1.Effect and mechanism of Wnt5a knockdown on the efficacy of M1 bone marrow-derived macrophage in treatment of liver cirrhosis
Feifei XING ; Danyang WANG ; Xinrui ZHENG ; Yannan XU ; Shihao ZHANG ; Junyi ZHAN ; Wei LIU ; Gaofeng CHEN ; Jiamei CHEN ; Ping LIU ; Yongping MU
Journal of Clinical Hepatology 2026;42(3):618-628
ObjectiveTo observe the effect of M1 bone marrow-derived macrophages (M1-BMDM) with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis, and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDMWnt5a-KD cells. A rat model of liver cirrhosis induced by CCl4/2-AAF was established, and at the end of week 8, rats were randomly divided into model group, M1-BMDM group, M1-BMDM Wnt5a-knockdown empty vector group (M1-BMDMKD-EV group), and M1-BMDM Wnt5a-knockdown group (M1-BMDMWnt5a-KD group), with 6 rats in each group. On the first day of week 9, the rats in each group were given a single injection of the corresponding cells via the caudal vein, along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology, serum liver function parameters, hepatic stellate cell activation, and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group, all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase (AST) in serum (all P<0.01), and the M1-BMDMWnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group (P<0.05). The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group, all cell treatment groups had a significant reduction in the percentage of CD68-positive area (all P<0.05), and compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area (both P<0.05). Compared with the model group, all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α (all P<0.05) and the protein expression level of CD68 (all P<0.01); compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 (both P<0.05), significant reductions in the protein and mRNA expression levels of CD68 (both P<0.05), and a significant reduction in the protein expression level of tumor necrosis factor-α (P<0.01). Sirius Red collagen staining and alpha-smooth muscle actin (α-SMA) immunohistochemical staining showed that compared with the model group, all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area, with the most significant changes in the M1-BMDMWnt5a-KD group, and compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue (all P<0.05). Compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β (all P<0.05). Compared with the model group, all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue (all P<0.05), and the M1-BMDMWnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDMKD-EV group (both P<0.05). The M1-BMDMWnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDMKD-EV group (P<0.01). Immunofluorescence co-staining showed that compared with the model group, all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 (all P<0.01), and the M1-BMDMWnt5a-KD group had a significantly higher number of such cells than the M1-BMDMKD-EV group (P<0.05). ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl4/2-AAF, which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.
2.Distribution characteristics of bacterial communities in central air-conditioning ventilation systems of a Grade 3A hospital in Shanghai based on 16S rRNA sequencing
Jun NI ; Haiyun ZHANG ; Jian CHEN ; Lijun ZHANG ; Yongping LIU ; Xiaojing LI ; Yiming ZHENG ; Liping ZHANG
Journal of Environmental and Occupational Medicine 2025;42(6):732-739
Background A diverse cohort of patients and susceptible individuals congregate in healthcare facilities, where exposure to pathogenic microorganisms associated with respiratory infectious diseases constitutes a significant risk factor for cross-infection. Central air-conditioning ventilation systems improve some indoor environment indicators while exacerbating the risk of transmission of respiratory infectious diseases. Objective To investigate the distribution characteristics of microbial communities in the central air-conditioning ventilation systems of hospitals, providing a scientific basis for the selection of microbial indicators in hygiene standards for hospital central air-conditioning ventilation systems and for hospital risk early warning systems. Methods In October 2023, two central air-conditioning ventilation systems were selected from a Grade 3A hospital in Shanghai: one was an all-air air-conditioning system serving the waiting area on the ground floor, and the other was a fan coil plus fresh air system serving the outpatient area on the third floor. Samples from four different components of the ventilation systems—air outlets, filters, surface coolers, and condensate trays—were collected for high-throughput sequencing of the 16S rRNA gene to analyze bacterial communities. Alpha-diversity and beta-diversity analyses were performed to investigate the microbial community composition and diversity characteristics of the hospital central air-conditioning ventilation systems. Functional analysis was conducted to determine the relative abundance of bacterial functions in these systems.Results A total of 528 operational taxonomic units (OTUs) were identified, encompassing 20 bacterial phyla, 37 classes, 79 orders, 123 families, and 240 genera. The analysis revealed that the bacterial community was predominantly composed of Proteobacteria, Gemmatimonadates, Bacteroidetes, and Actinobacteria. The diversity analysis indicated that bacterial community richness and diversity were highest in the condensate trays, while no statistically significant differences (P > 0.05) were observed in the bacterial community composition among the air outlets, filters, and surface coolers. The functional analysis showed that the bacterial communities in the central air-conditioning ventilation systems primarily exhibited chemoheterotrophic, oxidative energy-dependent heterotrophic, and ureolytic functional characteristics. Conclusion The dominance of Proteobacteria suggests that this phylum exhibits strong adaptability in the central air-conditioning ventilation systems, possibly related to its ability to survive and reproduce under varying environmental conditions. The diversity analysis indicates that the condensate tray is a critical area for bacterial proliferation in the central air-conditioning ventilation systems. The similarity in environmental conditions among the air outlets, filters, and surface coolers result in similar bacterial community structures. The functional analysis reveals that the bacterial communities possess robust energy conversion and metabolic capabilities, potentially contributing to processes such as organic matter decomposition and nitrogen cycling within the central air-conditioning ventilation systems.
3.Construction and validation of a risk prediction model for intraoperative acquired pressure injury in neurosurgical children
Shanshan HAN ; Yongping QIN ; Hong QU ; Xianlan ZHENG
Chinese Journal of Nursing 2025;60(8):928-933
Objective To construct a risk prediction model for intraoperative acquired pressure injury(IAPI)during neurosurgery in pediatric patients,and verify the predictive effect of the model,to provide a reference for preventing IAPI during neurosurgery in pediatric patients.Methods The clinical data of 776 pediatric patients undergoing neurosurgery in a tertiary-level hospital in Chongqing from January to June 2023 were retrospectively collected.The risk factors for IAPI were explored through univariate analysis and binary Logistic regression analysis.The fitting degree and predictive effect of the model were verified by Hosmer-Lemeshow test and receiver operator characteristic(ROC)curve,respectively.The model was validated internally by Bootstrap.Results The incidence of IAPI during neurosurgery in pediatric patients was 7.99%.Logistic regression analysis showed that bleeding volume,anesthesia time,age,intraoperative use of instruments such as drills and milling cutters that increase external force,and surgical position were the factors influencing IAPI in neurosurgical children(all P<0.05).The results of the Hosmer-Lemeshow test showed that x2=3.636,P=0.888.The results of internal verification showed that the sensitivity of the model was 0.59;the specificity was 0.81;the area under the ROC curve was 0.79.Conclusion This study analyzes the risk factors for IAPI during neurosurgery in pediatric patients and constructs a line chart prediction model with good predictive performance,which can provide a reference for individualized prediction of the risk of IAPI during neurosurgery in pediatric patients.It can provide a scientific basis for clinical nursing staff to identify high-risk children with IAPI early and take personalized preventive measures in time.
4.Study on the mechanistic role of the Fuzheng Huayu formula against cholestatic liver fibrosis in mice
Zheng ZHANG ; Yue LIANG ; Enqi TANG ; Xiaoxi ZHOU ; Yonghong HU ; Gaofeng CHEN ; Wei LIU ; Yongping MU ; Ping LIU ; Jiamei CHEN
Chinese Journal of Hepatology 2025;33(9):889-897
Objective:To investigate the interventional effects of the Fuzheng Huayu (FZHY) formula and its partial mechanistic role on cholestatic liver fibrosis in mice.Methods:Mdr2 gene knockout (Mdr2-/ -) mice were randomly divided into a model group, FZHY group, and Obeticholic acid group. Wild-type C57BL/6J mice of the same age served as the control group. Mdr2-/ -mice were given the corresponding drugs starting from the first day of 9 weeks of age by oral gavage in each group. The control and model groups were administered 0.3% sodium carboxymethylcellulose by oral gavage and were sacrificed at 12 weeks of age for specimen collection. High-speed biochemistry analyzer was used to detect serum alkaline phosphatase and alanine aminotransferase activity in mice. Hematoxylin-eosin staining and Sirius red staining were used to observe pathological changes in liver tissues. Hydroxyproline content was measured to assess collagen in liver tissues. Immunohistochemical staining, Western blotting, and real-time fluorescence quantitative PCR were used to detect the expression of fibrosis markers Col-I and alpha-smooth muscle actin in liver tissues. The expressional condition of cholangiocyte response markers Epcam, CK7, CK19, as well as Pcna, Mki67, and Ccnd1, inflammatory related factors Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4, phosphorylated peroxisome proliferator-activated receptor alpha (PPARα) and nuclear factor kappa-B (NF-κB) were determined. Comparative analysis among multiple groups was performed using one-way ANOVA. The LSD method was used for comparisons between groups. Two-tailed statistical tests were used.Results:Compared with wild-type mice, Mdr2 -/ - mice had a significant increase in serum alanine aminotransferase and alkaline phosphatase activity ( P<0.001). The percentage of Sirius red-positive staining areas and hydroxyproline content in liver tissues was significantly increased ( P<0.01). The expression of Col-I, α-smooth muscle actin, Epcam, CK7, CK19, Pcna, Mki67, and Ccnd1, and the expression of Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4 were significantly increased ( P<0.01); however, both FZHY and Obeticholic acid significantly reversed the increases in these indicators ( P<0.05; P<0.01). Further results showed that compared to wild-type mice, the expression of PPARα was significantly reduced in liver tissues of Mdr2 -/ - mice, while NF-κB was significantly enhanced ( P<0.01). In contrast, compared to Mdr2-/- mice, the expression of PPARα in the liver tissues of FZHY group mice was significantly increased ( P<0.05), while NF-κB was significantly inhibited ( P<0.05). Conclusion:FZHY can significantly improve liver fibrosis, cholangiocyte response, and inflammation in Mdr2 -/ - mice with spontaneously occurring cholestatic liver fibrosis, and its mechanistic role is related to the regulation of the PPARα/NF-κB pathway.
5.Comparison of the efficacy of anatomical resection versus hepatic parenchymal preservation preference in patients with solitary small hepatocellular carcinoma and cirrhosis: a multicenter retrospective study
Liming HUANG ; Yun YANG ; Yuntong LI ; Xianming WANG ; Siming ZHENG ; Qiang LU ; Zisen LAI ; Yongping LAI ; Zongren DING ; Jiahui LYU ; Jiacheng ZHANG ; Xinfeng QIU ; Weiping ZHOU ; Kongying LIN ; Yongyi ZENG
Chinese Journal of Hepatology 2025;33(4):348-358
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.
6.Prognostic analysis of postoperative adjuvant therapy for hepatocellular carcinoma after con-version therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy: a multicenter study
Kongying LIN ; Jia LIN ; Zisen LAI ; Yongping LAI ; Kui WANG ; Jinhong CHEN ; Zhibo ZHANG ; Jingdong LI ; Sheng TAI ; Shifeng WANG ; Siming ZHENG ; Jianxi ZHANG ; Lu ZHENG ; Kai WANG ; Jiacheng ZHANG ; Jiahui LYU ; Liming HUANG ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2025;24(1):103-112
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.
7.Construction and validation of a risk prediction model for intraoperative acquired pressure injury in neurosurgical children
Shanshan HAN ; Yongping QIN ; Hong QU ; Xianlan ZHENG
Chinese Journal of Nursing 2025;60(8):928-933
Objective To construct a risk prediction model for intraoperative acquired pressure injury(IAPI)during neurosurgery in pediatric patients,and verify the predictive effect of the model,to provide a reference for preventing IAPI during neurosurgery in pediatric patients.Methods The clinical data of 776 pediatric patients undergoing neurosurgery in a tertiary-level hospital in Chongqing from January to June 2023 were retrospectively collected.The risk factors for IAPI were explored through univariate analysis and binary Logistic regression analysis.The fitting degree and predictive effect of the model were verified by Hosmer-Lemeshow test and receiver operator characteristic(ROC)curve,respectively.The model was validated internally by Bootstrap.Results The incidence of IAPI during neurosurgery in pediatric patients was 7.99%.Logistic regression analysis showed that bleeding volume,anesthesia time,age,intraoperative use of instruments such as drills and milling cutters that increase external force,and surgical position were the factors influencing IAPI in neurosurgical children(all P<0.05).The results of the Hosmer-Lemeshow test showed that x2=3.636,P=0.888.The results of internal verification showed that the sensitivity of the model was 0.59;the specificity was 0.81;the area under the ROC curve was 0.79.Conclusion This study analyzes the risk factors for IAPI during neurosurgery in pediatric patients and constructs a line chart prediction model with good predictive performance,which can provide a reference for individualized prediction of the risk of IAPI during neurosurgery in pediatric patients.It can provide a scientific basis for clinical nursing staff to identify high-risk children with IAPI early and take personalized preventive measures in time.
8.Prognostic analysis of postoperative adjuvant therapy for hepatocellular carcinoma after con-version therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy: a multicenter study
Kongying LIN ; Jia LIN ; Zisen LAI ; Yongping LAI ; Kui WANG ; Jinhong CHEN ; Zhibo ZHANG ; Jingdong LI ; Sheng TAI ; Shifeng WANG ; Siming ZHENG ; Jianxi ZHANG ; Lu ZHENG ; Kai WANG ; Jiacheng ZHANG ; Jiahui LYU ; Liming HUANG ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2025;24(1):103-112
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.
9.Study on the mechanistic role of the Fuzheng Huayu formula against cholestatic liver fibrosis in mice
Zheng ZHANG ; Yue LIANG ; Enqi TANG ; Xiaoxi ZHOU ; Yonghong HU ; Gaofeng CHEN ; Wei LIU ; Yongping MU ; Ping LIU ; Jiamei CHEN
Chinese Journal of Hepatology 2025;33(9):889-897
Objective:To investigate the interventional effects of the Fuzheng Huayu (FZHY) formula and its partial mechanistic role on cholestatic liver fibrosis in mice.Methods:Mdr2 gene knockout (Mdr2-/ -) mice were randomly divided into a model group, FZHY group, and Obeticholic acid group. Wild-type C57BL/6J mice of the same age served as the control group. Mdr2-/ -mice were given the corresponding drugs starting from the first day of 9 weeks of age by oral gavage in each group. The control and model groups were administered 0.3% sodium carboxymethylcellulose by oral gavage and were sacrificed at 12 weeks of age for specimen collection. High-speed biochemistry analyzer was used to detect serum alkaline phosphatase and alanine aminotransferase activity in mice. Hematoxylin-eosin staining and Sirius red staining were used to observe pathological changes in liver tissues. Hydroxyproline content was measured to assess collagen in liver tissues. Immunohistochemical staining, Western blotting, and real-time fluorescence quantitative PCR were used to detect the expression of fibrosis markers Col-I and alpha-smooth muscle actin in liver tissues. The expressional condition of cholangiocyte response markers Epcam, CK7, CK19, as well as Pcna, Mki67, and Ccnd1, inflammatory related factors Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4, phosphorylated peroxisome proliferator-activated receptor alpha (PPARα) and nuclear factor kappa-B (NF-κB) were determined. Comparative analysis among multiple groups was performed using one-way ANOVA. The LSD method was used for comparisons between groups. Two-tailed statistical tests were used.Results:Compared with wild-type mice, Mdr2 -/ - mice had a significant increase in serum alanine aminotransferase and alkaline phosphatase activity ( P<0.001). The percentage of Sirius red-positive staining areas and hydroxyproline content in liver tissues was significantly increased ( P<0.01). The expression of Col-I, α-smooth muscle actin, Epcam, CK7, CK19, Pcna, Mki67, and Ccnd1, and the expression of Ccl2, Ccl5, Tnf-α, Il10, and Cxcl4 were significantly increased ( P<0.01); however, both FZHY and Obeticholic acid significantly reversed the increases in these indicators ( P<0.05; P<0.01). Further results showed that compared to wild-type mice, the expression of PPARα was significantly reduced in liver tissues of Mdr2 -/ - mice, while NF-κB was significantly enhanced ( P<0.01). In contrast, compared to Mdr2-/- mice, the expression of PPARα in the liver tissues of FZHY group mice was significantly increased ( P<0.05), while NF-κB was significantly inhibited ( P<0.05). Conclusion:FZHY can significantly improve liver fibrosis, cholangiocyte response, and inflammation in Mdr2 -/ - mice with spontaneously occurring cholestatic liver fibrosis, and its mechanistic role is related to the regulation of the PPARα/NF-κB pathway.
10.Comparison of the efficacy of anatomical resection versus hepatic parenchymal preservation preference in patients with solitary small hepatocellular carcinoma and cirrhosis: a multicenter retrospective study
Liming HUANG ; Yun YANG ; Yuntong LI ; Xianming WANG ; Siming ZHENG ; Qiang LU ; Zisen LAI ; Yongping LAI ; Zongren DING ; Jiahui LYU ; Jiacheng ZHANG ; Xinfeng QIU ; Weiping ZHOU ; Kongying LIN ; Yongyi ZENG
Chinese Journal of Hepatology 2025;33(4):348-358
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.

Result Analysis
Print
Save
E-mail