Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.

OBJECTIVE To screen the best compatibility ratio and administration conditions of Panax ginseng -Poria cocos pair against aging ，and investigate its mechanism . METHODS P. ginseng-P. cocos pair extracts with different compatibility ratios （1∶1，1∶2，2∶1，1∶4，4∶1，m/m）were prepared ；taking Saccharomyces cerevisiae as the aging model organism ，the S. cerevisiae growth curve was drawn by MTT method ，the best compatibility ratio ，administration concentration and administration time point of P. ginseng-P. cocos pair were screened out ；the activities of antioxidant related enzymes [superoxide dismutase （SOD），peroxidase （POD），catalase（CAT）]，the levels of reactive oxygen species （ROS）and malondialdehyde （MDA），the content of adenosine triphosphate（ATP），and the mitochondrial membrane potential （MMP）in S. cerevisiae cells were detected ；mRNA expressions of SOD1，CTT1，GSH1，ATP1，MRS1 and CDC 19 were also detected . RESULTS The optimal ratio of P. ginseng-P. cocos pair for anti-aging activity was 1∶4（m/m），the optimal administration concentration was 220 μg/mL，and the optimal administration time point was the 28th hour . The extracts of P. ginseng-P. cocos pair（1∶4，m/m）could significantly increase the activities of SOD ， POD and CAT ，ATP content ，MMP，mRNA expression of CTT 1，GSH1 and MRS 1（P＜0.01），but decrease the levels of MDA and ROS ，mRNA expressions of SOD 1，ATP1 and CDC 19（P＜0.05 or P＜0.01）. CONCLUSIONS P. ginseng-P. cocos pair（1∶4， m/m）has a good anti -aging effect on S. cerevisiae ，its mechanism may be related to the positive regulation of oxidative stress and energy metabolism of S. cerevisiae cell.

Objective:To investigate the effects of heme oxygenase-1 (HO-1) on hepatic sinusoidal endothelial cells (LSECs) proliferation, migration, and hepatocyte proliferation.Methods:Eighteen male C57BL/6 mouse aged 6-8 weeks old were underwent partial hepatectomy. Cell proliferation and HO-1 expression in residual liver tissue were detected by immunofluorescence histochemistry at 0 d, 2 d and 4 d after operation. In vitro, LSECs were transfected with adenovirus carrying HO-1 gene (HO-1 group), and the cells were transfected with empty vector adenovirus and the non-transfected cells were used as control. In addition, LSECs from different transfection groups were co-cultured with hepatocyte without contact to evaluate the effect of HO-1 expression on promoting hepatocyte proliferation. Western Blotting and RT-PCR were used to detect the protein and mRNA expression of HO-1, inhibitor of DNA binding and or differentiation (Id1), hepatocyte growth factor (HGF) and Wnt2. Cell proliferation was detected by EdU. The ability of cell migration was detected by Transwell migration assay.Results:Compared with 0 d after hepatectomy, LSECs proliferation and HO-1 expression within LSECs were increased significantly at 4 d after surgery. EdU positive rate of LSECs in HO-1 group (27.20±4.80)% was higher than that in empty vector group (12.47±3.30)% and non-transfected group (15.97±2.50)%. The number of LSECs migration in HO-1 group (258.70±36.56) was higher than that in empty vector group (122.00±38.16) and non-transfected group (107.70±30.01). The protein and mRNA expression level of HO-1, Id1, HGF and Wnt2 in HO-1 group were higher than that in empty vector group and non-transfected group. EdU positive rate of hepatocytes that co-cultured with LSECs in HO-1 group (18.33±2.52) % was higher than that in empty vector group (11.33±1.53)% and non-transfected group (11.7±2.08)%. The differences were statistically significant (all P<0.05). Conclusion:Up-regulation of HO-1 promoted LSECs proliferation and migration of, as well as up-regulation of HO-1 in LSECs enhanced the capacity of LSECs to promote hepatocyte proliferation.

Liver sinusoidal endothelial cells (LSECs) play a positive role in maintaining microcirculation of the liver to achieve liver homeostasis, and they also mediate a balance between regeneration and fibrosis in the process repair of liver injury. After acute liver injury, LSECs are the regulators of liver regeneration, while in chronic injury, abnormally activated LSECs promote development of liver fibrosis. In this paper, we summarized the recent progress in research on the balance between LSECs-mediated liver regeneration and fibrosis, with the aim to provide new ideas in treating liver fibrosis and promoting liver regeneration by targeting LSECs.

Objective To investigate the protective effect of gastrodin (Gas) on the hepatic ischemia-reperfusion injury (HIRI) in mice,and study possible mechanisms.Methods Forty male C57BL/6 mice were randomly divided into sham-operated group (Sham),HIRI group,gastrodin-treated groups with low and high does (Gas-L,Gas-H,respectively),and cobalt protoporphyrin(CoPP) group(n =8).Mice in Gas-L,Gas-H,and CoPP groups were injected intraperitoneally with individual drugs and dose before operation.Except for Sham group,an 70％ volume HIRI model was established by means of 60 minutes ischemia and then 6 hours reperfusion in the other groups.The levels of serum AST and ALT in each group were compared.The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver tissue were measured;The level of TNF-αt,IL-6,IL-10 and heme oxygenase-I (HO-1) mRNA level were detected by real time quantitative PCR.Liver tissue was stained with H&E.The hepatocyte apoptosis was studied by TUNEL.Results Respectively,the serum ALT level in the HIRI,Gas-L,Gas-H and CoPP groups was (5 057.34±290.80)U/L,(3 917.49±198.10) U/L,(3 645.63± 171.10) U/L,(2 977.78± 179.00) U/L,and the ALT level was (5 871.25 ± 819.01) U/L,(4 660.88 ± 505.96) U/L,(4 182.00 ± 507.51) U/L,(3 788.65±462.14)U/L.The serum level of ALT and AST in Gas-L,Gas-H and CoPP groups was lower than HIRI group (P＜ 0.05).The apoptotic index in Gas-L,Gas-H and CoPP groups respectively was (37.89±4.27)％,(32.59±3.78)％,(20.45-±2.49)％,which was lower than group (58.92±3.32)％ (P＜ 0.05).Compared with HIRI group,the TNF-α and IL-6 mRNA level in Gas-L,Gas-H and CoPP groups were decreased,and the levels of IL-10 and HO-1 mRNA were increased.Simultaneously,the activity of SOD was promoted,whereas the levels of MDA was reduced (P＜0.05).Conclusions Gastrodin shows an protective function aganist liver ischemia-reperfusion injury in mice by inhibiting inflammation,oxidative stress and cell apoptosis.The up-regulation of HO-1 by gastrodin may be the possible mechanism.

Objective To investigate the clinical features,diagnosis and treatment of von Hippel-Lindau (VHL) disease in order to improve the understanding of this disease.Methods The clinical features,imaging features,pathological data and treatments of 7 patients in 3 families admitted to our hospital from December 2005 to August 2017 were retrospectively analyzed.Results Ten oprations were performed under the guidance of neural navigation system for the 7 patients.There were 4 enjoying total resection at once;one achieved primary surgical resection of the primary lesions,and residual lesions grew up and the patient accepted surgical treatment at the 7th and 9th years;one patient achieved primary surgical resection of the primary lesion,the residual lesions grew up and surgical treatment was performed 8 months later;another one underwent surgical resection of the primary lesion,and the residual lesion was treated with gamma knife therapy 3 months after surgery.The pathological results of the 10 operations of the 7 patients were proved to be hemangioblastoma.No operative deaths were noted.The symptoms of these patients when they were discharged from the hospital were significantly better than those when they were on admission.The 10 patients were followed up so far,no symptoms of neurological impairment were noted,and they could work and live a normal life.Conclusions Surgical treatment is still the preferred method of VHL,and radiotherapy is effective for small lesions.

Objective To examine the stability of high-density lipoprotein cholesterol (HDL-C)during serum incubation at different temperature and time periods.Methods Ten healthy volunteers (4 males and 6 females,aged 24 to 59 years)from Beijing Hospital were recruited in May 2015.Fasting venous blood samples were collected and centrifuged to separate the sera.Serum samples were incubated at 4℃ for 24 h,25℃for 0,1,8 and 24 h (with or without an LCAT inhibitor).Serum to-tal cholesterol (TC),total free cholesterol (TFC)HDL-C and HDL-FC were measured by the HPLC Method.Results HDL-FC and HDL-C changed -6.91% and -2.17% during serum incubation at 4℃for 24h.TFC,HDL-FC and HDL-C changed significantly (averaged -13.70%,-25.88% and -1.53% respectively)during serum incubation at 25℃ for 24 h,in which the decrease of TFC and HDL-FC were inhibited by the addition of the LCAT inhibitor.The decrease of HDL-C was even higher in the presence of the LCAT inhibitor.Conclusion Serum TFC,HDL-C and HDL-FC levels changed during serum incubations,which were caused by the LCAT and CETP activities and the transfer of cholesterol among lipoproteins. For accurate measurement of serum HDL-C,prolonged serum storage should be avoided in clinical laboratories.