1.Proctor's Reporting Guideline for Implementation Strategies: Interpretation, Application, and Challenges
Jiangyun CHEN ; Jinghan LIU ; Youping ZHUANG ; Xueying CHEN ; Siyuan LIU ; Xiaoshan CHEN ; Yeqing ZHAN ; Dongmei ZHONG ; Huadan HUANG ; Dong XU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):263-273
The Proctor's reporting guideline for implementation strategies represents a landmark framework in the field of implementation science, aiming to address the issue of inconsistent reporting in implementation research by standardizing the naming, definition, and operationalization of implementation strategies, thereby enhancing the credibility and utility of research findings. This paper provides an in-depth interpretation of the core connotations of this reporting guideline and illustrates its application in developing interview outlines and specifying implementation strategies, using a brief smoking cessation intervention project as a case study. Through this reporting guideline, abstract recommendations for implementation are systematically transformed into clear, multidimensional operational guides, significantly improving the transparency of strategy connotations and the replicability of actual execution. Meanwhile, the case study highlights the flexibility of the guideline, which allows researchers to adapt the content and format of strategies based on local resources and cultural contexts, thus enhancing practical adaptability while maintaining scientific rigor. However, the application of Proctor's reporting guideline still faces challenges, primarily manifested in the potential confusion surrounding the constructs of temporality and dose in practice, as well as the challenges that the inherent flexibility of the guideline may pose to the assessment of fidelity and effectiveness. Despite these limitations, the reporting guideline remains a vital tool for implementation research; future efforts should focus on optimizing its application—through refining operational guidelines, standardizing flexible adaptations, and involving stakeholders—to better guide implementation studies and continuously promote high-quality development in the field.
2.Analysis of factors influencing total corneal surgically induced astigmatism following implantable collamer lens implantation
Wanghua ZHAO ; Shutian HUANG ; Lanhua XU ; Xia CHEN ; Liangyong ZHU
International Eye Science 2026;26(3):540-545
AIM: To analyze the factors influencing total corneal surgically induced astigmatism(SIA)following implantable collamer lens(ICL)implantation.METHODS:This prospective study enrolled 162 patients(162 eyes)who underwent ICL implantation at our hospital between July 2023 and January 2024. Based on preoperative assessment of anticipated postoperative residual astigmatism, different incisions were selected. Superior incision was selected for patients with expected residual astigmatism with the rule in 75 eyes, and temporal incision was selected for patients with expected residual astigmatism againist the rule in 87 eyes. Parameters including total corneal refractive power, incision length, internal ostium-to-visual axis distance, central corneal thickness, preoperative total corneal astigmatism, and corneal diameter were measured using the Pentacam anterior segment analyzer before and at 3 mo after surgery. Postoperative total corneal SIA was calculated based on the changes in total corneal refractive power. Multiple linear regression analysis was performed to assess the influence of the above parameters on postoperative total corneal SIA.RESULTS:A total of 162 cases(162 eyes)that implanted with ICL were included in the analysis, and 8 cases were lost to follow-up, with a loss rate of 4.9%. Eventually 154 cases(154 eyes)completed the research. The superior incision group comprised 72 cases(72 eyes), including 17 males and 55 females, with a mean age of 25.96±6.17 years, while the temporal incision group comprised 82 cases(82 eyes), including 20 males and 62 females, with a mean age of 27.79±6.47 years. No significant difference in postoperative total corneal SIA was observed between the two groups [0.31(0.21, 0.49)D vs. 0.27(0.13, 0.485)D, P=0.159]. Multiple linear regression analysis revealed that internal ostium-to-visual axis distance and preoperative total corneal astigmatism significantly influenced postoperative total corneal SIA in the superior incision group(P=0.001). The regression equation was: postoperative total corneal SIA=0.71-0.381×internal ostium-to-visual axis distance+0.16×preoperative total corneal astigmatism. No significant influencing factors for postoperative total corneal SIA were identified in the temporal incision group.CONCLUSION: During ICL implantation, the magnitude of total corneal SIA is comparable between superior and temporal incisions. For patients receiving a superior incision, the internal ostium-to-visual axis distance and preoperative total corneal astigmatism value can be used to quantitatively predict postoperative total corneal SIA to a certain extent, thereby aiding in the optimization of postoperative visual quality.
3.Development trajectories of clustered health risk behaviors and their association with self esteem and loneliness among junior high school students
XU Tao, LIU Lü ; hao, CHEN Jiajia, WANG Yongsheng, ZHANG Tiancheng, YANG Xuejing
Chinese Journal of School Health 2026;47(2):189-193
Objective:
To analyze the developmental trajectories of clustered health risk behaviors and their association with self-esteem and lonelinesss among junior high school students, so as to provide a reference for formulating comprehensive prevention and control measures of health risk behaviors among adolescents.
Methods:
In October 2023, 1 165 first year junior high school students from two schools of Jishou City in Hunan Province were selected by convenient sampling method for three follow up surveys (T1:October 2023; T2:April 2024; T3:October 2024). The Adolescent Health Risk Behavior Questionnaire, Rosenberg Self esteem Scale and Loneliness Scale were used to assess health risk behaviors, self esteem and loneliness, respectively. Latent growth curve modeling and latent growth mixture modeling were applied to analyze the developmental trajectories of clustered health risk behaviors among junior high school students. Logistic regression was used to analyze the association of the developmental trajectories of clustered health risk behaviors with self esteem and loneliness among junior high school students.
Results:
The overall developmental trajectories among junior high school students showed a declining trend (intercept=0.15, slope=-1.65, both P <0.05), with three heterogeneous categories:low risk improvement group ( n =862, 74.0%), moderate risk stable group ( n =260, 22.3%), and high risk deterioration group ( n =43, 3.7%). After adjusting the status of the left behind individuals,using the low risk improvement group as the reference category in multinomial Logistic regression analysis, results indicated that higher loneliness scores among junior high school students increased the risks of belonging to the moderate risk stable group ( OR=1.02, 95%CI =1.00- 1.04 ) and the high risk deterioration group ( OR=1.04, 95%CI =1.00-1.08), while higher self esteem scores reduced the risks of belonging to the moderate risk stable group ( OR=0.93, 95%CI =0.91-0.96) and the high risk deterioration group ( OR=0.88, 95%CI =0.83-0.94) (all P <0.05).
Conclusions
The overall trend of clustered health risk behaviors among junior high school students gradually improves, and the self esteem and loneliness are significant correlative factors. Targeted intervention measures should be developed for the junior high school students, with a focus on enhancing their self esteem and alleviating loneliness.
4.Research Progress in VEXAS Syndrome
Xianghong JIN ; Jin XU ; Miao CHEN ; Junling ZHUANG ; Min SHEN
JOURNAL OF RARE DISEASES 2026;5(1):82-89
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset, X-linked clonal autoinflammatory disease caused by somatic mutations in the
5.Clinical Efficacy of Gandou Fumu Decoction in Treating Hepatolenticular Degeneration with Liver Fibrosis of Liver-kidney Deficiency and Phlegm-blood Stasis Syndrome
Pingping YANG ; Meixia WANG ; Changchang CAO ; Zhuang TAO ; Jiang DU ; Yun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):182-191
ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction (GDFMD) in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome, thereby providing evidence-based medical evidence for the treatment of Wilson's disease (WD)-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1, 2023, to October 1, 2024. Participants were divided into a control group and an observation group, with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate (DMPS). On this basis, the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days, for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses, respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement (LSM), liver serological markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅳ collagen (C-Ⅳ), laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP), and hyaluronic acid (HA)], fibrosis index based on 4 factors (FIB-4), AST to platelet ratio index (APRI), unified Wilson's disease rating scale part Ⅱ (UWDRS-Ⅱ), traditional Chinese medicine (TCM) syndrome score, 24-hour urinary copper, and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment, LSM levels decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses, and the improvement of LSM levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the levels of HA, LN, PⅢNP, and C-Ⅳ decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses, and the levels of HA, LN, and PⅢNP were more obvious (P<0.05). After four treatment courses in the observation group, the levels of HA, LN, PⅢNP, and C-Ⅳ were improved more significantly (P<0.05). Compared with those before treatment, ALT and AST levels decreased in both groups after two and four treatment courses (P<0.05). Compared with the control group after treatment, there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses, and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, APRI score and FIB-4 index level decreased in both groups after two and four treatment courses (P<0.05). Compared with those in control group after treatment, there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses, and the APRI score in the observation group was more obvious after four treatment courses (P<0.05), with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment, the levels of TCM syndrome scores decreased in both groups after two and four treatment courses (P<0.05). Compared with that of the control group after treatment, there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses, and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously, and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses (P<0.05). Compared with those of the control group after treatment, there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses, and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious (P<0.05). Compared with those before treatment, the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses (P<0.05). Compared with those in the control group after treatment, the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses (P<0.01). After two treatment courses, the 24-h urine copper level in the observation group showed a gradual decreasing trend, although it was higher than that before treatment. After four treatment courses, the control group had an improvement rate of 91.43%, an effective rate of 34.29%, and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%, an effective rate of 71.43%, and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group (P<0.05). Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy, and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety, which is worthy of clinical popularization and application.
6.Clinical Efficacy of Gandou Fumu Decoction in Treating Hepatolenticular Degeneration with Liver Fibrosis of Liver-kidney Deficiency and Phlegm-blood Stasis Syndrome
Pingping YANG ; Meixia WANG ; Changchang CAO ; Zhuang TAO ; Jiang DU ; Yun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):182-191
ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction (GDFMD) in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome, thereby providing evidence-based medical evidence for the treatment of Wilson's disease (WD)-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1, 2023, to October 1, 2024. Participants were divided into a control group and an observation group, with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate (DMPS). On this basis, the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days, for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses, respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement (LSM), liver serological markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅳ collagen (C-Ⅳ), laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP), and hyaluronic acid (HA)], fibrosis index based on 4 factors (FIB-4), AST to platelet ratio index (APRI), unified Wilson's disease rating scale part Ⅱ (UWDRS-Ⅱ), traditional Chinese medicine (TCM) syndrome score, 24-hour urinary copper, and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment, LSM levels decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses, and the improvement of LSM levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the levels of HA, LN, PⅢNP, and C-Ⅳ decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses, and the levels of HA, LN, and PⅢNP were more obvious (P<0.05). After four treatment courses in the observation group, the levels of HA, LN, PⅢNP, and C-Ⅳ were improved more significantly (P<0.05). Compared with those before treatment, ALT and AST levels decreased in both groups after two and four treatment courses (P<0.05). Compared with the control group after treatment, there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses, and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, APRI score and FIB-4 index level decreased in both groups after two and four treatment courses (P<0.05). Compared with those in control group after treatment, there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses, and the APRI score in the observation group was more obvious after four treatment courses (P<0.05), with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment, the levels of TCM syndrome scores decreased in both groups after two and four treatment courses (P<0.05). Compared with that of the control group after treatment, there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses, and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously, and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses (P<0.05). Compared with those of the control group after treatment, there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses, and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious (P<0.05). Compared with those before treatment, the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses (P<0.05). Compared with those in the control group after treatment, the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses (P<0.01). After two treatment courses, the 24-h urine copper level in the observation group showed a gradual decreasing trend, although it was higher than that before treatment. After four treatment courses, the control group had an improvement rate of 91.43%, an effective rate of 34.29%, and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%, an effective rate of 71.43%, and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group (P<0.05). Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy, and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety, which is worthy of clinical popularization and application.
7.Inhibitory effects of different concentrations of auranofin on M1 macrophage function and its therapeutic potential in diabetic wound healing
Hongfei PAN ; Zhenbing ZHUANG ; Baiyun XU ; Zhangyang YANG ; Kairui LIN ; Bingqing ZHAN ; Jinghan LAN ; Heng GAO ; Nanbo ZHANG ; Jiayu LIN
Chinese Journal of Tissue Engineering Research 2026;30(6):1390-1397
BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.
8.Inhibitory effects of different concentrations of auranofin on M1 macrophage function and its therapeutic potential in diabetic wound healing
Hongfei PAN ; Zhenbing ZHUANG ; Baiyun XU ; Zhangyang YANG ; Kairui LIN ; Bingqing ZHAN ; Jinghan LAN ; Heng GAO ; Nanbo ZHANG ; Jiayu LIN
Chinese Journal of Tissue Engineering Research 2026;30(6):1390-1397
BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.
9.A Nomogram for Predicting Metachronous Gastric Cancer After Endoscopic Submucosal Dissection of Early Gastric Cancer Following Successful Helicobacter pylori Eradication
Shangtao MAO ; Miao LIU ; Tao ZHAO ; Qiong YAN ; Ying XIANG ; Hai WU ; Wenjun LI ; Hongji TAO ; Duanming ZHUANG ; Lei WANG ; Guifang XU
Journal of Gastric Cancer 2026;26(2):279-294
Purpose:
Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori.
Materials and Methods:
A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection.
Results:
A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively.
Conclusions
Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.
10.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.


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