1.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
2.Effect of donor blood lipid levels and pancreatic surface fat on islet isolation outcomes
Jiaqi ZOU ; Biqi ZHANG ; Xuejie DING ; Peng SUN ; Boya ZHANG ; Tengli LIU ; Rui LIANG ; Shusen WANG
Chinese Journal of Organ Transplantation 2025;46(8):592-598
Objective:To investigate the effect of donor blood lipid levels and the degree of fat deposition on the pancreatic surface on the outcome of islet isolation.Method:A retrospective analysis was conducted on 171 cases of islet isolation data from organ donors between May 2015 and December 2024. According to the percentage of fat deposition area on the surface of the pancreatic capsule after trimming, the samples were divided into three groups: mild surface fat group (<30%, 60 cases) , moderate surface fat group (30%–70%, 55 cases) , and severe surface fat group (>70%, 56 cases). The modified Ricordi method was used to digest pancreatic tissue, and islets were purified by continuous density gradient centrifugation. The digestion efficiency, digestion time, islet yield (islet equivalent/quantity) , purity, score, and size were analyzed and compared among groups. One-way ANOVA was used for inter-group comparisons, and Pearson correlation analysis and multiple linear regression analysis were used to explore the relationship between blood lipid levels and islet isolation parameters.Result:The severe surface fat group had significantly higher pre-purification and post-purification islet equivalents, islet number, amount of digested pancreatic tissue, donor triglyceride levels, and low density lipoprotein (LDL) levels than the other groups (all P<0. 05) . Correlation analysis showed that LDL level was positively correlated with pre-purification islet equivalents (62 cases, r=0. 298, P=0. 019) and islet number (58 cases, r=0. 285, P=0. 030) . Donor high density lipoprotein (HDL) level was negatively correlated with post-purification islet equivalents (54 cases, r= – 0. 282, P=0. 039) ; donor triglyceride level was positively correlated with the amount of digested tissue (56 cases, r=0. 268, P=0. 046) and negatively correlated with purity (51 cases, r= - 0. 297, P=0. 035) ; donor very low density lipoprotein (VLDL) level was positively correlated with the amount of digested tissue (67 cases, r=0. 337, P=0. 005) and negatively correlated with purity (61 cases, r=- 0. 348 , P=0. 006) ; donor total cholesterol level was negatively correlated with pancreatic digestion efficiency (34 cases, r= - 0. 370, P=0. 032) , and the above differences were all statistically significant. Conclusion:Pancreata with heavier surface fat deposition can yield a higher number of islets. Meanwhile, donor blood lipid levels are correlated with islet isolation outcomes and can serve as important indicators for donor pancreas selection.
3.The journey of islet organoid transplantation: past, present and future
Ziyuan ZENG ; Xue WANG ; Kai WANG ; Shusen WANG ; Xi WANG
Chinese Journal of Organ Transplantation 2025;46(7):538-545
Diabetes mellitus is a chronic metabolic disorder, currently affecting more than 530 million people worldwide. Based on differences in pathogenesis, it is classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM is primarily caused by autoimmune destruction of pancreatic β cells, whereas T2DM results from insulin resistance due to β cell failure and dysfunction. Current treatments for diabetes include insulin injections, oral medications, and islet transplantation. As a curative therapy, islet transplantation still faces challenges such as limited donor cell availability, systemic immunosuppression-related side effects, and low long-term survival of transplanted islets. Transplantation of stem cell-derived islet organoids is expected to replace primary human islet cells and overcome these issues, making it one of the most promising therapies for T1DM and advanced-stage T2DM. This review provides an in-depth overview of the development of islet transplantation, with a focus on recent progress in stem cell differentiation into islet organoids and the engineering of islet organoids. Meanwhile, we also discuss the current opportunities and future challenges in islet organoid transplantation. These explorations and efforts lay the groundwork for future clinical applications and offer hope for a potential cure for diabetes.
4.Natural killer cell-derived granzyme B as a therapeutic target for alleviating graft injury during liver transplantation.
Kai WANG ; Zhoucheng WANG ; Xin SHAO ; Lijun MENG ; Chuanjun LIU ; Nasha QIU ; Wenwen GE ; Yutong CHEN ; Xiao TANG ; Xiaodong WANG ; Zhengxing LIAN ; Ruhong ZHOU ; Shusen ZHENG ; Xiaohui FAN ; Xiao XU
Acta Pharmaceutica Sinica B 2025;15(10):5277-5293
Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB+ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg -/- Rag2 -/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.
5.Expert Consensus on Classification of Hand Degloving Injures and Emergency Repair of Avulsion Skin
Jihui JU ; Gang ZHAO ; Yongjun RUI ; Xin WANG ; Weiyang GAO ; Xiaoheng DING ; Qingtang ZHU ; Xianyou ZHENG ; Yongqing XU ; Shanlin CHEN ; Juyu TANG ; Lei XU ; Jianxi HOU ; Huaqiao WANG ; Jingyi MI ; Haifeng SHI ; Shusen CUI ; Chunlin HOU ; Liqiang GU
Chinese Journal of Microsurgery 2025;48(2):121-134
Hand degloving injury represents one of the most severe forms of hand trauma, characterised by challenging treatment and a complex prognostic outcome. It is crucial to effectively utilise the degloved tissues in emergency or primary repair of a hand degloving injury. This consensus provides a comprehensive review of the existing literature on definition, classification, emergency assessment, debridement, judgment of skin viability, in situ repair of the degloved skin, and adjunctive treatment for degloving injury of hand. Based on conclusion of both domestic and international experiences, this expert consensus on the classification of hand degloving injury and the emergency repair with the avulsed skin is established, aiming to provide a guidance to surgeons on standardised treatment strategy and improve the management of hand degloving injury.
6.Research progress of stereotactic body radiation therapy for hepatocellular carcinoma with porta vein tumor thrombus
Shungang LI ; Xueyao WANG ; Shusen JIANG ; Hongbing YAO
Chinese Journal of General Surgery 2025;34(7):1514-1522
Portal vein tumor thrombus(PVTT)is a common manifestation of advanced hepatocellular carcinoma(HCC),associated with poor prognosis and significant treatment challenges.Although various therapeutic options-including surgery,systemic therapies,and local treatments such as interventional procedures and radiotherapy-are available for HCC with PVTT,monotherapies often yield limited efficacy,highlighting the need for combined treatment strategies.With the advancement of radiotherapy technologies,stereotactic body radiation therapy(SBRT)has gained increasing recognition due to its high precision,ablative doses,and fewer treatment fractions.SBRT plays a crucial role in palliative care,conversion therapy,neoadjuvant,and adjuvant settings.Recent studies have demonstrated that SBRT,either alone or in combination with other modalities,significantly improves overall survival and local control rates in patients with HCC and PVTT.This review summarizes the current research progress of SBRT in the management of HCC with PVTT,emphasizing both monotherapy and combined approaches with surgery,interventional therapy,targeted agents,and immunotherapy,aiming to provide insights for clinical decision-making.
7.Research progress of stereotactic body radiation therapy for hepatocellular carcinoma with porta vein tumor thrombus
Shungang LI ; Xueyao WANG ; Shusen JIANG ; Hongbing YAO
Chinese Journal of General Surgery 2025;34(7):1514-1522
Portal vein tumor thrombus(PVTT)is a common manifestation of advanced hepatocellular carcinoma(HCC),associated with poor prognosis and significant treatment challenges.Although various therapeutic options-including surgery,systemic therapies,and local treatments such as interventional procedures and radiotherapy-are available for HCC with PVTT,monotherapies often yield limited efficacy,highlighting the need for combined treatment strategies.With the advancement of radiotherapy technologies,stereotactic body radiation therapy(SBRT)has gained increasing recognition due to its high precision,ablative doses,and fewer treatment fractions.SBRT plays a crucial role in palliative care,conversion therapy,neoadjuvant,and adjuvant settings.Recent studies have demonstrated that SBRT,either alone or in combination with other modalities,significantly improves overall survival and local control rates in patients with HCC and PVTT.This review summarizes the current research progress of SBRT in the management of HCC with PVTT,emphasizing both monotherapy and combined approaches with surgery,interventional therapy,targeted agents,and immunotherapy,aiming to provide insights for clinical decision-making.
8.Expert Consensus on Classification of Hand Degloving Injures and Emergency Repair of Avulsion Skin
Jihui JU ; Gang ZHAO ; Yongjun RUI ; Xin WANG ; Weiyang GAO ; Xiaoheng DING ; Qingtang ZHU ; Xianyou ZHENG ; Yongqing XU ; Shanlin CHEN ; Juyu TANG ; Lei XU ; Jianxi HOU ; Huaqiao WANG ; Jingyi MI ; Haifeng SHI ; Shusen CUI ; Chunlin HOU ; Liqiang GU
Chinese Journal of Microsurgery 2025;48(2):121-134
Hand degloving injury represents one of the most severe forms of hand trauma, characterised by challenging treatment and a complex prognostic outcome. It is crucial to effectively utilise the degloved tissues in emergency or primary repair of a hand degloving injury. This consensus provides a comprehensive review of the existing literature on definition, classification, emergency assessment, debridement, judgment of skin viability, in situ repair of the degloved skin, and adjunctive treatment for degloving injury of hand. Based on conclusion of both domestic and international experiences, this expert consensus on the classification of hand degloving injury and the emergency repair with the avulsed skin is established, aiming to provide a guidance to surgeons on standardised treatment strategy and improve the management of hand degloving injury.
9.Effect of donor blood lipid levels and pancreatic surface fat on islet isolation outcomes
Jiaqi ZOU ; Biqi ZHANG ; Xuejie DING ; Peng SUN ; Boya ZHANG ; Tengli LIU ; Rui LIANG ; Shusen WANG
Chinese Journal of Organ Transplantation 2025;46(8):592-598
Objective:To investigate the effect of donor blood lipid levels and the degree of fat deposition on the pancreatic surface on the outcome of islet isolation.Method:A retrospective analysis was conducted on 171 cases of islet isolation data from organ donors between May 2015 and December 2024. According to the percentage of fat deposition area on the surface of the pancreatic capsule after trimming, the samples were divided into three groups: mild surface fat group (<30%, 60 cases) , moderate surface fat group (30%–70%, 55 cases) , and severe surface fat group (>70%, 56 cases). The modified Ricordi method was used to digest pancreatic tissue, and islets were purified by continuous density gradient centrifugation. The digestion efficiency, digestion time, islet yield (islet equivalent/quantity) , purity, score, and size were analyzed and compared among groups. One-way ANOVA was used for inter-group comparisons, and Pearson correlation analysis and multiple linear regression analysis were used to explore the relationship between blood lipid levels and islet isolation parameters.Result:The severe surface fat group had significantly higher pre-purification and post-purification islet equivalents, islet number, amount of digested pancreatic tissue, donor triglyceride levels, and low density lipoprotein (LDL) levels than the other groups (all P<0. 05) . Correlation analysis showed that LDL level was positively correlated with pre-purification islet equivalents (62 cases, r=0. 298, P=0. 019) and islet number (58 cases, r=0. 285, P=0. 030) . Donor high density lipoprotein (HDL) level was negatively correlated with post-purification islet equivalents (54 cases, r= – 0. 282, P=0. 039) ; donor triglyceride level was positively correlated with the amount of digested tissue (56 cases, r=0. 268, P=0. 046) and negatively correlated with purity (51 cases, r= - 0. 297, P=0. 035) ; donor very low density lipoprotein (VLDL) level was positively correlated with the amount of digested tissue (67 cases, r=0. 337, P=0. 005) and negatively correlated with purity (61 cases, r=- 0. 348 , P=0. 006) ; donor total cholesterol level was negatively correlated with pancreatic digestion efficiency (34 cases, r= - 0. 370, P=0. 032) , and the above differences were all statistically significant. Conclusion:Pancreata with heavier surface fat deposition can yield a higher number of islets. Meanwhile, donor blood lipid levels are correlated with islet isolation outcomes and can serve as important indicators for donor pancreas selection.
10.The journey of islet organoid transplantation: past, present and future
Ziyuan ZENG ; Xue WANG ; Kai WANG ; Shusen WANG ; Xi WANG
Chinese Journal of Organ Transplantation 2025;46(7):538-545
Diabetes mellitus is a chronic metabolic disorder, currently affecting more than 530 million people worldwide. Based on differences in pathogenesis, it is classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM is primarily caused by autoimmune destruction of pancreatic β cells, whereas T2DM results from insulin resistance due to β cell failure and dysfunction. Current treatments for diabetes include insulin injections, oral medications, and islet transplantation. As a curative therapy, islet transplantation still faces challenges such as limited donor cell availability, systemic immunosuppression-related side effects, and low long-term survival of transplanted islets. Transplantation of stem cell-derived islet organoids is expected to replace primary human islet cells and overcome these issues, making it one of the most promising therapies for T1DM and advanced-stage T2DM. This review provides an in-depth overview of the development of islet transplantation, with a focus on recent progress in stem cell differentiation into islet organoids and the engineering of islet organoids. Meanwhile, we also discuss the current opportunities and future challenges in islet organoid transplantation. These explorations and efforts lay the groundwork for future clinical applications and offer hope for a potential cure for diabetes.

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