1.A preclinical and first-in-human study of superstable homogeneous radiolipiodol for revolutionizing interventional diagnosis and treatment of hepatocellular carcinoma.
Hu CHEN ; Yongfu XIONG ; Minglei TENG ; Yesen LI ; Deliang ZHANG ; Yongjun REN ; Zheng LI ; Hui LIU ; Xiaofei WEN ; Zhenjie LI ; Yang ZHANG ; Syed Faheem ASKARI RIZVI ; Rongqiang ZHUANG ; Jinxiong HUANG ; Suping LI ; Jingsong MAO ; Hongwei CHENG ; Gang LIU
Acta Pharmaceutica Sinica B 2025;15(10):5022-5035
Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as 131I,177Lu, or 18F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, 18F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).
2.Effectiveness of oral probiotics for hepatectomised patients:a Meta-analysis
Caifang GONG ; Yongfu XIONG ; Junyu ZHAO ; Chuan YOU
Chinese Journal of Pharmacoepidemiology 2024;33(3):319-329
Objective To systematically review the effectiveness of perioperative oral probiotics in hepatic resection patients,and provide evidence-based clinical evidence.Methods PubMed,Cochrane Library,Web of Science,EMbase,SinoMed,WanFang Data,CNKI and VIP databases were electronically searched to collect randomized controlled trials(RCTs)on perioperative oral probiotics in hepatectomized patients from inception to June 30,2023.Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was performed by RevMan 5.4 software.Results A total of 10 RCTs were included,including 715 patients.The Meta-analysis showed that compared to placebo or blank controls,the incidence of postoperative infections in oral probiotic patients(RR=0.60,95%CI 0.48 to 0.74,P<0.001),serum endotoxin levels(MD=-0.88,95%CI-1.53 to-0.22,P=0.009),cumulative antibiotic use(MD=-1.48,95%CI-2.17 to-0.78,P<0.001),AST levels(MD=-9.68,95%CI-11.36 to-8.01,P<0.001),ALT levels(MD=-21.24,95%CI-34.81 to-7.68,P=0.002),TBiL levels(SMD=-0.70,95%CI-0.95 to-0.45,P<0.001),CRP levels(SMD=-0.52,95%CI-0.91 to-0.13,P=0.009),procalcitonin levels(MD=-0.19,95%CI-0.32 to-0.05,P=0.006),IL-6 levels(MD=-7.30,95%CI-14.26 to-0.33,P=0.04),and the first flatus time(MD=-1.16,95%CI-1.51 to-0.82,P<0.001),hospital stay(MD=-0.62,95%CI-0.83 to-0.41,P<0.001),hospitalisation costs(SMD=-0.65,95%CI-0.95 to-0.34,P<0.001)were lower.Conclusion Current evidence shows that perioperative oral probiotics can significantly reduce the postoperative infection rate and decrease the release of inflammatory factors in liver resection patients,promote the recovery of postoperative hepatic and gastrointestinal functions,and shorten the length of hospital stay and costs.Due to the limited quality and quantity of the included studies,more high quality studies are needed to verify the above conclusion.
3.Efficacy and safety of transhepatic arterial chemoembolization combined with tyrosine kinase inhibitor and programmed death receptor-1 inhibitors in the treatment of intermediate and a-dvanced unresectable hepatocellular carcinoma
Jianwei XIONG ; Qiang LI ; Tao TANG ; Lixin ZHANG ; Bao YING ; Kaifeng ZHAO ; Yongfu XIONG ; Jingdong LI ; Guo WU
Journal of Clinical Surgery 2024;32(2):176-181
Objective To investigate the clinical effect of transhepatic arterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptors-1(PD-1)inhibitors(TACE+TKIs+PD-1 antibody)in the treatment of moderate advanced unresectable hepatocellular carcinoma(HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate(ORR),disease control rate(DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 p-atients with hepatocellular carcinoma was 49.2%(32/65),and the DCR was 89.2%(58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6%(18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months(95%CI:12.3~16.6 months)and 8.8 months(95%CI:6.9~10.6 months),respectively.After treatment,65 patients all had post embolism syndrome(abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient(1.5%)stopped using TACE because of stubborn vomiting,and 5 patients(7.6%)stopped using Lenvatinib because of severe liver function damage during treatment,2 patients(3%)stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient(1.5%)stopped using Tislelizumab because of severe hypothyroidism,one patient(1.5%)stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3~4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.
4.Progress on nutritional assessment and nutritional support for liver transplant recipients
Caifang GONG ; Yongfu XIONG ; Junyu ZHAO ; Chuan YOU
Organ Transplantation 2023;14(6):905-912
Patients with end-stage liver disease after liver transplantation constantly suffer from malnutrition due to primary diseases and transplantation-related factors. Malnutrition will worsen clinical condition of the patients, increase the incidence of complication, length of hospital stay and medical expense after transplantation, and lower the survival rate. Sufficient nutritional support at all stages of liver transplantation is of significance. Accurate assessment of nutritional status and timely intervention are prerequisites for perioperative nutritional treatment in liver transplantation. In this article, the latest nutritional risk screening indexes and evaluation tools, nutritional support methods and other perioperative nutritional intervention measures for liver transplantation were reviewed, aiming to deepen the understanding and cognition of perioperative nutritional therapy for liver transplantation and provide reference for improving nutritional status and clinical prognosis of liver transplant recipients.
5.Influence of lymphadenectomy on efficacy of patients with intrahepatic cholangiocarcinoma at different locations
Xujian HUANG ; Chun MENG ; Jianjiao ZHU ; Jiawen LU ; Weinan LI ; Gang YANG ; Yongfu XIONG ; Jingdong LI
Chinese Journal of Digestive Surgery 2023;22(7):891-898
Objective:To investigate the influence of lymphadenectomy on efficacy of patients with intrahepatic cholangiocarcinoma (ICC) at different locations.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 123 patients with ICC who were admitted to the Affiliated Hospital of North Sichuan Medical College from January 2015 to January 2022 were collected. There were 78 males and 45 females, aged 55(rage, 50?60)years. All patients underwent radical resection. Observation indicators: (1) clinical characteristics of patients with ICC; (2) follow-up; (3) surgical situations in ICC patients with different number of lymph nodes dissected. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with ICC. Of the 123 patients, 81 cases had peripheral ICC and 42 cases had central ICC. The albumin-bilirubin grade (grade 1, grade 2?3), preoperative lymph node metastasis risk assessment (low risk, high risk), the number of lymph nodes dissected (<6, ≥6), lymph node metastasis (positive, negative) were 57, 24, 51, 30, 49, 32, 15, 66 in patients with peripheral ICC, versus 19, 23, 17, 25, 14, 28, 16, 26 in patients with central ICC, showing significant differences in the above indicators between them ( χ2=7.40, 5.66, 8.17, 5.62, P<0.05). (2) Follow-up. All the 123 patients were followed up for 28(range, 21?38)months. The 3-year overall survival rate was 57.8% in the 81 patients with peripheral ICC, versus 32.3% in the 42 patients with central ICC, showing a significant difference between them ( χ2=5.98, P<0.05). Of the 42 patients with central ICC, there were 25 cases with high risk of lymph node metastasis before surgery and 17 cases with low risk of lymph node metastasis before surgery. Of the 25 central ICC patients with high risk of lymph node metastasis before surgery, the 3-year overall survival rate was 28.9% in the 18 cases with the number of lymph nodes dissected ≥6, versus 14.3% in the 7 cases with the number of lymph nodes dissected <6, showing a significant difference between them ( χ2=8.90, P<0.05). (3) Surgical situa-tions in patients with the different number of lymph nodes dissected. Of the 123 patients, cases with the number of lymph nodes dissected <6 and ≥6 were 63 and 60, and there was no significant difference in the operation time, intraoperative blood transfusion, postoperative complications, bile leakage, liver insufficiency, pulmonary infection, pleural effusion, abdominal effusion, or lymphatic leakage between them ( P>0.05). One patient might have multiple complications. Conclusions:The prognosis of patients with peripheral ICC is better than that of patients with central ICC. For patients with central ICC who are at high risk of lymph node metastasis before surgery, adequate lymph node dissection may result in a better prognosis.
6.Safety and efficacy evaluation of laparoscopic and open hepatectomy for hepatolithiasis: a propensity score matched analysis
Xujian HUANG ; Yi HE ; Li HE ; Yanjie FENG ; Gang YANG ; Yongfu XIONG ; Jingdong LI
Chinese Journal of Surgery 2022;60(6):593-598
Objective:To compare the safety and efficacy of laparoscopic and open hepatectomy for hepatolithiasis.Methods:Between January 2014 and May 2020, the clinicopathological data of 254 patients with hepatolithiasis who underwent laparoscopic or open hepatectomy at the First Department of Hepatobiliary Surgery,Affiliated Hospital of North Sichuan Medical College were collected retrospectively. There were 74 males and 180 females with age of (56±8) years (range: 38 to 77 years). Of the 254 patients, 162 underwent laparoscopic surgery (laparoscopic group) and 92 underwent open surgery (open group). Propensity score matching(PSM) was performed to match baseline characteristics of the two groups,and then the perioperative results and follow-up efficacy were compared between the two groups. The t-test, Mann-Whitney U test, χ 2 test or Fisher′s exact probability method was used to compare the perioperative data and follow-up results of the two groups after matching, respectively. Results:Each group had 63 patients after PSM with well-balanced baseline characteristics. There was no statistic difference in the type of hepatectomy,combined common bile duct exploration rate,T tube drainage placement rate,operation time,intraoperative transfusion rate,intraoperative accidental injury rate,initial and final stone clearance rate,and stone recurrence rate between the two groups. However,compared with the open hepatectomy group, the laparoscopic group had significantly lower intraoperative blood loss ( M(IQR))(300(175)ml vs. 350(145)ml, Z=3.227, P=0.001),shorter postoperative hospital stay((10.6±4.1)days vs. (14.0±4.0)days, t=4.634, P<0.01),shorter time to postoperative oral intake ((1.8±1.1)days vs. (2.9±1.6)days, t=4.556, P<0.01), and lower postoperative complication rate (25.4%(16/63) vs. 49.2%(31/63), χ2=7.635, P=0.006). Conclusion:Laparoscopic hepatectomy is safe and effective for hepatolithiasis with the advantages of less intraoperative blood loss,lower postoperative complications and faster postoperative recovery.
7.Safety and efficacy evaluation of laparoscopic and open hepatectomy for hepatolithiasis: a propensity score matched analysis
Xujian HUANG ; Yi HE ; Li HE ; Yanjie FENG ; Gang YANG ; Yongfu XIONG ; Jingdong LI
Chinese Journal of Surgery 2022;60(6):593-598
Objective:To compare the safety and efficacy of laparoscopic and open hepatectomy for hepatolithiasis.Methods:Between January 2014 and May 2020, the clinicopathological data of 254 patients with hepatolithiasis who underwent laparoscopic or open hepatectomy at the First Department of Hepatobiliary Surgery,Affiliated Hospital of North Sichuan Medical College were collected retrospectively. There were 74 males and 180 females with age of (56±8) years (range: 38 to 77 years). Of the 254 patients, 162 underwent laparoscopic surgery (laparoscopic group) and 92 underwent open surgery (open group). Propensity score matching(PSM) was performed to match baseline characteristics of the two groups,and then the perioperative results and follow-up efficacy were compared between the two groups. The t-test, Mann-Whitney U test, χ 2 test or Fisher′s exact probability method was used to compare the perioperative data and follow-up results of the two groups after matching, respectively. Results:Each group had 63 patients after PSM with well-balanced baseline characteristics. There was no statistic difference in the type of hepatectomy,combined common bile duct exploration rate,T tube drainage placement rate,operation time,intraoperative transfusion rate,intraoperative accidental injury rate,initial and final stone clearance rate,and stone recurrence rate between the two groups. However,compared with the open hepatectomy group, the laparoscopic group had significantly lower intraoperative blood loss ( M(IQR))(300(175)ml vs. 350(145)ml, Z=3.227, P=0.001),shorter postoperative hospital stay((10.6±4.1)days vs. (14.0±4.0)days, t=4.634, P<0.01),shorter time to postoperative oral intake ((1.8±1.1)days vs. (2.9±1.6)days, t=4.556, P<0.01), and lower postoperative complication rate (25.4%(16/63) vs. 49.2%(31/63), χ2=7.635, P=0.006). Conclusion:Laparoscopic hepatectomy is safe and effective for hepatolithiasis with the advantages of less intraoperative blood loss,lower postoperative complications and faster postoperative recovery.
8.The difficulties and surgical decision analysis of laparoscopic technique in treating complicated hepatolithiasis
Weinan LI ; Yongfu XIONG ; Jianjiao ZHU ; Gang YANG ; Ji SUN ; Jingdong LI
Chinese Journal of Surgery 2021;59(4):279-283
Objective:To explore the difficulties and surgical decision of laparoscopic technique in patients with complicated hepatolithiasis.Methods:The clinical data of 13 patients with complicated hepatolithiasis who underwent laparoscopic hepatectomy at Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College from December 2019 to December 2020 were collected. There were 3 males and 10 females with average age of 50.8 years (range: 14 to 67 years). All patients had upper abdominal pain and a history of cholecystectomy, 4 of them had fever.Seven cases underwent laparoscopic left hemihepatectomy+bile duct exploration, 2 cases underwent laparoscopic right hemihepatectomy+bile duct exploration, 2 cases underwent laparoscopic quadrate hepatectomy (liver 4B+Part 5)+hilar cholangioplasty+bile duct exploration, 2 cases underwent laparoscopic quadrate lobe resection (liver 4B+Part 5)+cholangioplasty+cholangiojejunostomy. All patients were re-examined with abdominal ultrasound and choledochoscope 3 months after operation.Results:The median operation time was 5.2 hours (range: 3.6-6.5 hours), blood loss was 278 ml (range: 120-580 ml). During the operation, 1 case had duodenal bulb injury, and the defect area was about 1.0 cm × 1.2 cm. After timely detection, the defect area was carefully evaluated and trimmed. Absorbable suture was used to suture duodenal bulb, and gastrojejunostomy was performed after repair. One case had small intestinal serosa injury, which was intermittently sutured and embedded with absorbable suture. All the patients recovered smoothly without death. Three months after the operation, 12 patients completed abdominal ultrasound and T-tube sinus choledochoscopy. Residual stones were found in 3 patients, stones were removed in 2 patients by T-tube sinus choledochoscopy 3 months after the operation, 1 patient was still in the recovery period (within 3 months after surgery). No residual stones were found in the remaining 10 patients.Conclusion:The three key laparoscopic techniques in operation of complex hepatolithiasis: adhesiolysis and porta hepatis exposure, laparoscopic hepatectomy, and laparoscopic choledochojejunostomy are very important.
9.The difficulties and surgical decision analysis of laparoscopic technique in treating complicated hepatolithiasis
Weinan LI ; Yongfu XIONG ; Jianjiao ZHU ; Gang YANG ; Ji SUN ; Jingdong LI
Chinese Journal of Surgery 2021;59(4):279-283
Objective:To explore the difficulties and surgical decision of laparoscopic technique in patients with complicated hepatolithiasis.Methods:The clinical data of 13 patients with complicated hepatolithiasis who underwent laparoscopic hepatectomy at Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College from December 2019 to December 2020 were collected. There were 3 males and 10 females with average age of 50.8 years (range: 14 to 67 years). All patients had upper abdominal pain and a history of cholecystectomy, 4 of them had fever.Seven cases underwent laparoscopic left hemihepatectomy+bile duct exploration, 2 cases underwent laparoscopic right hemihepatectomy+bile duct exploration, 2 cases underwent laparoscopic quadrate hepatectomy (liver 4B+Part 5)+hilar cholangioplasty+bile duct exploration, 2 cases underwent laparoscopic quadrate lobe resection (liver 4B+Part 5)+cholangioplasty+cholangiojejunostomy. All patients were re-examined with abdominal ultrasound and choledochoscope 3 months after operation.Results:The median operation time was 5.2 hours (range: 3.6-6.5 hours), blood loss was 278 ml (range: 120-580 ml). During the operation, 1 case had duodenal bulb injury, and the defect area was about 1.0 cm × 1.2 cm. After timely detection, the defect area was carefully evaluated and trimmed. Absorbable suture was used to suture duodenal bulb, and gastrojejunostomy was performed after repair. One case had small intestinal serosa injury, which was intermittently sutured and embedded with absorbable suture. All the patients recovered smoothly without death. Three months after the operation, 12 patients completed abdominal ultrasound and T-tube sinus choledochoscopy. Residual stones were found in 3 patients, stones were removed in 2 patients by T-tube sinus choledochoscopy 3 months after the operation, 1 patient was still in the recovery period (within 3 months after surgery). No residual stones were found in the remaining 10 patients.Conclusion:The three key laparoscopic techniques in operation of complex hepatolithiasis: adhesiolysis and porta hepatis exposure, laparoscopic hepatectomy, and laparoscopic choledochojejunostomy are very important.
10.CCAAT/enhancer binding protein δ inhibits invasion and metastasis of liver cancer by regulating M1 type macrophages polarization
Meng LI ; Yongfu XIONG ; Xujian HUANG ; Taian CHEN ; Jingdong LI
Chinese Journal of Hepatology 2021;29(8):794-798
Objective:To explore the regulation of macrophage polarization and its effects on liver cancer invasion, metastasis and apoptosis by CCAAT/enhancer binding protein δ (CEBPD).Methods:THP-1 stable transfected cells with knockdown CEBPD (shCEBPD) and negative control shNC were constructed by lentviral transfection technique. THP-1 transfected cells were induced into macrophages, lipopolysaccharide (LPS) and interferon γ(IFNγ) by phorbol 12-tetradecanoate 13-acetate (PMA), and then the polarized macrophages were further induced to M1 type. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect M1 type macrophage related interleukin 1β (IL-1β) genes, IL-6, tumor necrosis factor α (TNFα), and inducible nitric oxide synthase (iNOS) mRNA expression level. Flow cytometry was used to detect M1 macrophage-specific surface marker CD80 expression levels. M1-induced macrophages were co-cultured with liver cancer MHCC97H cells using Transwell non-contact small sized co-culture dishes. MHCC97H cells invasion and metastasis were detected by Transwell and scratch assay under co-culture conditions, and the MHCC97H cells apoptosis was detected by flow cytometry.Results:The mRNA expression levels of M1 macrophage marker genes iNOS, TNFα, IL-6 and IL-1β in THP-1 derived macrophages were decreased after CEBPD knockdown. M1 macrophage-specific surface marker CD80 expression levels were decreased (23.7% ± 2.1% and 62.5% ± 2.0%, t = 9.58, P < 0.05). THP-1 were co-cultured with MHCC97H in shCEBPD and shNC group, respectively. Compared with shNC group, the invasion [(158.0 ± 3.5) and (75.0 ± 4.5), t = 39.87, P < 0.01] and metastatic ability (54.6% ± 1.5% and 24.3% ± 1.0%, P < 0.01) of MHCC97H cells co-cultured in shCEBPD group were stronger and the apoptosis rate was reduced [(9.4% ± 1.0%) vs. (23.7% ± 1.2%), t = 12.68, P < 0.01]. Conclusion:CEBPD can inhibit the invasion and metastasis and increase the apoptosis by amplifying M1 type macrophages polarization in liver cancer cells.

Result Analysis
Print
Save
E-mail