linxun LIU ; Jinyu YANG ; Pengcai FENG ; Mingjie TANG ; Yansong LU ; Shile WU ; Kechang ZHAO
Chinese Journal of Digestive Surgery 2018;17(1):84-88
Objective To investigate the clinical efficacy of three-dimensional (3D) laparoscopic surgery in treatment of hepatic cystic echinococcosis.Methods The retrospective cross-sectional study was conducted.The clinical data of 40 patients with hepatic cystic echinococcosis who underwent 3D laparoscopic surgery in the Qinghai Province People's Hospital from March 2016 to July 2017 were collected.All the 40 patients were treated using 100 mg hydrocortisone on preventing intraoperative anaphylaxis.The experienced surgeons with proficiency in the laparoscopic technology in the same team finished surgery.Patients underwent respectively 3D laparoscopic excision of internal capsule in hepatic echinococcosis + residual cavity treatment,external capsule resection in hepatic echinococcosis and partial hepatectomy based on their conditions.Observation indicators:(1) intraoperative situations:operation completion,surgical procedures,operation time,volume of intraoperative blood loss and blood transfusion;(2) postoperative recovery situations:time to initial anal exsufflation,time for initial fluid diet intake,time for out-of-bed activity,time of indwelling drainage-tube,wound healing,postoperative complications and duration of postoperative hospital stay;(3) follow-up:number of patients with follow-up,follow-up time,oral anti-echinococcosis medical therapy during follow-up,hepatic echinococcosis recurrence and abdominal cavity implantation metastasis.Follow-up using outpatient examination and telephone interview was performed to detect the abdominal symptoms,oral anti-echinococcosis medicine,hepatic echinococcosis recurrence and metastasis up to September 2017.Measurement data with normal distribution were represented as (x)± s.Measurement data with skewed distribution were described as M (range).Results (1) Intraoperative situations:all the 40 patients underwent successful laparoscopic surgery,including 17 undergoing excision of internal capsule in hepatic echinococcosis + residual cavity treatment,15 undergoing external capsule resection in hepatic echinococcosis and 8 undergoing partial hepatectomy.Two patients were combined with abdominal and pelvic hydatids and underwent 3D laparoscopic excision.Operation time and volume of intraoperative blood loss of 40 patients were respectively (100 ± 28) minutes and (86± 24) mL,without intraoperative blood transfusion.(2) Postoperative recovery situations:time to initial anal exsufflation and time for initial fluid diet intake in 40 patients were (2.4± 1.8)hours and (1.7±0.9)days.Forty patients had out-of-bed activity on the day of surgery.Of 40 patients,abdominal drainage-tubes of 39 were placed for 2-3 days;abdominal drainage-tube of 1 with postoperative residual cavity-induced bile leakage was indwelled for 2 months and then was removed.Wound healing and duration of postoperative hospital stay in 40 patients were Class-A healing and (10.5 ± 2.1) days.During hospitalization,39 patients didn't have bleeding,bile leakage,anaphylactic shock,intestinal adhesion and obstruction;1 patient with postoperative residual cavity-induced bile leakage had indwelling drainage-tube removal at 2 months postoperatively.(3) Follow-up:all patients were followed up for 2-15 months,with a median time of 9 months.During the follow-up,40 patients were not complicated with discomforts and received oral antiechinococcosis medical therapy,without hepatic echinococcosis recurrence and abdominal cavity implantation metastasis.Conclusion The 3D laparoscopic surgery is safe and feasible in the treatment of hepatic cystic echinococcosis,and has an obvious advantage in the treatment of irregular hepatic cystic echinococcosis,with good short-term outcomes.

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